A 22-year-old male presented to the emergency room following a motor vehicle accident with an open right ankle, evidence of a femoral fracture, and shortness of breath. His past medical history was not significant for any medical conditions. He denied any drug abuse or smoking as well as any family history of heart disease. On initial exam, he was awake and afebrile; his blood pressure was 124/68 mm Hg and heart rate was 140 beats per minute, with an O2 saturation 100% on room air. Cardiovascular exam was notable for abnormal vital signs with a diastolic click heard best at the right second intercostal space. Cardiology was consulted on hospital day 6 due to runs of asymptomatic supraventricular tachycardia. Following the appreciation of a diastolic murmur, a TTE was performed showing moderate to severe aortic regurgitation by color Doppler () with a borderline normal left ventricular end-diastolic diameter concerning acute aortic regurgitation. A TEE was then performed to further delineate the aortic valve pathology, revealing an eccentric severe aortic regurgitation jet directed toward the anterior mitral valve leaflet () along with a prolapsing right coronary cusp concerning traumatic avulsion. The hospital course was then complicated by development of Clostridium difficile colitis for which patient received treatment. Following this, on hospital day 23 the patient underwent open heart surgery where he was found to have a tricuspid aortic valve with a left coronary cusp tear near the annulus as well as an enlarged prolapsing right coronary cusp. The valve was replaced with a 21 mm mechanical St. Jude Regent valve. Pathology revealed myxoid degeneration of the aortic valve leaflets without evidence of prior endocarditis or calcifications. The patient recovered without sequelae and is doing well at 2-month follow-up.


A 53-year-old Japanese woman was referred to our department for the treatment of a right, large, obstructive renal pelvic stone and smaller lower pole calyceal stone (Figures a and b). She had no remarkable previous or family history, and the laboratory data showed no remarkable findings, except for microhematuria on a urine analysis. In April 2011, she was admitted to our department for PCNL to treat a right renal stone located at her ureteropelvic junction. In brief, under general and epidural anesthesia, she was placed in a modified-Valdivia position (Galdakao-modified Valdivia position) []. A flexible URS (Flex-X2, Karl Storz, Germany) was inserted through an inserted ureteral access sheath (Flexor® 12-Fr, 35cm, Cook Urological, USA) into her ureter. A stone occupied the area around her ureteropelvic junction, and the URS could not be advanced to the target calyx. Therefore, we first made a root using holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy in order to reach the target calyx. Intracorporeal lithotripsy was subsequently performed using a Ho:YAG laser (with a 200μm fiber, 1.0J, 5Hz; VersaPulse® 30W, Lumenis Surgical, USA), and the URS was then advanced to the target spot in order to puncture it through the root.
Next, a Lawson retrograde nephrostomy puncture wire (Cook Urological) was inserted into the flexible URS, and the calyx was successfully punctured from the target spot to the skin. A 24-Fr percutaneous NAS (X-Force® nephrostomy balloon dilation catheter, BARD Medical, USA) was passed over the balloon under continuous visualization with the URS, and, following insertion of the NAS into the renal collecting system, calculus fragmentation was undertaken using a Swiss LithoClast® pneumatic lithotripter (EMS, Switzerland) through a rigid nephroscope (percutaneous nephroscope, Karl Storz, Germany). A postoperative kidney, ureter and bladder film showed no residual stones (Figure c). The length of the operation was 175 minutes; no major or minor complications were observed. The postoperative ureteral stent was removed 2 weeks after the procedure, and no residual stone fragments or signs of postoperative ureteral stricture were noted on computed tomography . A stone analysis showed the stone to be composed of calcium oxalate.


In April 2013, a 51-year-old male presented to Peking University Shenzhen Hospital (Shenzhen, China) with the chief complaint of a three-year history of repeated dull pain in the right flank and painless gross hematuria for six months. The patient had undergone two previous surgical procedures of extracorporeal shock wave lithotripsy for renal calculus in 1997 and 2009. Physical examination revealed percussion pain over the right kidney region and laboratory analysis identified a marginal increase in alanine aminotransferase (59.8 U/l; normal range, 5.0–40.0 U/l) and creatine (118.5 μmol/l; normal range, 62–115 μmol/l) levels. In addition, an abundance of red blood cells (2,103 cells/μl; normal range, 0–12 cells/μl) was detected upon urinalysis, while urine cytology identified the presence of inflammatory cells but no atypical cells. Intravenous pyelography (IVP) was performed, demonstrating an obstruction to the right renal pelvis and, therefore, no visualization of the later ureter (). A right kidney tumor was suspected based on the results of a dynamic CT scan, which revealed a marginally-contrasted space-occupying lesion in the right kidney. Furthermore, ureteroscopy verified the presence of a solid intraluminal mass (0.6×0.8 cm), spreading into the upper urinary tract in close proximity to the renal pelvis. The renal pelvic masses exhibited wide bases with high central densities and a brittle surface, which bled easily. A ureteroscopic biopsy was performed prior to placing a double-J stent in the right ureter, which was histologically and cytogenetically analyzed to determine a diagnosis of clear-cell RCC. No apparent metastases to the lung, liver, adrenal glands or lymph nodes were observed.
Based on the aforementioned results, a diagnosis of a clear-cell RCC of the right kidney was proposed; however, TCC was not be completely excluded. Therefore, to further define the renal pelvic mass, CTU was performed, revealing a 2.0×1.6×3.4 cm papillary right renal pelvic mass without renal parenchymal (). In the early phase, the tumor presented contrast enhancement and was considered to predominantly consist of TCC (). Furthermore, the CT value of the tumor was 25 Hounsfield units (HU) in the pre-contrast films and 56 HU in the post-contrast films. However, due to the tentative diagnosis of clear-cell RCC based on the ureteroscopic biopsy, the patient was subjected to open right radical nephrectomy with retention of the ureteral stump. During surgery, frozen section analysis revealed an inflammatory polyp-covered transitional epithelium of mild hyperplasia with blood clots and kidney stones.
Macroscopically, the localized tumor originated in the renal calices of the right kidney lower pole, was attached to the renal pelvis by its base and measured 4.0×1.0×0.5 cm. Microscopically, the tumor was composed of atypical epithelioid cells with a wide distribution, with interstitial edema and infiltration of the focal lymphoid tissue; however, no invasion of the ureteral wall was observed. Immunohistochemically, the tumor exhibited diffuse positive staining for vimentin and P504S, while it was only focally and weakly positive for cytokeratin (CK) 7, cluster of differentiation 10 and Ki-67. In addition, immunostaining for CK20, uroplakin, kidney-specific cadherin and prostate-specific antigen was negative. These findings were in accordance with a diagnosis of RCC; however, it remains unclear whether the tumor was a clear-cell or papillary RCC as the patient declined to undergo further assessment. No malignancy was observed in the local renal pelvic or ureteral mucosa.
The patient was discharged nine days after surgery, following an uncomplicated postsurgical recovery. No evidence of recurrence or residual disease was detected on CT scans during the nine-month follow-up period.


In April 2014, a 50-year-old male patient was admitted to Basmane Hospital of Sifa University (Basmane, Turkey), presenting with right flank pain. Ultrasonography (US) revealed an 80×81×57-mm mass ( and ) located in the lower pole of the right kidney with solid-cystic components and heterogeneous echogenicity. Computerized tomography (CT) scans identified a primary mass in the lower pole of the right kidney measuring 86×83×66 mm and the left adrenal metastatic mass (), which extended to the posterior pararenal area in the inferior region, and to the renal pelvis and hilus in the superior region. Furthermore, the metastatic right renal mass demonstrated marked central contrast uptake in the arterial phase. Additionally, two metastatic masses, measuring 69×51×53 mm and 18×12×10 mm, were detected in the left () and right adrenal gland (), respectively, with central necrosis and peripheral contrast uptake.
Serum adrenocorticotropic hormone (ACTH; 12 pg/ml; normal range, 9–52 pg/ml), cortisol [19 μg/dl; normal range (morning), 7–28 μg/dl; normal range (afternoon), 2–18 μg/dl], urinary hydroxymandelic acid (HMA; 253 mg/l; normal range, 21.7±3.2 kg/m2) and vanillylmandelic acid (VMA; 3 mg/24 h; normal range, 2–7 mg/24 h) levels were within normal ranges; therefore, the mass was considered to be hormonally inactive. Additionally, biochemical tests were conducted and the results were as follows: Glucose, 90 mg/dl; creatinine, 1.1 mg/dl; urea, 42 mg/dl; white blood cells, 8.2×103/μl; hemoglobin, 13.9 g/dl; and platelet count, 185,000. Mineralocorticoid and glucocorticoid replacement therapy were administered to reduce the risk of developing iatrogenic Addison’s disease. The patient subsequently underwent US-guided biopsy on the renal mass, as well as right radical nephrectomy, right partial adrenalectomy (with frozen section examination) and left adrenalectomy. Postoperatively, cortisol levels were within the normal range and the patient did not exhibit adrenal insufficiency.
The specimens obtained from the right kidney using the US-guided biopsy technique demonstrated characteristics typical of clear cell RCC, and high magnification examination of the right radical nephrectomy, right partial adrenalectomy and left adrenalectomy specimens revealed tumor cells with an alveolar structure, clear cytoplasm and small nucleolus (hematoxylin and eosin staining; magnification, ×200; ). Furthermore, immunohistochemical examination revealed positive staining for RCC and cluster of differentiation 10 ( and ). Thus, a diagnosis of bilateral adrenal metastasis from clear cell RCC was established.


