A 10-week-old male infant presented to our pediatric outpatient department with complaints of gradually progressive noisy breathing since birth. The parents also noticed a bulge over the anterior fontanelle in the past 1 month, which was reportedly increasing in size. Noisy breathing was not associated with the posture but was attenuated during sleep. No history of fever was reported. Birth history revealed normal full-term vaginal delivery with immediate cry. No history of seizure episodes was found. The infant has two older siblings (6 and 2.5 years in age) with no significant ailments. Developmental milestones were normal. Social smile and neck holding were developed. Clinical examination revealed proptosis, abnormal shape of the head with an occipitofrontal diameter of 40 cm. Bulging of the anterior fontanelles and overriding of the cranial sutures were noticeable. Facial development appeared abnormal, which revealed hypertelorism, curved nose and frontal bossing [Figure -]. Respiratory, cardiovascular, abdominal and central nervous system examinations were normal. Ear, nose and throat examination was performed because of the noisy breathing. Flexible laryngoscopy was performed but was not successful, as the scope could not be negotiated until the nasopharynx. Computed tomography (CT) of the paranasal sinuses suggested the presence of bilateral ethmoid sinusitis, otomastoiditis and deviated nasal septum. Nasopharynx appeared normal. Bilateral lateral ventricles, third and fourth ventricles were prominently evident. Features of hydrocephalus were not evident. There was benign prominence of the subarachnoid space.
Three-dimensional volume-rendering technique CT images revealed the fusion of the sagittal sutures. A focal fusion of the right coronal suture along with decreased space of the coronal and lambdoid sutures could also be noticed [Figure -]. Mild dilatation of the bilateral lateral ventricles was found []. Hypoplastic maxilla was noticeable []. Both the orbits appeared normal and no intra-orbital mass/collection was noted. Ultrasonography (USG) of the cranium revealed prominent ventricles, while USG of the abdomen was normal. Retinoscopy findings were +0.25−1 × 90° (right eye) and +0.25−1.5 × 90° (left eye), which were not suggestive of significant refractive errors.[] The fundus examination was normal with no disc edema.
Visual evoked potential (VEP) test was also performed for the electrophysiological evidence of the secondary signs of raised intracranial pressure (ICP). Flash VEP was performed by light-emitting diode goggle stimulation. VEP waveforms were recordable and reproducible in both the eyes. P100 latencies were 127 milliseconds and 119 milliseconds in the right and left eyes, respectively []. Interocular latency difference was increased (right eye with slightly greater P100 delay). If VEPs are recordable (indicating maturation of P100) and replicable (the sign of the validity of responses) in the patient of infantile age group (<6 months), it reveals little possibility of optic nerve dysfunction at this stage.
Based on the clinical features and characteristic radiological findings, the diagnosis was confirmed as CS. The patient was started on oral acetazolamide (45 mg/kg/day in three divided doses) (total 187.5 mg daily) and nutritional supplements. As the infant did not show signs of hydrocephalus at the time of presentation, an expectant approach with careful clinical, ophthalmological, respiratory and radiological monitoring for raised ICP was adopted. The parents of the child were instructed to consult with no delay if the child developed symptoms such as vomiting, loss of consciousness, episodes of seizure or head size enlargement. The result of genetic studies revealed heterozygous mutation of FGFR 2 gene, located on chromosome 10. At the patient’s follow-up visit after 3 months of initial presentation, multistage surgical correction procedures for the craniofacial deformity were advised; however, despite adequate counseling, the parents refused this treatment.


A 25-year-old woman with WPW syndrome () presented to our urology clinic complaining of a nine-year history of nonobstructive urinary retention. Three years prior, she had undergone cardiac ablation, which was unsuccessful, and she was prescribed a 250-mg daily dose of verapamil (Pfizer co, New York, USA) an antiarrhythmic medication to normalize her cardiac rhythm. She had no other medical conditions or family history of urinary retention. She reported multiple visits to the emergency department for urgent decompression by urethral catheterization and having attended multiple urology clinics over the last nine years and undergone multiple diagnostic ultrasounds for the investigation of her urinary retention. The ultrasound images showed an unremarkable upper urinary tract and a smooth bladder with a volume of one liter. Urodynamic studies revealed no measurable detrusor activity. Despite a bladder volume greater than 487 mL, the patient had no urge to void, and her electromyographic study was normal (). She was unable to void after the urodynamic study. As a result, she was diagnosed with nonobstructive urinary retention and was prescribed clean intermittent catheterization four times daily. In addition to her nine-year history of nonobstructive urinary retention, the patient had also experienced constipation over the same time period. She had no other past urologic history and no known neurologic disorders.
The patient was referred to the author’s clinic for further investigation and treatment. A one-liter postvoid residual volume was drained through a Foley’s catheter (Sterimed Group, India). We attempted a two-week trial of tamsulosin hydrochloride 0.4 mg daily (omnic ocas, SAJA CO, Jeddah SA). However, this was discontinued due to serious side-effects (palpitations and orthostatic hypotension), and the patient was advised to continue with the clean intermittent catheterization every four to six hours. This posed no problems, aside from a few urinary tract infections, which were treated according to the urine cultures and sensitivities with oral antibiotics. For the last nine years, intermittent catheterization had not succeeded in achieving any improvement in symptoms or spontaneous voiding. We ordered an outpatient magnetic resonance imaging (MRI) of the spine and pelvis one week after her initial consult at the author’s clinic, where no neurologic, urinary, or gynecological abnormalities were observed. Based on the surgeon’s preference, we then recommended two-stage SNM as a definitive treatment for her urinary retention.
The patient gave consent for a two-staged SNM procedure. Under local anesthesia, conscious sedation, and ﬂuoroscopic guidance, the first SNM stage was performed using the Medtronic unit InterStim therapy (Medtronic Inc., Minnesota, USA). The patient was placed in the prone position with both feet at the edge of the operating table to evaluate hallux movement with stimulation. After marking the sacral spine, local anesthesia with lidocaine 2% (AstraZeneca Pharmaceuticals India Ltd, India) was administered in the S3 region. The sacral neuromodulation kit was used including spinal needles, an introducer, a tined permanent lead, a portable generator, a disposable wire, and connector (Medtronic Inc., Minnesota, USA). Thereafter, a spinal needle was inserted into the left S3 foramen, and we tested for contractions of the levator ani and movement of the hallux. An introducer then replaced the spinal needle, 2 cm deep to the sacral foramen. Finally, the components of the InterStim (Medtronic Inc., Minnesota, USA) were implanted by feeding a tined permanent lead over the introducer and connecting it to a portable generator using a different incision site, disposable wire, and a connector. The procedure was performed under continuous ECG monitoring. The patient was discharged home with a portable generator the following day.
The patient presented for her first follow-up appointment one week after the first stage of the implantation. At that time, she reported spontaneous voiding four times daily and a reduction in the frequency of catheterization to once daily with a urinary drainage of only 200 mL. The patient tolerated the first stage well, with no reported side-effects; therefore, we planned the second-stage SNM to be implanted ten days later. This consisted of the implantation of an implantable pulse generator (IPG) from InterStim (Medtronic Inc., Minnesota, USA) in the left buttock under sterile technique and local anesthesia. At her six-week follow-up appointment, the patient reported a consistent reduction in the frequency of clean intermittent catheterization from six times to once daily with a urinary drainage of only 250 mL.
We consulted the Cardiology team both pre- and postoperatively. They requested continuous intraoperative cardiac monitoring and a postoperative ECG. The ECG did not show any significant changes, and there was no exacerbation of her cardiac symptoms. Furthermore, the one-month postoperative ECGs, which were performed when the SNM device was on and then when the device was off, showed no changes in her cardiac rhythm (). This study was approved by the Institutional Review Board at King Fahad Medical City (IRB Log No. 19-636E) and was performed in accordance with the Declaration of Helsinki. Written informed consent for publication of data was obtained from the patient.


An asymptomatic 70-year-old man, with a history of gastrectomy for gastric cancer, presented with KD and ALSA detected on follow-up computed tomography (CT). The diameter of KD from the opposite aortic wall to the tip of the diverticulum was 53 mm (). Preoperative coronary angiography revealed no significant coronary artery disease, and echocardiography revealed normal cardiac function. The ALSCA originating from KD passed behind the trachea and esophagus, and the bottom of the diverticulum was located on the left side of the vertebra. The CT also revealed severe aortic arch angulation and no landing zone from the arch vessels to KD. The patient was not eligible for TEVAR, and in situ reconstruction of the ALSCA via right thoracotomy appeared challenging. Thus, we planned hybrid repair, left carotid artery (LCA) to the left subclavian artery (LSCA) bypass, and embolization of the LSCA prior to replacement of the descending aorta via right thoracotomy to prevent tremendous backflow from the ALSCA on the same day.
First, the LCA to LSCA bypass was performed using a 7-mm expanded polytetrafluoroethylene graft. Next, a 16-mm Amplatzer vascular plug II (Abbott Medical Japan Co., Ltd., Tokyo, Japan) was placed from the LSCA just distal to KD and proximal to the left vertebral artery. Following LSCA embolization, the patient was shifted to the left lateral recumbent position.
Right lateral thoracotomy was performed through the fourth intercostal space, and the fifth rib was divided posteriorly. Cardiopulmonary bypass was established using an aortic cannulation on the descending aorta and bicaval drainage. Traction sutures were placed on the pericardium to obtain a good working space to insert the left ventricular (LV) vent tube via the right pulmonary vein and anterograde and retrograde cardioplegia cannula. During cooling, the left phrenic and vagus nerves were preserved, and the intercostal arteries were clipped from the outside to prevent steal phenomenon before the aneurysm was opened. The ascending aorta and descending aorta were clamped with deep hypothermia (tympanic temperature, 20°C), and cardiac arrest was induced by anterograde and retrograde cardioplegia. The aneurysm was transected, and open proximal anastomosis was performed just distal to the right SCA using a 22-mm single-branched J Graft SHIELD NEO (J Graft, Japan Lifeline Co., Ltd., Tokyo, Japan) with deep hypothermic circulatory arrest (DHCA) and retrograde cerebral perfusion. Following re-warming, the bottom of KD was closed with 4-0 polypropylene sutures just in case, and distal anastomosis to the descending aorta was performed (). The surgical time was 435 min; bypass time, 136 min; myocardial ischemia time, 29 min; and circulatory arrest (retrograde cerebral perfusion) time, 29 min. About 2 U of red cell concentrates and 10 U of platelet concentrates were transfused. The patient had a normal recovery in the intensive care unit. He was discharged without any symptoms and remained uneventful at 1 year after the operation.


