We report a white 34-year-old male patient referred to our institution with a
one-year lesion on the right first digit. The lesion appeared as an erythematous
papule, which markedly progressed in the last six months. The patient reported local
pain and bleeding after minor traumas, but denies pruritus. He had been diagnosed
with HIV six years before. His latest examinations revealed undetectable viral load
and CD4 718 cells/mm.
Antiretroviral drugs included tenofovir, lamivudine, lopinavir, and ritonavir. He
denied other comorbidities and similar family history. Dermatological examination
showed erythematous, keratotic, scaly plaques with raised ridges and an atrophic
center on the dorsal surface of the right first digit ( and ). We observed no
other lesion. Histopathological examination revealed a large cornoid lamella with
parakeratotic cells. Hypogranulosis and dyskeratosis were observed at the base,
features suggestive of PM. Superficial dermis showed rare perivascular mononuclear
cells ( and ). Considering the possibility of cancer in an
immunocompromised patient, we decided to perform a surgical removal of the entire
lesion – preserving the functionality of the limb – and to use a skin graft for
acceptable esthetics ().


A 54-year-old man presented to our hospital with a 10-day history of diffuse, dull, aching, non-radiating abdominal pain that was associated with a documented high-grade fever and bloody diarrhoea (3–4 episodes/day). He had travelled to Pakistan and, during the preceding three months, he had noticed an increase in the frequency and looseness of his stool. The patient had no history of diarrhoea before this. He was previously diagnosed with hypertension but had no history of diabetes mellitus, tuberculosis, smoking or alcohol consumption. The patient’s HIV and hepatitis B surface antigen status were negative. No significant medical or surgical history was present.
On physical examination, the patient looked unwell and had shortness of breath (respiratory rate: 35) with desaturation [peripheral capillary oxygen saturation (SpO2) 88 %]. The abdomen was mildly tender with no palpable abdominal mass. Hepatomegaly was present (the liver measured 17 cm), but no splenomegaly. On digital rectal examination, the rectum was empty, and the examining finger was tinged with blood and mucus. Blood tests showed marked neutrophilic leukocytosis (white cell count: 24.6 × 109−L) and mildly deranged liver function tests. In the emergency ward, he developed renal impairment and was immediately started on dialysis. Because of SpO2 desaturation, the patient received bilevel positive airway pressure (BiPAP), and was moved to the intensive care unit (ICU).


We describe the case of a 54-year-old man who was admitted to the infectious diseases clinic of the University Hospital of Palermo, Sicily, Italy in August 2014 because of MSF complicated by sepsis-induced multi-organ failure and myocarditis. He presented with fever for a few days. On admission, the patient was febrile, lethargic and with slurred speech, not oriented in space and time (GCS 11), with no signs of meningeal irritation. Vital signs were: pulse, 102 min−1; blood pressure, 80/50 mmHg; respiratory rate, 40 min−1. A diffuse maculopapular rash, involving the palms, was present. A dark crusted lesion, tache noire-like, was present on the left thigh. Diffuse wheezes were heard on pulmonary auscultation. Heart auscultation revealed paraphonic tones. The blood exam showed: white blood cell (WBC) 8.600 cells mm−3 (N 86.7 %, L 5.5 %), PLT 80.000 cells mm−3, AST/ALT 543/188 U l−1, creatinine 3.71 mg dl−1,and blood urea nitrogen (BUN) 66.8 mg dl−1; arterial blood gas analysis showed pH 7.39, pCO2 38.6 mmHg, pO2 41.9 mmHg, sO2 78.9 %, lactates 1.1 mmol l−1, bicarbonate 23.3 mmol l−1. We observed an increase in cardiac enzymes (peak of creatine kinase MJ3 fraction and troponin I of 800 UI l−1 and 2.52 mg ml−1, respectively). An electrocardiogram showed normal sinus rhythm with T-wave inversion in I, aVL, V4–V5–V6. An echocardiogram showed a dilated ventricle, reduced ejection fraction (35 %), and diffuse moderate hypokinesis. The cranial computed tomography (CT) scan was normal, the chest CT scan showed signs of severe emphysema, patchy interstitial infiltrate in the right lower lobe and mild pericardial effusion. Because of the multi-organ failure, the patient was transferred to the ICU, intubated, and given intravenous fluid therapy after the cranial CT results. Serological tests to detect R. conorii IgM and IgG [indirect immunofluorescence assay (IFI) and ELISA] were negative. Rickettsia PCR on blood was positive. Based on a presumptive diagnosis of MSF, the patient was promptly treated with chloramphenicol 3.5 g four times per day and ciprofloxacin 400 mg twice daily intravenously. A cardiology consultation suggested myocardial protection therapy with bisoprolol 1.25 mg orally once daily and ramipril 1.25 mg orally once daily. After two days the patient became afebrile, and after six days, the patient’s condition improved sufficiently that he was transferred to the Infectious disease unit. The R. conorii IFI and ELISA were repeated after one week, showing elevated IgM and IgG titers (IFI IgM–IgG 1/320–1/640; ELISA IgM–IgG 1/200–1/800). After six days of chloramphenicol, antibiotic therapy was switched to doxycycline 100 mg orally twice daily until the patient was discharged on hospital day 16. A follow-up electrocardiogram performed after two weeks demonstrated T-wave normalization. Echocardiogram findings after two weeks and one month were unchanged. At the six-month follow-up the patient was in good clinical condition.


A 64-year-old woman, with hypertension and 1 year of left cerebellar infarction was admitted due to sudden early morning onset of dizziness, followed by unconsciousness and left-sided weakness. There was no history of neck manipulation, trauma, or pain.
On arrival to the ER, the patient was somnolent and dysarthric with a Glasgow coma score of 8. She reacted well to external stimuli and followed verbal orders. However, in the absence of continuous external stimulation, she fell asleep within a few moments. Cranial nerve examination revealed absence of pupillary reaction to light and anisocoria (Fig. ), where the right and the left pupil measured 5 and 4 mm, respectively (bilateral internal ophthalmoplegia). She had bilateral ptosis and upward gaze palsy of the right eye (Fig. ) (bilateral incomplete external ophthalmoplegia), along with a slight left-sided facial drooping and left-sided deviation of uvula. She had weak adduction of both eyes and abduction nystagmus of the contralateral eye (bilateral internuclear ophthalmoplegia). She had normal facial sensory response, however decreased sensation in the upper extremities on the left side. Motor function showed left-sided hemiplegia with grade 1/5 in upper extremities and 2/5 in lower extremities. Deep tendon reflexes on the left side were weak and an upgoing plantar response was found on the same side.
A brain computed tomography (CT) scan performed on the same morning showed normal findings. Electrocardiogram showed sinus tachycardia with AV-block grade I. Furthermore while in the ER, patient had irregular pulse from 80 to 110. Her situation continued to worsen during the day of admission. The situation was complicated by dysphagia which led to aspiration pneumonia, further worsened by the patients’ refusal to have a nasogastric tube. Later on, percutaneous endoscopic gastrotomy (PEG) was planned, and the patient was given subcutaneous dalteparin, because oral anticoagulants could not be given. She mainly slept during the day and had episodes of confusion and mild agitation during the night.
MRI cerebrum with angiography was performed 2 days following admission, which showed brisk infarcts in the rostral central portion of the midbrain, ventral to the aqueduct, affecting the paramedian structures involving the right ventro-medial midbrain and right cerebellar hemisphere near vermis (Fig. ). Apart from these findings, there were bilateral paramedian thalamic infarcts involving left hippocampus (Fig. ). MR angiographic images (Fig. ) demonstrated low blood flow in the hypoplastic basilar artery, which seemed to end in superior cerebellar arteries. DWI images (Fig. ) show bilaterally symmetrical high signal intensity in the thalamus, left hippocampus, in the central portion of the upper mesencephalon affecting paramedian structures bilaterally and, the right ventromedial part of mid-mesencephalon, involving the right cerebellar hemisphere close to the vermis.
Computed tomography angiography of the neck performed on the fourth day of admission showed a slim left vertebral artery with the flow-restricting stenosis at the caudal part. Echocardiography performed on the same day showed no cardiac source to emboli. On the ninth day, patient showed AF and was treated with digoxin.
The patient showed signs of improvement after 7 days of admission where she was more conscious, less agitated, cooperating well with physiotherapy, and was more awake during daytime. She could slightly lift her eyelids, but showed minimal improvement with her hemiparesis. Later on, a PEG was placed and the patient was discharged on the 25th day to our rehabilitation center for further rehabilitation and physiotherapy.


A 24-year old female presented to the accident and emergency department following a high energy motor vehicle accident in which she was dragged off her motorbike by her right upper limb by a truck. She was brought in with a Glasgow Coma Scale (GCS) of 8/15, tachycardic, hypotensive and tachypneic. The initial chest radiograph showed bilateral pneumothorax and chest tubes were inserted (). She was intubated and appropriately resuscitated and later transferred to the intensive care unit.
CT cervical spine revealed an odontoid fracture. She had bruising and gross swelling over her right shoulder and scapula and closed fracture of her right femur. She had a right scapula fracture with scapula-thoracic dissociation and acromioclavicular disruption. (). She also had right transverse process fractures of T4-6, T12, and L1-4. Her abdomen revealed tenderness and guarding over the right quadrant. CT abdomen revealed grade 3 liver and kidney injuries Both the liver and kidney injuries were treated conservatively and she was appropriately transfused. It was noted that there was no movement of her right upper limb and peripheral pulses were absent despite having a warm hand with good capillary refill time. An urgent computed tomography angiography revealed subclavian artery avulsion ().
This vascular injury was treated conservatively as she had good hand perfusion from collateral blood supply with no evidence of on-going exsanguination. As her general condition improved, she was gradually weaned off the ventilator and chest tubes and her right upper limb neurology was re-assessed. She had a postganglionic supraclavicular complete brachial plexus injury. After a week, she subsequently underwent internal fixation for her right femur and halo vest immobilisation for odontoid fracture. The scapula fracture and the scapulothoracic dissociation were treated conservatively and she was put on arm sling. The complete brachial plexus injury was approached conservatively and she was started on physiotherapy.


A 55-year-old Chinese male, with no contributory medical and family history, was admitted to our hospital because of exertional chest pain for 10 days. Physical examination revealed a systolic murmur (Grade II) in the left third intercostal space. Laboratory tests were unremarkable. The transthoracic echocardiography showed a pedunculated hyperechoic mass (2.1 × 1.9 × 1.6 cm) at LVOT, with a 0.5 cm pedicle adhere to the interventricular septum (Fig. ). The transvalvular blood flow velocity through aortic valve on Doppler mode was 4 m/s, indicating severe LVOT obstruction caused by the mass. Further assessment by computed tomographic angiography of coronary artery showed a spherical high density mass, which located at the LOVT, without coronary artery disease.
Tumor resection was performed via median sternotomy under general anesthesia and the cardiopulmonary bypass was established with aortic and right atrial cannulation. An aortotomy revealed a mass, about 3 × 2.5 cm in size, locating at the LVOT inferior to the aortic valve with a pedicle, about 0.5 cm in diameter, rising from the interventricular septum (Fig. ). In addition, the aortic valve was found extensively invaded by the tumor, especially the right coronary cusp and the non-coronary cusp. Simply tumor resection seemed impossible owing to the tumor location and widely involvement. Finally, the patient received complete tumor resection as well as aortic valve replacement with a 23 cm mechanical valve (Carbomedics, Sorin Group, Italy) (Fig. ). The pathological examination confirmed the diagnosis of IMT (Fig. ). The patient had an uneventful recovery without any complications and he was discharged home on the 7th postoperative day. The patient has been followed up for 2 years without any sign of recurrence.


