The proposita, a 30-year-old Moroccan woman, was born from healthy, apparently non-consanguineous parents and had a healthy younger sister. Perinatal distress was absent. At birth, measurements were within normal range; neonatal hypotonia and slight delayed motor development were noted. In infancy, progressive height deficit not related to GH deficiency was present, and a clinical diagnosis of unspecified EDS was given for skin hyperextensibility and generalized JHM. At age 28, dual-energy X-ray absorptiometry disclosed low bone mineral density for sex and age (z-score < 2 SD); audiometric test revealed mild neurosensorial hearing loss. Genetic analyses were not performed.
On examination, disproportionate short stature (145 cm, genetic target 160 cm, standard deviation from ethnic average stature – 2, arm span/height ratio 1.09, n.v. <1.05), soft, doughy, hyperextensible skin, small atrophic scars on knees and a single transverse palmar crease were observed (Fig. ). gJHM according to the Beighton score (7/9), skeletal abnormalities (scoliosis, severe hallux valgus, pes planus, low-set thumb, clinodactyly of the 5th fingers), generalized muscle hypotonia, facial dysmorphism (light blue sclerae, wide forehead, flat face, sparse scalp hair, and narrow mouth), and edema of the lower extremities were also noticed (Fig.). Complication of gJHM were recurrent sprains, temporomandibular joint dislocation and chronic pain at cervical spine, right shoulder, and ankles. Doppler ultrasound of lower limbs established edema of lymphatic origin; lymphography was not performed according to the patient’s choice. The most frequent causes of secondary lymphedema, i.e., cancer, infection, and surgery, were not present. Ophthalmologic evaluation was unremarkable for refractive errors including hypermetropia. Forearms, left wrist, pelvis, lower limbs, feet and spine X-ray disclosed dextroscoliosis, L5 hemisacralitation, L4-L5 disc space narrowing, metatarsophalangeal subluxation, pes planus, and hallux valgus (Fig. ). Heart ultrasound detected normal cardiac/valve morphology and function. Cognitive development and mentation were normal.
This phenotype was suggestive for spEDS, since the patient fulfilled 2 major and 4 minor criteria according to the 2017 EDS nosology (Table ), and the evaluation of the gene-specific minor criteria suggested B4GALT7 as causative gene (Table ).
Therefore, after written informed consent was obtained, B4GALT7 mutational screening was performed by Sanger sequencing of all coding exons/intron boundaries. This analysis disclosed in the patient the homozygous c.829G>T (p.Glu277*) variant; both parents and her sister were heterozygotes (Fig. ). All these carriers did not show any sign of the disease including short stature, muscle hypotonia, craniofacial dysmorphism, as well as hearing loss and lymphedema.
The identified variant represents a very rare allele seen only twice in 122,600 samples from the genome Aggregation Database (gnomAD) with an allele frequency of 8.157e−6. Though patient's parents firmly denied consanguinity, the presence of some not-so-distant relatedness should not be excluded; homozygosity mapping was not performed, since they did not consent further investigations. Alternatively, the allele might be more common in Morocco, but no population-specific data are available. The transversion affects the first nucleotide of the last exon and the splice site prediction tools of the Alamut Visual version 2.9.0 software suggested that the variant alters the canonical splice acceptor site. To verify the possible splice effect of the variant, RT-PCR was carried out by standard procedures on RNA extracted from patient’s whole blood. That demonstrated multiple splice outcomes. In particular, agarose gel electrophoresis of patient’s cDNA amplified with primers encompassing exons 4–6 showed, in addition to low amounts of wild type fragment (188 bp), the presence of an aberrant band (713 bp). Sanger sequencing of this RT-PCR showed in addition to mRNA resulting from the use of the canonical site, the presence of 2 further splice products: i) an allele derived from the activation of a cryptic splice acceptor site 3 bp downstream generating in-frame deletion of the amino acid residue at position 277, and ii) mRNA with entire intron 5 retention causing the insertion of 10 amino acids followed by a stop codon (Fig. ). The mutation should therefore result in different amounts of truncated (p.Glu277* and p.Glu276_Glu277ins11*) and internally deleted polypeptides (p.Glu277del) leading to reduced galactosyltransferase activity. The resulting functional implication on GAG synthesis was not studied, since fibroblasts were not available.


A 31-year-old male has experienced hot flashes for the past five to six years; this is associated with obvious erythema of the face and is accompanied by hypertensive episodes as high as 226/128 mmHg with no palpitations. In the past year, these spells had become more frequent with headaches in both temples. He also reports decreased peripheral vision during these episodes. Lying down seems to reduce the severity and duration of these spells. He often feels light-headed in the upright position and experiences vertigo while lying on his side, at times; this is always relieved by changing his position on the bed. His symptoms are relieved by sublingual medication, such as nifedipine, but the patient states that his episodes are brought on by excitement such as watching a football game, walking barefoot on hard surfaces, having a bumpy car ride, or making sudden head movements. He also reports heat intolerance and excessive sweating. The patient's past medical history was positive for SCI, after which he developed pain in the neck and lower back, with numbness and tingling in his upper extremities and pain radiating down his hip. Table lists the common signs and symptoms of AD generally experienced by patients with SCI.
Laboratory results revealed an increased excretion of epinephrine and dopamine but a normal output of norepinephrine. His epinephrine levels were increased by injections of intravenous glucagon, a response highly suggestive of the presence of pheochromocytoma. He also had prolonged spells of tachycardia induced by exercise despite taking propranolol, which was further suggestive of the production of large amounts of epinephrine, overriding the effects of propranolol.
He underwent an evaluation for pheochromocytoma. An octreotide scan, a metaiodobenzylguanidine (MIBG) scan, and a magnetic resonance imaging (MRI) scan of the adrenal glands were all negative. After some time, the patient reported episodic anxiety and hypertension with a full bladder and immediate relief after voiding. He was sent for cystoscopy and urodynamic studies, which were all negative as well. Given his history of SCI, the patient underwent spinal cord imaging, which showed disk herniation at C3-C4 and C4-C5, as shown in Figure . After ruling out other possible etiologies, he was diagnosed with AD (a functional spinal cord disorder) in light of his symptoms appearing after trauma to the spinal cord.


A 51-year-old Chinese male had undergone living-donor kidney transplantation for end-stage renal disease (ESRD) due to 8 years of nephrotic syndrome in 2011 at the age of 46 years. His immunosuppression regimen included a combination therapy with tacrolimus 2.5 mg/d, mycophenolate mofetil 1.5 g/d, and prednisolone 10 mg/d. The blood concentration of tacrolimus (FK-506) was monitored regularly at a target level of 4 to 10 ng/mL. No colonoscopy had been performed prior to transplantation, and he did not receive colonoscopic surveillance postoperatively. Renal graft function remained stable in him without any rejection episodes.
Four years after transplantation, the patient presented with recurrent hematochezia (bright red blood per rectum mixed with stools), and a change in bowel habits manifested by frequent loose stools. He did not pay attention to these abnormal conditions until he began to suffer from progressive general malaise and weight loss of 3 kg during the period of 1 month. A colonoscopy was taken subsequently in January 2016, which revealed a near-circumferential mass at the middle rectum about 8 cm from anal verge accompanied by moderate luminal stenosis. The friable lesion proved to be adenocarcinoma by further biopsy. Having made a definite diagnosis, the patient was admitted to our institution in February 2016. He had a previous history of hypertension for 7 years that could be generally controlled by medication, and cigarette smoking for more than 30 years. Regarding his family history, there were no remarkable findings.
On admission, detailed physical examination revealed a temperature of 36.5°C, pulse of 80 bpm, and blood pressure of 106/60 mm Hg. No special signs were noted except for a healed surgery scar on his right lower abdominal wall. The lower margin of a solid, irregular mass was touched about 6 cm from anal verge through a digital rectal examination. Laboratory tests showed hemoglobin was 133 g/L, fecal occult blood test was positive, serum creatinine was 88 μmol/L, liver function test was normal, and most serum tumor markers (AFP, CEA, CA19-9, and CA72-4) were within the normal range but CA242 was slightly elevated. The following computed tomography (CT) scan demonstrated a soft tissue density mass protruding into the lumen of upper-middle rectum, with the wall thickening and peripheral lymph node metastasis and the transplant kidney was located in the right pelvic cavity (Fig. ). No evidences of distant metastasis were suggested. FK-506 was 4.7 ng/mL at that time. According to recommendation of interdisciplinary team including urologists, medical physicians, and general surgeons, immunosuppressive therapy with previous regimen was extended perioperatively. Meanwhile, 100 mg of intravenous hydrocortisone was added before anesthesia induction, and turned to a dose of 50 mg/8 h postoperatively for 1 day to prevent acute renal failure caused by the attack of surgery.
Without any surgery contraindications, a laparoscopic assisted low anterior resection with total mesorectal excision (TME) was performed then. After induction of general anesthesia, the patient was positioned in the lithotomy position. Complete exploration of the abdominal cavity suggested that there was no liver and peritoneal carcinomatosis. The tumor was identified locating at the middle-lower rectum. Specific surgical procedures started with lysis of abdominal adhesions from previous surgery. The sigmoid mesocolon and mesorectum were dissected along the inner side of the ureters by harmonic scalpel, and the vessels and lymphatics were ligated at the root of the superior rectal vessel with Hem-o-lock. The distal rectum was transected intracorporeally 3 cm from the distal margin of tumor with a EC45-A laparoscopic linear stapler (Johnson & Johnson, Cincinnati, OH, USA). After that, a 6 cm left supraumbilical incision was made to remove the proximal rectum, the distal sigmoid colon, and the surrounding tissues of the rectum 10 cm from the proximal margin of tumor. The specimen was obtained for further pathological evaluation (Fig. ). Reconstruction was performed intracorporeally in the manner of straight end-to-end colorectal anastomosis using a 28 mm transanal circular stapler (COVIDIEN, Mansfield, MA, USA) (Fig. ). Finally, 2 drainage tubes were placed in the pelvic cavity surrounding the anastomosis site. In order to prevent postoperative anastomotic leakage, a loop transverse colostomy was performed (Fig. ). The operation was completed successfully within 2 h with a proximate blood loss of 100 mL. Histopathology revealed a well-moderately differentiated adenocarcinoma measuring 4.2 × 5 × 2.3 cm, with invasion through the muscularis propria into pericolorectal tissues (Fig. ). The resection margins were free of tumor. Among the removed 14 lymph nodes, 3 contained metastatic cancer, indicating the tumor stage of pT3N1M0. Furthermore, immunohistochemistry showed the tumor was negative for MLH-1, MLH-2, MLH-6, and PMS-2.
Approximately 4 h after surgery, the patient developed archorrhagia (dark red blood and clots per rectum), and the amount of blood loss increased up to 200 mL within 1 h. After exploration per anus, a bleeding wound near the anastomosis was identified and the control of hemorrhage was performed timely. There was no recurrence of archorrhagia ever since. The further postoperative course was uneventful. Graft function stayed well, and serum creatinine levels were always within the normal limits, ranging from 80 to 104 μmol/L. The ostomy was opened on the third postoperative day, and flatus was passed then. The patient went on a liquid diet 4 days after surgery and made a recovery soon. He stayed in hospital for 9 days after surgery, and drainage tubes were removed at discharge.
During 4 months of follow-up period, immunosuppressive therapy with tacrolimus 2.5 mg/d, mycophenolate mofetil 1.5 g/d, and prednisolone 10 mg/d continued, no allograft rejection and complications were observed. Considering his tumor stage, he received adjuvant chemotherapy with a regimen of FOLFOX (oxaliplatin/5-fluorouracil/calcium folinate). After 8 cycles of chemotherapy, repeated CT scan indicated no evidences of local recurrence and distant metastasis. To date, the patient was in a good condition.