A 67-year-old woman without previous medical history felt emotionally affected during the funeral of a close relative. Four days later, she felt sudden chest pain and shortness of breath. In the local health centre, her haemodynamic state deteriorated within a few minutes with a blood pressure drop to 60/30 mmHg. She had worsening chest pain. Troponin-T was elevated and the ECG () showed wide-spread ST-elevations in the anterior and inferior leads with Grade 3 ischaemia. There were no cardiac murmurs but auscultation of the lungs revealed fine crepitant rales suspecting cardiac ödema.
Ticagrelor, Enoxaparin, and Aspirin were administered and she was immediately transported to hospital for primary percutaneous coronary intervention. At hospital arrival, she had intense chest pain and her blood pressure was 60/30 mmHg. The ECG () showed extensive ST elevations in all precordial leads and also in the inferior leads. The ST elevations had a triangular or lambda shape in II, III, aVF, and V3–V6. Oxygen saturation was 75%. Echocardiography showed an ejection fraction (EF) of 20%.
The patient had repeated episodes of non-sustained ventricular tachycardia (VT) at 165 b.p.m. During the VT episodes, she lost her consciousness, electrical cardioversion was not required.
In emergent coronary angiography, a 7-Fr guiding catheter was introduced into the left coronary artery immediately because of a suspicion of left main occlusion. Surprisingly, there were no signs of coronary artery disease. Coronary flow was slightly reduced (TIMI II) most probably due to severe hypotension. The patient was haemodynamically unstable, and optical coherence tomography was performed to rule out plaque rupture or thrombosis of the left main or left anterior descending coronary artery; the findings were completely normal. Ticagrelor and Aspirin therapy was not continued.
The patient was admitted to the intensive care unit with a suspicion of Takotsubo syndrome. Cardiogenic shock was treated with non-invasive ventilatory support, levosimendan infusion, and parenteral furosemide. Repeated VTs were treated with 300 mg amiodarone bolus + 1200 mg/24 h infusion and one 30 mg lidocaine bolus.
Troponin-T elevated to maximum of 500 ng/L (<15 ng/L) and P-Probnp to 6900 ng/L (<285 ng/L).
The ECG () remained severely distorted with triangular QRS-ST-T waveforms and the patient continued to have haemodynamic compromise and repeated non-sustained VTs. Echocardiography showed typical apical ballooning and an ejection fraction of 20% with thrombus in the left ventricular (LV) apex (). Low-molecular weight heparin was started 100 mg × 2 s.c.
Mechanical LV support therapy was considered, but our hospital does not provide such equipment, and patient transfer to the nearest university hospital was not considered safe because of haemodynamic instability. If transport would have been necessary in case of further clinical deterioration, the LUCAS chest compression system would have been considered. The patient’s condition improved steadily within a few days, and after a week, she was discharged home with an EF of 35%. Because of the thrombus, warfarin was started during the initial hospital stay. Low-molecular weight heparin therapy was discontinued on the 6th day of hospital stay when INR reached 2.0.
Within a week, the ECG showed almost complete ST resolution with minor T-wave inversions in V3–V4. The QRS complex was narrow and inferior and anterior Q waves had developed.
At 1-month follow-up, the patient was asymptomatic with an almost normal EF of 50% and no signs of apical thrombus. The ECG () showed complete ST resolution and resolution of Q waves with T-wave inversions in I, aVL, and V2–V6.
After 2 months, cardiac magnetic resonance imaging was performed. The thrombus had dissolved and only mild hypokinesia and late enhancement in the LV apex compatible with Takotsubo syndrome was found. Warfarin was stopped.
Nine months after the event, the patient was completely asymptomatic, but the ECG still showed T-wave inversions in V2–V6. Two years after, the event the ECG and echocardiography were completely normal and patient had a betablocker as the sole medication.


A 36-year-old man presented to the hospital with subacute onset heart failure, palpitations, and atypical chest pain. He had schizophrenia (with an admission 10 years prior for paranoia and suicidal behaviour) and several cardiovascular risk factors, including hypertension, smoking habits, dyslipidaemia, and obesity (body mass index 48 kg/m2). His medication included bisoprolol 2.5 mg o.d., ramipril 5 mg o.d., simvastatin 20 mg o.d., metformin 1000 mg b.i.d., lamotrigine 25 mg o.d., risperidone 4.5 mg o.d., and lorazepam 2.5 mg o.d.
Upon initial examination, he was tachycardic at 150 b.p.m., had a blood pressure of 110/55 mmHg, and a peripheral oxygen saturation of 90%. Heart sounds were rapid with no murmurs, jugular venous pressure was raised at 45°, there were bilateral pulmonary rales and pedal oedema. Electrocardiogram revealed rapid atrial flutter (150 b.p.m.) and non-specific ST changes (). A transoesophageal echocardiogram was done in the emergency room and excluded left atrial appendage thrombus, allowing for safe cardioversion (1 synchronized 150 Joules shock) that successfully reverted the patient back to sinus rhythm. The transthoracic echocardiogram performed at the echo laboratory disclosed an extrinsic compression on the left atrium and left ventricular (LV) moderate systolic dysfunction with global hypokinesia (, Video S1).
Given the patient’s risk factors and clinical presentation, a coronary angiography was performed to evaluate for coronary disease. There was no epicardial coronary disease, but the angiography showed a large vascularized mass located posteriorly to the heart. The mass was supplied mainly by an anomalous feeder branch arising from the left circumflex coronary (; , Video S2).
Contrast computed tomography (CT) scan revealed a large mediastinal mass (61 × 53 × 33 mm) with heterogeneous arterial-phase enhancement and compression of the left atrium (). The poorly defined borders of the mass suggested local invasion of the pulmonary arteries and the pericardium. These CT findings raised the suspicion of a PG. There were no other masses or suspicious ganglia in the thoracic, abdominal or pelvic compartments.
Hormonal analysis showed significant elevation of 24-h urinary and plasmatic normetanephrine values, revealing that this was a functional(catecholamine-secreting) PG. A subsequent whole-body 123-MIBG scintigraphy confirmed an isolated enhanced uptake in the mediastinum.
The final diagnosis was consistent with the presence of a large non-metastatic functional mediastinal PG, with a left circumflex coronary anomalous feeder branch. Catecholamine secretion and direct mass effect were the most likely causes for atrial flutter and subsequent tachycardiomyopathy.
Anticoagulation with rivaroxaban (20 mg o.d.) was started. Alpha and beta blockade was achieved by adding the alpha-blocker phenoxybenzamine (10 mg initially slowly titrated until 30 mg/day) to the selective beta-blocker bisoprolol (2.5 mg o.d.). The case was subsequently discussed at a multidisciplinary meeting with the cardiology and neuroendocrine thoracic tumours teams.
Surgical risk was deemed high due to (i) patient comorbidities (metabolic syndrome, LV dysfunction, and schizophrenia), (ii) tumour vascularization and proximity to major thoracic structures, and (iii) risk of catecholamine surges. The team’s approach to try to optimize the patient prior to surgery, namely by trying to decrease tumour size and the risk of perioperative complications, consisted of three steps. The first was alpha and beta blockade, the second was to perform embolization of the anomalous coronary branch, and the third was peptide-receptor radionuclide therapy with 177-Lu-DOTATE. The patient’s 68-Galium-DOTANOC positron emission tomography scan showed high expression of somastostatin receptors (), making him a good candidate for radionuclide therapy.
Cardiac catheterization was performed via radial artery. For the embolization procedure, the interventional cardiologists used the EBU 3.5–4 (Medtronic®) guiding catheter, the BMW guidewire (Abbot®), and the microcatheter finecross (Terumo®). Two hydrocoils (AZUR®) were deployed in the anomalous branch of the circumflex artery achieving significant reduction in distal flow (, Video S3). Subsequently, the patient underwent radionuclide therapy with 177-Lu-DOTATE and completed two cycles during the following year (1 cycle every 3–5 months).
A CT coronarography performed 1 month after the procedure and confirmed the successful embolization of the anomalous branch. A second follow-up CT was performed after the second cycle of radionuclide therapy (11 months after embolization) (). It confirmed a reduction both in tumour vascularization and size (from 61 × 53 × 33 mm to 59 × 50 × 29 mm). The patient was followed monthly via outpatient consultations. His symptoms slowly improved and there was no evidence of arrhythmia recurrence. Echocardiography was done every 6 months and showed an improvement in LV function (39–50% in LV ejection fraction by Simpson’s biplane). Hormonal analysis revealed a decrease in catecholamine levels [plasmatic normetanephrine (upper limit of normal < 983): initial value: 4530 pmol/L, at 12 months: 4420 pmol/L; urinary normetanephrines (normal-range: 480–2424): initial value 10454 nmol/day, at 12 months: 8894 nmol/day]. Genetic testing for SDHAF2, SDHB, SDHC, SDHD, MAX, TMEM127, and VHL genes was negative.
The adjunctive strategies to reduce surgical risk showed positive results. Unfortunately, the patient expired due to unrelated causes (suicide) before the procedure (18 months after initial presentation).


A 36-year-old man with no medical history presented to the Stomatology Department of Peking University Third Hospital, Beijing, China, complaining of a toothache during mastication in the maxillary left posterior region for approximately 3 mo.
He had a history of spontaneous and intermittent toothache for the past month. The pain was spontaneous and severe, particularly at night.
The patient had a free previous medical history.
Clinical examination revealed a deep mesio-occlusal carious lesion on the left maxillary first molar (tooth 2.6). Palpation of the buccal and palatal aspects of the involved teeth did not reveal any tenderness. However, the left maxillary first molar exhibited tenderness to vertical percussion. The teeth were not mobile, and periodontal probing around the teeth was within physiological limits. Thermal testing of the involved tooth with heated gutta-percha and dry ice caused intense lingering pain; electronic pulp stimulation (Parkell Electronics Division, Farmingdale, NY, United States) showed pulpal vitality for the tooth.
A preoperative X-ray radiograph revealed carious lesions closely approximating the pulp with a widened periodontal ligament adjacent to the mesiobuccal root with respect to the left maxillary first molar (Figure ).
The medullary bottom could be explored with four root canal ports (Figure ). The root canal length was measured (PROPEX II, Densply Maillefer CH-1338 Ballaigues, Israel). CBCT images revealed two mesiobuccal root canals, one distobuccal root canal, and one 1-2-1-shaped palatal root canal for the left maxillary first molar (Figure ).
Endodontic therapy was proposed and accepted by the patient. Written informed consent was obtained from him. The tooth was isolated with a rubber dam after local infiltration anesthesia. After removing the crown pulp, the medulla chamber was found to be rectangular. Cleaning and shaping were performed using rotary instruments (X-SMART, Dentsply France SAS, 4, rue Michael Faraday, Japan) along with 17% EDTA gel (canal lubricant and chelating agent, Pulpdent Corporation, 80 Oakland St. Watertown, MA, United States); 3% sodium hypochlorite was used as the working solution. All the mesiobuccal and distobuccal canals were enlarged to size 30/0.04, whereas the palatal canal was enlarged to size 40/0.04.
Master cones (Dentsply Maillefer) were selected corresponding to the size and taper of the last file used to the working length, which was confirmed radiographically (Figure ). The canals were dried with absorbent paper points (Dentsply Maillefer, Ballaigues, Switzerland), and obturation was performed using gutta-percha (Dayading, Beijing, China). Final radiographs were taken to establish the quality of the obturation (Figure ). The postobturation clinical image is shown in Figure . Then, the tooth was filled with resin sealer on the chamber.