A 74-year-old male was evaluated for refractory anemia. He had a history of gallbladder cancer treated with radiation (RT) in 2010. His Hb, mean corpuscular volume (MCV), and red cell distribution width (RDW) were 8.3 g/dL, 86.1 fL, and 19.8%. White blood cell count, absolute neutrophil count (ANC), and absolute monocyte count (AMC) were 5400/μL, 3800/μL, and 1080/uL. There was no evidence for basophilia or thrombocytosis. His reticulocyte count, erythropoietin (EPO), and vitamin D level were 0.8%, 25.8 MIU/ML (2.6–18.5), and 76 pg/mL. Ferritin level was 120 ng/mL. Physical exam demonstrated no hepatosplenomegaly. Peripheral blood smear showed normocytic, normochromic anemia with scattered target cells. White blood cells were unremarkable and platelets were adequate. His bone marrow was hypocellular with trilineage dysplasia. His erythroid cells showed nuclear irregularities, budding, and nuclear/cytoplasmic desynchronization (Figures and ). Micromegakaryocytes were hypolobated (). Immunohistochemistry revealed no evidence of blasts or monocytosis. Bone marrow findings were consistent with refractory cytopenia with multilineage dysplasia (MDS-MLD) []. Karyotype was 46, XY, t (9:22) [4], XY [16] (). MDS fluorescence in situ hybridization (FISH) including probes for 5q31, 7q31, 8 centromere, 11q23, and 20q12 was negative. Chromosome microarray analysis (CMA) showed no pathogenic copy number variation (CNV) or copy number neutral loss of heterozygosity (LOH). Next generation gene sequencing demonstrated no relevant leukemia mutations in CSFR1, SF3B1, SRSF2, U2AF1, NRAS, KRAS, FLT3, JAK2, JAK3, DNMT3A, KIT, PHF6, PDGFRA, CDKN2A, IDH1, IDH2, TET2, EZH2, CEBPA, EP300, PTPN11, P53, CREBBP, IKZF1, IKZF3, NOTCH1, RUNX1, WT1, and NPM1. Real time polymerase chain reaction (PCR) for BCR-ABL1 (Major p210 form) was 24.1180%, International Scale (IS). Estimated R-IPSS score was 3 (hemoglobin [8.3 g/dL] = 1; platelets [341000/μL] = 0; absolute neutrophil count [3800/μL] = 0; cytogenetic = 2; blast = [0%] = 0). Trilineage dysplasia, refractory anemia without basophilia, karyotypic, and molecular clonal evidence for Ph + disease prompted treatment with Dasatinib at 20 mg orally daily. A low dose was selected given potential risk for worsening cytopenias. His hemoglobin progressively increased by 3 g/dL after 12 weeks of treatment (). Response was maintained for a total of 24 weeks (). BCR-ABL1 transcripts were undetectable (0.0006%, IS) after 4 months of treatment. After 7 months of follow-up, patient opted for hospice care after developing pneumonia that led to respiratory failure.


A 22-year-old nulliparous, with no medical history, presented to our hospital in established labor after a spontaneous rupture of membranes, at 40 weeks of pregnancy. The first stage of labor lasted for 6 hours. During labor, she refused to receive any form of analgesia. At the end of the second stage of labor which had lasted for 2 hours, the patient began to cough; she also complained of shortness of breath and pain over the chest and the neck regions.
Physical examination revealed conscious patient; the blood pressure was 120/90 mmHg, pulse was 96/min, and the oxygen saturation was 98% on 3 L/min of oxygen. The patient had mild dyspnea with breath rate of 24 cycles/minutes. No edema was present and the patient was afebrile; the cardiopulmonary auscultation was normal.
Palpation showed crepitus underneath the skin of the anterior neck and bilateral subclavian regions consistent with subcutaneous emphysema. The patient had not undergone any radiological examination due to the imminent delivery and the stability of the respiratory function. She received oxygen by facial mask and remained stable. 15 minutes later, the labor ended with a vaginal delivery requiring an episiotomy. The patient delivered a healthy, live infant with Apgar score of 10/10 in the first and fifth minute. One hour later, the cripitations extended to the upper anterior chest wall and to the face including the eyelids without any deterioration in respiratory status. A chest X-ray showed pneumomediastinum with subcutaneous emphysema extending to the soft tissue of the axillary region. Computed tomography (Figures and ) confirmed pneumomediastinum and subcutaneous emphysema extending to the thoracic, cervical, and abdominal regions. It showed also a minimal pneumothorax. There were no anomalies in the pulmonary parenchyma and thoracic great vessels. Routine blood tests and arterial gas were found to be normal.
The patient had been followed up for 4 days in hospital, without a specific medication. The symptoms have regressed and chest X-ray showed disappearance of pneumomediastinum. The patient had been discharged home. Regular follow-up showed complete recovery without any sequelae.


An 82-year-old male patient presenting with lethargy in consciousness, malnutrition, multiple bedsores [an 8 × 10 cm2 at level I (containing a 5 × 6 cm2 at level II) on the sacrococcygeal region, two 5 × 5 cm2 at level I on the both heel, two 2 × 2 cm2 at level I on both external malleolus] was admitted on December 14, 2009. He had a history of surgery for esophagus cancer at 73 years old, hypertension at level III, two hospitalizations due to lower respiratory tract infections (treated by azithromycin, cefoperazone/tazobactam, levofloxacin, meropenem, linezolid, piperacillin/tazobactam, and ciprofloxacin) 4 months before this final hospitalization. He demonstrated expectoration and shortness of breath for 7 days before admission. The blood gas analysis and blood biochemical test at admission showed respiratory acidosis (pCO2 97 mm Hg, pO2 122 mm Hg), metabolic alkalosis (pH 7.48, > 60 mmol/L, CO2 36.8 mmol/L), very low blood K+ (2.1 mmol/L), renal dysfunction (BUN 23.9 mmol/L), and extremely low Cl− (68.6 mmol/L). He came into deep coma with BP 58/34 mmHg within 2 h after admission. Emergency salvage was given, including assisted ventilation, raising BP by dopamine and L-noradrenaline, supplement of potassium chloride, and anti-infection treatment with piperacillin/tazobactam and ciprofloxacin. In the subsequent 2 days, he recovered from coma gradually, but presented clear sign of lung infection (fever, moist rale sound in both sides of lower lung lobes, blood WBC 9.8 × 109/L, NEUT 94.61%, CRP 146 mg/L). Diagnoses of shock, multiple organ dysfunction syndrome (MODS), and lower respiratory tract infection were made. The infection and the respiratory acidosis combined with metabolic alkalosis lasted for nearly the whole 52 day-hospitalization. On the 45th day of hospitalization, a fistula between the esophagus and trachea was found through gastroscopy and further verified by bronchoscopy. It was treated with tracheal stenting 2 days later. However, 5 h after post-tracheal stenting, sudden cardiac arrest occurred, complicated with a loss of spontaneous breathing, then he went into coma (combined with dilated pupils and disappeared light reflex of both sides) again. BP and SpO2 could not be measured while his pulse and spontaneous breathing returned 5 min after salvage. BP, SpO2, and light reflex of both pupils returned to normal gradually within the subsequent 5 h. However, the patient was still in coma and was discharged after 7 days at his family's request to terminate treatment.
During the hospitalization, the separately or jointed isolated pathogenic microbes for the lung infection included Acinetobacter calcoaceticus–Acinetobacter baumannii complex (7 times isolated from sputum, 7 TIFS), Acinetobacter baumannii (4 TIFS), Enterobacter cloacae (3 TIFS), Pseudomonas aeruginosa (2 TIFS), Serratia marcescens (2 TIFS), molds (2 TIFS), and E. anophelis (7 TIFS) (named as 12012 PRCM). E. anopheles 12012 PRCM was verified by 16S rRNA gene sequencing (GenBank accession no. ) of the genomic DNA with the forward primer 27F (5′-AGAGTTTGATCCTGGCTCAG-3′) and the reverse primer 1492R (5′-GGTTACCTTGTTACGACTT-3′; Lane, ). It was resistant to all the 20 antibiotics in the antibiotic susceptibility tests (AST) panel, including β-lactams (ampicillin, piperacillin, ampicillin-sulbactam, piperacillin-tazobactam, ceftazidime, cefotaxime, cephazolin, cefepime, aztreonam, imipenem, and meropenem), aminoglycosides (amikacin, gentamicin), tetracycline, chloramphenicol, and polymyxin, quinolones (ciprofloxacin, levofloxacin, moxifloxacin), and sulfamethoxazole-trimethoprim. The strain was also resistant to another antibiotic amoxicillin-clavulanate tested. To investigate the resistance mechanisms, extended spectrum β-lactamase (ESBL) detection was performed on the E. anophelis 12012 PRCM using BD's PhoenixTM-100 Automated Microbiology System with the NMIC/ID-4 panel (Becton, Dickinson, and Company; Stefaniuk et al., ; Liu et al., ). The cephalosporin test was positive and the carbapenem-hydrolyzing β-lactamases and carbapenemases (CHBLs) were detected. In addition, we found this strain was co-positive between EDTA (Ethylenediaminetetraacetic acid) and imipenem. These laboratory findings indicated strain 12012 PRCM could produce metal-beta-lactamase, possibly conferring the β-lactamases resistance.