A 60-year-old female presented to the Otolaryngology Department of the Shanghai Pudong New Area Gongli Hospital (Shanghai, China) with hyposmia that had been present for a six-month period, without rhinorrhea or epistaxis. Clinical examination did not identify a nasal obstruction, and the patient did not possess a history of headaches or visual problems. Endoscopy identified the presence of a neoplasm in the bilateral olfactory cleft, with the nasal polyp morphology necessitating a radiological examination.
A magnetic resonance imaging (MRI) examination in the Radiology Department of Shanghai Pudong New Area Gongli Hospital revealed sphenoid sinusitis on the left side of the olfactory cleft and a high-density shadow in the bilateral olfactory cleft five months prior to presenting at the Otolaryngology Department, where a CT scan of the paranasal sinus was conducted. Radiological examination of the nasal cavity prior to surgery identified the presence of soft tissue shadows in the bilateral olfactory cleft area and sinusitis in the left side of the sphenoid. MRI and CT scans of the orbit and nasal cavity revealed that the soft tissue mass was situated exclusively in the bilateral olfactory cleft region and did not invade other sinuses or the orbit ().
The histopathological appearance of the lesion was meningothelial, a common tumor type in which the cells present in a lobulated arrangement and are spaced along collagen fibers. The tumor cells also varied in size. They demonstrated a high nucleocytoplasmic ratio and a marginal oval nucleus, with nucleoli discernable in each cell. Fibroblasts were arranged in a matrix rich in collagen and crosslinking reticular fibers. Spiral structures were visible and did not contain psammoma bodies. Mitosis was inconspicuous, and no necrosis was observed ( and ).
Immunohistochemical examination identified the presence of the epithelial membrane antigen expression. However, the immunoreactivity was focal and generally weak, identifying only a small number of positive cells in the sample examined. Other epithelial markers were also identified, including the S-100 protein in the nucleus and the cytoplasm. Isolated tumor cells were stained for the expression of Ki-67 in the nucleus.
The tumor was excised from the sinus by functional endoscopy surgery. The patient continues to experience disease-free survival seven months subsequent to surgery. Post-operative nasal endoscopic examination revealed no residual mass. Follow-up visits were scheduled every three months, with no evidence of recurrence to date. The patient’s olfactory recovery and nasal ventilation were normal subsequent to surgery.


A 35-year-old woman who presented with severe dyspnea and sweating was admitted to our tertiary referral hospital in March 2009. Her chief complaint was severe worsening dyspnea. Plain chest radiography and CT scan demonstrated huge parasternal lymphadenopathy and a massive left pleural effusion (). She underwent left thoracentesis in another facility and 400 cm³ of clear fluid was aspirated and sent for biochemistry and cytologic examinations.
She was referred to our facility for further work-up. An informed consent was obtained from the patient in order to use the clinical data and imaging studies for research purposes. In our hospital a second contrast-enhanced chest CT scan and the same techniques was performed 40 days after the initial CT scan. A giant cystic mass was found in the mediastinum extending to both hemithoracis measuring (35×25×9 cm). She was subsequently prepared for urgent surgical intervention.
In the right anterior thoracotomy, a right cystic mass (10×9×8 cm) was identified protruding to the anterior mediastinum and left hemithorax. Left anterior thoracotomy was also performed for resection of the left sided component of this large cystic mass (20×15×10 cm) extending from the anterior mediastinum to the left hemithorax (). There were no pleural effusions in both exploratory thoracotomies. Cystic masses adhering to the left and right lower horns of thymus were resected without any damage to phrenic nerves. Chest tubes were removed on postoperative day 4 and the patient was discharged on postoperative day 6 with no postoperative complication.
On gross pathology, the mass was demonstrated as a brown-gray colored lesion measuring (35×25×9 cm). Gross pathologic examination of specimens showed a membranous appearance with cystic areas filled with clear fluid (). The microscopic histopathology revealed variable size cystic lesions lined by flat endothelium and fragments of thymus tissue. There was no evidence of capsular invasion or malignant features such as atypical nuclei or mitotic figures (). The operation was uneventful. The patient has been followed in our thoracic surgery clinic and no recurrence has been observed in two years later after surgery.


A 43 year-old Caucasian woman with a history of hypertension and nicotine abuse was hospitalized with acute onset of chest pain, nausea, and dizziness. Shortly before, she had a vigorous argument with her partner about child education. In the course of the altercation, she was accused to be “a bad mother”. The patient was overwhelmed by the allegations that instantly lead to perceptions of tension, fear and derealisation. At the hospital she appeared anxious with a blood pressure of 168/78 mmHg, a pulse of 78 bpm, shallow breathing and oxygen saturation of 96%. The physical exam and a chest x-ray showed normal findings. Tentative diagnosis was non-STEMI myocardial infarction as ECG was normal and Troponin T levels rose to 0.22 ng/ml. A coronary angiogram revealed no obstructive coronary artery disease or plaque rupture. A left ventriculography demonstrated hypokinetic apical, diaphragmal, and posterobasal segments (Figure
). The diagnosis of Tako-Tsubo cardiomyopathy (TTC) was established and medication with beta blocker, ACE inhibitor, and aspirin was initiated. An echocardiography five days later showed normal wall movement and an ejection fraction of 72% on echocardiography. The patient was discharged after declining psycho-somatic support.
Six months later, weekly recurrent chest pain increased dramatically while reading a newspaper. Following hospitalization, all results of an examination were very similar to the first event and the diagnosis of recurrent TTC was established.
Nine months after the first cardiac event the patient was admitted to the emergency ward again after dyspnoea, chest pain, nausea, and vertigo had increased for several days. This time, the physical exam revealed rales in the right lung field. ECG showed T-wave inversions in leads V2-V3 (Figure
), and Troponin T levels were at 0.14 ng/ml. Echocardiography demonstrated normal left ventricle function (LVEF > 55%), akinesia of apical segments (septal, lateral, anterior, inferior), and a thrombus of 19 × 11 mm in the left ventricle. Despite administering an anticoagulant, thrombembolism to the right lower leg occurred and had to be surgically removed. After normalized echocardiographic and angiographic results, the patient was discharged a few days later. The last event of TTC emerged another four weeks later. The patient suffered from dyspnoea and pain of the chest and both arms. Physical examination was normal, ECG showed ST depression in leads V2-V4, Troponin T level was 0.06 ng/ml. Cardio-MRI revealed normal left ventricular function (LVEF = 70%) and hypokinetic wall movement of apical and lateral segments. Nonischemic patchy late enhancement was present in the apical, apical inferior septal and lateral regions. A month later late enhancement demonstrated inhomogeneous, inferior-apical transmural scar tissue (Figure
) which did not change significantly at another follow-up after 9 months. During the fourth event and due to a depressive syndrome, psychosomatic support was once again recommended. This time the patient agreed and for the first time, an antidepressant was administered. Because of latest reports of TTC associated with the use of serotonine and noradrenaline reuptake inhibitors, we selected Mirtazapine in order to avoid increased plasma catecholamine concentrations
[–]. The psychosomatic history revealed several chronic stress factors. At the age of 27, the patient was pregnant (gestational age 14 weeks) and was advised to undergo surgery of the uterus due to a fast growing myoma. 4 months later fetal death was diagnosed and the pregnancy had to be interrupted shortly before calculated date of birth. This was experienced as a traumatic event by the patient. Since then, she suffered from recurrent solitary symptoms indicative of post traumatic stress disorder (occasional flashbacks, hyperarousal) which did not qualify for a diagnosis of PTSD according to diagnostic manuals. Additionally she described a prolonged grief reaction with rumination about the loss of her child, peaking annually in the month of the fetal death. Three years later, the patient gave birth to a healthy premature child. The patient experienced the incident as a distressing life-event as well and felt chronically concerned about her daughter. Therefore, final diagnoses were recurrent TTC, a chronic posttraumatic stress syndrome with solitary symptoms of PTSD, and a prolonged grief disorder with depressive anniversary reactions.


A 61-year-old male was admitted to our urology department with complaints of abdominal pain, hematuria, a known mass in the abdomen, and discharge of fluid from the umbilicus. He had been evaluated 25 years ago for macroscopic hematuria, and an urachal tumor was identified. Transurethral resection of the bladder tumor (TUR-BT) revealed mucinous adenocarcinoma of the urachus, and a partial cystectomy was performed. After the operation, the patient was noncompliant with the recommended follow-up protocol. Twenty years later, he was examined by a urologist for the same complaint. Cystoscopy and TUR-BT confirmed the same diagnosis. Thoracoabdominal computed tomography (CT) verified a local recurrence of urachal carcinoma, but revealed no distant metastases. Radical cystectomy was recommended to the patient, but he did not consent. The patient underwent a second partial cystectomy at another hospital 6 months later but the umbilical remnant was not resected at that time. Three months later, local recurrence was identified, and local excision of both tumor and umbilicus was performed. Two years later, intraperitoneal invasion had occurred and the patient underwent a total colectomy. All laboratory findings were normal except for hematuria. In radiological investigation, a CT scan revealed a massive lesion filling the bladder lumen with extension to the anterior wall of the abdomen, a heterogeneous internal structure, and amorphous punctate calcifications (). The lesion was approximately 20 cm in size and formed an air-fluid level at the umbilicus. The central aspect of the lesion had a necrotic appearance. The tumor extended to the level of the symphysis pubis. There was a mass surrounding and wrapping the rectum, the sigmoid colon, and the small intestine, causing narrowing in several areas (Figures and ). An enterocutaneous fistula connected to the mass was seen. There were metastatic implantations, as well as ascites in the peritoneum, which had spread on the serosal surfaces (pseudomyxoma peritonei) (). Disseminated metastases were observed in intra- and extraperitoneal areas, on pleural surfaces, and on the pericardial fat pads. Suspicious lesions concordant with potential metastases were also found in the basal segments of the left lung ().
The patient was deemed to be inoperable and chemotherapy was subsequently initiated. The patient ultimately was treated symptomatically, as he was unable to tolerate the chemotherapy, and died 6 months later.


A 53-year-old female patient was admitted to the emergency department with 4-day progressive polyarthritis. Previously, the patient presented with controlled systemic hypertension and recovery from a major depression a couple of years ago. She started with a throat pain 10 days before admission. An anti-inflammatory (sodium diclofenac) was prescribed by a general practitioner for three days with improvement of the pain. Four days after the sore throat she presented with edema, pain, and hyperemia at her right ankle progressively involving her left ankle, knees, wrists, and elbows, followed by prolonged morning stiffness (around 2 hours) and diffuse erythema in both legs. She also reported fever twice, since she started a sore throat, with 38 and 38,5 degrees Celsius. There was no headache or gastrointestinal or urinary symptoms. There was no sign of pulmonary involvement too. Her close contacts had been well. At the admission, there were no signs of sepsis or neurological alterations including meningeal signs at her physical exam. She presented without any temperature alterations, with no tachycardia and normal blood pressure, and she was breathing normally. There were clear signs of arthritis at both ankles (Figures and ) and at the left wrist. The referred joints were tender and swollen at the physical exam. There were also discrete petechiae (Figures and ).
Prednisone 20 mg was started after a few days with improvement in articular signs. Laboratorial exams showed a high white cell count, 15,9 × 109 (reference: 4–10 × 109) with neutrophilia, elevated C-reactive protein (CRP), 41,5 mg/dL (reference: < 1 mg/dL), and hemosedimentation rate of 120 mm/h (reference: < 15 mm). Arthrocentesis was not performed due to polyarticular involvement. Three days after her admission two hemocultures showed Neisseria meningitidis serogroup C. After these results a cerebrospinal fluid analysis was performed and showed no significant alterations. The patient did not present fever, neurological dysfunction, or hemodynamic alteration at the follow-up. Intravenous ceftriaxone 2 g twice daily was started and prednisone increased to 60 mg. Seven days after the beginning of the treatment, she was asymptomatic, with CRP of 2,4 mg/dL, and was discharged home. All patient close contacts were prescribed ciprofloxacin as a chemoprophylaxis.