A 63-year-old woman was admitted to our hospital on May 23, 2018 due to weakness for 10 d and unconsciousness for 6 d.
In the 10 d before admission (May 13, 2018), the patient was weak (platelets, 21 × 109/L; hemoglobin, 91 g/L). Her bone marrow test at another hospital showed a moderate number of megakaryocytes with poor function. She was administered with immunosuppressive therapy with dexamethasone. However, scattered ecchymosis in the whole body, irritability, aphasia, and gradual unconsciousness occurred on May 19, 2018.
The patient had no remarkable previous medical history.
The physical examination revealed unconsciousness, lethargy, and scattered ecchymosis in the whole body.
On May 20, 2018, the patient had a platelet count of 9 × 109/L, hemoglobin level of 81 g/L, and ADAMTS13 activity < 5%. She was given immediate treatment with fresh frozen plasma infusion (400 mL) and methylprednisolone 40 mg. However, her coma deepened on May 23, 2018. Upon admission, she had a white blood cell count of 11.5 × 109/L, hemoglobin level of 74 g/L, and platelet count of 19 × 109/L.


A 54-year-old man was admitted to our hospital with complaints of 10 days of fever and left-sided chest pain on November 18, 2017. He had noted the onset of a moderate grade fever (38.4°C) and severe left chest pain with a visual analog scale (VAS) score of 6 on November 8, 2017. He was admitted to the local hospital 2 days later. The results of his blood tests were as follows: white blood cell count (WBC) 13 × 109/L, 90% neutrophils, hemoglobin (Hb) concentration 134 g/L, platelets 252 × 109/L, erythrocyte sedimentation rate (ESR) 98 mm/h, and C-reactive protein (CRP) 245 mg/L. A chest computerized tomography (CT) scan (Fig. A) showed left pleural effusion. He had been given intravenous antibiotic injections daily for 1 week. However, this patient continued to suffer from a fever, and his chest pain progressively worsened, with a VAS score of 8 to 9. At that point he was referred to our hospital. His physical examination showed the following: body temperature 38.3°C, pulse 90 beats/min, breathing rate 18 breaths/min, blood pressure 99/72 mm Hg, and percutaneous oxygen saturation 95% (room air). His respiratory system examination findings were consistent with mild to moderate left-sided pleural effusion, and no abnormalities were detected in the other systems. He had a history of type 2 diabetes mellitus for 10 years, which was not well controlled and monitored. A repeated CT scan showed increased left pleural effusion (Fig. B) and newly formed encapsulated effusion in the left interlobar fissure (Fig. C). The results of the laboratory examination were as follows: WBC 12 × 109/L, neutrophils 80%, Hb 134 g/L, platelets 603 × 109/L, ESR 98 mm/h, CRP 143 mg/L, procalcitonin negative, and T-SPOT.TB (tuberculosis test) 0 spot-forming cells/106 peripheral blood mononuclear cells. The rheumatology-associated antibody titers were negative, including the antinuclear, anti-dsDNA, antineutrophil cytoplasmic, and antiextractable nuclear antigen antibodies.
CT-guided therapeutic thoracentesis and chest tube drainage were performed. The pleural aspirate was viscous and purulent. An analysis of the pleural aspirate showed the following values: WBC 1576/mm3, neutrophils 84%, total protein 59 g/L, albumin 30 g/L, lactate dehydrogenase 4240 IU/L, pH 7.0, adenosine deaminase 60.6 IU/L, glucose 5.8 mmol/L, T-SPOT.TB 0 spot forming cells (SFCs)/106 peripheral blood mononuclear cells (PBMCs), normal carcinoembryonic antigen, negative tuberculosis/nontuberculous mycobacterium DNA amplification, and negative acid-fast bacilli staining. The pleural fluid culture was negative for aerobic bacteria, fungi, and mycobacteria. Only the anaerobic bottle was positive after 5 days of incubation. The positive strain was inoculated on blood agar and anaerobically cultured. Visible white, small, smooth, round, neat-edged colonies emerged on the blood sheep agar plate (Fig. A), and Gram staining revealed gram-positive cocci under a microscope (Fig. B). The matrix-assisted laser desorption/ionization-time of flight examination indicated that the organism was S saccharolyticus [identification rate 99.9%, supplemental digital content (e-Fig. 1)]. Molecular identification via the polymerase chain reaction amplification of the gap gene was performed, and the amplification product was sequenced. The resulting gene sequences were submitted to GenBank for Basic Local Alignment Search Tool (BLAST) alignment. Based on the BLAST analysis of the gap gene, only S saccharolyticus showed 99% homology. The minimum inhibitory concentration of the isolate was <0.002 μg/mL for penicillin, <0.016 μg/mL for amoxicillin-clavulanate, 0.032 μg/mL for ceftriaxone, 0.064 μg/mL for cefotaxime, 0.25 μg/mL for oxacillin, <0.016 μg/mL for cefoperazone, <0.002 μg/mL for ertapenem, 0.006 μg/mL for imipenem, 0.023 μg/mL for moxifloxacin, <0.002 μg/mL for levofloxacin, 0.064 μg/mL for clindamycin, 3 μg/mL for chloramphenicol, 0.5 μg/mL for linezolid, 0.75 μg/mL for vancomycin, and 256 μg/mL for metronidazole.
Before the culture and drug susceptibility test results becoming available, the patient was given an empirical intravenous antibiotic treatment consisting of ceftazidime (2 g two times daily) and moxifloxacin (0.4 g one time daily). At the same time, his blood glucose was monitored and controlled by insulin. This patient responded well, with resolutions of the fever and left-sided chest pain and reductions in the WBC to normal, ESR to 35 mm/h, and CRP to normal. A repeated CT scan before discharge showed significant improvement in the left pleural effusion (Fig. D) and disappearance of the encapsulated effusion in the left interlobar fissure (Fig. E). At this point, the treatment was switched to the oral administration of moxifloxacin (0.4 g one time daily) for 4 weeks.


A 33-year-old woman with the dizziness as a chief complain. Magnetic resonance imaging (MRI) found a sellar lesion with a diameter of 18 mm invading into the bilateral cavernous sinus []. The physician suspected it to be a pituitary adenoma. A normal pituitary gland was seen on top of the tumor. The posterior gland was found superoposterior to the tumor. Despite the tumor’s lack of impingement to the optic apparatus, she was recommended to have regular visits but were lost to follow-up later. Six years later, she noticed bilateral visual disturbance and visited the clinic. MRI showed an extensive growth of the tumor.
On admission to Kagoshima University Hospital, the patient had clear consciousness. Her vision was 0.3 in the right and 0.7 on the left. Bitemporal hemianopia was found on perimetry. Her serum sodium (Na) level was 127 meq/L. MRI showed a large tumor with a maximal diameter of 56 mm, involving the sellar, suprasellar, retroclival, and bilateral cavernous sinus regions and strongly compressing the optic nerve and optic chiasm []. The tumor was slightly hypointense on T1-weighted MRI and hyperintense on T2-weighted MRI compared to white matter. The bilateral internal carotid arteries were completely encased. A postgadolinium scan showed a heterogeneous enhancement. The relatively well- enhanced thick bundle suggested that the pituitary gland was located in the upper left part of the tumor. A computed tomography (CT) scan showed that the tumor was slightly hyperdense []. Neither bleeding nor calcification was seen. The sellar floor was remarkably thickened.
The assessments of the anterior pituitary hormonal function showed hyperprolactinemia (53.9 ng/mL) and growth hormone deficiency, but the other four hormonal axes showed normal secretory functions. There was no manifestation of diabetes insipidus.
Decompression surgery of the optic chiasm was conducted through an endoscopic transsphenoidal approach. The removal of the thickened sella and thinned fibrous tissue presumed to be a remnant of the dura mater revealed the tumor, which was basically fibrous and easy to bleed. Tumor removal was continued until the suprasellar arachnoid membrane and tough tissue consistent with a pituitary gland appeared, leaving the tumor in the cavernous sinuses. Postoperative MRI demonstrated the sufficient decompression of the optic chiasm and an intact pituitary gland []. Postoperatively, a significant improvement of visual field deficit and normalization of vision (1.2 in both) was noted. The anterior pituitary function did not worsen. The blood prolactin level normalized (11.2 ng/mL).
Pathologically, the tumor was composed of a proliferation of round to oval neoplastic cells with scant to moderate cytoplasm and chromatin-rich short rod-like nuclei against a background of intercellular neuropil-like fibrillary matrix []. Cellular pleomorphism was mild. There were a few ganglion cells accompanied by elongated cells. These cells were partly packed, showing a lobular arrangement separated by a fibrovascular stroma []. The neoplastic cells and fibrillary matrix were immunohistochemically positive for neuronal markers, including synaptophysin [], neurofilament protein [], neuron-specific enolase, and NeuN [] chromogranin A []. The neoplastic cells were also positive for arginine vasopressin (AVP) []. The S-100 protein [] and vimentin were positive, mainly in spindle cells surrounding the fibrovascular stroma. They were negative for any anterior pituitary hormones, epithelial membrane antigen (EMA), glial fibrillary acidic protein (GFAP), or thyroid transcription factor-1 (TTF-1). These pathologic findings were suggestive of sellar neuroblastoma. The MIB-1 index was 6%.
A postoperative whole-body CT scan revealed a right ovarian cyst, which was later pathologically proven to be a simple cyst; otherwise, no other abnormalities were found. She underwent 50-Gy of intensity-modulated radiation therapy to the residual tumor due to hospital’s standard operating procedure, which has controlled its growth for the 3 years []. The serum Na levels remained low postoperatively at 126–130 meq/L, which did not cause any disturbance in consciousness. She was diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion [SIADH]) at 12 months after surgery. The laboratory results were as follows: serum Na: 130 meq/L, osmolarity: 259 osmo/kg, AVP: 18 pg/mL, urinary Na: 96 meq/L, and urinary osmolarity: 507 osmo/kg. The patient had no hypoadrenocorticism, kidney dysfunction, and cardiac failure. She is currently working in a factory without neurological impairment or hormonal replacement.