A 47-year-old male with hypotension (BP 95/55 mmHg) was admitted to our hospital on August 21, 2015. He had history of exacerbated abdominal pain and abdominal distension for more than 10 days, shortness of breath for 3 days, complicated with stagnated exhaust and defecation. Before admission, his pressure was maintained by continuous pumping of L-noradrenaline and dopamine. Physical examination found weak breath sounds in both sides of lung lobes and severe subcutaneous edema on whole body. The arterial blood gas analysis displayed acidosis (pH 7.20, pCO2 11.1 mmHg, pO2 99 mmHg, −8.6 mmol/L, BE −23.3 mmol/L). He had a low white blood cell count (WBC) (2.35 × 109/L). Blood biochemical test showed several abnormal results (glucose 8.86 mmol/L, BUN 18.93 mmol/L, creatinine 271 μmol/L, GFR 24.20 ml/min, AST 827 U/L, ALT 197 U/L, albumin 30.5 g/L, T-BIL 29.5 μmol/L, D-BIL 12.8 μmol/L, total osmotic pressure 280 mOsm/L). Ultrasound imaging demonstrated liver cirrhosis, echo enhancement in parenchyma of both kidneys and effusion around left renal. Computed tomography scanning revealed inflammatory changes within both sides of the lower lung lobes, severe effusion within bilateral pleural, abdominal, and pelvic cavity, edema within subcutaneous soft tissue of chest and abdominal wall. Diagnoses of shock, MODS, electrolyte imbalances (low sodium, low calcium), diabetes and pulmonary infection were made. Within 16 h after admission, the patient further presented oliguria and aggravated during the 12-day hospitalization. On the 3rd day, hepatic virus infection [with positive HBsAg, anti-HBe antibody, and anti-HBc antibody (IgG)], abnormal blood coagulation [prothrombin time (PT) 16.7 s, partial prothrombin time (APTT) 67.8 s, fibrinogen (FIB) 1.75 g/L, D-dimer 8.32 mg/L, international normalized ratio (INR) 1.43], and thrombocytopenia (84 × 109/L) were diagnosed, with the latter lasting for the remaining hospitalization. The treatment strategies included drainage of bilateral pleural effusion, maintaining blood pressure as previously, improving liver function, daily hemodialysis, management of electrolyte, insulin injection and improving nutrition. The empirical antimicrobial therapy was started with IV piperacillin and tazobactam during the first 3 days of hospitalization, then changed to IV imipenem and cilastatin sodium for 1 day and further combined with vancomycin; the latter lasted for the remaining 8 days of hospitalization. The patient died of sudden cardiac arrest.
By using BD's Phoenix™-100 Automated Microbiology System with the NMIC/ID-4 panel as Case 1, we repeatedly isolate E. meningoseptica (on the 7th and 9th day of hospitalization respectively) and Stenotrophomonas maltophilia (on the 8th and 9th day of hospitalization respectively) from sputum cultures. Later, E. meningoseptica was verified as E. anophels (named as N107618, GenBank accession No. ) by 16S rRNA gene sequencing as Case 1. E. anophelis N107618 was resistant to 16 out of 20 antibiotics in the same AST panel used to test the E. anophelis 12012 PRCM, and was only susceptible to ciprofloxacin, levofloxacin, moxifloxacin, and sulfamethoxazole-trimethoprim.


A 31-year-old woman was referred by her general dentist to our dental implant department after being evaluated by the orthodontist. The clinical and radiological examination revealed a retained upper left primary canine tooth, agenesis of #22, permanent cusped (#23) in transposition with mesiovestibular rotation. On the contralateral side a peg lateral incisor (#12) was present. Patient's request was replacing #63 with an implant and reproducing its shape with no prior orthodontic treatment. The mid-facial gingival margin of #63 was slightly lower than transposed #23 and that of the contralateral tooth (Figures and ). The gingival tissue surrounding the crown was measured with a periodontal probe and characterized as thick []. Interproximal papilla was present and underlying bone level was at 1.5 mm from the margin, based on probing.
There were no medical contraindications, and patient agreed with dental implant treatment and signed the written consent form.
Alginate and Tropicalgin (Zhermack, Italy) impression of the surgical site and the opposite arch for stone models was taken using standard trays. Maximum intercuspal position was registered with vinyl polysiloxane bite registration material (Regisil, Dentsply, USA). For diagnostic accuracy a radiopaque stent, R2 tray® (Megagen, Korea), was customized on the maxillary arch with nonradiopaque silicon impression material (Speedex, Coltene, Switzerland). A medium volume CBCT using ProMax 3D (Planmeca, Finland) with the characteristics of rotation of 360 degrees, height and diameter of 160 mm and 160 mm, voxel size of 0.3 mm, and the exposure factors of 110 kV and 2 mA was performed.
A series of axially sliced image data were obtained and exported to a personal computer in DICOM (Digital Imaging and Communications in Medicine) format.
Stone models alone, maximum intercuspal position, and R2 tray were scanned using a D 700 3D scanner (3Shape, Denmark) and imported as STL (Standard tessellation language) files ().
On the scan models, a virtual wax-up was designed with the use of 3Shape® CAD (Computer Aided Design) software and saved as STL file ().
DICOM files obtained from CBCT and STL files were imported in a treatment plan software R2GATE® version 1.0 (Megagen, Korea) and implant insertion was planned according to the final restoration and bone anatomy.
To facilitate bone quality assessment the “Digital Eye” option of R2GATE treatment planning software was used. This option provides automat conversion of CBCT gray scale in 5 basic colors, corresponding to the 256 shades of gray, from the CBCT scan, visible on computer monitors. In figures treatment plan on R2GATE software 1.0 is illustrated ().
The temporary screw-retained crown was designed according to the planned position of the implant and was sent as STL file for evaluation by the patient and the restorative team ().
Surgical template was printed according to the established position of the implant, which was simulated in alveolar bone by the R2GATE software based on the obtained CBCT data, estimated bone quantity and quality, and digital wax-up of the future prosthetic reconstruction. Screw-retained provisional was manufactured according to the planed implant position and delivered before surgery with the computer aided design and manufacturing (CAD-CAM) surgical template (Figures and ).
Atraumatic extraction of the primary canine using periotomes was performed (Figures and ). Care was taken not to damage the labial bone, the socket was irrigated with saline, and the site was examined to verify an intact buccal plate. A 10 mm with 3,5 mm diameter Megagen AnyRidge® (Korea) was inserted flapless, under local anesthesia, according to the planned 3D position with the use of the stereolithographic template ().
Insertion drill sequence was recommended by the manufacturer according to the bone characteristics evaluated with the aid of the CBCT in order to acquire maximum bone to implant contact. Torque insertion value was 65N cm resulting in a good primary stability. The space between the inner surface of the labial osseous wall and the labial surface of the implant was filled with resorbable bovine bone graft material (Cerabone, Botiss, Germany). After implant insertion the prefabricated provisional crown was screwed into the implant and occlusal adjustments were performed ().
Eight weeks after implant surgery, after uneventful osseointegration, the provisional crown was unscrewed and an excellent healing of dentogingival complex and papilla preservation were observed (). Digital impression was performed () and a CAD-CAM zirconia customized abutment and ceramic crown were manufactured according to patient's request ().
Patient was very pleased with the final result (Figures and ).
At the annual recall the implant showed no signs of complications nor infection (). Clinical assessment of pink esthetic score (PES) [] and white esthetic score (WES) [], utilized to objectively evaluate single tooth implant restoration, rated 14/14 and 9/10, respectively, due to minor discrepancies between the two canines (left and right). On the CBCT evaluation no buccal bone resorption was observed after one year of function ().


A 14-year-old British born girl presented with a 1 month history of fever, weight loss, lethargy, arthralgia and diarrhoea. She had been investigated a month previously for an iron deficiency anaemia with no cause found. Travel history consisted of a trip to Israel 2 years ago.
Upon examination, she was pyrexial (38.5 °C) and tachycardic with a soft systolic murmur. There was a palpable splenic tip below the left costal margin.


A healthy 19-year-old man suffered SCA while playing football. His girlfriend (a
medical student) carried out cardiopulmonary resuscitation until the arrival of the
ambulance. Polymorphic ventricular tachycardia degenerating into ventricular
fibrillation (VF) was documented ()
and defibrillation was successfully performed (). At subsequent hospital admission, the electrocardiogram (ECG) showed
sinus rhythm (95 bpm), with a PR interval of 0.26-0.28 sec and a QTc interval of
0.45 sec. (). The echocardiographic
study (echo) was normal and reversible causes of SCA including ionic, infectious and
toxic were excluded. The patient had a normal clinical exam and no personal history
of severe illness. He took no medication. There was no family history of cardiac
disease or sudden death. Thoracic X-ray, cardiac magnetic resonance, exercise test
(treadmill) and coronary angiography were normal.
Electrophysiological study (EPS) showed a prolonged HV interval (80 ms) and
ventricular stimulation (600 ms cycle - 250-220-220 at RV apex) induced polymorphic
VT with no pulse (successfully terminated by external cardioversion). A provocative
test for Brugada syndrome (BrS) was postponed.
After written informed consent, genetic screening was performed on a panel of 9
genes: MYBPC3, MYH7, MYL2, SCN5A, TNNI3, TNNT2, KCNQ1, KCNH2 and
LQT5. The entire coding regions were tested by PCR and direct
sequencing. We found the mutation c.3622G>T; p.Glu1208* in the
SCN5A gene (NM_198056.2), that was already described in BrS.
Additionally, another sequent variant, c.446C>A; p.Ala149Asp, in the
MYBPC3 gene (NM_000256.3) was detected (). This alteration was reported as a rare sarcomeric
gene variant in a single case of the offspring cohort of the Framingham Heart Study,
including 1,637 unrelated individuals. Although this single individual did not show alteration of the
left ventricle wall thickness, only one wall segment was measured, without any
further detailed information, thus HC cannot be excluded. Besides, no information
was given whether the index case of this family was also harboring this sequence
variant in MYBPC3.
The p.Ala149Asp mutation in MYBPC3 affects an evolutionarily
conserved amino acid and it was absent in 100 age-matched Portuguese control
samples. Regarding the various in-silico mutation prediction programs, PolyPhen2
() predicted this alteration as
possibly damaging with a score of 0.65 (sensitivity: 0.87, specificity: 0.91). The
SNPs&Go program () predicted
this variant as disease associated variation (0.696).
Subsequent family analysis showed that the patient´s father was carrier of both
SCN5A and MYBPC3 mutations (). The father was submitted to EPS with
provocative test with flecainide. This test showed negative results. The sister of
our index patient was harboring the SCN5A mutation solely. Because
of the young age, we decided not to perform provocative tests or EPS.
A cardioverter defibrillator (ICD) was implanted in the index patient. Provocative
pharmacological tests were systematically refused by the patient thereafter. Serial
ECGs during hospitalization showed normal patterns except for mild PR prolongation
that persisted also during ambulatory follow up. Family screening (parents and
sister) revealed normal clinics, ECG and echo studies.