A 54-year old athletic male was a helmeted cyclist on a street race bicycle, when he fell over the handlebars and struck his head directly on cemented ground, sustaining a hyperflexion injury to his neck. He was able to get up at the accident scene and pushed his bicycle to the closest meeting point. Due to severe neck pain, he asked a friend to call an ambulance. He was initially brought to a local hospital in the Rocky Mountain region, where a CT of the head and cervical spine was obtained. The patient was placed in a C-collar and transported by ambulance to our level 1 trauma center for definitive management of his cervical spine fracture. Upon arrival, the patient was awake and alert with a GCS of 15. He stated to have felt some tingling sensation in his right hand after the accident, which apparently subsided by the time of his presentation to our hospital. His clinical exam demonstrated full symmetric motor strength (M5/5) in all four extremities, a normal rectal tone and bulbocavernosus reflex, and minimal hypoesthesia in the small finger on the right hand, related to the C8 dermatome. The review of his CT scan from the outside facility revealed a complex multi-level fracture-dislocation of the cervical spine from C6 to T1, with rotational instability (AO/OTA classification 51-C2.1). The injury pattern included a C7/T1 fracture-dislocation (Fig. ) with a left-side locked/perched facet at C6/C7 (Fig. ), a right side facet fracture-dislocation at C7/T1 (Fig. ), and a “saving” traumatic laminotomy at C6 and C7 on right side (Fig. ). A CT-angiogram was obtained which demonstrated a grade 1 intimal tear to the left vertebral artery at the C6 level. In light of the highly unstable fracture pattern, we decided to apply a Halo fixator for temporary external fixation. The Halo application was performed under local anesthesia without any closed reduction attempts, in order to mitigate the risk of an iatrogenic compression of the spinal cord. The patient was kept awake throughout and reported no change in symptoms. Thereafter, an MRI of the cervical spine was obtained for advanced imaging and preoperative planning. The MRI demonstrated a complete disruption of the annulus fibrosus of the C7/T1 intervertebral disc, a disruption of the anterior longitudinal ligament (ALL) and posterior longitudinal ligament (PLL) at the same level, and a complete extrusion of the C7/T1 disc into the spinal canal, positioned behind the C7 vertebral body (Fig. ). The interspinous ligament was disrupted at C6/C7, and there was mild spinal canal stenosis at C6/C7 without signs of cord compression or contusion.
A surgical plan was designed based on the following considerations:The posterior perched facet requiring posterior approach and open reduction to restore anatomic sagittal alignment of the spine; The extruded disc at C7/T1 requiring a C7 corpectomy and decompression through an anterior approach; The sequence of surgery being dictated by the intraspinal disc which requires (1) anterior decompression, followed by (2) posterior fracture reduction, and ultimately (3) an anterior completion fusion after posterior reduction and instrumentation.
As part of the preoperative shared decision-making process for surgery, the patient understood the detailed plan and the risks of intra- and postoperative complications. He agreed to proceed with surgery and provided a written informed consent. We took him to the operating room the next day for the 3-stage procedure under continuous neurophysiological monitoring. In supine position, the cervical spine was exposed from C6-T1 through a standard left side anterior Smith-Robinson approach. The dislocation at C7/T1 was visualized and the intervertebral disc at this level was obliterated, as expected from the preoperative MRI findings. A C7 corpectomy was performed which allowed decompression of the spinal canal by removal of the extruded intervertebral disc. The anterior wound was then closed temporarily. Under strict log-roll precautions, using the Halo ring for axial traction, the patient was carefully moved into prone position, for the 2nd stage of the procedure. We then performed a standard posterior approach from C4-T2. A completion laminectomy was performed through the laminar fractures at C6 and C7, for posterior spinal canal decompression. The perched facet at C6/C7 on the left and the facet fracture-dislocation at C7/T1 on the right were anatomically reduced, and a left side C6/C7 facetectomy was performed, which resulted in adequate rotational and sagittal alignment of the cervical spine. Spinal fixation was performed by posterior instrumentation with placement of lateral mass screws at C4, C5, C6, and pedicle screws at T1 and T2. The posterior wound was closed, and the patient was log-rolled back into supine position for the 3rd stage of the procedure. The previous anterior cervical wound was re-opened. The exposed dura was visualized through the preceding C7 corpectomy, and a 2-level anterior fusion from C6-T1 was performed with a PEEK cage filled with autograft bone from the resected C7 vertebra, and placement of a 2-level anterior locking plate (Fig. ). The anterior wound was then closed, the Halo was removed, and the patient was transitioned into a cervical collar. He tolerated the procedure well and was extubated in the operating room. His neurological exam was normal and the hypoesthesia in the right C8 dermatoma resolved postoperatively (Fig. ). The grade 1 vertebral artery intimal injury was managed conservatively with 325 mg acetylsalicylic acid (Aspirin) for three months. The patient was mobilized with physical therapy and discharged home on the 2nd postoperative day. He remained in a cervical collar for 6 weeks and was allowed to remove the collar for showering only during that period of time. The patient resumed full activity at three months. He was back riding his bicycle at 7 months, and by 10 months after surgery he had returned to competitive street bicycle racing in the 100 mile “Elephant Rock Century Ride” in Castle Rock, Colorado (Fig. ). The patient remained asymptomatic and continued his work as a financial consultant as well as unrestricted physical activity and exercises, including regular participation in competitive bicycle races, at follow up 7 years after the accident.


A 56-year-old woman with a two-year history of hyperlipidaemia was admitted to our hospital because of chest pain, especially during exercise. The physical examination and resting electrocardiogram (ECG) were normal and transthoracic echocardiography showed no wall-motion abnormality. Also, there was no abnormality in the standard biochemical tests. Her treadmill exercise test showed 1 to 2 mm down-sloping ST-segment depression in leads V4 to V6. Subsequently, the patient underwent coronary angiography for the evaluation of coronary artery disease.
Coronary angiography revealed a coronary artery anomaly of type IV dual LAD with a short LAD, which originated from the LMCA and terminated in the mid-portion of the AIVS. The long LAD originated from the RCA, entered into the distal part of the AIVS and travelled towards the apex of the heart. There was no haemodynamically severe stenosis in her coronary arteries and a decision was made to treat medically. The patient was discharged in good condition without any complications.


was a 69-year-old woman diagnosed with AML (M2) in December 2012. She received low-dose Ara-C (LDAC), and CR was achieved in August 2013. LDAC was maintained, but AML relapse was noted in March 2014. The blasts in the BM in March 2014 were 10.8%. She received another 2 weeks of LDAC from March 27 to April 10, 2014, and the blasts in BM were 9.2% on May 5, 2014. The WBC, hemoglobin and platelet counts of the peripheral blood were within normal ranges. Due the lack of further response to LDAC at approximately one month later, she started receiving ADI-PEG20 in May 2014. CR was noted after one cycle of ADI-PEG20 with a decrease in BM blasts from 9.2% to 3% (Fig. ). The patient had a precipitous decrease in blood pressure in the fifth cycle of ADI-PEG20, and the treatment was stopped in October 2014. The hypotension was suspected to be anaphylactic, and it resolved in a few days without sequelae after administration of an inotropic agent. The patient remained in CR until March 2015. The duration of response was 8.8 months.