Case 1 is a 46-year-old female with chart diagnoses of moderate-to-major depressive disorder; recurrent, moderate, obsessive-compulsive disorder; generalized anxiety disorder; other unspecified personality disorder with dependent features; and tardive dyskinesia who received ongoing care at the clinic for several years. She was referred by her psychiatrist to consider PGx testing after reporting ineffectiveness and adverse drug reactions to many psychotropic agents over 30 years, including antidepressants, antipsychotics, stimulants, and mood stabilizers. Her history included chronic suicidal ideation and multiple suicide attempts via overdose on venlafaxine, fluoxetine, and loxapine. At the time of her referral, she reported intrusive persecutory and suicidal thoughts, anxiety, and depression causing poor sleep quality and isolation. Additionally, the patient reported tongue swelling, headache, insomnia, and tardive dyskinesia symptoms attributed (per medical records) to loxapine, a CYP2D6, CYP1A2, and CYP3A4 substrate, which had been recently discontinued after a suicide attempt approximately 1 month prior to referral. At the time of referral, patient and provider were considering clozapine therapy to target suicidal ideation; however, she was reluctant to initiate this treatment due to the frequent blood monitoring and preferred to try an alternative treatment. Additionally, the psychiatrist, patient, and family all felt that escitalopram at 40 mg/d was ineffective but were reluctant to make any dose changes. At this point, PGx testing was offered to the patient and family to provide a clearer path to shared decision making. The hope was to address the growing frustration and anxiety verbalized by the patient and her family around these failed medication trials and multiple medication changes. The patient and family agreed and consented to PGx testing, and an escitalopram serum concentration was ordered to provide a better understanding of current drug exposure.
Pharmacogenomic testing identified her as a CYP2C19 rapid metabolizer (rapid metabolizer is the current nomenclature for individuals with a CYP2C19 *1/*17 genotype; thus, they fall between normal and ultrarapid metabolizers) and a CYP3A4 and CYP2D6 normal metabolizer. The escitalopram trough serum concentration ordered when she was taking 40 mg/d (twice the maximum recommended daily dose) was reported as 38 ng/mL (AGNP therapeutic reference range: 15 to 80 ng/mL). Although within the AGNP therapeutic range, based upon a lack of clinical response at high doses, concern for increasing the dose further beyond twice the maximum recommended, and discussion with the patient and her family, it was decided to discontinue escitalopram and switch to levomilnacipran, a serotonin/norepinephrine reuptake inhibitor and CYP3A4 substrate. Furthermore, based on her reluctance to try clozapine, she accepted a plan to start cariprazine (a CYP3A4 substrate) after review of PGx results indicated her CYP3A4 normal metabolizer status.
The patient's medication history was notable for previous trials to several other CYP2C19 substrates (eg, amitriptyline, citalopram, clomipramine, and sertraline). At standard doses, CYP2C19 rapid or ultrarapid metabolizer status would increase the likelihood of inadequate exposure and nonresponse. According to the Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines, if CYP2C19 rapid metabolizer status is known prior to drug selection, recommendations include considering avoiding escitalopram or citalopram. Considering PGx alone, this pattern of prior nonresponse might be exclusively attributed to metabolism. Knowing genotype information suggests that dosing of CYP2C19 substrates moving forward may be complicated by her rapid metabolizer status, which may necessitate higher than usual dosing for CYP2C19 substrate medications or choosing a drug not metabolized by CYP2C19. The normal CYP2D6 and CYP3A4 results provided important information that helped to rule out metabolic PGx contributors to some previously experienced antipsychotic side effects. This information was helpful in considering subsequent antipsychotic options and engaging the patient and family in the decision-making process. The patient has not had any further hospitalizations for overdose attempts since PGx/TDM testing and CMM consultation.


Case 2 is a 68-year-old female historically resistant to medication switches and dose reductions with chart diagnoses of bipolar I disorder in partial remission (most recent episode depressed), posttraumatic stress disorder (unspecified), attention deficit/hyperactivity disorder, anorexia nervosa (restricting type), borderline personality disorder, and mild opioid use disorder (postsurgery). Although currently not active problems, her past history of suicide attempts, substance use (alcohol, methamphetamines, psilocybin), and self-injurious behaviors since high school added complexity to her pharmacotherapy management history. She was referred to the CMM pharmacist for PGx testing and medication assessment due to ineffective drug therapy, her multiple requests for additional medications, dose increase requests, and suspected akathisia from aripiprazole along with several related or potentially contributing factors (eg, insomnia, restless leg syndrome, irritability). After PGx testing results were obtained, serum concentrations were also ordered for escitalopram, duloxetine, and aripiprazole to help determine if any notable deviations from expected exposure ranges might have been contributing to ineffectiveness and side effects.
Her PGx test results identified her as an intermediate metabolizer (ie, more activity than a poor metabolizer but less activity than a normal metabolizer) for CYP2C19 and a poor metabolizer for CYP2D6. Reduced (poor or intermediate metabolizer status) activity of both of these drug-metabolizing enzymes could have contributed to her lack of symptom improvement and adverse effects to several previously trialed psychiatric medications. Her escitalopram serum concentration at 30 mg/d was reported as 97 ng/mL (above the AGNP reference range of 15 to 80 ng/mL), which may be, in part, explained by her intermediate CYP2C19 metabolism. Her duloxetine serum concentration at 90 mg/d was within the normal AGNP reference range at 114 ng/mL (30 to 120 ng/mL). Finally, her aripiprazole and dehydroaripiprazole serum concentrations at 30 mg/d were reported as 342.8 ng/mL (therapeutic reference range: 100 to 350 ng/mL) and 68.3 ng/mL for a total of 411.1 ng/mL (therapeutic reference range: 150 to 500 ng/mL). Of note, duloxetine is also a substrate of CYP1A2 and aripiprazole a substrate of CYP3A4, which may also contribute to these results. Although duloxetine is an inhibitor of CYP2D6, this is not expected to further decrease metabolic activity in a genetically determined poor metabolizer.
The CMM pharmacist provided an explanation of PGx and TDM findings and recommendations. Based on this individual's CYP2D6 poor metabolizer status and adverse effect profile, the patient subsequently agreed to a dose reduction of aripiprazole after solidly resisting previous recommendations to decrease her dose. Initial dose reductions did not worsen depressive/anxiety symptoms, but there was an improvement of akathisia.


A 12-year-old girl was admitted to our department with mild dyspnea and 5-day history of abdominal swelling. There was no family history nor any disease or past history of drug use, toxin exposure, and immunization. On admission, her physical examination parameters were as follows: weight 39 kg (50 percentile), height 143 cm (25 percentile), temperature 37.2°C, heart rate 110/min, and blood pressure 96/54 mm Hg. An abdominal examination revealed severe distension caused by ascites without abdominal masses. There was no edema in the extremities. In a bilateral lung examination, decreased breath sound was heard in the lower lobes and there was dullness on percussion bilaterally in basal segments. Her routine laboratory values, serum carcinoembryonic antigen (CEA-19), alpha-fetoprotein, and quantitative β human chorionic gonadotropin, were within the normal range. However, elevated serum levels of CA-125 of 308 U/mL (normal: <35.0 U/mL) and lactic dehydrogenase [770 U/L (normal: 122-234 U/L)] were detected. Direct posteroanterior lung radiography revealed a mild bilateral pleural effusion. Abdominal and pelvic ultrasound demonstrated massive ascites of 9 cm at the deepest point, and there was a 2.5x2-cm mass on the posterior of the right ovary. Magnetic resonance imaging (MRI) performed on day 8 post onset of her symptoms showed bilateral pleural effusion, massive ascites, and masses with solid cystic components on both ovaries, 32x45 cm on the right, and 14x12 cm on the left, which were primarily thought to be malignant (), and also paraaortic-paracaval lymphadenopathies and implantation masses compatible with peritonitis carcinomatosa were observed.
An explorative laparotomy was arranged for diagnostic and therapeutic purposes. During the laparotomy, a 3x1x3-cm solid mass originating from the right ovary, and a 0.9x1x1-cm solid mass on the left ovary, both containing cystic and solid areas, were observed with approximately 6700 mL of serous ascites. The uterus and both adnexa appeared not to have pathologic appearance. The right ovary tumor was distinguished, and a bilateral ovarian mass were removed for biopsy. Omentectomy was performed and sent for frozen section examination. A metastasis-like involvement was observed on the left lobe of the liver as well as an involvement in the retroperitoneal lymph nodes. From the frozen section of the ovary and omentum, the mass was diagnosed as pure ovarian rhabdomyosarcoma. A retroperitoneal lymph node was also enucleated and together with the right ovary, cyst aspiration fluid was sent to the cytology laboratory. Pathologic evaluation of the ovarian tumor revealed an alveolar pattern (>50 percent alveolar component, predominantly) (). Postoperatively, the pleural effusion spontaneously resolved in a week. Finally, the diagnosis was pure ovarian alveolar rhabdomyosarcoma, which had metastases of liver, omentum, presenting with pseudo-Meigs’ syndrome (Stage 4, group IV alveolar rhabdomyosarcoma). The patient was referred to the oncology department and was started on chemotherapy. Informed consent was obtained from patients’ parents who participated in this case.


A 72-year-old man presented to the rheumatology department with a 1-month history of acute polyarthralgia involving the bilateral shoulders, knees, wrists, elbows, and metacarpophalangeal joints. He had been smoking 20 cigarettes per day for the last 40 years and had mild respiratory symptoms including an occasional cough. He had no history of morning joint stiffness, oral ulcers, Raynaud’s phenomenon, low back pain, heel pain, xerostomia, or xerophthalmia.
On physical examination, all superficial lymph nodes were normal, but his peripheral joints appeared mildly red, swollen, warm, and tender. Laboratory findings revealed an erythrocyte sedimentation rate of 60 mm/h (reference, <20 mm/h) and C-reactive protein concentration of 68.70 mg/L (reference, <8 mg/L). The results of all other tests were within the reference range. Plain radiographs of the patient’s painful joints revealed moderate degenerative changes. A plain chest radiograph showed a paravertebral spindle high-density shadow at the thoracic 8 to 11 spinal levels. Single-photon emission computed tomography with a technetium-99m methylene diphosphonate bone scan showed hypermetabolic changes in the right sternoclavicular and left knee joint, indicating benign degenerative changes. Noncontrast chest CT showed multiple bilateral paravertebral lesions of heterogeneous density and well-defined margins in the posterior mediastinum at the thoracic 8 to 11 spinal levels. The density of the lesions ranged from −97.0 to +70.0 Hounsfield units, and the largest section was 4.4 × 2.9 cm in diameter. None of the lesions contained calcification or heterogeneous contents. Thoracic magnetic resonance imaging (MRI) showed bilateral foci with an inhomogeneous signal (). The lesions were oval, asymmetric, fat-containing, and well demarcated from the descending aorta in the posterior mediastinum. Based on these imaging findings, the most probable diagnosis was liposarcoma or lymphoma. Considering the concomitant polyarthralgia, however, a neuroendocrine tumor could not be excluded.
The diagnosis was uncertain, and the patient declined a surgical operation because he had mild respiratory symptoms. After he provided informed consent, the patient underwent a percutaneous CT-guided core biopsy of the lesion (). Histopathologically, the mass consisted of mature adipose tissue combined with myeloid and erythroid cells (). Immunohistochemistry revealed negativity to synaptophysin, chromogranin A, CD56, and S-100 antibodies and positivity to myeloperoxidase. A diagnosis of mediastinal myelolipoma was made. The patient was prescribed celecoxib (Celebrex® capsules; Pfizer, New York, NY, USA) at 200 mg twice a day for 2 weeks, and his polyarthralgia significantly improved. Conservative observation was selected because the lesions were small. During 24 months of follow-up, imaging examinations showed that the lesions were nonprogressive, and the patient was thus able to avoid a surgical procedure.