A 13-year-old 32 kg male with a past medical history significant for dystonia and learning difficulties was directly admitted to the pediatric intensive care unit for evaluation and treatment of new-onset myoclonic status epilepticus. Burst suppression was achieved on hospital day one following administration and titration of the following medications (total daily mg/kg): lorazepam (0.4 mg/kg), levetiracetam (50 mg/kg), fosphenytoin (30 PE/kg), phenobarbital (40 mg/kg), midazolam (2 mg/kg/hr), pentobarbital (5 mg/kg load, 4 mg/kg/hr), pyridoxine (100 mg), and isoflurane (0.5%). Burst suppression was maintained for the subsequent two days with midazolam (2 mg/kg/hr), pentobarbital (4 mg/kg/hr), and isoflurane (titrated to burst suppression). The average daily PG exposure during the first three hospital days was 1 g/kg/day, 0.8 g/kg/day, and 0.8 g/kg/day, respectively. Renal and hepatic function during the first three days was within normal limits. On hospital day three, the patient developed acute, severe distributive shock refractory to four separate vasopressors at high doses (maximum infusion rate): norepinephrine (0.4 mcg/kg/min), epinephrine (0.3 mcg/kg/min), dopamine (20 mcg/kg/min), and vasopressin (0.15 units/kg/hr). In addition, the vasoplegia was refractory to administration of methylene blue. Physical examination was pertinent for warm extremities, flash capillary refill, bounding pulses, and a hyperdynamic precordium. Electrocardiogram demonstrated sinus rhythm with new-onset ST depression in anterior leads, T-wave inversion in inferolateral leads, 1st degree A-V block, biatrial enlargement, left axis deviation, and ST elevation, findings concerning for possible myocardial injury (see ). Bedside echocardiography was performed at a heart rate of 115 beats/minute demonstrating hyperdynamic biventricular function without evidence of pericardial effusion or regional wall motion abnormalities and normal biventricular systolic and diastolic function. Pulse-wave Doppler interrogation of the LVOT in the apical long axis view demonstrated a velocity-time integral (VTI) of 14.7 cm. Using the LVOT VTI method to measure cardiac output (LVOT area × LVOT VTI), the stroke volume (SV) was 42 mL. The body surface area (BSA) of the patient was 1.14 m2, thus the cardiac output (SV × HR) was 4.83 L/min and cardiac index (cardiac output/BSA) was 4.24 L/min/m2. Laboratory investigation revealed hyperosmolar anion gap metabolic lactic acidosis (anion gap 28, pH 7.05, bicarbonate 11 mmol/L, lactate 16 mmol/L, and osmol gap 24). Distal tissue perfusion appeared adequate secondary to ScvO2 90% and CO2 gap 1 (central PvCO2-PaCO2). Differential diagnoses of septic shock, PG toxicity, malignant hyperthermia, and adrenal insufficiency were considered. Subsequent therapy included broad spectrum antibiotics, cessation of PG-containing medications (pentobarbital), cessation of volatile anesthetic, administration of stress-dose hydrocortisone, and initiation of intermittent hemodialysis. Acidosis and hemodynamic instability rapidly normalized after the institution of hemodialysis and the electrocardiogram findings normalized. Blood cultures remained negative. A random cortisol level 16 hours prior to the onset of shock was 5.8 mcg/dL. Renal impairment occurred following the episode of acute decompensation on hospital day 3 before initiation of hemodialysis (peak creatinine 1.9 mg/dL) and quickly resolved (creatinine 1.1 mg/dL following the first hemodialysis treatment). The diagnosis of PG toxicity was confirmed when the PG level on predialysis serum sample returned in the toxic range at 35 mg/dL.


A 45-year-old female was referred by her general practitioner with a 5-year history of increasingly frequent episodes of cyclical diarrhoea, vomiting, abdominal pain and intermittent palpitations. Her bowels would open up to ten times a day and she described them as ‘explosive’ and loose in nature. There was no blood or mucus per rectum, or any nocturnal symptoms. She vomited approximately fifteen times a day and experienced non-specific abdominal pain. These episodes would last for several days and occur on a monthly basis. Other than a Laparoscopic Cholecystectomy, she had no significant medical, surgical or family history, and took no regular medications.
The patient’s persistent cyclical symptoms resulted in 7 identical short admissions to hospital, during which she was diagnosed with ‘non-specific abdominal pain’. Each time symptoms settled with conservative therapy, and she was discharged with the reassurance of normal routine bloods and simple abdominal imaging. During her latest admission, she was found to be hypertensive with a systolic of 160mmHg, which spontaneously resolved prior to discharge, and was not thought to be clinically relevant at the time.
Although being actively investigated as an outpatient, the patient requested a second opinion and so a referral was made to the regional tertiary centre. She was thoroughly investigated and returned to Milton Keynes Hospital with a list of possible differential diagnoses including Cyclical Vomiting Syndrome, Bile Salt Malabsorption and Visceral Hypersensitivity. No records of any work up are available.
Since the patient had a history of laprascopic cholecystectomy, it was hypothesised that her pain might be explained by a retained gallstone. However, two MRCPs were normal with no retained gallstone or common bile duct dilation was found. Abdominal and pelvic ultrasounds were also normal. Therefore, the pain was considered to be originating from her renal tract and although the first CT KUB was normal with no evidence of renal calculi or hydronephrosis, a subsequent CT KUB confirmed the peri-aortic lymphadenopathy. This incidental finding prompted a Contrast CT Abdomen/Pelvis in September 2015, which found a 36 x 33 x 46mm mass in the aorto caval region of her retro-peritoneum, just above the bifurcation.
While local and regional MDT meetings were being sought, the patient continued to be investigated for a co-existing pathology. Both OGD and Colonoscopy were normal, in addition to blood tests including thyroid function, autoimmune profile, porphyria, CA19-9 and HIV. She demonstrated no evidence of pancreatic insufficiency with a faecal elastase of >500µg/g and TB Elispot negative. The MDT outcome was to biopsy the retroperitoneal mass, but due to the complexity and proximity of the lesion to the aorta, she was referred to the national sarcoma team in Birmingham.
On the basis of her symptoms, CT findings and an elevated plasma metanephrine level of 2314pmol/L (normal range 80 – 510pmol/L), it was at this point a likely diagnosis of a Phaeochromocytoma was made. Furthermore, a meta-iodobenzylguanidine (MIBG) CT was performed and showed that the retroperitoneal aorto caval mass was clearly avid, in keeping with an ectopic Phaeochromocytoma. There was no abnormal activity elsewhere in the abdomen, and particular within the adrenal glands. She was subsequently reviewed by the Endocrinology team who commenced Doxazocin 4mg three times daily in order to control her hypertension, and she was listed for surgery. Despite a very labile systolic blood pressure, fluctuating between 40-300mmHg, the retroperitoneal mass was successfully resected, and the histology confirmed a Phaeochromocytoma (Para-ganglioma with lymph node metastases (3/9), Ki-67 less than 3%, less than 1/12 HPF mitosis). Her symptoms rapidly improved and she made a good recovery.


A 34-year-old previously healthy and nonsmoking man without any history of VTE or renal disease visited an emergency department (ED) because of a complaint of sudden dyspnea at rest and right lower extremity pain. He was Caucasian and from north Africa; his grandfather was from the Netherlands. There was no family histories of thrombosis. He did not have any VTE risks, such as obesity, cancer, surgery, immobilization or recent long travel. Two weeks before the visit, he fell off his bicycle during mountain climbing and strongly hit his right calf. His plasma D-dimer level in the ED was 31.6 μg/mL, and deep vein thrombosis (DVT) was suspected. A contrast-enhanced computed tomography (CT)-scan revealed a contrast deficit in the bilateral pulmonary artery (Fig. ) and in the right lower extremity (popliteal vein) (Fig. ). He was diagnosed with VTE and admitted to our department. On admission, his blood pressure was 133/72 mmHg, and his heart rate was 110 beats per minute. His degree of oxygen saturation (SaO2) on an arterial blood gas was 98%. His body mass index was 21.3 kg/m2. Although multiple VTEs in the bilateral pulmonary arteries were observed, electrocardiography and cardiac ultrasound did not indicate heart failure. His right ventricular function was intact (estimated pulmonary artery pressure = 32/18 mmHg on cardiac ultrasound). His plasma brain natriuretic peptide and high-sense troponin T concentration levels were less than 5.8 pg/mL and 0.004 ng/mL, respectively. Because of his recent history of a trauma, thrombolytic therapy was not recommended; therefore, anticoagulation therapy using heparin was initiated. Heparin was switched to a direct oral anticoagulant (DOAC); 20 mg daily administration of apixaban (trade name: EliquisTM, Pfizer) was initiated according to the results of the AMPLIFY trial [].
An ordinary investigation of most factors related to thrombus formation (including protein C (82%), protein S(92%), antithrombin(80%), and antiphospholipid antibodies(<8U/mL)) revealed that the blood concentrations of all such factors were within the reference range. The protein C and antithrombin were measured using commercially available reagents (Testzym®S PC for protein C, Testzym®S ATIII for antithrombin, Sekisui Medical Co., Tokyo, Japan) according to the protocol supplied by the manufacturer. Protein S (latex agglutination reaction) and antiphospholipid antibodies (ELISA) measurements were performed at SRL Inc., Tokyo, Japan. Therefore, we attempted to screen for the genetic cause of the VTE using NGS technology. We had designed a screening panel of genes for use with the Illumina TruSeq Custom Amplicon platform (Illumina, Inc., San Diego, CA, USA). The panel includes amplicons defining all coding exons of the genes mutations that are known to cause VTE: F5, SERPINC1, PROC, PROS1 and F2. Sequencing was performed using the MiSeq Illumina sequencer (Illumina, Inc.). A total of 14,828 base pairs were sequenced per sample from 107 amplicons. The obtained sequences were aligned to the reference genome (GRCh37̸hg19) using MiSeq Reporter software (Illumina, Inc.). A vcf file containing variant calls was generated, further reviewed, and filtered. The variant frequency which is the ratio of the sum of the called variant (C > T) depth to the total depth was 0.478 as assessed by NGS. Thus, we identified the heterozygous FV Leiden mutation. Therefore, we concluded that the FV Leiden mutation was the primary cause of the VTE. Then, according to a previous report [], we continued treatment with DOAC. After 7 days, a follow-up contrast-enhanced CT scan revealed a reduction in the thrombosis (Fig. ). The patient was followed up with apixaban.
The patient gave his consent for the publication of this study.


A 34-year-old female patient searched Dr. E.S. complaining the "lack of chin", "reversed
lower lip" and gummy smile. The patient had previous orthodontic treatment with dental
compensation, having both maxillary first premolars already extracted and the gap
closed. Clinically, the patient presented symmetric dolicocephalic face with
maxillomandibular retrusion; maxillary vertical excess; chin deficiency and an
accentuated facial convexity. In addition, healthy periodontal tissues and
temporomandibular joints (TMJs), tension of the orbicularis oris and mental muscles
during function and lower lip incompetency when relaxed were also observed.
In order to acquire proper positioning of the mandibular incisors, the right and left
first premolars were extracted and levelling and alignment of the maxillary arch was
performed to create a positive overjet (
and ). For the planning, Arnett, et al. (1999) soft tissue analysis was used. The
surgical plan consisted in maxillary impaction and advancement, mandibular
counter-clockwise rotation with an overall advancement of 9 mm in B point, 13.7 mm in
Pog and 3 mm of genioplasty. Under general anesthesia, the mandible was managed and
fixed as described below, followed by usual maxillary Le Fort I.
After BSSO according to Epker's
(1977) modified technique, the condyle was properly positioned and the osteotomy fixed with a 2.0 mm miniplate and two
monocortical screws in each segment. An inset bend was made at the plate to maintain the
gap and avoid condylar torque. Having the 4 screws in position, a transorally oblique perforation
was drilled in the retromolar region (visualising the proximal end of the distal
fragment), the hole was tapped and a 2.0 mm diameter x 16 mm long screw was inserted. A
second screw was placed distally from the first in the same manner. These screws were
positional and do not exert pressure between segments (). The same fixation was done on the other side. After completion of
the osteosynthesis, maxillomandibular immobilization (MMI) was removed and occlusion and
mouth opening were checked. The wounds were then sutured as usual.
The patient evolved well in the postoperative period and is still under follow up after
14 months, reporting satisfaction with the results ( to ). No damage to tooth
roots was done, maxillomandibular range of motion is within normality and regression of
the inferior alveolar nerve (IAN) paresthesia is observed bilaterally. The hybrid
mandibular fixation is clearly visible in the panoramic and cephalometric control
radiographs ( and ). shows
cephalometric tracing of the preoperative position and postoperative changes along the
16 months of treatment, including the removal of brackets.