A 29-year-old female patient had first reported to the ENT Department of the Cantonal Hospital in St. Gallen, Switzerland, in 2001, with severe and progressive nasal blockage. Symptoms had begun 5 years earlier but had been left untreated. She was however known to have an aspirin and histamine intolerance. In addition, she had suffered from symptoms that had been interpreted as hay fever and asthma since her youth and reported a positive family history for nasal polyposis.
Physical findings documented at the time included a normal appearing external nose, complete bilateral obstruction of the nasal cavities by nasal polyps, and anosmia. The anosmia was determined by testing with Sniffin' sticks whereupon the patient was able to identify 3 out of 12 possible odors.
A CT scan showed hypoplastic frontal sinuses and a complete obstruction of all the other paranasal sinuses, with normal bony anatomy of the external nose. After medical treatment with topical and systemic steroids failed, the patient underwent an endoscopic sphenoethmoidectomy and maxillary sinus fenestration in 2002. Upon histologic examination of the polyp tissue respiratory mucosa with severe chronic eosinophilic inflammation was found. Postoperative treatment included topical and systemic corticosteroids. Aspirin desensitisation therapy was repeatedly discussed but declined by the patient. The sense of smell returned and the patient now identified correctly 11 out of 12 possible odors. The patient was free of recurrence during 5 months of follow-up in the hospital before continuing follow-up in the vicinity of her home. During this further follow-up, the sense of smell was not documented.
In March 2014, the 38-year-old patient was again referred to the ENT Department of Cantonal Hospital in St. Gallen, Switzerland, because of complete bilateral nasal obstruction with polyps visible in both nares and a progressive widening of the bony and cartilaginous nose. The patient reported a recurrence of nasal obstruction and a loss of sense of smell over the last 2-3 years and an increasingly noticeable nasal deformity in the last 12 months. Also pressure was felt over the maxillary but not frontal sinuses frequently. Postnasal drip symptoms were present in most days. Nasal treatment consisted of sporadic application of topical mometasone spray. Bronchial asthma symptoms had been stable with regular inhalation with formoterol and budesonide and regular systemic check-ups had shown no sign of bronchiectasis.
Clinical examination showed a distinct broadening and bilateral enlargement of the nasal pyramid (). Anterior rhinoscopy revealed massive nasal polyps obstructing the cavum and vestibule of the nose on both sides (). On a CT scan, a complete obliteration of the nose and paranasal sinuses as well as thinning and massive expansion of the nasal bone was seen (). A comparison to the CT scan from 2002 was not possible. Since the picture data was archived for 10 years and then destroyed in 2012, the written radiologist's report describes no nasal bone thinning or expansion. The patient's test results with Sniffin' sticks again showed an anosmia (identification of 2 out of 12 possible odors). Medical treatment consisting of topical and systemic steroids failed and an endonasal endoscopic polypectomy and revision ethmoidectomy were performed in May 2014. Simultaneously, the bony nasal vault was narrowed by forced digital compression without osteotomies (). The bone appeared to be thinned sufficiently to give in upon digital compression. Impression of the bony nasal sidewall resulted in a visible depression in the overlying skin which was corrected by a transcartilaginous decollement of the skin and subcutaneous tissues in a supraperiosteal plane. No nasal packing was inserted. A nasal cast was applied and left in place for one week.
Histology of the polyps again showed squamous epithelium and respiratory mucosa with light to medium signs of inflammation, some fibrosis, and severe eosinophilia. The patient reported a dramatically improved nasal air passage. A strict postoperative regimen including nasal saline irrigation and topical application of mometasone spray and fluticasone nasal drops was installed. At 3-month follow-up, minimal polypoid tissue was noted in the ethmoidal region, the nasal air passage remained free, and the patient reported a return of the sense of smell and was able to identify correctly all 12 possible odors in the Sniffin' sticks test. The form of the exterior nose remained stable (). Again an aspirin desensitization was discussed but declined by the patient. The most recent follow-up in January 2015 (8 months after surgery) showed stable findings.


The proband was a 16-year-old Japanese girl, born at full term with a normal delivery. Her father showed short stature (−2 SD smaller than the average height for male individuals of the same age) and had a history of treatment for short stature in childhood. Her grandmother (paternal side) also exhibited short stature; however, no detailed information was available because she died 10 years previously (). At 3 years of age, the patient was evaluated for height retardation and slight mental retardation. She was diagnosed with hypophosphatemic rickets at 4 years of age based on her clinical features, such as short stature, dental abscess, osteopenia, genu valgum, and low serum phosphate levels. At this age, her height was 90 cm (−2.24 SD) and her weight was 17 kg (+0.9 SD). Treatment with 0.5–1.5 g/day of phosphate and 0.05–0.2 μg/kg/day of 1,25-(OH)2D3 was initiated to compensate for her lack of serum phosphate and vitamin D.
We measured the levels of serum minerals, FGF23, intact-parathyroid hormone (PTH), and kidney function of the patient and her parents using blood and urine samples. Ultrasound screening of the kidney was also conducted and X-rays were taken of the lower limbs. Serum FGF23 measurement was performed using the FGF-23 ELISA kit, which is a two-site enzyme-linked immunosorbent assay to measure full-length FGF23 (KAINOS Laboratories Inc., Tokyo, Japan), as described previously []. The institutional review board and the ethics committee of each organization approved the study. Informed written consent was obtained from all participants and volunteers.
shows the mean laboratory data of the patient undergoing medical treatment, which included phosphate (P) 2.0 mg/dL (normal range, 3.0–4.5 mg/dL), calcium (Ca) 9.2 mg/dL (normal range, 8.7–10.2 mg/dL), alkaline phosphatase (ALP) 2374 IU/L (normal range, 100–325 IU/L), intact PTH 68.5 pg/mL (normal range, 12–72 pg/mL), 25-hydroxyvitamin D3 (25-(OH)D3) 11.0 ng/mL (normal range, 9.7–41.7 ng/mL), 1,25-(OH)2D3 37.5 pg/mL (normal range, 20–60 pg/mL), and FGF23 400 pg/mL (normal range, 13.7–40.5 pg/mL). Urine P was 3.8 g/day (normal range, 0.4–1.2 g/day), the tubular maximum phosphate reabsorption per glomerular filtration rate was 2.1 mg/dL (normal range, 2.5–4.5 mg/dL), and the urine Ca/creatinine ratio was 0.09 (normal range, 0.05–0.25), which met the diagnostic criteria of XLH. FGF23 levels of the patient's father and mother were 68 and 29 pg/mL, respectively. Ultrasound showed normal kidney findings, while lower limb X-rays revealed a widening of the proximal tibial metaphysis with medial bowing.
To confirm the diagnosis, we conducted molecular studies, which included the direct sequencing analysis of PCR products. Genomic DNA was obtained and extracted from whole blood samples using the blood and cell genomic DNA extraction kit (Qiagen, Venlo, Netherlands). PCR amplified all 22 exons and exon-intron boundaries of PHEX and also all exons and exon-intron boundaries of FGF23, DMP1, and ENPP1 to exclude ADHR, ARHR1, and ARHR2, respectively, using previously described primer pairs [, , , ]. Additionally, for PHEX, we analyzed the approximately 2 kb promoter region upstream the start codon.
We identified a mutation in exon 9 (c.947G>T; p.Gly316Val) of PHEX in the patient (). Additionally, we sequenced PHEX from her parents and showed that the mutation was inherited from her father, who also exhibited short stature (). To determine the frequency of this mutation, we carried out restriction fragment length polymorphism analysis of genomic DNA from unrelated Japanese volunteers (100 were male and 100 were female; a total of 300 X chromosomes). DNA was amplified by PCR using primers on either side of the mutation in exon 9. Amplified products were digested using Acc I and separated on a 4% agarose gel. Digestion of the 233 bp fragment with Acc I would generate fragments of 177 plus 56 bp in the presence of the mutation (). This analysis showed that only one chromosome harbored the mutation (0.33%). We further analyzed the exons and exon-intron boundaries of FGF23, DMP-1, and ENPP1 and found no additional mutations.
When the PHEX mutation (Gly316Val) was identified, we conducted SIFT () [], PolyPhen-2 () [], and PROVEAN () [] in online in silico analyses of Gly316 and Tyr317, which is an amino acid adjacent to Gly316. It was previously reported that the Tyr317Phe mutant protein exhibits 50–60% of PHEX activity []. SHIFT, PolyPhen-2, and PROVEN analyses predicted both variants (Gly316Val and Tyr317Phe) to be tolerated, benign, and neutral, respectively (data not shown). However, residues Gly316 and Tyr317 were shown to be perfectly conserved among humans, mice, and rats.