A 56-year-old woman presented for presbyopic correction. Best-corrected visual acuity was 20/20 in both eyes. On slit-lamp examination, a translucent cyst with a central scolex, approximately 2 mm in diameter was seen floating freely in the anterior chamber of the left eye. The cyst wall had a shiny tinge to it and exhibited intermittent undulating movements on exposure to bright light []. A clinical diagnosis of live anterior segment cysticercosis was made. There was no associated inflammatory reaction in the anterior or posterior segment and fundoscopy was normal. The examination of the right eye was unremarkable.
Neuroimaging was done to rule out intracranial cysts, where multiple parenchymal cysts were detected. After discussion with the neurologist, ocular surgery was planned prior to initiation of anti-helminthic drugs. During the surgery, a 2 mm limbal incision was made and 2% hydroxypropyl methylcellulose was injected into the anterior chamber. Viscoexpression was attempted; however, it led to iris prolapse from the wound site []. Realizing the posterior placement of incision, the possibility of the cyst getting entangled or ruptured was imminent. Hence, further viscoexpression was avoided. Active aspiration of the cyst was planned as a rescue procedure. For this, a descemet membrane endothelial keratoplasty (DMEK) tissue injector assembly was made using an IOL cartridge. This assembly consists of a locking butterfly cartridge used for injecting hydrophobic IOLs and a straight lacrimal cannula attached to the aspirating end of the simcoe cannula []. The lacrimal cannula is cut along with the rubber tube and is inserted in the lumen of the butterfly cartridge. The cartridge is then locked and is ready for use. Visco-elastic was reinjected and the IOL cartridge was carefully inserted into the anterior chamber. It was brought close to the cyst gently, and the cyst was aspirated into the injector in one fluid movement []. Subsequently, visco-elastic was removed from the anterior chamber. Histopathology analysis confirmed a cyst with a scolex and hooks, consistent with diagnosis of cysticercus cellulose.


A 92-year-old man with history of chronic obstructive pulmonary disease (COPD) and hypertension was admitted to our emergency room with a 3-day history of dyspnoea, fever and thoracic pain. He denied previous trauma. On physical examination, the patient was lucid, but with abolition of breath sounds over the right hemithorax and a tender abdomen in the right upper quadrant. His blood pressure was 90/42 mmHg, heart rate was 98 bpm, respiratory rate was 30 per minute and oxygen saturation was 80% on room air. During his stay in the emergency room the patient experienced multiple episodes of vomiting which did not respond to antiemetic therapy.
Blood tests revealed a raised white cell count of 13.2×109 g/l (normal range 4–11×109 g/l) and a serum C-reactive protein of 83.5 mg/l (normal range <3.0 mg/l). Arterial blood gas analysis showed hypoxaemia (pO2 of 35 mmHg) and a lactic acid level of 4 mg/dl (normal range <2 mg/dl). Due to suspicion of pneumothorax, a chest x-ray was performed () and demonstrated a large radiolucent area in the right hemithorax but with the presence of an air–fluid level. To clarify the diagnosis, computed tomography (CT) of the thorax was performed () and revealed a large right posterior diaphragmatic hernia containing a segment of colon with an increased calibre of 93 mm, compatible with a large BH, which was not known previously. An emergency laparotomy was performed, but the patient did not improve clinically and died immediately after the procedure.


A 72-year-old female patient with haematuria, dysuria and pollakiuria was admitted with pyelonephritis. A thoracic and abdominal CT scan revealed accidental thoracic and abdominal adenopathy. Laparoscopic excision of the hepatic ganglia revealed non-necrotizing granulomatous lymphadenitis.


A 19-year-old man presented with odynophagia, fever, rash, asthenia, anorexia and weight loss. Hepatomegaly, right cervical adenomegaly and neurological worsening were documented. The patient underwent a cycle of chemotherapy due to high suspicion of a lymphoproliferative syndrome with central nervous system involvement. Subsequently, excisional biopsy of the cervical adenomegaly confirmed necrotizing lymphadenitis.


A 58-year-old woman was admitted with to a 2-month history of myalgia, asthenia, weight loss, nocturnal diaphoresis, dyspnoea and non-productive cough. In light of clinical worsening, and the development of unilateral pleural effusion and bilateral axillary adenomegaly, the patient started a chemotherapy regimen due to suspicion of lymphoma. A biopsy of the axillary adenomegaly later confirmed follicular hyperplasia.


A 58-year-old man was admitted for painful adenomegaly measuring 3 cm in diameter in the right inguinal region, associated with fever. A thoracic-abdominopelvic CT scan showed contrast uptake only in the enlarged gland proximal to the right external femoral vessels. Serology was positive for HBsAg, IgG CMV and IgM CMV. Excisional biopsy later confirmed necrotizing lymphadenitis.


A 31-year-old female patient with KFD, which had been histologically confirmed 3 years previously, developed scaly erythematous skin lesions on the face and scalp. A skin biopsy revealed discoid lupus erythematosus.


A 36-year-old woman presented at our clinic with abdominal pain. Her medical history was remarkable only for a cesarean section performed 8 years ago. Following the cesarean section, the incision was healed without any symptoms presented for 5 years. Before seeking treatment, the woman experienced pain in her left lower abdomen near the incision for 2–3 years without any gastrointestinal symptoms (nausea, vomiting, or diarrhea). Her pain presented intermittent pattern and could be induced by changing body position and worsened during her menstrual period. Recently, her symptoms got worse and became excruciating pain. In the emergency room, we performed physical examination and showed a bulging, palpable, and nonmovable lesion with local tenderness in the left lower abdominal region similar to an incisional hernia. Although the laboratory data showed a normal range of white blood cell count, and she still underwent abdominal computed tomography (CT) to rule out emergent surgical conditions, such as incarcerated incisional hernia. We noted a mass in the left rectus sheath region under the incision [], which led us to suspect postcesarean section-related granuloma tissue.
For symptom relief and to investigate further, we discussed the findings with the patient and arranged a surgical intervention viz-a-viz removal of the abdominal wall mass. Preoperative diagnostic tests, including blood tests and chest radiography, revealed no obvious abnormalities.
Subsequently, as planned, we removed the abdominal wall mass under general anesthesia. During the surgery, we noted a dense tissue in the rectus abdominis muscle with some residual blood clots. We removed the dense tissue with residual blood clots as much as possible and checked the bleeder thoroughly. We closed the fascia of muscle with 2-0 Vicryl and the skin with a 3-0 Nylon sutures. The patient was discharged 3 days after the procedure. The final pathology report revealed endometriosis []. During the outpatient follow-up, the surgical wound had gradually healed, and no complications occurred in the postoperative 30 days. No recurring symptoms were noted in the 6-month follow-up.


A previously healthy 5-year-old boy was transferred to our hospital because of melena and hematemesis. The child complained of periumbilical pain and vomiting four days before initial visit to our hospital, and a histamine 2 receptor (H2) antagonist and an antispasmodic agent were administered under the impression of acute enteritis. Powdered oral rehydration salts was also prescribed at a private clinic because of mild dehydration one day before the visit. Abdominal cramps and hematemesis occurred in two hours after taking ORS at home and the child was admitted at a private hospital. The medical history was unremarkable except that Helicobacter pylori infection was diagnosed in the mother of the child a few months ago. The vital signs at the first hospital were relatively stable and the hemoglobin level was 11.5 g/dL. However, the child was transferred to our hospital because of recurrent hematemesis, development of melena, and dizziness. Initial vital signs in our hospital were as follows: blood pressure, 104/66 mmHg; heart rate, 133/minutes; respiratory rate, 22/minutes; and body temperature, 36.8°C. The child looked acutely ill and dehydrated. Anemic conjunctivae and pale, dried lips were also noted. Chest auscultation revealed clear breath sounds and tachycardia. Abdominal examination revealed epigastric tenderness and rigidity. There was no hepatomegaly or splenomegaly. Pale skin without purpura or rash was noted. Mental status was alert. Abdominal X-ray was unremarkable, but abdominal computed tomography (CT), performed because of abdominal rigidity, showed duodenal and gastric wall thickening. Complete blood cell counts were, hemoglobin, 6.9 g/dL; white blood cell count, 12,970/mm3; and platelet count, 384,000/mm3. Among the blood coagulation tests, prothrombin time, activated partial thrombin time, and international normalized ratio were 15.4 (reference range: 11.9–14.3) s, 31.1 (29.1–43.5) s, and 1.20, respectively. Biochemical laboratory analyses were performed and the results were as follows: sodium, 130.0 mmoL/L (135–145); potassium, 4.4 mmoL/L (3.3–5.1); chloride, 93 mmoL/L; serum osmolarity, 272 mOsm/L (276–300); aspartate aminotransferase, 17 U/L (15–50), and alanine aminotransferase, 6 U/L(5–45). Urinary blood and red blood cells were negative. Stool wet smear and culture were unremarkable but occult blood in stool was positive (432.5 ng/mL, 0–12.0).
Transfusion of packed red blood cells, octreotide and a proton pump inhibitor were promptly initiated after exclusion of surgical abdomen. Gastroduodenofibroscopy was performed to identify the cause of melena and hematemesis, which revealed linear ulcers and scattered submucosal hemorrhages in the prepyloric area of stomach, and large circular ulcers in the first and second portions of the duodenum. The duodenal ulcers were along the folds. The mucosal margin of the ulcers was distinct and easily friable (). Pathologic examination showed ulcer debris, gastritis, and active duodenitis (). Serologic test for H. pylori immunoglobulin G and M, and rapid urease test were negative. H. pylori was also not detected on pathologic examination using Giemsa stain (). Additionally, there was no evidence of vasculitis on pathologic examination (). Serum gastrin level was 28.5 pg/mL (13–115). After the results were reported, the mother recalled that a packet of ORS was reconstituted with a lesser amount of water (≈50 mL) than the instructed amount on the manual (200 mL) when the aggravation of abdominal pain and hematemesis occurred. The ORS reconstituted in 50 ml of water had higher osmolarity (992 msom/kg) and higher concentrations of sodium (176.5 mEq/L), potassium (81.8 mEq/L), glucose (9,451 mg/dL), and citrate (122.6 mEq/L) compared with the ORS reconstituted in 200 mL of water (). The abdominal pain was resolved promptly and melena disappeared in two days after treatment was initiated. The child was discharged with good general condition after eight days of hospital stay. He has been in good general condition during the last six months.