A 48-year-old Asian woman initially underwent a tumorectomy 12 years ago, with a pathological diagnosis of fibroadenoma (pericanalicular pattern dominant). Five years later, the patient consulted another doctor regarding a growth in her left breast. A biopsy was performed, and a diagnosis of phyllodes tumor was made. The patient subsequently underwent a partial mastectomy. Five months after the mastectomy, her left breast began to show enlargement again. The attending physician suspected a relapse and proposed total mastectomy. The attending physician then referred the patient to our hospital for total mastectomy and reconstructive surgery.
The tumor of the left breast was elastic and hard, and it had mobility. The patient’s laboratory data were within normal ranges. Ultrasonographic images showed a large segmental tumor (Fig. ). The inside of the tumor was heterogeneous and had hypoechoic characteristics. Computed tomographic images also showed a large tumor of the left breast (Fig. ). There was no lymph node metastasis or distant metastasis. Magnetic resonance imaging scans showed a large tumor that was well-defined but attached to the greater pectoral muscle (Fig. ). We performed a total mastectomy and reconstructive surgery with the rectus abdominis muscle. The pathological diagnosis was malignant phyllodes tumor (Fig. ). There was a significant amount of mitosis but no evidence of infiltration to the surrounding muscle (Fig. ).
The patient had follow-up visits approximately 2–4 weeks after each surgery, with additional visits several months later. However, the patient often presented at our hospital prior to follow-up appointments with a chief complaint of breast enlargement. Because we could not predict relapse, it was not clear what follow-up period should be used. Ultimately, we decided to follow the patient within several weeks after the surgery. In total, the patient would have six episodes of relapse. The periods between consecutive episodes of relapse were short, with the smallest period being 20 days. The areas of relapse in the breast were different every time: sometimes under the nipple and another time near a drainage tube scar from a previous surgery. In every incident of relapse, the pathological diagnosis was always malignant phyllodes tumor. Despite attempting radiation therapy after previous surgeries, tumor control was not obtained. The sixth surgery was performed to treat a relapse under the nipple, with adjuvant radiation therapy also delivered. The patient currently lives relapse-free. Distant metastasis was not observed during any period in this case.


A 55-year-old man presented to our hospital with suspected carcinoma of the thyroid gland. The tumor in the center of the neck was large enough for us to suspect that the skin invasion had been present for many years, although the patient had no remarkable symptoms. Based on needle biopsy findings, the tumor was diagnosed as papillary carcinoma. In addition to total thyroidectomy, we planned for an optional skin excision with bilateral neck dissection based on the CT findings (Fig. ). We originally planned to use a local flap of the neck to cover the skin defect, but the size of the defect was too large and we had to make an extended skin incision (Fig. ). A DP flap was designed with substantial undermining to the pectoral region, followed by direct closure of the surgical wound and donor site, using suction drains and without a skin graft (Fig. ). No adverse events occurred during hospitalization. The patient initially declined multiple z-plasty 6 months after the initial surgery to treat the scar contracture around his neck, but later accepted our recommendation (Fig. and Additional file : Figure S1).


A 67-year-old woman presented to our hospital with undifferentiated carcinoma of the thyroid gland with local metastasis to neck lymph nodes that was diagnosed based on needle biopsy outside our hospital. The patient presented with no other remarkable symptoms while she had few past medical histories. The tumor size was large enough to raise suspicion of skin involvement during her evaluation at the referring hospital. She was then referred to our hospital due to skin involvement and the need to sacrifice the surrounding large vessels, such as the right common carotid artery and right subclavian artery and vein, during tumor resection and total thyroidectomy (Fig. ). At first, various flaps such as the DP flap, the pectoralis major myocutaneous flap, the latissimus dorsi flap, and free flaps were considered as candidates for reconstruction of the skin defect. We decided against using a pectoralis major myocutaneous flap because a portion of the right subclavian vein, brachiocephalic vein, and proximal portion of the right internal thoracic artery and vein would have to be sacrificed with dissection of the right neck and paratracheal lymph nodes, while salvaging the right common carotid artery (Fig. a, b). The right DP flap was likely to be excluded as an option before pulsation of the second intercostal perforator artery was confirmed using a Doppler stethoscope. Ultimately, the DP flap was designed and elevated in the usual manner because the 2nd and 3rd intercostal perforator arteries were detected by the Doppler stethoscope. Bleeding from the distal edge of the flap was enough to confirm blood supply of the flap, even after sacrificing the branch of the thoracoacromial artery, and the flap was elevated completely. A portion of the skin on the right side of the neck was undermined and used as a skin flap, followed by setting of the DP flap, which allowed for the airtight closure of the skin defect (Fig. c-e). A portion of the donor site of the DP flap was covered by a meshed skin graft taken from the lower left abdomen. The postoperative clinical course was uneventful to hospital discharge. Because the pathological diagnosis was undifferentiated carcinoma of the thyroid gland, chemoradiotherapy was administered, with no adverse effects. There were no signs of recurrence or metastasis 2 years postoperatively, while the range of motion of the right shoulder improved and no scar contracture developed around the skin graft (Fig. , Additional file : Figure S2 and Additional file : Figure S3).


Case 1: a 1-month-old preterm, very low birth weight (1300 g), male neonate belonging to Hindu (Indian) ethnicity, presented to our hospital with recurrent bile-stained vomiting, non-passage of stools and epigastric fullness for the last 2 weeks. Antenatal ultrasounds had not been done. On examination, the neonate was afebrile, moderately dehydrated with a pulse rate of 170 beats per minute and a respiratory rate of 62 breaths per minute. Chest auscultation revealed cardiac apex on the fifth right intercostal space along the midclavicular line. The abdomen was soft and distended and nasogastric aspirate was bilious. Laboratory investigations revealed a total lymphocyte count (TLC) of 16,200 mm3, a hemoglobin level of 11.6 g, and raised C-reactive protein levels. A babygram revealed dextrocardia, liver opacity on the left side of his abdomen, a splenic shadow and stomach bubble on the right side, which was suggestive of situs inversus totalis. There were few dilated bowel loops in his upper abdomen with a paucity of distal gas shadows (Fig. ). Upper gastrointestinal (UGI) contrast studies suggested a proximal jejunal obstruction and midgut volvulus (Fig. ). Preoperative optimization was performed and consent was taken for surgical intervention. Laparotomy findings confirmed situs inversus totalis with his liver and duodenum on the left side, his stomach and spleen on the right side of his abdomen along with malrotation and midgut volvulus with reverse rotation; the caecum and appendix were present in his left upper abdomen (Fig. ). There was a small gangrenous area in the proximal jejunal loop. A Ladd’s procedure was performed along with resection of the gangrenous jejunal loop (a few centimeters) and jejunojejunal anastomosis. Note was made of the unusual appearance of his intestines suggestive of either fibrous or fatty infiltration. Postoperatively, our patient passed greenish mucoid stool on the fourth postoperative day, but later developed septicemia with a precipitous downhill course, and finally died on the sixth postoperative day.


Case 2: a 4-day-old female neonate belonging to Hindu (Indian) ethnicity, full-term small (1320 g) for gestation, presented with non-passage of meconium since birth, refusal to accept feeds, and episodes of recurrent bilious vomiting with abdominal distension. There was no history of consanguinity. On examination, the neonate was hemodynamically stable, dehydrated, and mildly icteric with a pulse rate of 162 beats per minute and respiratory rate of 50 breaths per minute. There was upper abdominal distension with visible dilated bowel loops. Plain radiographs revealed dextrocardia, liver opacity on the left side of her abdomen, and a stomach bubble on the right side suggestive of situs inversus totalis. There were few dilated bowel loops in her upper abdomen with absence of distal gas shadows (Fig. ). Laboratory values revealed grossly deranged renal functions with abnormally raised urea (89 mg/dL) and creatinine levels (3.5 mg/dL), initially considered to be due to dehydration. Our patient was stabilized and resuscitated; a renal profile showed slightly improved creatinine levels (2.9 mg/dL). Ultrasonography of her abdomen revealed renal dysplastic changes in both kidneys. After optimization, an informed written consent was taken for an operative procedure. Abdominal exploration confirmed multiple jejunoileal atresias with situs inversus totalis (Fig. ). The proximal 15 cm of the dilated jejunum was resected and multiple anastomoses with end-to-back and end-to-end anastomoses and a Heineke–Mikulicz repair were performed for multiple atresias and webs. Our patient passed a few pellets of meconium stools on the fourth postoperative day. Oral feeding was initiated on the sixth day with gradual increments. Our patient passed a few pellet-like meconium stools every second or third day. She did not develop any episode of postoperative vomiting or abdominal distension. Later, our patient redeveloped oliguria with deranged renal parameters (renal failure), respiratory distress, and generalized edema requiring ventilatory support. A chest radiograph performed on the 13th postoperative day revealed infiltration of the lung fields (Fig. ), which was hypothesized as pneumonitis. Our patient died on the 18th postoperative day due to multiorgan failure.


A 38 yr old female patient from tribal area of Bankura district, West Bengal, India was admitted in surgery ward with complaints of pain at right hypochondrium, anorexia and weight loss and occasional fever for 3 wk. She had no history of exposure to tuberculosis. She had average built and vitals were stable. On physical examination, she had mild hepatomegaly and mild pallor. Routine blood examination revealed hemoglobin level 8.9% gm. and erythrocyte sedimentation rate (ESR) - 65mm/hr. Among liver function tests (LFT), patient had hypoalbuminaemia (3 gm/d1 and hyper-globulinemia (3.8 gm/d1), with hyper-bilirubinaemia (2.5 mg/d1, direct 1.7 mg/d1), elevated SGOT 94U/L and alkaline phosphatase 279U/L. Viral serological tests were negative for hepatitis and HIV virus. Blood biochemistry and renal function tests were in normal range. Informed consent was taken from the patient.
Chest X-ray of the patient had no abnormality. Ultrasound examination of the whole abdomen done and it revealed a 2.3 cm hypoechoic nodule at right lobe of liver and two small periportal lymph nodes of 0.8 cm and 0.5 cm diameter. On CT scan, liver was mild enlarged and there was a 2.3 cm X 1.8 cm hypoechoic nodule (SOL) at right lobe of liver without central necrosis. There were two small periportal lymph nodes but no perihepatic collection was found. CT guided FNAC was done from liver nodule and it revealed necrotic material only. The Ziehl–Neelsen stain from aspirated material did not reveal acid-fast bacilli.
The etiological diagnosis could not be clinched after routine diagnostic modalities. Diagnostic laparoscopy was done and biopsy was taken from the liver nodule. Histopathological examination of the biopsy specimen showed multiple well-defined epithelioid granulomas, caseation necrosis, and many multinucleated Langham's type giant cells surrounded by chronic lympho-plasmatic infiltration in the benign hepatocytes (, ). Mycobacterial culture in L & J media did not produce any growth. Histopathological diagnosis was confirmed as tuberculous lesion by polymerase chain reaction (PCR) of biopsy sample.
Further evaluation by sputum examination for AFB and Mantreux test, she had no evidence of acid-fast bacilli in the former and tuberculin test was negative. She was treated with CAT-1 anti-tubercular drug (ATD) therapy with extended continuation phase up to one year of therapy. She responded well in ATD and appetite improvement and weight gain was noted within two wk of therapy. She was followed up clinically as well as by USG and LFT at eight wk, 16 wk, six months and one year after starting therapy. She was completely asymptomatic after 8 wk of anti-tubercular therapy. The lesion was gradually reduced in size and vanished at six months. After one-year completion of ATD, she had no symptoms, no liver function abnormality and no evidence of tuberculous lesion.