A 39-year-old, right-hand-dominant female presented with a five-year history of left shoulder pain, acutely worsening in the four to five months prior to presentation. She denied loss of motion, weakness, or any preceding left shoulder trauma. She reported pain at rest and with activity, especially overhead motion, and occasionally awaking her from sleep. She denied constitutional symptoms. Her past medical history was remarkable only for active cigarette use with a 25-pack-year smoking history.
Physical examination revealed no erythema, warmth, drainage, or muscle atrophy about the left shoulder. Active motion of the involved (left) shoulder for forward flexion, external rotation, and internal rotation measured 150 degrees, 70 degrees, and T10 (10th thoracic vertebra), respectively. She reported pain at the ends of all planes of range of motion. On the right side her active motion was 180 degrees, 70 degrees, and T12. On the right she had full painless active range of motion. Her left side had no detectable rotator cuff weakness. Neer and Hawkins-Kennedy impingement tests elicited pain. She had no crepitus with range of motion.
Plain radiographs () of the left shoulder were interpreted by a musculoskeletal trained radiologist as calcific densities within the rotator cuff versus extratendinous loose bodies, as well as erosion of the acromioclavicular (AC) joint. Magnetic resonance imaging (MRI) was ordered to accurately assess the exact location of the calcific nodules. MRI () demonstrated multiple extratendinous ossific densities in the subacromial/subdeltoid bursa, consistent with synovial chondromatosis. MRI also demonstrated fraying of the anterior supraspinatus tendon with minimal tendon retraction suggesting a small, full-thickness tear.
It was felt that conservative management would not be beneficial. Therefore, the patient underwent a diagnostic shoulder arthroscopy in the sitting position. A standard posterior portal was established and findings within the glenohumeral joint included normal appearing biceps tendon and pulley, intact rotator cuff from the articular side, no synovitis, intact labrum, and normal-appearing chondral surfaces of both the glenoid and humeral head. There were no loose bodies. The subacromial and subdeltoid space was then examined with bursoscopy, initially via the same posterior skin incision. Findings included extremely adherent and inflamed bursal tissue, partial-thickness, bursal-sided supraspinatus rotator cuff tearing without retraction, and more than 10 osseous bodies. Some of these cartilaginous bodies were adherent to the synovium and others were loose in bursae (). One of the chondral bodies was adherent to the synovium and placed directly between the acromion and the greater tuberosity at the location of the rotator cuff tear. Several of the cartilaginous bodies were over 1.5 cm in diameter.
The patient underwent arthroscopic removal of all cartilaginous loose bodies, complete resection of the subacromial/subdeltoid synovial bursa, acromioplasty, and double row supraspinatus repair. Viewing from posterior, lateral, and anterior vantages facilitated removal of all loose bodies and bursal resection. After debridement of the footprint, an 80% thickness bursal-sided tear was observed. The remaining articular-sided fibers were left intact and a 5.5 mm double loaded BioComposite Corkscrew Anchor (Arthrex; Naples, Florida) was placed lateral to the intact tendon. Forty-five degree left and right curved lassos were used to pass both sutures through the tendon in a horizontal mattress fashion. The sutures were tied with alternating half-hitches on alternating posts and the tails were bought over to a 4.75 mm BioComposite SwiveLock anchor (Arthrex; Naples, Florida) laterally for a transosseous equivalent repair technique.
Mini C-arm fluoroscopy was used to assess that all osseous loose bodies were removed. No additional calcified bodies were identified. Pathology was consistent with synovial chondromatosis with multiple cartilaginous loose bodies throughout the bursa ().
Postoperatively, the patient was placed in a sling-immobilizer and underwent routine rotator cuff repair physical therapy. Two years after surgery, she denied symptoms of residual loose bodies including impingement or crepitus. Repeat radiographs showed no recurrence of detectable osteochondromatosis. She continued to smoke one pack per day although she was counseled against this. The American Shoulder and Elbow Surgeons (ASES) Evaluation Form score was 95/100, SF-12 physical component summary was 51.3, mental component summary was 54.2, the Simple Shoulder Test (SST) was 9/12, and the Single Assessment Numeric Evaluation (SANE) score was 90 [, ]. Her active ranges of motion at 24 months after surgery for forward flexion, external rotation, and internal rotation were 165 degrees, 75 degrees, and T9, respectively (). She had no pain at rest or with range of motion.


A 93-year-old man presented with gross hematuria and a red, translucent papule on his proximal right lower leg (). Twenty years ago he had ultrasound-guided needle biopsies after a suspicious digital rectal exam, which yielded a Gleason score of 6 (3+3), and he underwent a radical prostatectomy with negative regional lymph nodes. Perioperative laboratory records from the operation were not available. The patient remained under the supervision of his primary care physician, but his PSA levels had not been followed up for several years. At the time of this presentation, his PSA level was measured at 415 ng/mL, the papule was biopsied, and an abdominopelvic CT scan was ordered. Tissue obtained via shave biopsy was weakly positive at the luminal zones for PSA and strongly positive throughout the cytoplasm for PSAP, which proved the lesions to be metastatic prostate adenocarcinoma (). CT scan revealed multiple hepatic lesions, which were presumed to be metastatic, without any evidence of retroperitoneal nodal metastases. During cystoscopic evaluation of the patient's gross hematuria, a friable bladder neck mass was resected with loop electrocautery, and penile corporal tissue was also biopsied—both of which showed poorly differentiated prostatic adenocarcinoma (). The patient's gross hematuria resolved after the bladder neck mass was resected, but he did suffer from priapism secondary to corporal invasion. Given his age and extent of disease, the patient was managed for palliation with antiandrogen therapy—leuprolide and bicalutamide—for systemic control and focused radiation for local control. Three months after the initiation of therapy, his PSA was measured at 14 ng/mL, and no further disease progression was noted.


A 59-year-old Caucasian female patient was referred to our emergency department by ambulance from another hospital where no operative service was available at night. On arrival in the emergency department, the patient presented in circulatory shock with pulse around 160 bpm and blood pressure 65/35 mmHg. Her laboratory results were remarkable for: pH acidic at 7.13, pCO2 8.6 kPa, PO2 low at 5.3 kPa, lactate high at 9.2 mmol/L, BE −8.8 mmol/L. Her CRP was 48 mg/L and WBC low normal at 3.5*109/L. On examination, she showed all signs of general peritonitis. The patient was prepared for emergency laparotomy immediately.
According to the patient’s journal records she had undergone laparoscopic implantation of a gastric stimulator in 2004 due to gastroparesis. The patient had a medicated hypertension and a medicated hyperlipidaemia in her medical record but no further conditions. She had earlier been operated with open surgery for appendicitis, C-section and ovarian cysts. Between April 2012 and June 2014 the patient had shown up several times to different hospitals in our county (Figure ). She had then presented with abdominal pain, bloating and fever. Mechanical small bowel obstruction had been suspected each time but either the CT scans had been inconclusive or a sub-ileus condition had been resolved during small bowel series. Discussion with the respective gastric surgeons had revealed that the patient had a partial gastroparesis due to idiopathic neuropathy. The patient’s symptoms had eventually been interpreted as pseudo-obstruction and colonoscopy had been recommended. This examination however had not shown any pathology besides minor diverticulosis. The patient’s recurring symptoms had got better after initiation of a treatment with neostigmine and erythromycin before meals. Follow-up at a gastrointestinal centre had been planned. June 2014 the patient showed up to her nearest hospital during early morning, once again with abdominal pain and nausea. The abdominal tenderness was focused around the umbilicus but physical examination was otherwise without remark. Blood samples showed CRP at 1 mg/L, WBC at 10.8*109/L. Body temperature was 37.1°C, blood pressure 120/79 mmHg and pulse 51 bpm. The abdominal pain was assessed as functional and the patient was sent home. The same evening however the patient was referred by ambulance to the same hospital. She was tackycardic (around 140 bpm) and low in blood pressure (about 75/50 mmHg). Body temperature was 35.8°C. She had vomited several times before she had ringed the ambulance. Clinically she presented this time with peritonitis, no bowel sounds. After she’d been stabilized initially a CT scan showed signs of small bowel obstruction.
Our hospital was contacted when it became clear that surgery was inevitable and that there were no resources available at night at the other two nearer hospitals. This was when the patient was referred and presented as described above. After immediate admission to the operating room the abdomen was opened with a midline laparotomy and bloody-serous fluid was found in the abdominal cavity. Approximately two thirds of the small bowel were necrotic. No adherences between the bowel and the abdominal wall could be seen but interenteric adherences were present without causing a stricture. We identified that herniation of small bowel through the loop of the stimulation-leads was causing a mechanical strangulation ileus of the small bowel. To prevent recurring strangulation, it was decided to cut the leads. The strangulated bowel was not recovering and had to be resected. Continuity was provided with a hand-sewn end-to-end enteroentero-anastomosis. The patient was left with 120 cm small bowel (Figure ). The leads were shortened to the level of the abdominal wall and the stimulation device was left in place. Perioperatively a treatment with cefotaxime and metronidazole was started according to national standards. The patient was extubated the first postoperative day and was able to be discharged from our hospital on the eighth postoperative day.
Two months later the patient was seen in our day-clinic for follow up and for explanting the stimulation device under local anaesthesia. She was feeling well but experiencing some symptoms of her gastroparesis anew.