A thirty years old woman was admitted to the Affiliated Tumor Hospital of Harbin Medical University in July 2014 with the complaints of chest tightness, shortness of breath and chest pain of ten-day duration. She denied smoking and had no family history of malignancies. She had no other complaints and her past history was unremarkable. Tumor biomarker tests (alpha fetoprotein, antigen 19-9, carcinoembryonic antigen, prostate-specific antigen, Cytokeratin 19 Fragment, carbohydrate antigen 24-2, squamous cell carcinoma antigen, and neuron-specific enolase) were all normal on admission, as were the baseline serum chemistry screening, peripheral blood count and the urinalysis.
Chest computed tomography (CT) scan (July-31, 2014) revealed a heterogenous mass that measured 105.54 mm in longest diameter in the left lower lobe lung with pleural effusion and left lower lobe collapse (Figure ). Enhanced CT showed the mass obviously enhanced with heterogeneous density and obscure boundary. There were some areas of necrosis within the mass and it was extending up to the pleural surface. To establish the pathological diagnosis, a CT-guided biopsy of the mass was performed and sent for pathological evaluation. The histopathologic results showed small, round tumor cells that exhibited mild morphology; arranged in cords and embedded in fibrous tissue (Figure ). The immunostaining showed positive expression of vimentin, CD99, synaptophysin (Syn), friend leukemia integration 1 transcription factor (Fli-1) and NSE (Figure ), and negative expression of Chromogranin A (CgA) (Figure ), cytokeratin 7 (CK7), protein S-100 (S-100), thyroid transcription factor 1 (TTF-1), CD56, CD20, CD3, CD10, and p63 ().
The patient was initially treated with traditional chemotherapeutic regimen that consisted of cisplatin/paclitaxel (CP, cisplatin 270mg/m2 and paclitaxel 60mg/m2) and once intrapleural perfusion of bevacizumab (200mg) and then five additional cycles of CP alone. Chest CT scan was taken after every 2 cycles of CP treatment, which showed the regimen was effective (Figure and ). After 6 cycles of CP treatment, the mass measured 47.90 mm on CT (Dec 23, 2014), which indicated a 54.61% decrease compared with baseline, and met the RECIST (Response Evaluation Criteria in Solid Tumors) criteria for a partial response (PR) (Figure ). Argon-helium knife cryosurgery was then performed (Dec 26, 2014) however, multiple metastases were detected two months after the surgery (Jan 29, 2015). Chest CT scan (Feb 26, 2015) indicated clear evidence of disease progression, with left pleural metastases, left pleural effusion, mediastinal lymphadenopathy, and invasion of back muscles and ribs. As a cryosurgery has been performed on the main lesion, we then choose three main pleural metastases as targeted lesions (Figure ). Since progressive disease was apparent, the chemotherapy regimen was changed to nedaplatin/gemcitabine (NG, nedaplatin 60mg/m2 and gemcitabine). After 2 cycles of NG treatment, chest CT scan (Apr 22, 2015) revealed that the disease continued to progress (Figure ). The regimen was then changed to the third line nedaplatin/albumin-bound paclitaxel (NP, nedaplatin 60mg/m2 and albumin-bound paclitaxel 200mg/m2) therapy subsequently. Chest CT scan (July 21, 2015) after 4 cycles of NP treatment suggested a stable disease (SD) (Figure ). However, the regimen was discontinued because of severe neurotoxicity.
To explore the genomic profiling of the target lesion for target therapy, CT-guided biopsy of the tumor was performed, the tissue specimen and matched blood sample were sent for NGS panel after consent obtained from the patient and his family (May 22, 2015). We detected all genomic alteration types, including deletions and insertions, base substitutions and copy number alterations on over 390genes commonly associated with cancers (). The genomic profile of the tumor revealed CNL of VHL, CDKN2A/B and TP53 genes (Figure ). Since there was a CNL of VHL gene in this patient, it was reasonable to use bevacizumab, sorafenib or Sunitinib for target therapy. Given the disease progressed after multiple lines of chemotherapies potentially actionable VHL CNL, the patient was started on Sunitinib treatment (Jul-21, 2015). CT scan (Aug 18, 2015) indicated a SD by RECIST with a 14.12% decrease in the sum of longest diameters of the target lesions compared with the baseline of July 21 (Figure →Figure ), and the chest pain relieved significantly. After three months of Sunitinib therapy, CT scan showed a PR (Oct 9, 2015) by RECIST, with a 32.4% decrease in the sum of longest diameters of the target lesions (Figure →Figure ). And the Sunitinib therapy achieved a confirmed PR on Nov 13, 2015 (M1 lesion 43.13→23.01mm; M2 lesion 80.63→58.66mm; M3 lesion 67.05→38.96mm; Figure →Figure ). However, the regimen was discontinued because of severe toxicity, including bone marrow suppression (Grade IV) and hemorrhage. The patient's mental status and physical status worsened day by day. About three months after the stop of the Sunitinib treatment, the patient died.
Furthermore, we have reviewed the literatures of primary pulmonary PNETs in [–]. There were less than 30 PNET cases reported in the literatures. Presenting symptoms included cough, chest pain, dyspnea, and hemoptysis []. The diagnosis was usually made based on the typical morphological appearance characterized by a homogeneous population of closely packed small blue round cells and occasional Homer-Wright-type rosettes []. Histochemical and immunohistochemical studies were performed to confirm the diagnosis by demonstrating positivity of tumor cells with CD99, vimentin, NSE, and occasional periodic acid Schiff reactivity [–]. There were 13 cases with the overall survival in these 24 cases, ranging from 1 to 54 months, while 9 patients were still alive with a follow up ranging from 9 to 34 months. Seventeen cases underwent resection plus adjuvant chemotherapy or neoadjuvant chemotherapy.


A 35-year-old woman presented to our emergency department with a two-week history of breathlessness, palpitations, and generalized edema. She had a history of having lost approximately 10 kg of weight over a 3-month period but had regained weight in the month before presentation. She had no chronic illness and was not on any medication(s). On examination, she looked tired, was afebrile, and had a blood pressure of 103/58 mmHg, pulse rate of 92/min, and a respiratory rate of 20/min. She had exophthalmos, a raised jugular venous pressure, a diffuse goiter with a positive bruit, and bilateral pedal edema extending to the thighs. She had a third heart sound and bilateral fine basal lung crepitations. Her abdominal examination was unremarkable with no tenderness or organomegaly. An electrocardiogram showed a sinus rhythm with right bundle branch block and right ventricular strain.
Laboratory investigations (detailed in ) showed pancytopenia; raised bilirubin (mainly direct bilirubin) and alkaline phosphatase (ALP); and normal creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. Her thyroid functions were as follows: thyroid-stimulating hormone (TSH), <0.01 mIU/L (reference values: 0.45–4.5); FT4, 54.69 pmol/L (reference values: 9–20); FT3, >46.08 pmol/L (reference values: 2.6–5.7); and antithyroid peroxidase, >1000 U.
Echocardiography showed an ejection fraction of 50–55%, a right ventricular systolic pressure (RVSP) of 60.16 mmHg measured by Doppler, and severe tricuspid regurgitation. Therefore, a computed tomography pulmonary angiogram was performed; it was negative for pulmonary embolism. A thyroid uptake scan showed diffusely increased uptake, indicating GD, and ultrasound examination showed a diffuse goiter with no nodules. She was initially started on Lugol's iodine, 7 drops (8 mg/drop) every 8 hours, propranolol, 40 mg every 8 hours, dexamethasone, 1 mg every 8 hours, and cholestyramine, 4 grams every 6 hours, to control thyrotoxicosis and to prevent further worsening of the patient's complications which were suspected to be related to GD. Also, 2 doses of intravenous furosemide 40 mg were given on the first hospital day then it was discontinued and the basal lungs crepitations disappeared on the following day.
Workup did not reveal any specific reason other than GD for her pancytopenia, PH, and raised alkaline phosphatase (ALP) and bilirubin. Regarding the pancytopenia, a peripheral blood smear showed a moderate normocytic anemia with mild hypochromia; a few ovalocytes, burr cells, and schistocytes; and increased rouleaux formation. There was leukopenia with neutropenia, some toxic features, a few reactive lymphocytes, and minor platelet clumps. The reticulocyte count was 3.2% (reference values: 0.5–2.5%), erythrocyte sedimentation rate was 3 mm/h (reference values: 2–37), C-reactive protein was 9 mg/L (reference values: 0–5), and hemoglobin electrophoresis was normal. The levels of all the following parameters were normal: lactate dehydrogenase, 184 U/L (reference values: 135–214); haptoglobin, 95 mg/dL (reference values: 35–250); folate, 34.5 nmol/L (reference values: 4.0–45.3); and vitamin B12, 617 pmol/L (reference values: 133–675). Iron studies showed the following: iron, 5 μmol/L (reference values: 5.83–34.5); total iron binding capacity, 32 μmol/L (reference values: 45–80); iron saturation, 15% (reference values: 15–45); transferrin, 1.29 g/L (reference values: 2–3.6); and ferritin, 38 μg/L (reference values: 11–304). Coombs test and HIV serology were negative. Additional workup for cholestatic liver impairment, viral hepatitis serology, and antimitochondrial antibodies (AMA) was negative. The patient's abdominal ultrasound was unremarkable, with no hepatic or splenic enlargement. Further investigations for PH, rheumatoid factor, and antinuclear (ANA), anti-neutrophil cytoplasmic, anti-RO, anti-LA, anti-JO, anti-scleroderma 70, anti-RNP, and anti-smith antibodies were negative. Complements 3 (C3) and 4 (C4) were 110 mg/dL (reference values: 90–180) and 18.4 mg/dL (reference values: 10–40), respectively.
Bone marrow examination was not performed as the reticulocyte count was high and in the following two days of the initial treatment patient's white blood cells and platelets improved; at that point carbimazole 60 mg/day was started. After six days, she was ready for discharge from hospital on the same dose of carbimazole and propranolol, and furosemide was added for the lower limbs edema.
Follow-up investigations nine days later showed improvement in white blood cell and platelet counts. In addition, the gamma-glutamyl transferase (GGT) level was high (128 U/L [normal: 9–36]).
Two months after her initial presentation, the lower limb edema had improved but had not resolved completely. A month later (3 months after presentation), the lower limb edema disappeared. Moreover, the clinical and laboratory features of hyperthyroidism resolved with carbimazole therapy, and her bilirubin level and white blood cell and platelet counts normalized; and her hemoglobin, ALP, and GGT levels improved. ALP isoenzymes were checked; the raised ALP level was mainly of hepatic origin. Repeat echocardiography showed improvement of RVSP (52.64 mmHg) measured by Doppler, with moderate tricuspid regurgitation.