An 8-year-old boy presented with pain in his left hip joint that had persisted for several months. His height was 112.5 cm (−2.93 standard deviation), and his weight was 21.5 kg, from which body mass index was calculated to 67.1 percentile for age and sex. His growth had started to slow at 4 years of age (Fig. ). He presented with hirsutism, dry skin, and bradycardia. Hip joint radiography revealed Trethowan’s sign bilaterally in the frontal view and a posterior tilting angle of 34° on the left side and 25° on the right side in the Lauenstein view (Fig. ). Magnetic resonance imaging (MRI) of the hip joint showed separation of the proximal metaphysis of the femur. Based on these findings, the patient was diagnosed with chronic bilateral SCFE (mild on the right side, moderate on the left side).
Blood tests revealed hepatic dysfunction and hypercholesterolemia, with a very low free thyroxine level of 0.10 ng/dl and a very high thyroid-stimulating hormone (TSH) level of 1789 μIU/ml. The anti-thyroid peroxidase antibody level was >600 IU/ml, and the anti-thyroglobulin antibody level was 1720 IU/ml. At the age of 8 years 7 months, the bone age (assessed by the Tanner–Whitehouse 2 radius, ulna, short bones method) was 3 years 4 months. Ultrasonography showed marked atrophy of the thyroid, and color-flow Doppler sonography revealed decreased thyroid blood flow. Cardiac ultrasonography disclosed slight retention of pericardial fluid. MRI scans of the head showed that the anterior lobe of the pituitary gland was enlarged to a height of 17 mm. Although the pituitary gland displaced the optic chiasm superiorly, there were no visual acuity or field abnormalities. Hyperplasia of the anterior lobe of the pituitary gland caused by the overproduction of TSH was suspected. Therefore, atrophic thyroiditis was diagnosed.
For SCFE treatment, the patient was admitted and kept at rest, with the lower limbs in traction. Oral levothyroxine therapy was initiated with a low dose, followed by gradual dose increases. About 2 months later, the free thyroxine levels had increased to the normal range. In addition, the hirsutism, dry skin, and bradycardia had diminished, and his growth velocity had improved. MRI scans of the head showed reduction of the swollen pituitary gland. An arginine stimulation test (0.5 g/kg infused intravenously over 30 min) showed a normal growth hormone response (peak 7.26 ng/ml). Also, a human corticotropin-releasing hormone stimulation test (1.5 μg/kg infused intravenously) showed a normal adrenocorticotropic hormone response (peak 48.4 pg/ml) and cortisol response (peak 14.4 μg/dl). After 2 months of thyroxine treatment, the patient’s thyroid levels had stabilized, at which time surgery was performed for bilateral SCFE.
The CARE guidelines were followed in this case.


A healthy and athletic 62-year-old right-handed male with no previous history of shoulder pain sustained a direct fall on his right side during a skiing accident. He developed an immediate loss of active range of motion. A fracture was ruled out on standard radiographs, and the patient was referred two months later to a specialized shoulder clinic. On clinical examination, anterior active elevation was limited to 100 degrees, whereas passive motion was complete. Posterosuperior rotator cuff testing was deficient []. Magnetic resonance arthrography (MRA) revealed a complete lesion of the supraspinatus tendon at the musculotendinous junction () with associated muscular edema [].
The lesion did not fill the usual and undermentioned radiological Fosbury flop criteria [] but had a unique pattern; the lesion corresponded to a musculotendinous junction lesion of the rotator cuff [] that flopped on itself and healed on the anterior humerus and coracoid process ().
The medial muscular stump had a grade 3 retraction according to Patte [] and a grade 1 fatty infiltration according to Goutallier, supporting the traumatic nature of the lesion. An arthroscopy was performed three months after the trauma and confirmed the MRA aspect of the supraspinatus tendon lesion ().
A release was done but unfortunately it was impossible to reattach the tendon on the muscle. Therefore, a simple debridement and a tenotomy of the long head of the biceps were performed. The patient was allowed to move his shoulder freely the day after the surgery. The patient recovered active motion in elevation three months after the surgery. At one-year follow-up, the pain decreased by 6 points from 8 points at baseline to 2 points on the pain visual analog scale, active anterior elevation improved to 150 degrees (versus 160 degrees on the other side), active external rotation was 50 degrees and symmetric, and internal rotation was slightly limited to L1 versus T10 for the other side. The constant [] and the SSV [] scores improved from 21 and 20 points preoperatively to 74 and 80 at one year, respectively.


A 77-year-old Caucasian male with a past medical history of hypertension, vitamin D deficiency and paroxysmal atrial fibrillation presented to primary care clinic with a 2-week history of bilateral lower extremity edema, two months after completing 4 monthly intravitreal injections of bevacizumab for ARMD. Past surgical history was remarkable for a right hip replacement. Home medications included hydrochlorothiazide, cholecalciferol and lisinopril with no known drug allergies. Social history was remarkable for a 30-pack-year tobacco smoking, and no alcohol or illicit drug use. Vital signs were notable for a blood pressure of 187/91 mm Hg. Physical examination revealed significant bilateral lower extremity edema up to the thighs. Work up which included complete blood count (CBC), comprehensive metabolic panel (CMP), lipid panel, and echocardiography returned within normal limits, except for albuminuria of 491 mg/dL. Metoprolol and furosemide were added to patient’s medication regimen. Five months after presentation, patient was referred to nephrology clinic and laboratory testing was notable for urinalysis revealing 3 red blood cells/high power field (RBC/HPF), 24-hour urine protein of 8.6 g, and serum creatinine of 1.2 mg/dL. A percutaneous renal biopsy revealed mild focal increase in mesangial matrix, minimal interstitial fibrosis, scattered lipid droplets in proximal tubular epithelial cells and on silver-jones staining capillary basement membrane was thickened with spikes. On immunofluorescence, there was 3+ diffuse global granular glomerular basement membrane staining. On electron microscopy, there was global basement membrane thickening with subepithelial electron-dense deposits (immune complexes) with intervening basement membrane (spikes), widespread visceral epithelial foot process effacement, and a mild increase in mesangial matrix. The findings were consistent with membranous nephropathy (). Viral hepatitis panel, total complement activity (CH50), C3, C4, anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), serum and urine protein electrophoresis were all within normal limits. Computerized tomography (CT) scan of the chest and colonoscopy were unremarkable, and prostate-specific antigen (PSA) was elevated at 7.5 ng/mL. During follow up, random urine protein-to-creatinine ratio declined to 2 g/g and later to 0.56 g/g at 7 and 10 months, respectively () with subsequent improvement in his lower extremity edema. Serum blood urea nitrogen (BUN) and creatinine remained within normal range throughout the course of illness. Patient did not require any treatment with steroids or immunosuppressant therapy.


A 55-year-old Chinese Singaporean man with a background of Polycythemia Rubra Vera (PRV), currently on treatment with hydroxyurea and anagrelide, diabetes mellitus, and hypertension, was admitted with a four-day history of nonbilious, nonbloody vomiting accompanied with nonbloody diarrhea. This was associated with fever and also left leg pain and swelling. He had no other infective symptoms including cough, sputum production, or dysuria.
Physical examination revealed pyrexia (temperature: 38.9 degrees Celsius), blood pressure of 140/60 mmHg, and pulse rate of 80/min. His left calf was erythematous, swollen, warm, and tender. His abdomen was soft and nontender with no bruits. No pitting oedema was present. Routine blood investigations showed normal inflammatory markers and biochemistry (). Ultrasound of the left lower limbs showed thrombosis of the left posterior tibial vein. Blood and stool cultures on admission grew Group C Salmonella.
He was started on intravenous ceftriaxone and subcutaneous low molecular weight heparin (LWMH) for deep venous thrombosis.
However, he had persistent fever and became hypotensive on the 10th hospital day. Repeat blood cultures grew Group C Salmonella, but repeat stool culture grew Group B Salmonella. Transthoracic echocardiogram showed no evidence of vegetation. Computed tomography (CT) aortography did not reveal aortitis.
Magnetic Resonance Imaging (MRI) of the left lower limb was performed. It showed a multiloculated collection with enhancing rim and septa centered within the tibialis posterior muscle, measuring approximately 13.9 × 4.4 × 4 cm with adjacent myositis and fasciitis (Figures , , , , and ).
He was referred to orthopaedics for incision and drainage. Intraoperatively, a multiloculated intramuscular abscess in posterior tibialis muscle was observed; 15 mls of frank pus was drained. Two drains were inserted, with the inferior drain at the residual space of the posterior tibialis muscle and superior drain into the space between the posterior tibialis and soleus. Intraoperative pus culture grew Group B Salmonella.
His condition improved dramatically following the drainage with resolution of pyrexia and hypotension. IV ceftriaxone was continued for a total duration of six weeks with oral metronidazole. LWMH was administered for six weeks as well. He remained well six months after discharge.