A previously healthy 51-year-old man underwent a routine medical examination. An incidental pelvic solid mass was detected on ultrasonography (Figure ) and computed tomography (CT) (Figure ). The oval-shaped mass was about 50 × 40 mm in size and showed a low-density lesion with clear boundaries, a complete capsule, and two calcifications in the central part on the CT scan. The mass lay adjacent to the sigmoid colon in the left iliac fossa. The patient had no complaints or significant past medical history. No abnormality was found on physical exam including digital rectal examination. Tumor markers and other laboratory tests were within the normal range.
Based on the present imaging findings, the preoperative diagnosis of teratoma with core calcification or stromal tumor derived from the rectosigmoid colon was suspected. Accordingly, diagnostic laparoscopic surgery was performed. A yellow-white, egg-shaped body that was completely free from the pelvic cavity was found in front of the rectum (Figure A). Further laparoscopic exploration of pelvic and abdominal organs demonstrated that the liver, stomach, intestine, colon, and rectum were all normal. Finally, the peritoneal loose body was put into an endoscopic retriever bag, taken out through the enlarged port site in the right lower abdomen, and sent for histopathological examination (Figure B).
On gross pathologic examination, the peritoneal loose body measured 50 × 40 × 40 mm. It was yellow-white, oval in shape, and it had a bony-hard, smooth surface. The cross section displayed a thread-like appearance. There were two calcified cores filled with yellow cheese-like material, and the interval distance between the two cores was about 5 mm (Figure ). Histologically, the lesion consisted of well-circumscribed, unencapsulated, paucicellular tissue, with an obviously hyalinized fibrosclerotic center. At the periphery, the lesion was paucicellular, containing spindled fibroblasts embedded in a collagenous stroma (Figure ).
Our patient recovered well post-operatively. He was discharged from the hospital 2 days after surgery.
Peritoneal loose bodies are also called peritoneal mice. There is limited information about the incidence of peritoneal loose bodies around the world. They are very rare and usually incidentally diagnosed during surgery or autopsy. The characteristics of 22 cases that have been reported are shown in Table ; we found that peritoneal loose body is more common in males. The incidence rate ratio between males and females is 18:4. The age span of patients at the time of diagnosis ranges from 2 months to 79 years, and the majority occurs in patients between 50 and 70 years old. Most peritoneal loose bodies range from 5 to 25 mm in size and generally do not cause any symptoms. When the maximum diameter reaches more than 50 mm, they can be called giant peritoneal loose bodies. The largest peritoneal loose body measured 95 × 86 mm and was reported by Mohri et al. [] in 2007. Giant peritoneal loose bodies are not usually associated with specific symptoms except for chronic abdominal pain in some cases [-]. In our case, the giant peritoneal loose body was 50 × 40 × 40 mm in size and did not cause any discomfort; it was found incidentally on physical examination. Occasionally, if the peritoneal loose bodies are large enough and in a particular location, patients may be admitted to the hospital with acute urinary retention [,] or intestinal obstruction [-] due to extrinsic compression.
Thus far, the exact pathogenesis of peritoneal loose bodies has not been clearly defined. Possible sources include: (1) appendix epiploica, (2) omentum [], (3) autoamputated adnexa [], or (4) fat tissue in the pancreas []. The most common source is appendix epiploica. It is believed that the process is sequential. First, chronic torsion of the appendix epiploica occurs, and the blood supply is shut off, followed by saponification and calcification of fat tissue. Finally, the appendix epiploica detaches from the colon due to atrophy of the pedicle and becomes a peritoneal loose body. Many authors suggest that the body gradually absorbs protein from peritoneal serum. The size of the peritoneal loose body increases slowly, like a snowball. However, the growth speed of the peritoneal loose body and the factors that promote or inhibit growth are unknown. Mohri et al. [] discovered a peritoneal loose body in a 73-year-old man’s pelvic cavity that grew from 73 × 70 mm to 95 × 75 mm in 5 years. In addition, there was another case [] of a peritoneal loose body that did not significantly change in size or appearance in 3 years. Interestingly, Koga K et al. [] removed a 30 × 20 mm peritoneal loose body from a 33-year-old woman who, at 9 years of age, had adnexal torsion followed by calcification and autoamputation.
The differential diagnosis associated with peritoneal loose body include the following: (1) benign disease: leiomyoma, rhabdomyomas, teratoma, and fibroma; (2) malignant disease: colorectal cancer, ovarian cancer, and metastases; (3) calculous disease: urinary stones, gallstones, and appendix stones; (4) tubercular granuloma; and (5) others: calcification of lymph nodes, lymphoma, and foreign bodies. CT and MRI can be performed to distinguish peritoneal loose bodies from other lesions. For example, leiomyoma and some tumors enhance after injection of a contrast agent, while the appearance of peritoneal loose bodies remains unchanged.
Treatment is surgical removal because it is not easy to establish definite diagnosis preoperatively via physical examination and imaging technologies. Laparoscopic exploration is recommended [,-]. Laparoscopy not only reduces surgical trauma but also shortens the patient’s hospitalization time. In our case, the patient was discharged from the hospital 2 days after surgery. Moreover, the loose body can be removed through a slightly enlarged trocar incision, and patients will not have a scar.
Until now, there have been no reports about the leading cause of death or recurrence in patients with peritoneal loose body. No harm has been shown to patients who receive active treatment.


A 65-year-old male marathon runner presented to a primary care physician with abrupt onset of posterior left knee pain that began two days before. There had been no injury associated with the pain. He denied systemic symptoms, including fever, chills, night sweats, or malaise. Past medical history included asymptomatic severe mitral valve regurgitation secondary to bileaflet mitral valve prolapse, for which he underwent robot-assisted minimally invasive mitral valve repair and prosthetic ring placement approximately 6 months prior to presentation. There was also a history of hypertension and hyperlipidemia. He lived in the central United States with his wife and was employed as an attorney. He consumed approximately two alcoholic drinks per night, was a never smoker, and had no history of intravenous drug use. There were no other significant exposures or travel documented.
The patient recovered from his mitral valve repair, had stopped anticoagulation after 6 weeks, and had returned to walking and/or running 3–5 miles per day. A transthoracic echocardiogram that was done approximately 2 months postoperatively demonstrated a normal functioning valve, with only trace regurgitation.
He was initially treated with symptomatic pain relief with hydrocodone-acetaminophen but had no improvement in the left popliteal fossa pain and was therefore referred to an orthopedic provider. A plain radiograph demonstrated Baker's cyst and he was treated with a cortisone injection. Due to persistence of symptoms, he was subsequently evaluated for possible deep venous thrombosis via venous ultrasound which indicated a left popliteal thrombus and aneurysm. As a result of this finding, he was admitted to an outside hospital for further evaluation.
At the outside facility, he underwent MRI of the left knee, CT angiogram with bilateral extremity runoff, and transthoracic echocardiogram. These studies revealed left popliteal aneurysm with occlusive eccentric thrombus and incomplete clot of a right renal artery branch. The following day, a transthoracic echocardiogram was done and showed a highly mobile mass attached to the anterior mitral valve leaflet, measuring approximately 1.5 cm.
Due to the abnormal findings, he was transferred to our facility for further evaluation and management. On admission, the patient appeared well. Temperature was 36.8°C, blood pressure was 123/48, heart rate was 85 beats per minute, respiratory rate was 16 breaths per minute, and peripheral oxygen saturations were 98% on room air. A 1/6 holosystolic murmur heard best over the mitral valve was auscultated; the remainder of the physical examination was normal. There was no mention of onychomycosis. His laboratory evaluation demonstrated mild anemia (11.4 g/dL; reference 13.5–17.5 g/dL), elevated erythrocyte sedimentation rate (60 mm/1 hour; reference 0–22 mm/1 hour), and elevated C-reactive protein (75.9 mg/L; reference < 8.0 mg/L). The peripheral white blood cell count and differential, platelet count, INR, and prothrombin time were all normal.
The patient underwent transesophageal echocardiogram (TEE) which revealed two highly mobile masses attached to the mitral valve with the largest mass measuring approximately 1 cm by 3 cm. The patient underwent surgery the following day. Intraoperatively, the mitral valve had firm, white vegetations with destruction of both anterior and posterior leaflets. Samples were taken and sent immediately to pathology for review. The preliminary frozen pathology demonstrated fungal elements (Figures and ). He underwent aggressive debridement and mitral valve replacement with a porcine valve. The patient was started on intravenous liposomal amphotericin B 5 mg/kg/day intraoperatively and caspofungin 50 mg daily was added the next day for empiric treatment while waiting identification of the organism. Final pathology described active native valve endocarditis with fungal organisms involving the myxomatous mitral valve. The mitral valve tissue was cultured on inhibitory mold agar and ultimately grew a Scopulariopsis species with no other microbial growth, including negative bacterial and mycobacterial cultures. Fungal blood cultures were obtained but were negative for growth. Due to the severity of the disease and highly resistant nature of the organism, oral voriconazole dosed at 300 mg twice daily was also added to the antifungal regimen.
The day following mitral valve debridement and replacement, vascular medicine and vascular surgery were consulted regarding the suspected mycotic aneurysm and thrombus of the left popliteal artery. CT angiogram with lower extremity runoff was repeated and showed the left popliteal artery mycotic aneurysm and thrombus, as well as bilateral renal infarcts. Ten days after mitral valve surgery, he underwent resection of the popliteal artery and peroneal artery bypass. The pathologic examination revealed GMS-positive staining hyphae, and inhibitory mold agar cultures again grew a pure culture of Scopulariopsis species.
The Scopulariopsis species from the cultures was ultimately identified by combined phenotypic characterization and DNA sequencing as Scopulariopsis brevicaulis. Phenotypically, the organism was a tan powdery colony and microscopically demonstrated branching annellides with chaining, round conidia with a truncated base consistent with Scopulariopsis brevicaulis. From a sequencing standpoint, D2 ribosomal sequencing was utilized with the top 3 matches being a greater than 95% match (100%, 99.31%, and 95.45%) to Scopulariopsis species in the Mayo Fungal Library. Antifungal susceptibilities were completed utilizing broth dilution as per recommended guidelines from the Clinical and Laboratory Standards Institute and were consistent with those reported in the literature: amphotericin 2 µg/mL, caspofungin 1 µg/mL, micafungin 0.125 µg/mL, anidulafungin 4 µg/mL, posaconazole 2 µg/mL, voriconazole 8 µg/mL, itraconazole 2 µg/mL, and terbinafine 0.5 µg/mL [].
Liposomal amphotericin was discontinued after 18 days due to acute renal injury, and caspofungin and oral voriconazole therapy were continued. He completed 8 weeks of combination therapy and was continued on oral voriconazole for chronic suppression. Voriconazole was chosen despite susceptibility data given reported clinical efficacy combined with lack of correlation between the susceptibility data and patient outcomes []. He unfortunately developed peripheral neuropathy, suspected by his local neurologist to be secondary to the voriconazole, and he was transitioned to delayed-release oral posaconazole dosed at 100 mg daily for chronic suppression [, ]. Posaconazole levels were followed and remained therapeutic with levels >1.0 mcg/mL. The inflammatory markers normalized at 6 months. Follow-up TEEs at 3 months and 7 months postoperatively did not show recurrence of endocarditis. Further, after cessation of the voriconazole he reported improvement, but not full resolution, of his neuropathy symptoms.