A 34-year-old Hispanic male was found by his family unresponsive to verbal and noxious stimulation. His arms were asymmetrically extended. Emergency medical service was called. He was intubated in the field for airway protection and transported to the emergency department. His initial Glasgow Coma Scale (GCS) score was 5 (eyes: 1, verbal: 1, motor: 3). His computed tomography (CT) scan of the head showed a right thalamic hemorrhage (10.4 cc) with extension into the upper midbrain along with intraventricular extension resulting in obstructive hydrocephalus ().
The initial blood pressure (BP) was 163/115 mmHg. He was started on a nicardipine infusion to achieve systolic BP of <140 mmHg. His right pupil was dilated (4 mm) and nonreactive. He had extensor posturing of all extremities. An emergent external ventricular drain (EVD) was placed. Cerebral angiography was performed to evaluate for underlying aneurysm, vertebral dissection, arteriovenous malformation, or dural arteriovenous fistula. The cerebral angiography was negative. Magnetic resonance imaging (MRI) confirmed the hemorrhage without identifying any additional abnormality. Electroencephalogram (EEG) was negative for seizures. He was subsequently treated with intraventricular tissue plasminogen activator (t-PA; 1 mg q8 h) for three days (total 9 doses). The intraventricular hemorrhage improved significantly by day 9 of hospitalization (). His neurological examination, however, remained poor. EVD weaning was attempted. After multiple failed attempts, a ventriculoperitoneal shunt was placed.
During his admission, his core temperature rose to 39.3°C (102.7°F). Acetaminophen and cooling wraps (Gaymar Medi-Therm Hyper/Hypothermia System, Stryker, Kalamazoo, MI, USA) were initiated to control the fever. He was also on a fentanyl infusion for light sedation. A complete fever workup only showed leukocytosis. He was treated for presumed aspiration pneumonia. His fevers persisted with marked fluctuations despite antibiotic therapy. Other differential diagnoses such as malignant hyperthermia and neuroleptic malignant syndrome were ruled out due to normal creatinine kinase level (81 units/L; normal 20–200 units/L) and lack of causative medication.
He was started on bromocriptine in addition to the antipyretics and cooling wraps for treatment of his central hyperthermia. The fever spikes reduced to minor fluctuations that worsened with each attempt to wean off the bromocriptine (). Cultures remained negative. is a graph of the average core temperature (+/− standard error of the mean) and association of bromocriptine initiation and discontinuation. Note the significant improvement with initiation of bromocriptine and the significant worsening of fever with discontinuation of bromocriptine. There was no correlation with the resolution of the intracerebral and intraventricular hemorrhages and the administration of intraventricular tPA with the fever. Statistical analysis was performed using analysis of variance (ANOVA) on GraphPad Prism 7 (La Jolla, CA, USA). A p value of <0.05 was considered significant.
He required a tracheostomy and percutaneous gastrostomy tube. Neurologically, he remained in a coma with asymmetric posturing of the upper extremities and extension of the lower extremities. He was eventually transferred to a long term acute care facility.


Informed consent was obtained from a 48-year-old Chinese female patient with a 10-year history of type 2 diabetes, who complained of a 6-month history of blurred vision and metamorphopsia in her left eye and had no history of myopia, glaucoma, trauma or other prior interventions. Her fasting blood glucose concentration was 8.7 mmol/L and HbA1c was 8.1%. Her visual acuity was 24/60 in the left eye and 48/60 in the contralateral eye; intraocular pressure was 18 mmHg and 19 mmHg, respectively. Fundus photography of the left eye revealed sporadic retinal microaneurysms and a sub-macular round dark reflection involving the fovea, without drusen. Additionally, macular leakage, multiple hyperfluorescent dots, choroidal neovasculation (CNV) and normal background fluorescence originating from RPE except for leakage were observed in the late stage by fluorescein angiography and indocyanine green angiography, respectively. Moreover, a macular optic coherence tomography scan revealed subfoveal fluid together with detachment of the retinal pigment epithelium (RPE). According to Early Treatment Diabetic Retinopathy Study standards, these data confirmed the presence of CNV in non-proliferative DR []. The CNV was not secondary to AMD; hence, it was speculated that CNV formation resulted from the diabetes mellitus. Examinations of the contralateral eye also suggested the presence of non-proliferative DR (Figure ).


A 54-year-old white male presented to our outpatient clinic with complaint of angina chest pain and dyspnea. He had history of cigarette smoking and family history of coronary artery disease. His physical examination was not remarkable. On electrocardiography there was ST-depression in anterior leads. Myocardial perfusion scan performed and showed moderate to severe ischemia in anterior and inferior territories. Patient admitted and scheduled for coronary angiography. Several attempts to cannulate the coronary arteries were unsuccessful. Aortic root injection showed right coronary artery (RCA) originating from left aortic cusp near left main coronary artery and both are above sinotubular junction ().On computed tomography coronary angiography left main demonstrated high take off which resulted in long left main artery (). Left anterior descending artery (LAD) and left circumflex artery (LCX) showed normal course. There was intimal calcification and significant stenosis in proximal of LAD. RCA originated from left cusp and had separate ostium. There was significant stenosis in mid portion of RCA (). Patient underwent coronary artery bypass grafting. He discharged in good condition after 4 days.


A 70-year-old woman with a prosthetic mitral valve replacement (St. Jude Medical mechanical valve model 29MECJ-502; year 2002) presented herself at the Kardiologische Praxis Papenburg with dyspnoea and exhaustion. For preparation of an upcoming cataract operation, her GP discontinued her anticoagulant therapy with phenprocoumon several days ago. After three days of withdrawal of any anticoagulant medication, the GP started to treat the patient once daily with subcutaneous injections of 7500 units of unfractionated sodium heparin. The patient was under this anticoagulant therapy when she presented herself at the cardiac surgery. At that time, her INR value was 1.4.
Transthoratic echocardiography revealed a reduced mobility of the prosthetic mitral valve. On transoesophageal echocardiography, we confirmed the suspicion of a functional stenosed heart valve through blockage of the hinge-joint of one leaflet (). The patient was treated straightaway with subcutaneous injections of 8000 units of certoparin twice daily and was admitted to the hospital. Radioscopy confirmed the suspicion of a partially thrombosed mitral valve with obstruction of one leaflet of the bileaflet valve (). The damaged valve was surgically replaced with a bioprosthetic valve (Medtronic Mosaic Procine Bioprosthesis Model 310, diameter 31 mm). The excised valve clearly showed signs of deposits of thrombi on its rim (). From the atrial aspect, thrombotic deposits can be found on the hinge-joints and alongside one leaflet. Thrombotic material was also deposited on the ventricular side of the valve.


A 44-year-old male patient presented to the cardiology outpatient clinic with exertional severe pressure headaches and mild chest discomfort relieved after resting. The symptoms were triggered only by strenuous exertion like brisk walking or playing table tennis. He was a non-smoker and there was no past medical or cardiac history of note apart from family history of diabetes mellitus. However, he was noted to have hyperlipidemia on subsequent blood tests. Neurological and cardiological examinations were also unremarkable. He was investigated for the headaches by MRI and MRA of brain, both of which showed no abnormalities (, ). His random total cholesterol was elevated at 6.6 mmol/L and his electrocardiogram revealed normal sinus rhythm with no acute ischemic changes or evidence of previous infarction.
He was further investigated for suspected CAD with an exercise tolerance test, which showed non-diagnostic lateral ST segment depression associated with pressure headaches and chest discomfort, which resolved in few minutes during recovery. We therefore proceeded with coronary angiography which showed chronic total occlusion in the proximal left anterior descending (LAD) with normal left circumflex (LCX) and right coronary artery (RCA) (). The LAD was successfully treated with a single drug eluting stent with thrombolysis in myocardial infarction (TIMI) 3 flow ().
The patient was discharged on dual anti-platelet therapy and secondary preventive medications in addition to life style advice. At 4 months follow-up, the patient remained asymptomatic and resumed work and usual physical activities. Follow-up post procedure exercise tolerance test was reassuringly negative at a high workload.
Two years later, he represented acutely with intermittent frontal pressure-like headaches on exertion relieved by rest without any associated chest pains or dypnea. His medications included aspirin, statin and a beta-blocker. There were no acute ischemic ECG changes and but given his previous history of CAD and CC, a 12-h cardiac troponin T was checked and it was raised at 0.026 μg/L (normal value, < 0.01). An inpatient coronary angiogram revealed patent LAD stent with TIMI 3 flow, but it showed a new severe lesion in the proximal LCX coronary artery (). This was successfully stented with a single drug eluting stent ().
It is important to distinguish CC from migraine with or without autonomic symptoms, and other forms of exertional headaches, cluster headache and thunderclap headache.
Subsequent use of triptans or ergot derivatives could be disastrous in patients presenting with CC.


A 57-year-old female was brought to the hospital because of new onset of confusion and apraxia. The patient had a past medical history significant for nonischemic cardiomyopathy for 2 years. The patient had a stroke several weeks prior during an admission to another facility. At that time, work-up for the etiology of the stroke was negative except for cardiomyopathy with an ejection fraction of 30%. The patient did not have any residual focal motor neurologic deficits, although she was cognitively impaired. Medications at discharge included aspirin, carvedilol, lisinopril and atorvastatin.
On admission, the patient was hemodynamically stable without any distress. Her speech was incoherent and tangential. She had difficulty identifying objects and could not use eating utensils appropriately. Pupils were equal and reactive without any nystagmus or gaze disturbance. No other neurologic deficits were present. On cardiac auscultation, first and second heart sounds were heard normally without any murmur. Lungs were clear. Carotid and other peripheral pulses were palpable and symmetric. Trace bilateral ankle edema was present.
The patient had a normal complete blood count, electrolytes, liver function and thyroid function tests. The cardiac BNP value was 340 pg/mL. Electrocardiogram revealed normal sinus rhythm with T wave inversions in the lateral leads. A chest X-ray was negative for active cardiopulmonary disease. Non-contrast CT scan of the head showed areas of low attenuation in the right posterior frontal and parietal regions consistent with subacute infarctions which were outlined with high attenuation representing hemorrhagic conversion. Subsequent MRI was consistent with these findings with additional tiny acute infarcts in the parietal lobes ().
A transthoracic echocardiogram for an embolic source showed severe reduction of the left ventricular systolic function with ejection fraction of 10-15%. On close observation, there was a suspicious appearance of prominent trabeculations in the left ventricle (). Cardiac MRI showed signs of non-compaction cardiomyopathy with prominent trabeculations in the left ventricular myocardium (). A transesophageal echocardiogram with contrast showed more clearly the prominent trabeculations with contrast occupying recesses between the trabeculae (, ). A diagnosis of isolated LVNC syndrome was established which caused recurrent embolic stroke in the patient. Continuous telemetry revealed episodes of nonsustained ventricular tachycardia. An implantable cardiac defibrillator (ICD) was placed. The patient was started on systemic anticoagulation with warfarin to lower the risk of systemic embolism and recurrent stroke. Since non-compaction has a familial occurrence, the patient’s two sisters were recommended to undergo screening echocardiography. The patient was discharged home with resolution of her neurologic deficits.