An 18-year-old unmarried young Asian female came through the emergency department (ER) with a history of hematemesis for last twenty-four hours. The patient reported that this was the third episode of hematemesis in one day. She was managed in ER for non-variceal upper gastrointestinal bleeding (UGIB) with fluid support and urgent transamine injections. Her blood pressure was 100/60mm Hg and pulse were 100 per minute. After stabilization, she was transferred to the inpatient ward for further investigation and management.
On examination, the patient was in acute distress due to her recurrent bleeding episode. She had elicited tenderness on palpation in right upper quadrant (RUQ) and left lower quadrant (LLQ) of her abdomen. Rest of the physical examination is unremarkable. Her weight was 45kg and height was 162.5cm. She had never been to school and her education took place at home by her family.
Previously, she had severe headaches with 8/10 in intensity for three months. She had a computerized tomography (CT) scan done two months ago for her headache in a different hospital where she was admitted due to her complaints of a headache and blurry vision. She further claimed that CT scan showed the blood clot in her head and she was taking a blood thinner (unknown anti-platelet agent) for it. The patient was unable to present the reports when a physician asked for it. She took a blood thinner which was available over the counter (OTC).
According to her, she had first episode of bleeding from the ear when she was two years old. She never had any bleeding episode afterward. She had menarche at an age of thirteen years and she had regular menstruation and reported the use of one pad per day for four days every month. For last three months, she had menometrorrhagia and she also had watery discharge along with it. Complete work up for bleeding disorders (bleeding time, prothrombin time, quantiative analysis of platelets) and serology (autoimmune disorders) ordered came back normal.
Later, the patient also mentioned about seizure episodes associated with her menses. She told that she had three to four episodes of generalized tonic-clonic (GTC) seizures, each lasting for 10-15 minutes. Her last event of seizures was in the emergency department. The event was not witnessed by anyone (physicians, nursing staff or family member). She experienced a severe postictal headache in the frontal region.
She got symptomatic relief in a headache with acetaminophen. Upon admission, baseline labs were ordered including complete blood count (CBC), basic metabolic panel (BMP), liver function test (LFT), complete bleeding profile, antinuclear antibody (ANA), electroencephalogram (EEG), electrocardiogram (ECG), chest X-ray (CXR), stool detailed report and urine detailed report was ordered. All her tests came back normal.
She again had an episode of upper gastrointestinal bleeding on the third day of admission. This time patient had fresh blood on her shirt. This event was concerning for the possibility of a qualitative platelet defect or a rare collagen disorder. She underwent qualitative analysis which did not show abnormalities on Adenosine 5’- diphosphate (ADP) and collagen test. The patient was evaluated by a gastroenterologist and had an esophagogastroduodenoscopy (EGD) which showed mild gastritis. In addition, a viral panel (Hepatitis B and Hepatitis C) and a CT scan of the abdomen and the chest were non-suggestive of any pathology.
The patient was given omeprazole oral tablets twice a day and was managed symptomatically. Next day she had blood in tears as shown in figure #1 which was an alarming symptom and raised the concern of haemolacria secondary to ophthalmological disorder. Ophthalmology consult was made and after ruling out every serious possibility like trauma, tumors, etc., she was put under close surveillance for haemolacria episode. On the same night, she bled again from eyes with each layer of bloody tears coming from eyes. She also mentioned blood oozing from nipples and vagina. Repeat physical examination was done and a bottle was found beneath her bed which she refused to give initially and kept insisting that the bottle has medications. Upon opening the bottle, a nurse found blood in it which she said she collected from her nipples. There was no mark of any fresh or dried blood on a body orifice and her breast examination was also satisfactory.
On her sixth day of admission, the patient complained of continuous chest pain and she said she had it for three to four times per week since last three years. She added that she forgot to address it on the day of admission. Chest pain was sharp in quality and diffuse in nature. ECG had no acute changes. When asked about any previous episodes of chest pain, she told that she had an episode before and that always relieved by getting some fresh air.
On the eighth day of admission, the patient complained about dribbling of urine since eight months. According to her, she used to take bath five times in a day. But on examination, she had not changed her clothes since admission. On observation, she was in acute distress and in severe need of any kind of management. Patient demanded medical or surgical treatment to relieve her different symptoms. She was from the low socioeconomic group and family was concerned about her illness and prompt treatment. They had incurred a huge financial loss for last eight months in seeking medical opinions about her various conditions. She was given different treatments but none of them ever helped.
Such plausible and fabricated medical history raised our concern for a psychiatric consult. After having a long session individually with the patient alone and then with her relatives revealed the fact that she was the only female in her family and therefore; the center of attention and care. Our psychiatrist advised close camera surveillance and vigilant observation of the patient after getting consent from the family. It was found patient used that bottle of blood as a source for her tears. They counseled family members about her symptoms in detail and advised to keep her occupied in different activities with paying less attention to her complaints. A conclusive diagnosis of Munchausen syndrome was made after a detailed assessment. We discharged her after one week and followed-up with serial cognitive behavioral therapy (CBT) sessions.


A 27-year-old man was referred to our hospital after presenting with hemoptysis. Plain radiography revealed right hilar anomalies. A chest CT scan demonstrated consolidation in the right lower lobe, and congenital lung and vascular anomalies, including bronchial malformations (tracheal bronchus), abnormal pulmonary venous drainage (triple-arched vein connecting the superior and inferior pulmonary veins with partial drainage into the inferior vena cava), and a systemic and numerous arterial supply to the right lower lobe from the abdominal aorta through the diaphragm (Fig. ). In light of his clinical presentation, we elected to perform semi-emergent surgery.
We quickly planned the operative procedure using 3D images and virtual bronchoscopy, constructed from enhanced thin-slice CT images using computer software (Aquarius iNtuition Client Viewer; TeraRecon, Inc., Tokyo, Japan), which clearly showed the unique vascular and bronchial anatomy of this patient. In particular, the abnormal pulmonary veins were running in disorder, penetrating multiple lobes. Although pneumonectomy appeared to be the first-choice operation, careful examination using 3D images indicated that the right upper lobe could be preserved safely (Fig. c). We decided not to preserve the middle lobe because of the risk of thrombus development in the abnormal vein and resultant systemic thromboembolism. Demarcation of the relatively well-developed interlobar fissure also was helpful to ensure a safe approach to the interlobar vascular structures, although the locations of the fissures also were abnormal (Fig. a, b).
Surgery was performed by complete VATS. Intraoperative findings included a hypoplastic right pulmonary artery, complex anomalous lobulation, and anomalous venous return with veins bridging the diaphragm. All of these intraoperative findings were consistent with the preoperative 3D images, allowing for safe completion of the right middle and lower lobectomies. The postoperative course was uneventful and the clinical course remained uneventful at the 2-year follow-up visit.
Congenital pulmonary venolobar syndrome is characterized by combined lung and vascular anomalies. In cases involving large abnormal draining veins, such as “meandering veins,” conventional open thoracotomy or median sternotomy often is required [, ]. Conversely, if possible, excessive operative procedures, such as pneumonectomy, should be avoided. Accurate preoperative evaluation is important to determine the most suitable surgical approach.
Several articles have reported the feasibility of 3D imaging in patients with congenital lung disease []. Most congenital lung malformations are diagnosed in adulthood, but can be treated effectively with minimally invasive surgical techniques []. From the viewpoint of minimally invasive surgery, preoperative evaluation is the most important factor in patients with congenital lung malformations. Preoperative pulmonary angiography and evaluation of the pulmonary-to-systemic flow ratio (Qp/Qs) may have use in revealing vascular abnormalities [, ]; however, this approach was considered to be unnecessary as long as the abnormal connection between the systemic and pulmonary circulation is identified and surgically excised.
Instead, as reported previously [], we used 3D–CT and virtual bronchoscopy as preoperative evaluation to familiarize ourselves with the anatomy of our particular patient (Figs. , ). Moreover, by accurately accessing the vascular anatomy and lobulation of the lung, we preoperatively decided to preserve the upper lobe while considering the risk of systemic thrombosis, which might have occurred if we had preserved the abnormal drainage veins, particularly in the middle lobe in this case. Additionally, this meticulous preoperative assessment allowed us to safely approach the interlobar pulmonary tissue through the abnormal interlobar fissure (Fig. c, d). As a result, we were able to safely and confidently accomplish complete VATS as if we had been very familiar with this unusual anatomy. Such an approach utilizing 3D–CT would be useful not only in open surgery as well as in VATS.