A 63-year-old white male, born in the Northeast of Brazil and now living in Rio de Janeiro, presents a history of hepatic cirrhosis diagnosed nine years before, related to alcohol and hepatitis C virus infection, with previous admissions due to decompensation of cirrhosis. At the time he was on propranolol 20 mg t.i.d., omeprazole 40 mg s.i.d., spironolactone 150 mg s.i.d., and furosemide 40 mg s.i.d.
He was admitted to the emergency room with a three-day history of fever, progressive worsening dyspnea up to orthopnea, and abdominal distention with a diffuse pain. There was no alteration in his mental status or bowel movements. He had no previous history of nephropathy or heart disease.
A general physical exam revealed tachycardia of 100 beats per minute and tachypnea with respiratory effort and peripheral saturation of 94% in room air. His extremities were cold and his blood pressure was 90/70 mmHg with no postural fall. There were clinical signs of malnutrition, pallor, and voluminous ascites, with 69 k of body weight. In his respiratory examination, vesicular sounds and vocal fremitus on the right hemithorax were reduced. Cardiovascular exam and venous jugular pressure were normal. Abdomen showed tense ascites, with collateral circulations and peritoneal irritation without splenomegaly. There was neither a peripheral edema nor signs of hepatic encephalopathy. Laboratory tests showed a hematocrit of 27%, platelets of 104 × 103/μL, and white blood count of 6.600 × 103/μL (6% bands). Serum creatinine was 0.88 mg/dL and blood urea nitrogen (BUN) was 15 mmol/L. Prothrombin activity time was 16.4 seconds, albumin, 2 g/dL, and total bilirubin, 2.2 mg/dL (1.7 mgL/dL of direct fraction), Child-Pugh score C, 10 points, and Meld score, 15 points. Urine exam was positive for 3-4 leukocytes/mm3 and 2-3 red blood cells/mm3, with a protein-to-creatinine ratio in spot urine of 935 mg/g. Urine culture was negative.
Electrocardiogram revealed a sinus rhythm with normal waves morphology and corrected QT interval (QTc) of 460 msec for Bazett's formula.
Upper endoscopy showed large esophageal varices, erosive gastritis, and congestive gastropathy.
Spontaneous bacterial peritonitis was confirmed by a diagnostic and therapeutic paracentesis, and the fluid had a turbid appearance, with 600 leukocytes/μL (50% of polymorphonuclear) and with albumin of 3 g/L, which was diagnostic of spontaneous bacterial peritonitis. The patient was started on ceftriaxone and because his clinical condition got worse, the scheme was changed to meropenem, with improvement of the infectious status. Abdominal fluid was indicative of intraperitoneal infection, and the clinical improvement after antibiotics supported this diagnosis, but blood cultures were negative.
On the fourth day after the antibiotic replacement, there was a reduction of the urinary output and a rise of BUN and creatinine. He was then prescribed albumin and noradrenaline at 8 μg/kg/hour. Serum creatinine rose to 1.81 mg/dL. After three days, the patient continued to exhibit a urinary output lower than 200 mL/24 h, despite therapeutic measures, with a creatinine rise of up to 2.63 mg/dL. Because of this poor response, the NT pro-BNP was measured, 444 pg/dL (normal value: 135 pg/dL), suggesting a possible cardiomyopathic component associated. The therapeutic decision was to start dobutamine on 2.5 mcg/kg/minute, even in the absence of an echocardiographic study, which was unavailable at that time. The patient recovered diuresis 12 hours after the inotrope was started. Naturally, as a positive inotrope was started, as adjunctive therapy to the usual measures (albumin and noradrenaline infusion), the beta-blocker was temporarily held.
After 24 hours of dobutamine infusion, an echocardiogram was done and showed an ejection fraction of 62.3% (Simpson's method) and a global longitudinal strain of 29%. Dobutamine was then withheld, and his condition was reevaluated after 30 minutes, with a reduction of the systolic global strain to 18% and the ejection fraction to 51.8%. After dobutamine infusion was restarted, there was a normalization of the parameters, as shown in .
On the following five days, the urinary output progressively increased, with a reduction of serum creatinine to 1.29 mg/dL, when the dobutamine was withheld ().
The patient was discharged after fifteen days of the intervention, in association to normal urine output and serum creatinine at 1.25 mg/dL.


A fifty two year old male was admitted via Emergency department with complaints of shortness of breath. Patient had history of intermittent episodes of shortness of breath for last two years with each episode being worsened from the previous one. The last episode started one month ago restricting his physical activity only to few steps; Shortness of breath is partially relieved by lying laterally. It was also associated with productive cough with white scanty, non-foul smelling sputum, occasionally mixed with blood. Patient also received ATT (anti tuberculosis therapy) for last fifteen days without any betterment in his status. He holds past two year record of admissions, where he was treated for pneumonia initially; later two admissions were done with extensive workup firstly in August 2012 and latter January 2013. Biopsies were done both the time and both confer the diagnosis of solitary fibrous tumor. Patient was advised for followup in both institutes, but never returned and finally landed in our institute in order to avoid a possible surgical resection.
Clinically patient was restless, tachycardic and tachypneic but maintained oxygen saturation on 3-4 liter of oxygen. His chest examination showed decrease right sided movements with dull percussion note, decrease breath sounds. Lab investigations further revealed anemia with Hemoglobin of 8.0 gm/dl, blood gases showed mild hypoxia with PO2 of 80mm Hg while rest of his metabolic panel & co-agulation profile were within normal limit.
Chest X-ray showed a large homogenous opacity on right side with mediastinal shift. CT Scan of chest confirmed the finding of a large heterogeneous mass with few sparks of calcification occupying almost whole of the right hemi thorax. Medially the mass was abutting and pushing superior vena cava, Aorta, right pulmonary artery and heart. Mass was also causing compression effects on the right hemi-diaphragm. It is displacing the mediastinal contents on to the left and caused compression collapse of right medial and lover lobe. Minimal pleural effusion with pleural thickening was also noted. ( and )
After thorough discussion and multiple settings; patient was counselled for surgical removal of the mass and its catastrophic outcome in case of further delay. Explorative thoracotomy was done and a huge extra pleural mass was removed. Right upper lobe of the lung was also adherent to the mass. Careful incision was performed to remove the mass preserving the surrounding vascular structures with minimal blood loss. The size of excised mass 24 x 20cm x 8cm and it was 3150gm in weight. (). The lower and middle lobe collapse was relieved partially and later fully. Two drains were placed and wound was approximated.
The pathological examination revealed a single multi nodular encpsulated pale white firm piece of tissue. On serial sectioning two collapsed cavities were also indentified with larger one measuring 5 x5 cm filled with yellow pleurant exudate. A flap of pleura id identified too measuring 12x6 cm.
Microscopic examination revealed demarcated lesion composed of spindloid cells. The nuclei are oval to elongated with evenly dispersed chromatin. Cytoplasm is abundant. Scattered mitotic figures are seen. Areas of hyalinization and fibrosis are noted. Conclude as neoplastic lesion; solitary fibrous tumor as possibility.
Patient was kept on mechanical ventilation, but, as per plan, the ICU team could not wean him off in next two days. Patient also developed fever spikes and later developed ventilator associated pneumonia. Tracheal cultures revealed acinetobacter. Intravenous anti-biotics were given as per sensitivity and after six days patient was finally extubated. Drains were removed on third day of surgery. Physical capacity continues to increase slowly and patient was able to walk short distances without any discomfort.


The patient was a 33-year-old Hispanic man who had a history of Philadelphia-positive CML, diagnosed in the chronic phase 5 years ago. After diagnosis, he received treatment with imatinib 400 mg QD, demonstrating complete hematological and cytogenetic bone marrow response within 4 months of therapy initiation. This treatment was maintained in the following years without relapse. The patient presented to the emergency department having experienced an eight-day history of severe headaches, nausea, and confusion and 3 days of low-grade fever. Upon direct examination the patient was febrile (100.4°F), tachycardic, and lethargic, showed nuchal rigidity, and had 3 episodes of tonic-clonic seizures. The patient did not present with evidence of lymphadenopathy or hepatosplenomegaly. Head and thoracoabdominopelvic computed tomography scans were normal. WBC count was 12 960/μL (75% neutrophils, 3% bands, 4% monocytes, and 18% lymphocytes). CSF showed 1010 cells/μL (100% mononuclears), glucose of 41 mg/dL (N: 40–76), and proteins of 29 mg/dL (N: 15–45); Gram stain and HIV antibody detection were negative. PCR testing of the CSF and viral culture for herpes simplex were not available at our institution. The patient received treatment with ceftriaxone, vancomycin, acyclovir, mannitol, and anticonvulsants. Imatinib was discontinued thereafter. Five days later the patient's symptoms improved, he was alert, oriented, and afebrile, and the leukocytosis resolved. He subsequently was managed with acyclovir and anticonvulsants after obtaining negative bacterial CSF and blood cultures.
Eighteen days after admission the patient again developed severe headaches, vomit, confusion, and worse nuchal rigidity. A brain magnetic resonance imaging (MRI) scan was normal (). BM aspiration assessment indicated complete hematologic, cytogenetic, and molecular remission. New CSF study showed 760 cells/μL (100% mononuclears), glucose of 24 mg/dL, and proteins of 79 mg/dL, and cytocentrifuge preparations lead to cytological identification of leukemic blasts.
CSF cytogenetic study showed 46XY, t(9;22)(q34:q11). Fluorescence in situ hybridization (FISH) analysis detected BCR-ABL fusion signals in 4.1% International Scale (IS) of cells. Flow cytometry to determine the blast type and measurement of imatinib concentration in serum and CSF were not available at our institution at the time. One month following admission, the patient received intrathecal methotrexate (12 mg), cytosine arabinoside (30 mg), and dexamethasone (4 mg), a total of 4 doses in a month. Few days after the first dose, the neurological symptoms improved substantially and the patient was able to initiate dasatinib 70 mg BID PO. However, when fully oriented, the patient manifested decreased visual acuity. Funduscopy showed pale discs without edema suggestive of optic nerve atrophy. Optic MRI did not evidence abnormalities (). After a few weeks the patient achieved full recovery except for the persistence of severe visual deficit. CSF became negative for blasts after 2 weeks of intrathecal therapy. The patient was discharged on dasatinib treatment. Follow-up at 6 months after discharge indicated the patient remained in complete cytogenetic response without signs of systemic or central nervous system (CNS) relapses; unfortunately, the severe visual impairment persisted.


A 31-year-old female was admitted with a swelling in her soft palate. On examination, an approximately 3 cm sessile, nontender swelling with normal mucosa and smooth surface was observed on her soft palate. Magnetic resonance imaging (MRI) revealed a 26.5 × 22.5 × 8 mm lump near the right tonsillar palate, which retained contrast substance at its surface and appeared to contain iso- to hypointense fibrils in T1 images and hypointense fibrils in T2 images (Figures and ).
Based on the initial findings, we thought that this mass might be a cyst of the minor salivary glands, fibroepithelial polyp, benign nerve sheath tumour, or nasopharyngeal tumour. After surgical excision, the specimen was sent to the pathology department. Grossly, the greatest diameter of the mass was 29 mm. The tumour was clearly separated from the surrounding tissues. There was minor salivary gland tissue near the mass.
Histologically, the mass contained adipocytes and spindle cells and had centres with myxoid character and fine rope-like collagen between these centres (Figures and ). All immunohistochemical (IHC) staining procedures, including deparaffinisation and antigen retrieval, were performed using the Dako LV-1 Automated Immunostaining System (Dako, Denmark). The mass was strongly positive for CD34 (IR632, FLEX ready to use, Dako, Denmark) () with focal areas that were weakly positive for S-100.
Based on the morphological and IHC findings, the mass was interpreted as a SCL.