A 67-year-old woman presented with a six-year history of recurrent focal seizures with impaired consciousness suggesting a left hemispheric origin. The patient had a recent increase in the frequency of seizures with poor response to medical treatment. Magnetic resonance imaging (MRI) at the onset of seizures revealed multiple heterogeneous intracranial lesions located in the ventral midbrain and in the left frontal white matter. The MRI features of the lesions were fairly similar, demonstrating hypointensity on T1- and T2-weighted images. The lesion in the left frontal lobe showed moderate contrast enhancement as well as a mild adjacent hyperintense signal on T2-weighted images. Minimal to no contrast enhancement was observed around the lesion in the brainstem (Figure ).
Computed tomography (CT) demonstrated dense calcifications in the supratentorial lesion and peripheral calcifications in the brainstem mass (Figure ).
Of note, the patient had a remote history of infection with multiple brain abscesses and a mycotic aneurysm of the right posterior cerebral artery. Reportedly, the infection occurred 30 years before the onset of seizures and was attributed to rheumatic heart disease and infective endocarditis. Her physical examination showed a partial right third cranial nerve palsy, which was the sequelae of her aneurysmal subarachnoid hemorrhage, and a new right pronator drift. An MRI scan performed six months later showed interval growth of the left frontal mass and an increased area of T2-weighted hyperintensity in the adjacent brain (Figure ).
Based on imaging characteristics of the lesions, the differential diagnosis included multiple cavernous malformations, calcified meningiomas, intracranial infections, and other less likely diagnoses, including primary osseous and chondroid malignant tumors (e.g. chondrosarcoma). After reviewing the management options, the patient elected to proceed with left frontal tumor resection, as it was likely responsible for her worsening symptoms. Informed patient consent was obtained for her treatment.
The lesion was approached and resected through a left frontal craniotomy. The arachnoid was noticeably thickened over the mass. The lesion was extremely firm and near entirely calcified with an irregular, tanned/pink appearance as well as minimal internal vascularity. The lesion was dissected from the surrounding brain tissue and “en bloc” resection was achieved with no complications. Postoperative MRI demonstrated complete resection.
The specimen consisted of heterogeneous tissue containing nodules of chondromyxoid material with palisading spindle-to-epithelioid cells at the edges. The chondromyxoid matrix was coarsely fibrillar and had a focal alveolar pattern with dystrophic calcifications and osseous metaplasia. Both immature and mature bone with trabeculae and lacunae that contained osteocytes were present. There were sparse chronic inflammatory cells in the fibrovascular stroma between chondromyxoid nodules (Figure ).
Immunohistochemical staining was performed and revealed negative staining for S-100 protein, GFAP, and minimal MIB-1 labeling. The trichrome stain revealed a mesenchymal origin.
The clinical course following surgery was unremarkable. The patient was discharged home on postoperative day 5 with no changes in her neurological exam. At her four-month follow-up visit, the patient was clinically stable and remained seizure-free. Follow-up MRI showed postoperative changes along the resection bed without evidence of residual or recurrent tumor. The brainstem lesion showed no change or growth.


A 14-year-old boy reported to the Department of Oral and Maxillofacial Pathology with an asymptomatic firm and sessile gingival mass in between 12 and 13 (). Swelling had gradually increased over a period of 2 years to the present size. No discharge or redness was observed, and mucosa was normal in appearance. The patient’s physical status was good and investigation of his medical history was not relevant. A provisional diagnosis of fibroma was made with a differential diagnosis of PGCG and POF. There were no significant radiographic findings on periapical view, performed with a small standard film to verify possible calcification or osseous involvement. An informed consent was obtained from the parents and patient. The surgical modality included excision of the lesion under local anesthesia following standard aseptic precautions. The excised tissue was subjected to histopathological examination.
The hematoxylin and eosin-stained sections revealed a lesion consisting of fibrocellular connective tissue with multiple small islands and strands of odontogenic epithelium resembling remnants of the dental lamina ( to ). The connective tissue was overlined by proliferating parakeratinized stratified squamous epithelium. Histological diagnosis of peripheral odontogenic fibroma (POdF) was established. The patient was followed up for 6 months and showed no evidence of any recurrence ().


The patient is a 52-year-old African American man with past medical history of HIV infection, Mycobacterium avium complex (MAC) infection, seizure disorder, and recurrent genital herpes. The patient was receiving antiretroviral therapy (ART) with emtricitabine/tenofovir and ritonavir-boosted darunavir, with a CD4 count of 399 cells/μL (normal range 404–1612/μL) (22%; normal range 33–58%) and an undetectable HIV viral load. He was admitted for intravenous foscarnet therapy of a recurrent genital herpes infection that was unresponsive to oral valacyclovir. His first episode of genital herpes had occurred three years prior to admission; he was treated at that time with valacyclovir (1000 mg twice daily for 14 days) with complete resolution. However, there was a recurrence about 18 months later for which he received oral valacyclovir (1000 mg twice daily for 14 days) with nearly complete resolution of the lesions. Acyclovir (400 mg po bid) was maintained for chronic suppressive therapy; however, three months later he had another recurrence. Intravenous cidofovir was administered for four weeks (three doses), but there was no significant improvement in the ulcerative lesions so he was switched to foscarnet. The patient completed a 21-day treatment with foscarnet along with topical imiquimod with partial response. He was placed back on valacyclovir (1000 mg orally twice daily) for ongoing treatment of herpes. After four months of valacyclovir treatment, he presented with four tumorous lesions in the perineal and scrotal areas. Physical exam was unremarkable except for three exophytic, nontender nodular lesions, about 1-2 cm in diameter, along the left side of the scrotum and a 5 cm in diameter mass in perineal region (). Initial routine laboratory results (complete blood count and comprehensive metabolic profile) were within normal limits. He was started on intravenous foscarnet 40 mg/kg twice a day in addition to topical imiquimod. Due to concern for malignancy, a biopsy of one of the lesions was obtained.
The biopsy specimen revealed an ulcerated epidermis with an associated acute inflammation and prominent lymphoplasmacytic infiltrate (). Along the base of the ulceration were epidermal cells demonstrating viral cytopathic changes and multinucleated giant cells (Figures and ). These cells stained positively with HSV-1 and HSV-2 immunostains (Figures and ). Cytomegalovirus (CMV) immunostain, Epstein-Barr virus (EBER) in situ hybridization, and Gomori methenamine silver (GMS) and Fite stains were negative. Viral cultures of the lesions were negative. Two weeks into treatment with foscarnet there was no significant change in the size of the lesions. Based on the report of Henao-Martínez on the successful use of leflunomide in an HIV patient with HSV-2 proctitis [], leflunomide 20 mg orally twice daily was then started; intravenous foscarnet and topical imiquimod were continued. Herpes virus was not cultured during this episode, so susceptibility testing could not be performed. The patient received 23 days of foscarnet, 14 days of topical imiquimod, and 11 days of leflunomide with approximately 80% reduction in the size of the perineal lesion compared to the size at the time of hospital admission (). This initial response may have been due to the combination of foscarnet, imiquimod, and leflunomide. He was discharged on leflunomide 20 mg orally twice a day. The lesions continue to improve over time; after nine months of leflunomide, there was complete regression of the large perineal lesion and only two small ulcerations remained on the scrotum.


A 56-year old male was admitted to hospital for liver transplantation. He had end-stage liver disease (MELD score 22) due to cirrhosis caused by hepatitis C virus infection and alcohol abuse. In addition, he had diabetes and was moderately overweight (body mass index of 32 kg/m2). He had no other risk factors for ischaemic heart disease and had normal renal function.
Pre-transplant echocardiography revealed a left ventricular ejection fraction (LVEF) of 75% and moderate pulmonary hypertension with a systolic pulmonary artery pressure (PAP) of 41 mmHg. Cardiac catheterisation and coronary angiography prior to transplantation revealed normal coronary arteries and a mean PAP of 28 mmHg, falling to 23 mmHg after nitric oxide inhalation. His pulmonary vascular resistance was found to be 2.05 Wood units.
The patient underwent an orthotopic liver transplantation. Standard procedure during the transplantation required cross clamping of the abdominal aorta while the hepatic artery anastomosis was being performed.
Post transplantation he developed acute left ventricular dysfunction (LVEF 23%) with apical ballooning and basal hypercontractility, which is typical of Takotsubo cardiomyopathy, requiring inotropic support . His ECG showed sinus tachycardia with no ischaemic changes. The hs-troponin T level was 0.154 ng/ml and pro-BNP concentration was also elevated to 22 842 ng/l. However, 72 hours later he showed no improvement in his left ventricular function and despite increasing doses of inotropic support, he remained hypotensive.
A decision was therefore made to insert the Tandem Heart left ventricular assist device (LVAD). The patient’s haemodynamics were stabilised with the LVAD and the inotropes were gently weaned. Therapy was commenced with carvedilol, enalapril and spironolactone. His left ventricular function gradually improved and he was weaned from the LVAD after nine days.
He recovered well and at discharge 25 days post transplantation, his LVEF was 69%. At the four-month posttransplantation review he remained asymptomatic and his LVEF had improved to 75%.