Patient A, a 9-year-old boy, was sent to the emergency department of our hospital because of fever, jaundice, and dark urine. On the day of presentation, he appeared increasingly icteric and had a mild fever. He is a Syrian refugee and resided with his aunt and two nieces in the nearby asylum seekers center. Since his biological mother was still staying in Syria and his biological father had died, his medical history was largely unknown. Physical examination showed a moderately ill boy, who was very icteric with pale mucous membranes. His blood oxygen level was 81%, which did not improve with 100% oxygen and he had a tachycardia. His urine appeared black and foamy; further physical examination showed no abnormalities. Additional laboratory tests were performed, yet the results were difficult to interpret as a result of severe hemolysis. His hemoglobin (Hb) was 4 mmol/L (normal 7.4–9.0 mmol/L), reticulocytes were 21 × 109/L (normal 25–120 × 109/L), platelets were 288 × 109/L (normal 150–450 × 109/L), indirect bilirubin was 90 μmol/L (normal 3–21 μmol/L), haptoglobin was 0.16 g/L (normal 0.3–2 g/L), and direct antiglobuline test (DAT/Coombs) was negative. A stained blood smear showed no malaria parasites. Based on these results, we diagnosed an acute hemolytic anemia, which was most likely not immune-mediated (DAT negative).
Upon further inquiry, he was found to have eaten fava beans 3 days before, suggesting an underlying glucose-6-phosphate dehydrogenase (G6PD) deficiency as the cause of this hemolytic crisis. He was admitted to the pediatric department for further analysis and treatment. He was treated with a red cell transfusion, leading to both clinical and hematological improvement. Analysis of G6PD levels demonstrated a markedly reduced glucose-6P-dehydrogenase enzyme activity in erythrocytes (0.1 IU/g Hb, normal 3.8–5.9 IU/g Hb) in fluorescent spot test.
Since G6PD deficiency is a hereditary disorder, we asked about the welfare of the patient’s family members. Patient B, a 6-year-old girl (niece of patient A), was becoming increasingly icteric and also produced dark urine, after having the same fava-bean dinner. She had no physical complaints and had always been healthy. Physical examination showed a mildly icteric girl with normal vital parameters, who also produced dark urine. Further physical examination showed no abnormalities. She had a mild hemolysis, most likely due to G6PD deficiency. Diagnostic tests were performed, followed by clinical observation and no therapeutic interventions. She turned out to be a heterozygous carrier of G6PD deficiency based on a reduced glucose-6P-dehydrogenase enzyme activity in erythrocytes (2.7 IU/g Hb, normal 3.8–5.9 IU/g Hb) in fluorescent spot test.


In early March 2017, the Nephrology service was consulted to see an overweight 83-year-old female patient admitted to the Hospitalist service a week earlier with dyspnea and volume overload from symptomatic heart failure complicated by rapid ventricular response atrial fibrillation, against a background history of hypertension and stage 3 CKD. Other pertinent past medical history include hypertension, sarcoidosis, COPD, atrial fibrillation and type 2 diabetes mellitus. A month earlier, she was discharged after 5 days with symptomatic hypotension and dizziness associated acute kidney injury with peak creatinine of 2.21 mg/dL, and then associated with UTI that was treated with Bactrim. At the time she was also on Lisinopril, which was then discontinued. Subsequently following conservative management in the hospital, kidney function as measured by the serum creatinine had returned to near baseline of 0.96 mg/dL at discharge.
This time in March 2017, she had become increasingly short of breath and hypotensive as well and serum creatinine had risen back up again to as high as 1.79 mg/dL at the time of the Nephrology consultation. Temperature was 36.9 °C, heart rate 67 per/min, respiratory rate 18 per/min, oxygen saturation 90% on room air, and blood pressure was 106/60. She weighed up to 75.4 kg, height was 163 cm, with a BMI of 28.4 kg/m2. She was dyspneic, JVD was elevated, with 2+ bilateral extremity edema and reduced breath sounds in both lung bases bilaterally, with bibasilar inspiratory rales evident posteriorly. Admission chest radiograph showed cardiomegaly, new bilateral pleural effusions, pulmonary vascular congestion and hypoventilation. Echocardiogram revealed normal left ventricular systolic function with ejection fraction of 64%, mild mitral valve regurgitation, bi-atrial enlargement, normal right ventricular function with right ventricular systolic pressure of 29 mmHg. At the time of this consultation, serum albumin was 2.8 g/dL, sodium was 134 mmol/L, potassium 3.6 mmol/L, chloride 94 mmol/L, bicarbonate 24 mmol/L, calcium 8.9 g/dL, hematocrit 24.9%, WBC, platelets, TSH, Free T4, AST, ALT and total bilirubin were all normal. Pro Pro B Naturetic Peptide level that was elevated at 581 pg/mL on 2 February 2017 had rapidly escalated to 4907 pg/mL by 23 February 2017, three weeks later, just prior to this admission (Pro Pro B Naturetic Peptide reference range ≤ 450 pg/mL).
Earlier in the admission, she was started on intravenous amiodarone for rate control of atrial fibrillation. Furthermore, oral Diltiazem, 120 mg three times a day, was subsequently discontinued when she became hypotensive. She had been started on continuous intravenous Furosemide infusion at 10 mg/h but the previous 24-h urine output was only 1500 cc.
We doubled the dose of intravenous continuous infusion of Furosemide to 20 mg/h and added intravenous Chlorothiazide 500 mg every 12 h. The chlorothiazide was discontinued after one dose when the patient raised concerns for a history of drug-induced pancreatitis. We then increased the dose of intravenous Furosemide to 25 mg/h, added daily intravenous Albumin 25 gm infusion to run concurrently with the continuous Furosemide infusion because of severe hypoalbuminemia. The edematous legs and feet were elevated and wrapped with ACE wraps. Overnight, urine output had more than doubled to 3450 cc (). Subsequently, twenty-four urine output increased to over 3–4 L (). After 5 days of the Furosemide infusion, she was switched to oral Bumetanide 2 mg twice daily. She continued to make urine in excess of 2.5 L an day and was discharged after another two days, much improved with edema, dyspnea and orthopnea resolved, together with significant weight loss (). She had achieved a weight loss of 12 kg during the last nine days of the admission. Her serum creatinine trajectory also improved during the second half of this admission and serum creatinine at discharge was 1.29 mg/dL ( and ).


In mid-May 2017, an 84-year old Caucasian male was readmitted to our hospital, after two months, from a Nursing Home with worsening shortness of breath, orthopnea, and inability to get around his assisted living facility despite the use of 24/7 nasal cannula oxygen at 2 L/min. Past medical history was significant for severe oxygen-dependent COPD in an ex-smoker, chronic diastolic heart failure, obstructive sleep apnea, type II diabetes mellitus, atrial fibrillation, hypertension, tricuspid regurgitation, cor pulmonale with worsening pulmonary hypertension, previous coronary artery bypass and chronic kidney disease stage IIIB with serum creatinine of 1.93 mg/dL (eGFR = 33 mL/min/1.73 sq. m BSA in late March 2017). Outpatient medications included Metoprolol 25 mg twice daily, insulin and Torsemide 10 mg twice daily. In the Emergency Department, his oxygen saturation was 87% on 2 L per minute nasal cannula oxygen. Temperature was 36.4 °C, pulse was 76/min, respiratory rate 22/min and BP was 120/87. His oxygen saturation improved to 97% on high flow oxygen. He weighed 75 kg, height was 193 cm, with a BMI of 20.1 kg/m2. Jugular venous distension was present and he had bilateral pitting pretibial edema. The lungs revealed bilateral basal inspiratory crepitations. Hemoglobin was 13.3 g/dL, Pro B Naturetic Peptide level was grossly elevated at 38,547 pg/mL (<450), from a level of 16,711 pg/mL in January 2017 (Pro B Naturetic Peptide reference range ≤ 450 pg/mL). Simultaneously, the serum creatinine had increased from a baseline of 1.65 mg/dL in January 2017 to 3.09 mg/dL (). Other pertinent laboratory indices were chloride 91 mmol/L, bicarbonate 31 mmol/L but with otherwise normal other electrolytes. Chest radiograph revealed cardiomegaly, hypoventilation, bibasilar atelectasis and pulmonary vascular congestion. On echocardiogram, the left ventricular function was preserved at 55–60% but the right ventricular systolic pressure had risen from 64 mm Hg in December 2016 to 72 mm Hg in mid-May 2017, together with severe right atrial enlargement.
He was started on continuous infusion Furosemide at 20 mg/h, together with concurrent intravenous Chlorothiazide 500 mg every 8 h. Overnight, in just over 12 h, he had made 1.8 L of urine with only 207 cc as intake. Over the next two days, diuresis continued with increasing urine output () and decreasing weight (). He continued to improve and by the third admission day, both intravenous diuretics were discontinued. Leg edema had resolved, dyspnea had stabilized and serum creatinine had continued to improve ().
He was switched to oral Torsemide, 20 mg twice daily, together with oral Metolazone, 2.5 mg every other day, as an adjunct diuretic agent. Foley catheter was removed and he was discharged much improved to the Nursing Home. Nevertheless, two days after his discharge to the Nursing Home, he became increasingly weak, despite improved dyspnea and still improving kidney function. The patient at this point, with the support of the family, in view of all the concurrent comorbidities, opted for hospice care and he peacefully passed away about a week afterwards.