A 52-year-old man was admitted to our institution on October 25, 2014 with a space-occupying lesion in upper lobe of left lung in association with a solitary mass on his left chest wall detected by chest computed tomography (CT) scan during a health examination in October 2014. The patient had a smoking history of 31 years with 20 cigarettes a dayand he denied any other medical or family history. According to the biopsy findings from the solitary mass on the left chest wall, the patient was diagnosed as lung adenocarcinoma with metastasis on the left chest wall, suggesting metastatic disease (). Immunohistochemistry outcomes were presented as: TTF-1 (positive), CK (positive), Napsin-A (positive), CK5/6 (negative), P63 (negative), CD56 (negative), CK7 (positive), and Ki-67 (10%). Because of the deletion of EGFR exon 19 detected by ARMS-PCR (amplification refractory mutation system) with tumor tissue, he started on icotinib as first line treatment in November 2014. According to the criteria of response evaluation criteria in solid tumors (RECIST) version 1.1, best response during the first line was partial response (PR). After 18 months duration time with icotinib, progressive disease (PD) of the primary lesion in lung, as well as pleural effusion was detected with chest CT in May, 2016. Subsequently, he received combined chemotherapy (pemetrexed, cisplatin, docetaxel) with bevacizumab as second-, and third-line treatment, respectively (). The cytotoxic administration was terminated because of the emerging lesion in mesocephalon in January, 2018. Next generation sequencing (NGS) using a plasma sample suggested the emerging EGFR exon 20 T790M mutation this time. Then he received systematic therapy with osimertinib and bevacizumab, as well as stereotactic body radiation therapy (SBRT) for the single lesion in mesocephalon. Response efficacy of the systematic therapy was evaluated as PR. The duration time from that regimen was 23 months. On December 23, 2019, the patient received repeated chest CT because of the aggravating chest distress, which revealed the enlarged primary mass in the upper lobe of his left lung, as well as the significantly increased pleural infusion. Oral anlotinib, a small molecule multi-targeted tyrosine kinase inhibitor, was administered as salvage treatment. Bevacizumab was also given by intrapleural injection for the control of pleural infusion. NGS, including 550 tumor-related genes using a plasma sample was conducted to search the potential targets, the results of which suggested EGFR exon 20 mutation (p.T790M, c.2369C>T, frequency as 4.17%), EGFR exon 20 mutation (p.C797S, trans to T790M, c.2390G>C, frequency as 0.37%), and CTNNB1 exon 3 alteration (p.S37F, c.110 C>T, frequency as 2.03%, ). With the results of NGS, the patient started to receive gefitinib combined with osimertinib as further-line treatment in February, 2020. However, the sudden emerging and rapid enlarged mass on his right neck saw him admitted to our hospital again on March 10, 2020. Cervical magnetic resonance imaging (MRI) showed the emerging lesion, which was finally confirmed with pathologic findings by biopsy (). NGS (panel of 1021 cancer related genes) using tissue from the cervical mass was conducted again in April 2020, the results of which re-conformed CTNNB1 exon 3 alteration with higher frequency (p.S37F, c.110 C>T, frequency as 17.6%), as well as the other former alterations including EGFR exon 19del (p.E746-A750del), and EGFR exon 20 mutation (p.T790M, c.2369C>T). However, the C797S alteration (whether trans or cis) was missing this time. Because of the regional pain, especially at the time of feed, he received oral oxycodone 10 mg Q12h, and SBRT again for the cervical lesion. The emerging mass, as well as the pain was controlled well now. The patient is undergoing a regimen of camrelizumab and albumin-bound paclitaxel as salvage treatment. In addition, he also receives oral celecoxib 200 mg twice a day for CTNNB1 exon 3 mutation. Chest CT scans and brain MRI findings during the whole treatment are listed in the .


A 28-year-old pregnant woman who worked as a nursing assistant, was a primigravida with 31 weeks of gestation age who sought the emergency unit with fever and hyperemic lesions in the right lower limb, suggestive of a bacterial skin infection. The patient did not smoke or report a prior history of asthma, tuberculosis or pneumonia. Treatment was initiated with intravenous ceftriaxone (2 g) associated with 40 IU per day of heparin, though after two days, the patient began to exhibit acute dyspnea. The room oxygen saturation was found to be 95%, and symptoms were accompanied by tachypnea and hypotension. Fifteen liters of oxygen per minute were provided by mask, and the patient was transferred to the intensive care unit (ICU) of another public institution. She was admitted in critical conditions requiring urgent intubation and mechanical ventilation. The lactate dehydrogenase (LDH) was 268 U/L, D-dimer less than 300 ng/mL (normal values below 500 ng/mL) and 3,900 white blood cells (WBC). Computed tomography (CT) scans revealed bilateral patchy ground glass opacities, and the patient was considered as a suspicious case of SARS-CoV-2 infection. Considering the CT findings and the severe evolution in the third trimester of gestation, she was medicated with 500 mg azithromycin per day, 75 mg oseltamivir phosphate twice a day and 400 mg hydroxychloroquine twice a day for five days, in addition to the ventilation support. Pulmonary embolism was excluded by using specific diagnostic tests.
She tested negative for coronavirus by the real-time reverse transcription polymerase chain reaction (RT-PCR) testing nasopharyngeal secretions swabs during the initial hospitalization. Owing to the severe clinical conditions, a cesarean section (C-section) was performed. A healthy 31-week gestational age infant, weighting 2,380 g, was delivered and transferred to the neonatal care unit because of the prematurity, the Apgar score was 8 on the 1st minute of life and 9 on the 5th minute and the preterm newborn was adequate for gestation age. The puerperal woman remained hospitalized for 18 days in the intensive care unit (ICU) due to her respiratory conditions, receiving supportive care. The patient tested positive for COVID-19 by RT-PCR on the 12th day after hospitalization. The newborn tested negative for COVID-19 by RT-PCR and was released after 5 days. The puerperal woman evolved favorably and was discharged without sequelae after 23 days.


A 34-year-old puerperal woman who was a housewife in her second pregnancy, with one previous delivery, sought the emergency unit on the fifth day after delivery owing to an acute respiratory insufficiency. She did not report abnormalities during the antenatal care or during hospitalization for delivery. Her medical record showed that she gave birth by C-section at 40 weeks of gestational age and gave birth to a female newborn, weighing 3,875 g, with an Apgar score of 8 and 9 in the 1st and 5th minutes, respectively. The mother reported severe dry cough and acute dyspnea associated with lower back pain and mild fever occurring 24 hours before the hospitalization. The chest CT scan was suggestive of viral pneumonia with an acute inflammatory feature compromising 25 to 40% of the pulmonary parenchyma, but the findings were not suggestive of COVID-19. The angiotomograpy of the thorax was negative for pulmonary embolism and the oxygen saturation was 91%. The LDH was 328 U/L, D-dimer less than 300 ng/mL and the initial leukogram showed 5,000 WBC.
The patient was medicated with ceftriaxone (2 g/day), azithromycin (500 mg/day), oseltamivir (75 mg twice a day), and enoxaparin (initially with 40 mg daily, with increments up to 80 mg/day). The RT-PCR for SARS-CoV-2 was positive three days after the delivery, and hydroxychloroquine (400 mg twice a day) was administered initially, followed by 400 mg daily for five subsequent days along with meropenem (500 mg three times a day) and vancomycin (1 g twice a day). Ceftriaxone was discontinued.
Afterwards, the patient's respiratory condition worsened, she remained in the ICU in critical conditions with a persistent high fever that last 13 days, receiving supportive care covering oxygenation, ventilation, and vasoactive drugs. The patient no longer needed the ICU hospitalization following this period and was transferred to the rehabilitation ward. Her husband and the newborn tested negative for COVID-19.


A 25-year-old pregnant woman, who was a housewife in her third pregnancy and two previous deliveries, was referred to the hospital at 28 weeks and six days of gestational age with upper respiratory symptoms, fever, myalgia, and diarrhea for five days. Thereafter, the patient's clinical condition worsened to a non-productive cough and intense fatigue. She did not report comorbidities, but her husband presented with fever in the previous 24 hours and reported contact with two coworkers that had positive tests for COVID-19. She was transferred to the ICU. Corticosteroid therapy with 2 g hydrocortisone was initiated to accelerate the fetal lung maturation along with oseltamivir, azithromycin, ceftriaxone, and enoxaparin in standardized doses. The patient also needed mechanical ventilation. D-dimer levels were normal (308 ng/mL), and pulmonary embolism was excluded using specific diagnostic tests. The oxygen saturation was 94% and the initial leukogram showed 4,000 WBC and 11% of lymphocytes.
The COVID-19 serological tests resulted negative twice, while the RT-PCR on nasopharyngeal swab secretions was positive for SARS-CoV-2. Hydroxychloroquine was initiated (400 mg twice a day), followed by 400 mg daily for five subsequent days. A C-section was performed owing to the critical conditions of the mother, as well as severe oligohydramnios.
A female infant weighing 1,255 g, adequate for gestational age was delivered. The Apgar score was 6 on the 1st minute and 7 on the 5th minute. The newborn tested negative for COVID-19 by RT-PCR, but was referred to the neonatal ICU because of the extreme prematurity, where she underwent a systemic antibiotic therapy owing to a right hemi thorax atelectasis. The neonate was released after 30 days in good conditions.
The mother remained in the ICU for 22 days, where she was treated with meropenem (500 mg three times a day) associated with vancomycin (1 g twice a day) and polymyxin-B, requiring intubation and mechanical ventilation. The LDH result went from 226 U/L to 524 U/L during the hospitalization. . Despite the ICU stay and a continuous epinephrine drip, the patient's blood pressure decreased to 60/40 mmHg and her condition evolved to irreversible refractory shock, multiple organ failure and death. The blood cultures were all negative.