A 56-year-old female patient with an unremarkable medical history visited our clinic with complaints of swelling, ecchymosis, and pain on the left side of her face. The dental history revealed that an endodontic retreatment therapy had been initiated on her maxillary left first premolar tooth 10 days previously, which was followed by a second session on the previous day. During the first session, the patient had felt light swelling, which resolved spontaneously a few hours later. At the second appointment, the treatment had to be stopped because of severe pain and hemorrhage from the root canal during irrigation of the root canal. No attempt had been made to restore the tooth other than placing a cotton pellet into the endodontic cavity. Another appointment had been scheduled by the general dentist to complete the treatment. The patient noticed swelling in her cheek several hours following the procedure, but she did not contact her doctor. However, her facial swelling worsened significantly over the next 24 hours, and the general dentist referred her to our clinic.
Approximately 48 hours after the incident, extraoral examination revealed significant soft tissue swelling extending from the left infraorbital region to the mandibular border. Infraorbital ecchymosis and slight bruising near the nasolabial fold were observed (). Intraorally, there were no signs of mucosal ulceration or necrosis. The tooth being treated was tender to vertical and horizontal percussion. Panoramic radiography showed evidence of a previous root canal therapy with periapical radiolucency ().
The root canals were irrigated with saline solution, and the tooth was restored temporarily. To prevent the risk of infection, intramuscular clindamycin (600 mg twice a day) was administered for three days, and ibuprofen (400 mg) was prescribed for pain management, to be taken as required. Use of cold packs externally for the first day was replaced by warm compresses on the second day for treatment of the swelling. On the first recall, an increase in the ecchymosis was noticed; however, the swelling had decreased significantly (). Both swelling and ecchymosis kept progressively decreasing during the follow-up period, and the patient became asymptomatic on the 10th day after the procedure (). For the evaluation of the relationship between the tooth, alveolar bone, and the maxillary sinus, dental volumetric tomography (DVT) (Newtom 3G, QR s.r.l., Verona, Italy) was performed. DVT images revealed that the apex of the buccal root canal had perforated the maxillary cortical bone, creating a pathway for the solution into the soft tissues (Figures and ). After 10 days, the symptoms had completely resolved. At this time, a root canal dressing with Ca(OH)2 was placed in the canal. At the final appointment approximately 4 weeks after the procedure, the root canals were filled with AH Plus (Dentsply Maillefer) and gutta-percha ().


In 1996, a 60-year-old man presented with an elevated PSA of 19.2 ng/mL. Digital rectal examination indicated a suspected tumor of the right prostatic lobe. The patient underwent a transrectal biopsy of the prostate. Histologically, a well to moderately differentiated adenocarcinoma of the prostate was found and a radical retropubic prostatectomy was performed. The preoperatively performed skeletal scintigraphy revealed no signs of bone metastases. A well to moderately differentiated adenocarcinoma of the prostate was confirmed, reaching the margin of the apical right prostatic lobe with infiltration of the prostatic capsule. Furthermore, focal lymphangiosis carcinomatosa was found. The tumor was finally classified as pT3a, pR1, pV0, pL1, and G2 (according to the 4th edition of the TNM system from 1992). At that time a Gleason grading was not conducted. Six weeks after surgery the PSA level was 0.00 ng/mL.
Due to the pathological findings an adjuvant androgen deprivation was recommended. However, the patient called for a therapy regime with as few side effects as possible and preservation of quality of life. For this reason also adjuvant local radiotherapy was refused by the patient. Only a prophylactic radiotherapy of the mamillae (cumulative dose 12 Gy) was conducted and androgen deprivation therapy with flutamide 250 mg (three times a day) started in July 1996. Hereunder, PSA levels remained stable around 1.5 ng/mL and androgen deprivation was stopped in November 1997.
According to the PSA level course, a total of six on-phases were performed (combined 129/221 months in 18 years); see . Trigger for reconvening on-phases was a PSA level between 10 and 20 ng/mL without a specific threshold. This was individually discussed with the patient at each visit. Therapy was changed to bicalutamide 50 mg once daily when it became available in 2001. Restaging examinations with bone scintigraphy in June 1997 and June 2004 as well as magnetic resonance imaging in August 1998 did not reveal any signs of progression. Regular clinical examinations including digital rectal examinations were also without pathological findings. PSA values never exceeded 20 ng/mL. Testosterone levels slowly increased over the years (December 2010: 26.9 nmol/L; September 2012: 37.6 nmol/L; August 2013: 41.4 nmol/L), but this is well known for bicalutamide monotherapy [, ]. Androgen resistance could not be observed as there was always immediate response to bicalutamide in on-phases with a repeated PSA decline below 3 ng/mL. In view of this positive response there was no need for considering salvage radiotherapy. During the course of therapy the patient never reported any serious side effects. The last PSA level was 3.5 ng/mL, and the patient is again in on-phase since November 2013.


A 60-year-old woman suffered a roadside accident. Her right leg was run over by one of the track tires and sustained a non-circumferential multi-planar degloving injury (); her left foot was abraded below the medial malleolus.
She was admitted and underwent debridement of devitalized tissues, but because a clear hypo-perfused area of the skin could not be documented, the leg wound was thoroughly washed, sutured and drained. The patient was obese and diabetic, so the delayed full-thickness necrosis of skin and subcutaneous tissue affected almost the full length of the medial, posterior and lateral areas of the right leg, fortunately spearing a narrow bridge of skin in front of the tibia. After one week, the necrotic tissue was surgically removed and the wound responded favorably to daily changes of dressing under intravenous penicillin and gentamicin. Two weeks later the recipient bed was clean, covered with early granulation and no clinical sign of residual necrosis or infection. The final debridement was achieved with a method commonly referred to as tangential hydrodissection, by using the VERSAJET Hydrosurgery System (Smith & Nephew) connected to a 45°/8 mm hand piece and power settings of 5 to 7 ().
In the same surgical procedure, a full-thickness single piece skin graft was harvested from the lower abdomen by using a standard panniculectomy excision pattern and the same Hydrosurgery System was used for defatting the graft. The abdominal donor site was directly closed with a minimal undermining and without an umbilical transposition. The skin graft was tailored to the defects and sutured in place under mild tension with very few stab incisions to allow fluid passage ().
A gauze-based negative pressure wound therapy (NPWT) system (Renasys EZ Plus, Smith & Nephew) at 90 mm Hg continuous pressure was used for graft-recipient site dressing. The initial dressing was left undisturbed for 5 days, when the graft was uniformly pink, adherent and with a healthy capillary refill. Another 5 days of NPWT were added and the local treatment with zinc paste bandage (Varolast, Hartmann) was continued up to 2 weeks when the patient was allowed to resume walking. She stayed in the hospital for a total of 55 days and was discharged fully ambulatory. The patient considered the cosmetic appearance of his lower limb excellent () and the reduction of the abdominal panniculus a bonus. In the past 3 years she did not experience any breakdown, nor did she develop contracture or suffered limitation of her range of motion.


A 46-year-old Caucasian woman complained of constant right eye tearing for 6 months, and it had worsened to cause blurry vision and interfered with wearing contact lens. She had intermittent pressure pain in the right medial canthus that improved after treatment with tobramycin-dexamethasone drops. Past history included deviated septum, anxiety, mitral valve prolapse, and venous insufficiency of the legs, and her medications were calcium and multi-vitamins. Visual acuity was 20/20 in each eye. Confrontation visual fields, extraocular motility, and pupillary exam were normal. The intraocular pressure was 15 mmHg in each eye. Pooling of clear tears was noted on a normal-appearing right lower lid without an enlarged, erythematous, or tender lacrimal sac. Nasolacrimal dilation and irrigation revealed complete reflux of clear saline, and the remainder of the ocular exam was unremarkable.
The patient underwent an uneventful external dacryocystorhinostomy with placement of Crawford stent. Milky purulent material, found upon entering the lacrimal sac, was sent for Gram stain and culture. The Gram stain showed Gram-positive cocci in pairs and clusters and pleomorphic coccobacilli (Figure A). The patient was discharged with oral cephalexin 250 mg four times daily for 5 days along with erythromycin ointment and tobramycin-dexamethasone drops. Routine cultures initially revealed suspected Granulicatella/Abiotrophia species based on biochemical phenotype, good growth on chocolate agar, and colony satellitosis on sheep blood agar within beta-hemolysis zones of co-inoculated Staphylococcus aureus (Figure B,C,D). The isolate was subsequently identified as G. adiacens with intermediate susceptibility to penicillin (MIC = 0.25 mcg/mL). The patient had an unremarkable postoperative course with resolution of tearing and pain symptoms, and the stent was removed at 3 months follow-up.