A morbidly obese 62-year old Caucasian male patient was transferred from a Nursing Home in June 2017 by ambulance with worsening dyspnea, oxygen desaturation of about 70% and hypotension to our Emergency Department. Past medical history was significant for morbid obesity, likely sleep apnea, chronic hypercapnic respiratory failure from COPD, peripheral vascular disease, venous insufficiency, generalized debility, preserved left ventricular ejection fraction of 72%, and hypertension with early stage II CKD, with baseline serum creatinine of less than 1 mg/dL. Pertinent outpatient medications included potassium chloride 40 mEq twice daily, spironolactone 25 mg daily which was started two days before this admission, Furosemide 20 mg twice daily, Duonebs, baby Aspirin, Gabapentin 600 mg twice daily, Oxycodone 10 mg extended release twice daily, pantoprazole and Atorvastatin. The patient had undergone an aortogram with run off followed by a left lower extremity angioplasty for a high-grade proximal left femoral-popliteal bypass in situ vein stenosis two days prior to the admission—he had required temporary intubation for this procedure that was otherwise successful and without other complications.
Initial blood pressure was 88/63, pulse 71/min and oxygen saturation quickly improved to 99% on BIPAP. He weighed 133.5 kg, height was 190 cm, with a BMI of 36.84 kg/m2. He had 2+ bilateral lower extremity edema, and chest examination revealed reduced breath sounds with bibasilar inspiratory rales heard posteriorly. Serum creatinine was 3.14 mg/dL, a significant increase from a week previously (). Other pertinent laboratory indices were serum potassium 7 mmol/L, serum bicarbonate 27 mmol/L, phosphorus 7.1 mg/dL with a normal anion gap of 13 mmol/L. He was in respiratory acidosis and respiratory failure with arterial blood gas pH of 7.18, pCO2 of 84 mm Hg, and bicarbonate of 30 mmol/L. His Pro B Naturetic Peptide level that was nearly normal in August 2016 at 151 pg/mL was grossly elevated at 1426 pg/mL in mid May 2017, and had further escalated to 5503 pg/mL on the day of admission in June 2017 (Pro B Naturetic Peptide reference range ≤ 125 pg/mL). There was in addition, mild rhabdomyolysis with total CK of 1720 U/L, ALT was normal at 17 U/L but AST was mildly elevated at 54 U/L. Lactic acid was normal. EKG was abnormal but the first degree AV block, possible inferior infarct and prolonged QT interval were not new and T waves were not prominent. Chest radiograph revealed worsening cardiomegaly when compared to October 2016, hypoventilation, pulmonary vascular congestion and basal atelectatic changes without overt infiltrates evident. Echocardiogram was not available. He received two 500 cc boluses of normal saline and his blood pressure stabilized with SBP > 120 mm Hg. Other emergent therapies for the hyperkalemia included Ipratropium-Albuterol nebulizer treatments, two ampoules of intravenous Dextrose 50 (25 gm each) infusions, intravenous regular insulin and oral Kayexalate, 15 gm in 60 mL given once [].
Nephrology service was consulted. Evaluation confirmed gross 2+ to 3+ bilateral lower extremity edema, ascites, anasarca with reduced breath sounds with bibasilar inspiratory rales heard posteriorly. A Foley catheter was inserted due to evidence of urinary retention. The working diagnosis was contrast-induced nephropathy, further complicated by severe dyspnea likely the combination of chronic obstructive pulmonary exacerbation, narcotic/Gabapentin toxicity, with volume overload and diastolic congestive heart failure, given an otherwise normal echocardiogram in August 2016 with left ventricular ejection fraction of 72%. Spironolactone, Oxycodone, Gabapentin and potassium chloride were promptly discontinued. Continuous intravenous Furosemide infusion was started at 20 mg/h together with concurrently administered intravenous Chlorothiazide 500 mg every 8 h, and serum creatinine and electrolytes were monitored every 6 h. In addition, oral Doxycycline for longstanding cough and discolored sputum production, together with oral Prednisone and inhaled steroids were added later during the admission. He also went back on the BiPaP machine, which had been discontinued by the patient some months earlier for unclear reasons.
Overnight, the patient exhibited a very prompt, excellent and sustained diuresis with the combination diuretic regimen as he made nearly 10 L of urine the first admission day (). He felt much better, was off the BiPaP during the day, was less dyspneic and leg swelling was significantly reduced bilaterally. His weight quickly dropped, and the serum potassium was normalized about 15 h into the admission and continued to decrease thereafter ( and ). Simultaneously, serum bicarbonate had risen sharply, a reflection of contraction alkalosis. Moreover, hyperphosphatemia improved concurrently with acutely falling serum creatinine values ( and ).
By day 3, he was feeling so much better that intravenous diuretics were discontinued and he was switched to oral Furosemide 40 mg 2 times a day together with oral Metolazone 2.5 mg daily with continued monitoring of intake/output and daily chemistry. The Foley catheter was also discontinued. He continued to improve, lost more weight with loss of anasarca and edema fluids and was discharged after 5 days on the combination oral Furosemide 40 mg twice daily (double the preadmission dose) and oral Metolazone 2.5 mg daily (a new additional diuretic). At discharge, four days later, serum creatinine had fallen to 1.32 mg/dL, phosphorus was normal and he needed potassium supplements for hypokalemia. Besides, the serum bicarbonate was beginning to trend towards normal levels again (). Discharge medications included Prednisone taper and he was to complete five days of oral Doxycycline. Lisinopril and Spironolactone remained discontinued at the time of the discharge. He was seen the following week at follow up, in the Nephrology office, on 12 June 2017, much improved, and his weight had come down from a peak of 327 lb to 293 lb, serum creatinine was down to 1.05 mg/dL and he was requiring more potassium chloride supplements, on the same dose of Furosemide (40 mg twice daily) and Metolazone (2.5 mg daily), together with Spironolactone that was reintroduced by his Internist sometime after discharge, at a lower dose of 12.5 mg daily.


A 58-year-old woman presented with a slow-growing multilobulated plaque on the left proximal arm of approximately 2 years' duration. The lesion was asymptomatic with no history of ulceration or discharge. There was no history of preceding trauma. The patient was otherwise in good health. Family history was noncontributory.
Physical examination revealed a soft, skin-colored, multilobulated, nontender, well-defined, discrete, dome-shaped plaque on the left lateral proximal arm adjacent to the axilla (). There was no axillary lymphadenopathy. There was no comedo-like lesions, café au lait macules, or hypertrichosis on the surface of the lesion. The rest of the physical examination was normal.
Excisional biopsy of the lesion showed islands of mature adipocytes in the papillary dermis, confirming the clinical diagnosis of nevus lipomatosus superficialis ().


A 59-year-old male presented to the emergency department complaining of a 3-day history of suprapubic pain and macroscopic hematuria. The patient denied fever or dysuria. His physical examination was unremarkable, except suprapubic tenderness to palpation. Past medical history was consistent with smoking (30 pack-years, stopped 10 years prior to presentation), morbid obesity (135 Kg), hypertension for 7 years, diabetes mellitus for 15 years, hepatitis C virus (diagnosed during the pretransplant evaluation), and end-stage renal disease (on hemodialysis for 3 years). He received a kidney transplant from a deceased donor five years before the time of presentation. The donor was a 17-year-old male with no evidence of malignancy who died from a head injury. As part of the patient's pretransplant workup, an abdominal ultrasound revealed no kidney masses, but a liver biopsy showed stage 2 cirrhosis. The patient received induction immunosuppression both during and after the transplant that included thymoglobulin (1 mg/kg) and methyl prednisolone (500 mg Intravenous) for three daily doses and basiliximab (20 mg) for two daily doses. He was maintained on steroid-free immunosuppressant therapy consisting of low-dose tacrolimus (12-hour trough level: 6–8 ng/ml) and enteric coated mycophenolate sodium.
In the emergency department, an abdominal ultrasound showed a normal appearing kidney allograft; however, the native kidneys were not properly visualized. For better assessment of the urinary tract, a computerized tomography scan (CT) was ordered. A suspicious heterogeneous mass was noted within the left native kidney that measured 6.0 × 5.5 × 7.3 cm in anteroposterior, transverse, and craniocaudal dimensions (). Those findings were confirmed by MRI of the abdomen, raising the possibility of renal malignancy. No distant metastasis was identified. Consequently, hand-assisted laparoscopic radical nephrectomy was performed a few days later.
Gross examination of the kidney revealed an ill-defined gray tan solid mass present in the middle lower pole of the left kidney, measuring 7.5 × 6.5 × 5.0 cm. The tumor extended into the renal sinus and perinephric adipose tissue with metastasis to a regional lymph node. Histologic examination demonstrated widely infiltrative high-grade adenocarcinoma with variable architectural patterns. Some areas showed solid tumor nests (), while another showed linear and single cell infiltration with prominent desmoplasia (). The tumor cells had marked nuclear pleomorphism, high nuclear : cytoplasmic (N : C) ratio, and prominent nucleoli (). Mitosis was brisk and the Fuhrman nuclear grade was 4 (ISUP/WHO Grade 4) []. The criteria for grade 4 include extreme nuclear pleomorphism and/or sarcomatoid and/or rhabdoid differentiation. In this case, sarcomatoid or rhabdoid component was not found; however, extreme nuclear pleomorphism was identified and characterized the specimen as a grade 4. Immunohistochemistry revealed that the tumor cells retained INI-1. The specimen was also positive for Pax8 and CK7 and negative for GATA3 and p63. Based on these morphologic and pathologic features, a diagnosis of collecting duct carcinoma was rendered. The American Joint Committee on Cancer (AJCC) pathology staging was pT3aN1M0.
The morphologic differential diagnosis included medullary carcinoma and urothelial carcinoma (UC). Medullary carcinoma is usually seen in patients with sickle cell trait, with a different history and patient age. Retention of INI-1 unequivocally ruled out medullary carcinoma. High-grade UC may also have similar morphology, although the absence of p63 and Gata-3 is inconsistent with high-grade UC.
Consequently, his immunosuppression regimen was modified to include sirolimus instead of mycophenolate sodium, as well as the addition of low-dose tacrolimus and oral prednisone. The patient was kept on close metastatic surveillance. Six months later, multiple bilateral pulmonary and bone metastases were noted on follow-up imaging. Cancer progression was confirmed pathologically by CT guided biopsy of the lesions. He was subsequently started on a tyrosine kinase inhibitor (TKI) in the form of sunitinib 37.5 mg daily for 4 weeks on and 2 weeks off as a first-line therapy while his immunosuppression regimen was adjusted to include tacrolimus and everolimus (0.75 mg twice daily). At that time, his kidney function was optimum (serum creatinine 0.6 mg/dl). Palliative radiation therapy was required to control his bone pain. Later, sunitinib was stopped after the development of drug toxicity, which included altered mental status, urinary tract infection, fatigue, anemia, leukopenia, thrombocytopenia, and diarrhea. However, the allograft function remained stable with a serum creatinine of 0.8 mg/dl. Follow-up imaging demonstrated worsening metastatic disease, so palliative care was established.