On February 18, 2019, a 60-year-old woman with severe dyspnea, fine rales in the lung, tachycardia, and tachypnea was admitted at the emergency department of Heart Center of Mazandaran University of Medical Sciences, Sari, northern Iran. She suffered from multiple comorbidities, including diabetes mellitus, obesity (BMI 36.1 kg/m2), hypertension, and hypercholesterolemia. Her medical history revealed that she had been operated on 5 years ago for mitral valve (MV) replacement due to rheumatic heart disease. Laboratory data showed prothrombin time 18 seconds, international normalised ratio 2, white blood cells 4,000 /µL, and hemoglobin 12g/dL. Fluoroscopy evaluation showed that the motion of one leaflet of the prosthetic MV was fixed, while the other had severely restricted motion (). Transesophageal echocardiography demonstrated a mechanical prosthetic bileaflet MV, fixed medial leaflet MV, elevated MV mean pressure gradient (22 mmHg), pressure half-time (225 mL/s), MV left ventricular–outflow tract velocity time integral(48%), and a large obstructive mass (1.5×2 cm) on the prosthetic MV medial leaflet, which was highly suggestive of a large thrombus. Severe tricuspid regurgitation, mild–moderate aortic insufficiency, and severe pulmonary hypertension (pulmonary artery pressure 80 mmHg) was also present. Coronary angiography revealed normal arteries. Based on the hemodynamic condition of the patient (functional class IV) and large thrombus, urgent cardiothoracic surgery consultation took place, and she was a candidate for surgery. The thrombotic prosthetic MV was removed and replaced with another mechanical prosthetic MV (21 mm; CarboMedics, Austin, TX, USA) and tricuspid valve repair performed. Gross pathology showed a severe thick pannus formation with large thrombus on the prosthetic MV that caused malfunction (). Operation accomplished successfully and patient was discharged from the hospital with good condition.
On April 13, 2019, about 2 months after discharge, she went back to the emergency department with acute pulmonary edema refractory to vasodilator and diuretic therapy (). She also complained of fever and weakness for 2 weeks. Fluoroscopy showed normal leaflet motion. Chest X-ray revealed severe pulmonary venous congestion throughout the lungs, alveolar edema, and consolidation. She underwent transesophageal echocardiography (TEE). Upon reaching the TEE room, she complained of sudden vision loss in her right eye. TEE was done, and data revealed severe left ventricular systolic dysfunction (ejection fraction 30%), a bileaflet mechanical prosthetic MV, normal leaflet motion, a small mobile mass on the anteromedial swing ring, and severe aortic insufficiency. Due to destruction of the left coronary cusp of the aorta, the large size mobile mass (2.2×2 cm) protruded to the left ventricular outflow tract (vegetation mostly). Periaortic thickening with echo-free space around aorta (abscess) extended to the intervalvular fibrosa ( and ). Noncontrast brain computed tomography showed hyperdense intracranial hemorrhage in the left parietal lobe. On the second day of admission (April 15, 2019), due to prosthetic MV and native aortic valve infective endocarditis with decompensated heart failure and after consultation with a neurologist, she underwent second emergency redo surgical MV repair in combination with mechanical aortic valve replacement and aortoplasties.
The explanted valve and vegetation were sent to the laboratory for further evaluation. Direct microscopic examination (KOH preparation, 20%) of tissue biopsies showed a mass of dichotomous branching hyphae (), which was confirmed by histopathology (periodic acid–Schiff staining, ). Culture of biopsied tissue onto Sabouraud dextrose agar medium after a 24-hour incubation at 27°C yielded Aspergillus spp. On slide culture, the grown Aspergillus showed echinulate and hyaline conidiophores with globose to subglobose vesicles and uniseriate phialides. Conidia were globose to subglobose and echinulate (). On the basis of microscopic and macroscopic characteristics, the fungus was identified as Aspergillus section Flavi. Accurate identification of grown Aspergillus colonies was performed by polymerase chain reaction (PCR) assay using the two universal fungal primers Bt2a and Bt2b targeting the β-tubulin gene (). Amplicons were sequenced and compared with the GenBank database () for final identification at species level. The isolate was assigned to A. flavus based on the complete identity with corresponding sequences of the A. flavus strain CBS 816.96. Then, they were submitted to GenBank and received the accession number MN097724. Prior to antifungal therapy, three consecutive blood samples were taken and inoculated with blood cultures containing brain–heart infusion (BHI) broth and BHI agar and processed. The blood cultures had no microbial growth after 2 weeks of incubation at 37°C. DNA was extracted from negative blood culture bottles using a QIAmp DNA blood minikit and subjected to β-tubulin gene amplification. The β-tubulin amplicon from the negative blood culture sequenced and its DNA-sequence data were in complete agreement with the DNA sequences of A. flavus strain CBS 816.96, similar to the aforementioned finding regarding the colony grown from the explanted valve (). Liposomal amphotericin B at a dose of 5 mg/kg body weight/day (350 mg) together with broad-spectrum antibiotics (ciprofloxacin, meropenem, and vancomycin) were administered via a peripherally inserted venous catheter. On day 11 of admission, after 7 days’ antifungal therapy, the patient expired from presumed severe sepsis, probably related to progressive AE.
In our institution, antifungal susceptibility testing is not a routine workup; however, in vitro antifungal-susceptibility testing was performed according to document M38-A2 of the Clinical and Laboratory Standards Institute (CLSI) on Aspergillus isolates after the patient had died. Minimum inhibitory concentrations were obtained for amphotericin B(2 μg/mL), fluconazole (16 μg/mL), itraconazole (0.016 μg/mL), voriconazole (0.25 μg/mL), posaconazole (0.032 μg/mL), and minimum effective concentrations for caspofungin; (0.008 μg/mL, anidulafungin; (0.008 μg/mL and micafungin (0.008 μg/mL).This case report was performed in compliance with the Declaration of Helsinki, and written informed consent was obtained from the legal guardian for its details to be included in the manuscript and for publication. No institutional approval was required to publish the case details.


A 22-year-old woman, a recently diagnosed case of guttate psoriasis, was started on tablet MTX 7.5 mg/week. Three weeks after starting the drug, the patient presented with a complaint of acute-onset diffuse loss of about 30%–40% hair from the scalp over the past 4 days [Figures and ]. She denied the use of any other medication, any change in cosmetic, and a history of any other illness in the past 6 months.
Her general and systemic examination was normal. Dermatological examination revealed diffuse involvement of the complete scalp in the form of hair loss and empty follicles. No scarring was seen. Hair pull test was positive. Dermoscopy revealed a few black dots, yellow dots, and few miniaturized hair []. Light microscopy revealed dystrophic anagen hair bulbs [].
Her hematological and biochemical parameters were within normal limits. Thyroid profile and antinuclear antibodies were normal. Scalp biopsy revealed no significant findings and only mild perivascular lymphocytic inflammatory infiltrate. No foamy histiocytes or granuloma was noted, and no evidence of dysplasia or malignancy was noted.
Based on the above clinical, trichoscopic, light microscopic, and histopathological findings, a diagnosis of anagen effluvium was given likely due to the drug MTX.
MTX was stopped, and the patient was managed with counseling, multivitamins, and advice to eat a healthy diet. The hair loss gradually stopped over the next 3 months []. For psoriasis, she was managed with topical steroids and emollients with regression of skin lesions.


A 23-year-old male presented to skin outpatient department with complain of nonprogressive patch of hair loss over the right side of scalp since birth. The patient had consulted an ayurvedic practitioner for the same with no improvement by oral medications, hair oil, and shampoo. There was no history of joint pain, bone, or teeth abnormalities. No history of itching, contact with chemicals, or dandruff over scalp. No significant past and family history or any comorbidities present.
Cutaneous examination showed single, well-defined, triangular patch of alopecia measuring approximately 4 cm × 2 cm with sparse hair in between over right frontotemporal region []. The overlying skin was normal with no inflammation or atrophy.
Dermoscopy done with hand held LED ILLUCO dermoscope IDS-1100 having polarized light illumination having ×10 magnification showed normal follicular openings with vellus hairs surrounded by terminal hairs on the outskirts of the lesion [] with the absence of yellow and/or black dots, brittle hair, and “exclamation mark” hairs.
The patient was treated with topical minoxidil (5%) to be applied over the affected area once in a day. New vellus hair [Figure and ] developed after 3 months of treatment.


A 78-year-old woman living in rural South Korea and with no history of other diseases except for hypertension presented with a painful erythematous plaque with oozing ulcers on the left forearm that had lasted for 7 weeks (). She did not complain of any systemic symptoms such as fever and myalgia. Before the lesions developed, she was injured by a sickle while cutting grass. She was treated for 3 weeks with cefoperazone/sulbactam under the suspicion of cellulitis; however, the lesions became wider and worsened. We performed bacterial and fungal cultures, as well as an incisional biopsy. The biopsy specimen was stained with the following: Gomori methenamine silver stain (GMS), periodic acid-Schiff stain (PAS), and acid-fast stain. Histopathologically, granulomatous inflammation with aggregated histiocytes and multinucleated giant cells were observed in the dermis, along with multiple intracytoplasmic yeasts (, ). Furthermore, the yeasts were also identified on staining with GMS and PAS (, ). No specific findings were observed on other investigations such as complete blood cell count; serum chemistry analysis; and tests for HIV infection, beta-D-glucan, and C. neoformans antigen in the blood. C-reactive protein level was elevated at 3.95 mg/dL. No abnormalities were observed on radiography of the chest, computed tomography (CT) of the thorax and brain, and cerebrospinal fluid (CSF) examinations for evaluation of systemic cryptococcosis. The patient was treated with intravenous fluconazole at doses of 400 mg/day for 4 days and 200 mg/day for 10 days. Two weeks later, several cream-colored smooth colonies were observed in cultures, which were identified as Cryptococcus neoformans var. grubii by sequence analysis of the internal transcribed spacer gene. Thus, the anti-fungal agent was changed to oral fluconazole 200 mg/day. One week later, however, her symptoms became aggravated, and the dose was increased to 400 mg/day, that maintained for 3 months. After 3 months of follow-up, the lesions improved with post-inflammatory hyperpigmentation () and without evidence of recurrence.
The informed consent was obtained for the use of patient information and photographs.


A 32-year-old woman, with no other history of clinical significance, developed slow and progressive hair loss over a period of 6 months before her visit. The patient reported a considerable decrease in hair volume, with no other associated symptoms except the negative influence of this hair loss on her self-image and mental state. There was no family history of hair loss and no history of drug use. Possible factors that may precipitate or exacerbate alopecia, including chronic illness, nutritional alteration, metabolic and endocrinolic alteration, recent surgical intervention and medical treatment, were excluded.
Clinical examination showed hair loss in the median line of the head, with a Christmas tree pattern of hair distribution, Olsen scale type II, with greater involvement of the central line and conservation of the frontal hair implantation line (). Pull test was negative. No signs of excess sebum production were observed. The patient had no present terminal hair loss from other locations and no nail changes. Effluvium was ruled out by the absence of a diffuse loss of scalp hair, the absence of laboratory abnormalities, and no history of drug use. Laboratory testing included a hemogram (complete blood count), assessment of iron and ferritin levels, and of the following hormones: thyrotropin hormone, thyroid T4, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estrogen, free testosterone and dehydroepiandrosterone sulfate (DHEAS). All test results were within the normal range. Gynecological examinations showed no gynecological conditions.
The patient was diagnosed with FPB with no underlying endocrine disorder. Treatment with oral EE/CMA 0.03 mg/2 mg plus daily application of topical minoxidil 2% in a 2 mL aqueous solution was initiated. After 3 months, minoxidil treatment was suspended because of local adverse drug reaction, erythema and irritation. After 6 months’ treatment with EE/CMA, the patient reported subjective improvement in hair loss and mental state. Examination showed stabilization of the hair loss process (Olsen type II). The pull test remained negative. shows hair regrowth after 1 year of treatment (Olsen type I).


The female patient was 29 years old with a history of chronic ferropenic anemia receiving oral ferrotherapy, but with no other significant medical or surgical history. Since menarche at the age of 13 years the patient had had an irregular menstrual pattern (3–4/45–79) for which she received ethinylestradiol/cyproterone acetate 35 μg/2 mg treatment, which resulted in eumenorrhea. At age 28 years contraceptive treatment was voluntarily stopped. After 1 year without contraceptive treatment her menstrual irregularity returned and the patient reported an increase in dermatological lesions.
Physical examination revealed facial acne with over 20 inflammatory lesions and over 30 non-inflammatory lesions (blackheads in the frontal, nasal and chin area). There was no presence of hirsutism. Bodyweight had increased by 6 kg since the last check-up 1 year previously when the patient was aged 28 years, i.e. when oral contraceptive treatment was voluntarily stopped. Gynecological examination showed that the genitalia, vagina and uterine cervix were of normal appearance. Bimanual examination revealed the uterus in anteflexion was of normal size and morphology, and no adnexal masses were felt. Transvaginal ultrasonography revealed that the uterus in anteflexion measured 73 × 45 × 48 mm, the endometrium was 8 mm and the myometrium was homogeneous. Both ovaries had over 12 follicles each (each follicle 2–9mm in size). There was no fluid in the pouch of Douglas. Hormone serum levels were within the normal range (17 beta estradiol 49 pg/mL, progesterone 1.1 ng/mL, LH 18.27 mIU/mL, FSH 6.61 mIU/mL) except for androstenedione (7.3 ng/mL; normal range 0.30–3.30 ng/mL). The patient had had irregular menstruation since discontinuing oral contraceptive treatment, and she had not been menstruating for 3 months at the time of the laboratory tests.
The patient was diagnosed with acne associated with PCOS. Treatment with EE/CMA 30 μg/2 mg was prescribed. After 6 months, her acne improved (less than five inflammatory lesions; less than 15 non-inflammatory lesions). The patient was eumenorrheic (menstrual pattern 2–3/28) and her bodyweight stabilized, 77.4 kg before treatment and 75.1 at last measurement.