A 47-year-old male was referred to our hospital for a checkup before assisted conception. His clinical history was completely negative for (a) consanguinity; (b) infertility, since he is father of a daughter from a previous marriage; (c) pancreatic or acute pulmonary infection; (d) congenital bilateral aplasia of the vas deferens (CBAVD), mild pulmonary expression with bronchiectasis, idiopathic chronic pancreatitis, steatorrhea, hyperbilirubinemia, sinusitis, allergic bronchopulmonary, and asthma. Besides, semen investigation is completely normal. This individual refused to undergo sweat-test since he is often involved in training programs that do not allow performing this type of biochemical evaluation.
Genomic DNA was isolated from peripheral blood by a commercially available CE-IVD kit (High Pure PCR Template Preparation Kits, Roche Diagnostics, USA, ) and the DNA concentration and purity were spectrophotometrically measured (NanoPhotometer, Implen, München, Germany, ). Furthermore, the DNA integrity was verified by 0.8% agarose electrophoresis. Initially, the patient was screened using a standard panel of 59 different CF mutations, by reverse dot blots INNO-LiPA CFTR 19, CFTR 17+ IVS 8 polyT Update, and CFTR Italian Regional (Innogenetics, Ghent, Belgium). Dubious INNO-LiPA CFTR result was tested with CF70 kit (Nanogen, CA, USA) on NanoChip 400 machine.
NanoChip technology is basically a forward allele-specific oligonucleotide (ASO) based assay which is placed in an electronically controlled microarray format. Each NanoChip consists of 400 spots attached to platinum wire connections. DNA negatively charged is electronically guided to a test site where biotinylated samples bind streptavidin in the site. After denaturation, the CF 70 Data Analysis Spreadsheet indicates the genotype through the Green-to-Red signal ratio for each mutation fluorescent probes (green and red) and signal is detected after stringent washing procedures []. For the presence of two discordant results, full coding sequence and exon/intron junctions of the CFTR gene were performed by NGS. In particular, we used CFTR MASTR v2 assay (Multiplicom, Molecular Diagnostics), following the manufacturer's instructions. Amplicons were purified separately using Agencourt Ampure XP kit (Beckman Coulter) and subsequently quantified with Light Cycler 480 (Roche Diagnostics) by means of the Quant-iT PicoGreen dsDNA Assay kit (Invitrogen). The equimolar pool was amplified to generate an amplicon library using the GS Junior Titanium emPCR Kit (Roche Diagnostics) following the manufacturer's instructions. Four hundred fifty-four sequencing were subsequently performed on a 454 GS Junior v 2.7 system (Roche) using the GS Junior Titanium Sequencing kit (Roche Diagnostics). We employed a new in-house bioinformatics tool, named “Amplicon Suite,” able to automatically analyze each single GS Junior Sequencing run. The analysis included different steps: (a) quality control check of sequencing (“coverage” for each CFTR amplicon), (b) identification of variants (pathogenic or not), and (c) evaluation of functional effect of variants of uncertain significance (VUS) by processing them with several prediction tools (such as SIFT and PolyPhen). Several filters were applied to discard sequencing errors and to discriminate between polymorphisms and mutations. To confirm the p.M348K mutation, identified by NGS, Sanger sequencing of the CFTR exon 8 was carried out. Therefore, DNA sample was amplified using specific primers CFTR E8F: 5′-CTCAGGGTTCTTTGTGGTGT-3′ and CFTR E8R: 5′-AATGCCACTCTCATCCATCA-3′. Cycle sequencing reaction was carried out using same primers and Big Dye Termination Kit v. 3.1 (Applied Biosystems). Sequencing PCR products were analyzed using ABI3500 Genetic Analyzer (Applied Biosystems) and aligned to the reference sequences NG_ 016465.1 of the CFTR gene.
Preliminary analysis was collected by the Sequencing Software and performed by SeqScape Software v. 3 (Applied Biosystems).
CFTR screening by Inno-LiPA kit showed the presence of a weak wild-type band for p.R347P mutation. Since this result was also confirmed on a reextracted DNA sample, the patient was genotyped with an extensive 70 mutation panel through NanoChip technology. In this case NanoChip technology showed a green signal criteria for all CFTR markers with a G : R scaled value > 5. This finding highlighted the wild-type genotype for p.R347P mutation. Although this result could be reassuring, the discrepancy between the two technologies suggested a complete screening of CFTR gene to detect the possible alteration or mutation due to aberrant reaction found by Inno-LiPA assay.
The emerging NGS allowed us to analyze the full CFTR coding region and exon/intron junctions. “CFTR scanning” showed a homozygous replacement from T>A at position 1043 in the coding region. Codon 348 (ATG) changed to AAG, causing an amino acid substitution from methionine to lysine (p.M348K) (), which is not conservative, since methionine (an apolar amino acid) was replaced by the lysine (a polar amino acid). This result was then confirmed by Sanger sequencing ().


A 74-year-old Sinhalese man with diabetes mellitus and hyperlipidaemia was admitted to hospital with history of continuously high fever for four days duration. The fever was associated with chills and rigors. He had no myalgia but experienced nausea and had vomited twice before admission. He was a quite active before this illness and did not have any history of allergy. On clinical examination, he was ill looking and mildly dehydrated. His heart sounds were distinct with no additional sounds, and there were no abnormal signs in the other systems. The radial pulse rate was 72beats/min, regular and his blood pressure (BP) was 140/82 mmHg. Urine analysis showed 25-30 pus cell and 4-6 red blood cells (RBC) per high power field with a few organisms. His white cell count was 14.71×109/l with 75% neutrophils. C-reactive protein was 179 mg/dl, random blood sugar was 98 mg/dl, serum sodium-142 meq/l, potassium-4.5 meq/l. He was treated for urinary tract infection with amoxicillin-clavulanic acid 1.2 grams intravenously.
Twenty minutes after administrating the drug, the patient exhibited a generalized maculopapular rash on his trunk and limbs, which was accompanied by intense itching. He felt sense of instability, palpitations, central chest tightness and excessive sweating. His BP was 80/60 mmHg; peripheral oxygen saturation(SpO2) was 95%. Urgent ECG was taken(Figure ) showed ST elevation of 2 mm in leads 11,111,aVF,V3-V6. He was immediately treated for anaphylactic shock with 0.5 ml (1:1000) adrenalin intramuscularly (IM) Hydrocortisone 200 mg intravenously (IV) and chlorpheniramine 10 mg IV. He felt better and improved over the next 10 minutes. His rash was settling and blood pressure picked up to 102/78 mmHg. As electrocardiogram (ECG) shows widespread ST elevation aspirin 300 mg, clopidogrel 300 mg and atovastatin 40 mg stat doses were given. By this time his chest pain had settled.
As ECG showed evidence of ST elevation ACS, the patient was urgently transferred to the nearest tertiary hospital with coronary care unit(CCU) facilities.On admission to the CCU patients BP was 108/82 mmHg, pulse rate was 86/min, SaO2 96%in room air. He did not have chest pain. The ECG was taken on admission to the CCU (Figure ) revealed settling of ST elevations in Lead 11, Lead 111, aVF and V3-V6.The patient was managed with oxygen, heparin 1000 u/hour IV, aspirin 150 mg once a day(o.d), clopidogrel 75 mg o.d, atorvastatin 20 mg o.d, metoprolol 12.5 mg o.d and tolbutamide 500 mg three times a day. Echocardiography revealed no motility disorders or regional wall motion abnormalities but there was mild concentric left ventricular hypertrophy and mild diastolic dysfunction. The repeat ECG (Figure ) revealed further resolution of ST segment elevation. Patient was closely monitored over the next few hours and he did not develop further chest pain or complications. His troponin I, 6 hours after the onset of chest pain was 2.2 ng/ml. The patient was managed for allergic myocardial infarction (Kounis syndrome) and continued on ciprofloxacin 200 mg IV twice a day for urinary tract infection. The ECG taken the following day morning (Figure ) showed completely resolved ST segments elevation. He improved considerably over the next few days and the repeat C-reactive protein (CRP) and white blood cells (WBC) done on third day of illness was 56 mg/dl and 8.60×109/l respectively. The patient refused to undergo coronary arteries angiography and was discharged on day five of hospital admission.


A 35-year-old Iranian woman (GII, PII) initially presented with abdominal distention in May 2002. Imaging studies confirmed an ovarian tumor with a large volume of ascites. Cytodiagnosis of ascites revealed adenocarcinoma. Based upon these finding along with a clinical diagnosis of ovarian cancer, patient underwent laparotomy. The operation consisted of abdominal hysterectomy, bilateral adenexectomy, and omentectomy. The post-surgical pathological studies revealed serous cyst adenocarcinoma of ovary (stage IIIC). Thereafter, she received 6 courses ofcombination chemotherapy consisting ofTaxole (175 mg) and carboplatin (AUC 6) and patient showeda complete response to chemotherapy. The result of post treatmentabdominal pelvic computed tomography (CT) scan and serum CA125 levels were normal. The patient was under close observation and had been well for 8 months, without any symptom and sign of recurrence. Eight months after therapy, the patient presented suddenly withtonic- clonic seizures. The result of brain CT scan revealedmetastatic brain lesion ( and ), whereasabdominal pelvic CT scan findings and serum CA125 levels were normal. Abdominal and rectovaginal examinations did not detect any ascites or mass. The patient received whole brain irradiation (WBRT; 3500CGY) as well asa combination chemotherapy consisting of gemcitabine and carboplatin that subsequently decreased theneurological complains and she had no problem during 18 months ofpost-treatment follow-up. In December 2005, she developed visual disturbance and gait abnormality. Brain CT showed multiple brain metastases. The patient’s general health condition deteriorated and she died after a month.


This is the case of a 69-year-old man who presented to the emergency department (ED) with left sided chest pain for 3 days. The pain was sudden in onset, sharp in nature, and 5-6/10 in severity. He noticed the pain while walking and it radiated to the left shoulder. He took aspirin and his pain improved to 1/10, but he continued to have dull substernal chest pain without radiation. This pain was exacerbated by deep palpation and cold weather. He denied shortness of breath, dizziness, fever, chills, nausea, or vomiting. He was seen approximately 6 months ago for a nuclear stress test, which was negative. His ECG in September 2011 was sinus rhythm at 62 beats per minute, normal axis, and Q wave in lead III and upright T wave in lead aVL.
His past medical and surgical history included hypertension, benign prostate hyperplasia, gastroesophageal reflux disease (GERD), and surgery for colon cancer. He denied using alcohol or tobacco.
On presentation his vital signs were as follows: temperature 98.4 degrees Fahrenheit, respiration rate 18 breaths per minute, pulse 82 beats per minute, and blood pressure 145/80 mmHG. His physical examination was unremarkable except for mild sternal tenderness to palpation. His initial ECG showed sinus rhythm at 64 and T wave flattening in lead aVL (). The chest radiography was unremarkable. The repeat ECG showed sinus rhythm at 62 beats per minute with TWI in lead aVL along with biphasic T waves in leads V2 and V3 (). A comparative old ECG has normal T wave in lead aVL (). The patient was taken to the angiography suite and underwent a coronary angiogram. Angiography revealed a 99% mid-LAD lesion and he received a stent (Figures and ). Laboratory results were unremarkable except for mildly elevated triglyceride levels (202 mg/dL) and white blood cell count (15, 600 mm3). Cardiac troponins were within normal limits. The patient was subsequently discharged home to follow up as an outpatient. He remained symptom-free and on the follow-up clinic visit his ECG normalized with upright T waves in lead aVL ().