A 55-year-old Japanese woman, with no prior history of blood transfusion, drug addiction, or having tattoos was diagnosed as having an HCV infection at the local clinic where she had been treated for hypertension. At the age of 61, she complained of exanthems in both her lower extremities and arthralgia in her knees. She had purpura, and skin biopsy revealed leukocytoclastic angitis. Then, she was referred to a nephrologist since she had microscopic hematuria, proteinuria and renal dysfunction. At the time of referral, her blood pressure was 127/80 mmHg, her hight was 144.5 cm and her weight was 63.0 kg. She exhibited edema in her face and both lower extremities. Fresh purpura was present on her legs. Laboratory values at the time of referral were as follows: white blood cells 4470/μL, hemoglobin 11.4 g/dL, platelets 194 × 103 μL, hepaplastin test 120%, total protein 7.2 g/dL, albumin 4.2 g/dL, cholinesterase 280 U/l, lactate dehydrogenase 155 U/L, glutamate oxaloacetate transaminase 33 U/ml, glutamate pyruvate transaminase 32 U/L, γ-glutamyl trans peptidase 40U/L, blood urea nitrogen 21 mg/dL, creatinine 1.2 mg/dL, eGFR 36.1 ml/min/1.73 m2, C-reactive protein 0.2 mg/dL, MPO-ANCA <10 EU, PR3-ANCA <10 EU, anti nuclear antibody × 40 (normal limit < ×40), rheumatoid factor 436 (0–15) IU/ml, IgG 1752 (1100–1700) mg/dl, IgA 169 (110–410) mg/dl, IgM 228 (46–260) mg/dl, C3 51 (65–135) mg/dl, C4 3 (13–35) mg/dl, CH50 < 10 (23–46) U/ml and cryoglobulin was positive. Urinalysis showed hematuria (+++): sediment red blood cells >100/high power field (HPF) and proteinuria 0.78 g/day.
A renal biopsy was performed. On light microscopy, 30 glomeruli were observed and 4 glomeruli exhibited global sclerosis. Many other glomeruli exhibited mesangial hypercellularity, lobular accentuation and double contour of basement membrane (Fig. ). Pseudothrimbi and tubuloreticular inclusions were not observed. Immunofluorescent analysis showed a positive fringe pattern for IgG, IgM (Fig. ), C3. Staining for IgA was negative. Electron microscopy was not performed. Therefore, her case was diagnosed as having MPGN. Since, she was HCV positive, and had hypocomplementemia and cryoglobulinemia, she was diagnosed as having HCV-related cryoglobulinemic MPGN.
She was then referred to a hepatologist. Liver biopsy revealed chronic hepatitis and there were no signs of cirrhosis. She was diagnosed with chronic hepatitis due to HCV. At the time, she declined interferon therapy because she was regularly seeing a psychiatrist and taking anti-anxiety medication and was concerned about depression as a side effect. She was treated with antihypertensive medications, including renin-angiotensin system blockers as well as oral corticosteroid which were effective in reducing proteinuria. However, proteinuria was exacerbated following the reduction of corticosteroid and often reached nephrotic levels. She began anti-viral therapy using DAAs. Because of renal dysfunction, DCV and ASV were selected. Variation in Y93/L31, which is related to DCV resistance, was negative. DCV (60 mg/day) and ASV (200 mg/day) were initiated. Clearance of HCV RNA was obtained by 2 weeks and sustained, and liver function was normalized. In addition, microhematuria turned negative, proteinuria decreased, hypocomplementemia and eGFR improved, whereas cryoglobulinemia persisted. Arthralgia and purpura were not active during the treatment. Data are summarized in Table . She completed 24 weeks of therapy without significant adverse effects.


A 65-year-old male presented to the Ears, Nose, and Throat clinic in September 2015 with complaints of a nonhealing lower lip sore for the past 3 years. The slow growing lesion was described as a burning sensation with scabbing and occasional bleeding. It was slowly increasing in size. The patient had a greater than 50-year history of smoking tobacco (not chewing) which he quit about 7 months prior to his visit. He also complained of unintentionally losing 3 lbs in the last 2 weeks. He denied any fevers or chills. He had no other complaints.
Physical examination was significant for a single lesion on the lower lip 1.5 × 1 cm. A biopsy was performed and sent to pathology. The patient was worked up thoroughly for evidence of multiple myeloma/light chain disease. Laboratory testing was significant for no anemia, normal serum calcium, normal serum albumin, normal total protein, and normal creatinine. There was no Bence Jones protein in urine. Bone survey was done which was negative. Bone marrow biopsy showed <5% plasma cells, ruling out plasmacytoma of the bone. No monoclonal gammopathy was seen, which precluded immunofixation order. Kappa to lambda ratio was normal.
Hematoxylin-eosin staining of the lip biopsy revealed a dense plasmacytic infiltration in the deep dermis (see ). Immunohistochemical panel included CD3, CD20, and CD138 immunohistochemical stains as well as kappa and lambda light chain in situ hybridization. The superficial dermis and the epidermis were not seen to be involved. Immunohistochemistry was positive for CD138 (see ) and revealed that most plasma cells were lambda positive and with rare kappa-positive plasma cells (see Figures and ).
Based on the ISCL/EORTC Proposed on TNM Classification of Cutaneous Lymphoma our patient was staged at T1aN0M0. The patient was treated in November 2015 with radiation therapy as follows: 3000 cGy in 15 fractions using 3D conformal technique to his lower lip and level I lymph nodes and he received 2000 cGy boost bringing his total dose to 5000 cGy in 25 fractions. He responded well to treatment. At his last follow-up, there was no evidence of multiple myeloma or light chain disease.


A forty-five-year-old female reported to the Department of Conservative Dentistry and Endodontics, with the chief complaint of pain in #14 and #15 and extra oral swelling on the right side infraorbital region (). History revealed that the swelling was present for more than a year. It was asymptomatic and slow growing in nature. Patient had experienced occasional hypersensitivity with food impaction in #14 and #15 for the past few months. But a severe pain of sudden onset led her to seek dental assistance. General physical examination revealed that patient was normally built for her age. There was no defect in stature or gait. Her medical and family histories were noncontributory.
Extraoral examination revealed a diffuse swelling extending from the inferior border of orbit to the level of occlusal plane. The overlying skin was normal in colour. On palpation, swelling was soft and compressible in nature. Intraoral examination revealed carious involvement in 14 and 15 with both teeth exhibiting tenderness to percussion. There was no obliteration of the buccal vestibule in spite of the presence of extraoral swelling (). Intraoral periapical radiographs () revealed coronal radiolucency extending into the pulp accompanied by widening of the periodontal ligament space in both #14 and #15. Orthopantomographs () were advised to investigate the radiographic changes in relation to the extraoral swelling, but in vain. Both #14 and #15 responded positively to electric and cold pulp testing. Consequently, it was concluded that the swelling may not be of dental origin. Complete blood and urine investigations were performed which ruled out systemic conditions like diabetes mellitus, HIV, HSs, tuberculosis, or leukemic enlargement. Thereby any possibility of an infectious enlargement was dismissed.
The patient was referred to Department of General Medicine for opinion regarding the extraoral swelling. CT scans were taken which revealed an irregular soft tissue mass measuring 18 × 16 mm in the subcutaneous plane of the posterior maxillary region (Figures and ) on the right side. The lesion appeared separate from the maxillary antrum and there was no bony expansion. Duplex ultrasonography confirmed the presence of a single feeding vessel into the lesion and the lesion was diagnosed as haemangioma. Patient was referred to the vascular surgeon who was further briefed about the need for endodontic therapy. Patient was advised sclerotherapy under Duplex ultrasonographic guidance. 1 mL of foam 3% polidocanol was injected intralesionally and compression bandage was applied. A one-month follow-up CT showed a significant reduction in the size of the lesion (18 × 12 mm) and consent was given to proceed with endodontic treatment.
Local anaesthetic (Lignox 2%A) was administered via infiltration. Access opening was done in #14 and #15, under rubber dam isolation. Working length determination was done using an electronic apex locator (J Morita, USA, Inc.) and later confirmed radiographically to circumvent the risk of overinstrumentation. Canals were irrigated with 3% sodium hypochlorite. Root canals were cleaned and shaped with Protaper files (Dentsply-maillefer, Ballaigues) up to size F2 and obturated in a single visit (). Patient was reviewed after 1 week during which she was asymptomatic and postendodontic restoration was done with light cure composite resin (3M ESPE, USA). Patient continued to remain asymptomatic during follow-ups done at 3 and 6 months () and was under her regular sclerotherapy sessions. Informed written consent was obtained from the patient with regards to the publication of her extraoral, intraoral, and radiographic images.


One of the two patients was a 37-year-old male, who complained of severe headache with a typical sudden onset. He also reported nausea, vomiting, and pain in both legs for a few days, before being referred to our department for further diagnosis and treatment. His mental status was normal. Neurological examination showed positive nuchal meningeal symptoms, and bilateral positive Lasegue sign. Acute SAH (Hunt & Hess grade II) was suspected and the performed computer tomography of the head was negative for blood. A lumbar puncture was positive proving xanthochromic CSF, positive lactate and abnormally high level of protein. DSA was performed without detection of bleeding source.
MRI of the spinal axis showed a 3 cm intradural extramedullary mass at the level of L1-2 and further small lumbar and sacral lesions (). Surgical resection of the tumor of the filum terminale was performed and the histopathological examination of the specimen showed a hemorrhagic mixopapillary ependymoma (WHO grade I) [].


A-24-year-old man was admitted from another neurological department with suspected diagnosis of a SAH with ictus one week before. He presented severe progressive therapy-resistant headache starting from the neck and continuing "like a cold lightning" into the head, pain like "holes in the head" never suffered before since one week as the first symptom at onset, neck tensions, fever, severe cold, constant sickness, difficulties with equilibrium, eye pain during days, laboratory-defined infect constellation, formication (a tingling sensation under the skin) of the upper limbs, and in addition complained of leg pain on the left side. Three weeks prior to admission, patient has received the diagnosis of type 1 diabetes mellitus. Nine weeks previously, he underwent a laparoscopic knee operation under spinal anesthesia. He did not notice any motor or coordination impairment. Cognitive assessment was unremarkable; cranial nerves, motor and sensory examination was normal, except for a bilateral dysesthesia of the upper limbs caused by hyperventilation produced during a phase of anxiety and panic attack.
Subacute SAH (Hunt & Hess grade I) was diagnosed by positive lumbar puncture with xanthochromic CSF, proof of siderophages, and high abnormally level of lactate, ferritin and protein in CSF. The cerebral angiography was negative.
MRI of the spinal axis showed on the L1-2 level an intradural extramedullary tumor of the filum terminale, considered as the source of hemorrhage (). The patient underwent complete resection of the spinal mass. The histological examination of the tissue confirmed the diagnosis of a hemorrhagic mixopapillary ependymoma (WHO grade I).


A 62-year-old woman was admitted to the hospital for perforated gastric ulcer and underwent emergent exploratory laparotomy with repair of the perforation. She was intubated and sedated using fentanyl. During follow-up evaluation, she received methylene blue through nasogastric tube to test for integrity of the gastric wall. Subsequently, her urine was noted to be green (Fig. A), which gradually faded over a period of 5 days (Fig. B and C). Methylene blue is a water-soluble dye commonly used as a diagnostic aid to assess integrity of the bowel or used as a therapeutic agent in conditions such as ifosfamide-induced encephalopathy and methemoglobinemia. It is filtered by the kidneys and has no pathologic effects but may cause the urine to have a bluish or greenish hue that is self-limiting . Other known causes of green urine include indigo, Pseudomonas infection, drugs such as propofol, cimetidine, amitriptyline, promethazine, and indomethacin.