A 19-year-old female patient reported excess hair since childhood, which had increased since puberty, but no rapid increase before the visit was reported. The patient was nulliparous, experienced menarche aged 13 years and did not report menstrual disorders (menstrual pattern 4/28–35). The patient’s mother had excess hair, treated with laser hair removal, and had experienced two pregnancies and normal childbirths. The patient had no other significant personal or family medical history.
The patient’s excess hair was assessed using the Ferriman—Gallwey scoring system, with a total score of 16 (maximum 36), distributed as follows: upper lip 3, chin 3, thorax (periareolar) 1, abdomen 2, pubis 2, arms 2, legs 1, upper back 1, lower back 1. No acanthosis nigricans was found. Her body mass index was 23. Manual gynecological examination results were normal, with no hypertrophy of the clitoris or inguinal mass. The gynecological ultrasound revealed a normal genital system, with no suggestion of polycystic ovaries. Laboratory, hemogram and coagulation test results were within the normal range. The following serum hormone levels were assessed in the initial cycle and were all normal: prolactin, thyroid hormones, FSH, LH (LH:FSH ratio of 1.5), estradiol, testosterone, androstenedione, dehydroepiandrosterone, DHEAS, 17.OH. progesterone. Free urine cortisol levels were also normal.
We diagnosed the patient with idiopathic hirsutism. Treatment was initiated with oral EE/CMA 0.03 mg/2 mg. After 6 months’ treatment, the Ferriman—Gallwey score decreased to 11 (upper lip: 2, chin 1, thorax, 1 abdomen 1, pubis 2, arms 2, legs 1, upper back 0, lower back 1), with clear improvements in the facial area.


A 20-year-old woman presented in July 2010 with oligomenorrhea (menstrual pattern 3/35–50) and progressive acne since menarche (13 years). The patient was not taking any medications. The patient’s menstrual pattern was 3/35–50 and her longest period of amenorrhea had been 4 months. There was no history of an abnormal pap smear and the last one was obtained in July 2010. The patient denied pain with menstruation or intermenstrual bleeding. The patient also sought counselling for an appropriate contraceptive method. The patient and her parents’ medical history were otherwise unremarkable.
Dermatological examination revealed the presence of acne, especially on her face and only to a slightly mild degree on her back; the lesions were mainly papulopustular lesions, particularly on her face. She also showed slight hirsutism in the form of dark terminal hairs involving the chin. A significant increase of the seborrheic secretion on the face was also noticed upon clinical assessment.
There were no other signs of virilization. Gynecological examination revealed that the vulva, urethra, vagina and cervix were normal. On bimanual examination, no nodularity, mass or tenderness was noted on the uterus or ovaries. The uterus was normal in size, shape and mobility and no adnexal masses were noted. The cul-de-sac was smooth. Breasts were without dominant masses, skin changes or nipple discharge. Physical examination suggested an otherwise healthy individual (body mass index 22.86).
Gynecological ultrasound revealed a normal-sized uterus in anteversion. Both ovaries had multiple follicles (14 follicles of 4–6mm in diameter in the right ovary and 16 of the same dimensions in the left ovary). The volume of both ovaries was over 10 mL and the ovarian stroma was hyperechogenic. A complete blood count, coagulation testing and laboratory testing (including glucose and cholesterol levels) showed normal ranges, including a euglycemic—normoinsulinemic profile. Baseline hormone levels on the third day of the menstrual cycle were as follows: FSH 3.25 mUI/mL, LH 10.90 mUI/mL (with a ratio LH:FSH >3), estradiol 60 pg/mL, prolactin 15.10 ng/mL (normal values 4.50–40), total testosterone 0.59 ng/mL (normal values 0.20–0.90), DHEAS 270 μg/dL (normal values 10–340) and androstenedione 6.02 ng/mL (normal 0.30–3.3).
The patient was diagnosed with PCOS. Treatment with EE/CMA 0.03 mg/2 mg was initiated. After 6 months’ treatment, there were slight improvements in acne with the number of acne lesions decreased almost to half on her face, and a marked decrease in seborrheic secretion and facial hirsutism. The patient denied any laser hair removal or waxing of her face subsequent to treatment initiation. Androstenedione levels decreased from 6.02 ng/mL to 3.33 ng/mL. The patient’s menstrual cycle control improved, and cycles normalized without spotting at any time (menstrual pattern 3/28). At 10 months after treatment initiation, the patient remains on treatment with EE/CMA.


A 25-year-old man was admitted to our hospital due to perianal abscess and operated. His BMI was 27 klg/m and he had ASA II score due to anemia. Preoperatively, his chest examination results were normal, and a chest radiograph indicated clear lung fields. Standard monitorization of the patient was performed with electrocardiogram, noninvasive arterial blood pressure measurement and pulse oximetry. According to anesthesia induction protocol, 1.5 μg/kg fentanyl, 2 mg/kg propofol and 1 mg/kg rocuronium bromide were used after satisfactory muscular relaxation an orotracheal intubation was performed with an 8-mm-thick cuffed tube. The patient was ventilated with a 550 ml tidal volume in order to ensure 14 respirations per minute in a volume control mode. The respiratory parameters were set in order to have a CO2 end-tidal level between 35-40 mmHg. Anesthesia was maintained by providing fresh gas of 1-2% minimally alveolar consolidation (MAC) sevoflurane and 50% O2-air with 3 L/min. The surgery lasted for about 60 minutes. In the operation, 800 mL crystalloid (0.9% NaCl) infusion was made. The procedure was terminated without any complications. When enough respiratory depth was reached, severe agitation, laryngospasm and inspiratory effort developed following extubation. Negative pressure pulmonary edema was suspected due to the presence of foamy, pink colored, bloody secretion, auscultating common rales in both lungs, and oxygen-free saturation values of 86 percent. The patient was given oxygen and taken to intensive care unit for postoperative follow-up. In the first blood gas sample taken in the intensive care unit, pH was measured as 7.32, pO2: 53 mmHg, pCO2: 33 mmHg, HCO3: 18 mmol/L Lactate: 1.2 mmol/L. The patient did not need intubation and we performed NIMV with pressure mode and PEEP (positive end-expiratory pressure). In computed tomography of the patient, there were ground-glass opacifications and alveolar consolidations which were denser in the central interstitial area of both lungs. Noninvasive mechanical ventilation and 8 mg dexamethasone and 20 mg furosemide were given to the patient taken to intensive care unit. Following the treatments, both symptomatic and radiological improvement was seen ().


A 28-year-old, obese (BMI: 35,6), ASA score II man was admitted to hospital due to cholelithiasis and operated. Preoperatively, his chest examination results were normal, and a chest radiogram indicated clear lung fields. The patient was ventilated with a 500 ml tidal volume in order to maintain 15 respirations per minute in a volume control mode. The operation lasted for about 90 minutes. In the operation, 1200 mL crystalloid (0.9% NaCl) infusion was made. The procedure was concluded without any complications. Following extubation, severe agitation, bronchospasm and inspiratory effort developed in the patient. In recovery room, negative pressure pulmonary edema was suspected due to auscultation of common rales in both lungs and with 2-4 L/min oxygen saturation values of 91% at postoperative tenth minutes. In the first blood gas sample pH: 7.31, pO2: 52 mmHg, pCO2: 31 mmHg, HCO3: 19 mmol/L Lactate: 1.5 mmol/L in recovery room. Together with oxygen support, non-contrast computed tomography was obtained. There were ground-glass opacifications and alveolar consolidations which were denser in the central interstitial area of both lungs (). The patient was given oxygen and taken to intensive care unit for postoperative follow-up. Noninvasive mechanical ventilation and 8mg dexamethasone and 20 mg furosemide treatments were given to the patient taken to the intensive care unit. Following the treatments, both symptomatic and radiological improvement was seen. The patient did not need intubation and we applied NIMV for positive pressure ventilation strategy. The patient was discharged from the intensive care unit after two days of intermittent NIMV application.


A 33-year-old female patient with known Type 2 DM, receiving metformin therapy only, admitted to the emergency department with nausea and vomiting that started 2 hours after committing suicide by taking 30 tablets of metformin 1000 mg (0.4 gr/kg total). Her general condition was good, vital parameters were as follows: blood pressure: 120/70 mmHg, heart rate: 90 per minute, respiration rate: 22 per minute. spO2: %97 and no pathological finding was found in the physical examination of the patient. Electrocardiography showed 1:1 atrioventricular nodal conduction sinus rhythm with normal QRS and QTc distances.
After the gastric lavage and activated coal (1 g/ kg) therapy, hydration and symptomatic treatment were started.
No abnormality was observed in the patient’s first hemogram, liver and kidney function tests and no electrolyte imbalance was detected. Her blood gas analysis in admission was as follows: pH: 7.37, pCO2: 78.1 mmHg, HCO3: 19.6 mmol/L, lactate: 4.7 mmol/L and glucose: 186 mg/dl.
In the 2 hour of her follow-up, the patient’s general condition worsened and confusion developed and her vital signs were: blood pressure: 100/67 mmHg, pulse: 100 beats/min, spO2: 99%. In the control physical examination, widespread tenderness was observed in the abdomen, and no defenses and rebounds were detected. Creatinine in control laboratory parameters was seen to increase as 2.2 mg/dl. Control arterial blood gas parameters were as follows: pH: 7.27, pCO2: 25.5 mmHg, pO2: 75 mmHg, lactate: 9 mmol/L, hCO3: 10.6 mmol/L, anion gap: 23.4, glucose: 80 mg/ dL. The patient was observed to develop lactic acidosis with high anion gap due to metformin. Early hemodialysis was thought to be needed and the patient was followed up closely. Subsequent arterial blood gas parameters were as follows: pH: 6.89, pCO2: 19.5mmHg, pO2: 75 mmHg, lactate: 18 mmol/L, hCO3: 5.6 mmol/L, anion gap: 33.4, glucose: 52 mg/dL. Treatment of hypoglycemia was started by applying intravenous 20% Dextrose 125 cc. After intravenous 100 mEq (1.5 mEq/kg) sodium bicarbonate (NaHCO3) bolus was administered, 100 mEq NaHCO3 infusion was started. The patient, who had urinary output of 4 cc/kg/hour, was taken to hemodialysis early, as metabolic acidosis did not improve in serial blood gas follow-ups () despite the infusion replacement treatments. It was observed that lactic acidosis continued to deepen in the patient who was transferred to the intensive care unit after 2 hours of hemodialysis and continuous veno-venous hemodiafiltration (CVVHF) was applied due to ongoing resistant metabolic acidosis.
Patient who developed respiratory failure in the intensive care unit and invasive mechanical ventilation treatment was initiated, cardiac arrest developed at the 48th hour of her admission. After 45 minutes of cardiopulmonary resuscitation, patient was accepted as exitus.