A previously healthy 47-year-old man presented to the emergency department with a three-day history of shortness of breath, productive cough with yellow sputum, and fevers. He had a 20 pack-year and 25 joint-year history of smoking cigarettes and marijuana, respectively. He denied alcohol use. He had no significant occupational or animal exposures. On examination, vital signs were remarkable for a heart rate of 138 beats per minute, respiratory rate of 23 breaths per minute, and a temperature of 101.4 degrees Fahrenheit. Oropharyngeal exam was remarkable for marked pharyngeal edema and erythema. Chest examination revealed audible stridor, decreased breath sounds over the right hemithorax as well as in the upper half of the left hemithorax and left sided rales. The rest of the examination was unremarkable. Laboratory studies showed leukocytosis of 18,800 WBC/mm3, hemoglobin of 17 g/dl and a platelet count of 262,000 platelets/mm3. Comprehensive metabolic panel, cardiac enzymes, and electrocardiogram were within normal limits. Chest radiography showed a possible right pneumothorax, left sided apical bullae, and bibasilar opacities (Figure ). Computed tomography (CT) of the neck and chest were done and showed retropharyngeal abscess and bilateral bullous emphysematous lung disease with a giant bullous occupying nearly the entire right lung field (Figures -). Echocardiogram showed normal findings. A diagnosis of giant bullous lung disease with emphysema complicated by retropharyngeal abscess was made based on radiographic findings. Broad-spectrum antibiotics were initiated. Blood and sputum cultures grew no organisms. His alpha-1 antitrypsin levels were normal. He developed septic shock and worsening hypoxemia in the following 48 hours and required mechanical ventilation and vasopressors. Antibiotics were escalated to cover Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Repeat CT chest showed worsening left lung consolidation consistent with ARDS (Figures -). He showed no signs of improvement on mechanical ventilation requiring 100% FiO2. ARDS protocol mechanical ventilation was started and an arterial blood gas (ABG) showed: pH 7.27, paCO2 94, and paO2 55. Echocardiogram with bubble study was done to rule out intracardiac shunt as a concomitant cause of hypoxemia and did not show bubbles in the left ventricle. Veno-arterial extracorporeal membrane oxygenation (ECMO) was initiated due to severe refractory hypoxemia, septic cardiomyopathy, and severe metabolic acidosis. Unfortunately, he developed disseminated intravascular coagulation (DIC), went into cardiac arrest and could not be revived.


On routine examination, a 73-year-old male was found to have a prostate-specific antigen (PSA) level of 4.03 ng/mL while on finasteride. The elevated PSA prompted a biopsy that revealed 3 of 12 positive biopsy cores on the left side with Gleason scores of 6 (3+3), 7 (3+4), and 9 (4+5). Staging studies consisting of computerized tomography (CT) scans of the abdomen and pelvis and a bone scan were negative for evidence of nodal or distant metastasis. He was concurrently staged as T1cN0M0 high-risk prostate adenocarcinoma due to the Gleason 9 component.
The patient was started on leuprolide and referred for RT. His past medical history was significant for Crohn’s disease (CD) diagnosed eight years prior with colonoscopy and biopsy confirmation. The patient was generally asymptomatic with intermittent mild diarrhea, no prior history of blood or mucus in the stool, and no medical management for CD.
Given the patient’s history of CD, one week prior to RT, the SpaceOAR System (Augmenix; Waltham, MA) was utilized. SpaceOAR is a polyethylene glycol hydrogel that is injected into the perirectal fat and solidifies into an absorbable spacer that separates the prostate and the anterior rectal wall. Prior to spacer insertion, fiducials were placed. The hydrogel was then injected via transrectal ultrasound (TRUS) guidance with no perioperative complications and yielded a roughly 1.14 - 1.21 cm space between the anterior rectal wall and the prostate (Figure , Figure ).
Radiation Therapy
The patient was treated in the supine position with RT delivered to both the prostate and seminal vesicles via volumetric modulated arc radiotherapy (VMAT) (78 Gy/2 Gy fractions at a 100 percent isodose line with two full arcs and 10 MV photons) with an Elekta Infinity linear accelerator (LINAC) (Elekta AB; Stockholm, Sweden). A Pinnacle treatment planning system (Phillips Radiation Oncology Systems; Fitchburg, WI) was utilized. Figure outlines the dose distribution of the RT plan.
A dose volume histogram (DVH) that compares rectal irradiation for a VMAT plan with a rectal spacer as against without a rectal spacer can be seen in Figure . A diagnostic CT scan was utilized to simulate the VMAT plan without a rectal spacer for the same patient.
Notably, the maximum dose (Dmax) received by the rectum was 60.4 Gy with spacer placement as compared to 78.7 Gy without the hydrogel spacer, with dosimetric benefits most evident at higher doses. A more detailed comparison of toxicity to the rectum can be found in Table . Of note, given that the VMAT plan without the spacer was simulated using a diagnostic CT, no bowel prep was utilized and this may be responsible for the differing isodose lines and, subsequently, the relatively higher doses received by larger rectal volumes with the rectal spacer.
Toxicities
Over the course of treatment, RTOG Grade 1 GI toxicities of mild diarrhea with no associated pain or cramping were noted during the fifth and sixth weeks. RTOG Grade 1 GU toxicities of mild decreases in urinary stream were also reported during the third week of treatment, which resolved with tamsulosin at subsequent follow-ups.
One week following the completion of treatment, the patient reported an RTOG Grade 1 GI toxicity of mild diarrhea. At the 3, 6, 9, and 12-month follow-ups, bowel movements were reported as being back to baseline, and the patient's urinary stream was intact following discontinuation of tamsulosin with no other GU symptoms reported. PSA levels of 0.18 ng/mL and 0.03 ng/mL were noted at the three-month and nine-month follow-ups, respectively.


A 52-year-old man with history of hypertension developed sudden epigastric pain after dinner. Physical examination showed epigastric tenderness without guarding. His white blood cell count was 16,100 /μL, and his C-reactive protein concentration was 0.17 mg/dL. Abdominal contrast-enhanced CT revealed a low-attenuated area around left gastric artery (LGA) (Fig. a and b arrows) directly arising from the abdominal aorta (Fig. a arrowhead) without aneurysm formation or intestinal ischemia. We diagnosed spontaneous dissection without an aneurysm limited to LGA. Follow-up CT 6 days later showed dilatation of true lumen (Fig. a and b arrows).
Spontaneous dissection without an aneurysm limited to LGA is fairly rare. Only four such cases have been reported as LGA dissection; only one was limited to LGA and involved no aneurysm . We found no cases involving the same anatomic variant of LGA as in our case, which occurs in 0.5–15.0% of the general population . There is not marked difference in severity between spontaneous dissection limited to LGA and that of celiac artery, but this anomaly requires precise knowledge of vascular anatomy.
Physicians should be alert to the possibility of this condition in patients with sudden-onset abdominal pain.


A 29-year-old Japanese man with schizophrenia was transferred to our emergency department. On arrival, he presented with shock and coma. His blood pressure (BP) was 57/29 mmHg, heart rate (HR) was 135 beats per minute (bpm), respiratory rate was 40/minute, and his body temperature was 35.6 °C. His Glasgow Coma Scale score was (E1V1M1) 3. We immediately performed intubation because of his shock and coma. Fluid resuscitation of 3000 ml crystalloid temporarily increased his BP to 73/28 mmHg, but his shock still persisted. Before a central venous line was inserted, we tentatively initiated dopamine infusion at 5 μg/kg per minute, which was increased to 10 μg/kg per minute; however, his hypotension gradually worsened to 66/37 mmHg (Fig. ). Sixty minutes after arrival, we inserted the central venous line and initiated noradrenaline infusion at 0.1 μg/kg per minute, which was subsequently increased to 0.3 μg/kg per minute. Moreover, 90 minutes after arrival, we initiated dobutamine at 5 μg/kg per minute. However, his BP unexpectedly decreased to 59/40 mmHg. Head computed tomography, enhanced chest-abdominal computed tomography, point of care sonography, and laboratory data (Table ) did not reveal the cause of coma and hypotension. His systemic vascular resistance index (SVRI) was very low (432 dynes/second/cm/m2; normal range, 1970 to 2400 dynes/second/cm/m2; Vigileo FloTrac™, Edwards, USA). Thus, we suspected unknown distributive shock refractory to a large amount of catecholamine infusion. Therefore, in addition to catecholamine infusion, we initiated vasopressin at 3 U/hour 150 minutes after arrival. Subsequently, his BP markedly improved to 135/45 mmHg. Three hours after arrival, we transferred him to our intensive care unit. We performed continuous hemodiafiltration because of the presence of metabolic acidosis (Table ). We gradually decreased the amount of catecholamine infused. Approximately 12 hours after arrival, his SVRI improved to 2271 dynes/second/cm/m2 and his hemodynamic state became stable: BP, 140/80 mmHg; HR, 95 bpm. Subsequently, we completely terminated catecholamine infusion. Moreover, we terminated continuous hemodiafiltration because his metabolic acidosis was improved: pH, 7.386; partial pressure of oxygen in arterial blood (PaO2), 73.8 mmHg; partial pressure of carbon dioxide in arterial blood (PaCO2), 39.3 mmHg; bicarbonate (HCO3
-), − 1.2 mmol/l; lactate (Lac), 1.5 mmol/l; and fraction of inspired oxygen (FiO2), 0.3. On day 2, we terminated vasopressin infusion. After extubation, his condition was stable: BP, 123/75 mmHg; HR, 100 bpm; and Glasgow Coma Scale score (E4V5M6), 15. He was transferred to our general ward. He admitted to ingesting approximately 150 mg risperidone to attempt suicide. The risperidone concentration in his blood sample on admission was very high (398 ng/ml at admission, recommended therapeutic range, 20 to 60 ng/ml []), which decreased to 3.60 ng/ml on day 2. Consequently, we diagnosed risperidone overdose. Subsequently, his condition was stable without any event, and he was transferred to a psychiatric ward for psychiatric care on day 5.


In early summer of 2016, a 58-year-old woman experienced watery diarrhoea and vomiting. The patient had spent a weekend with her family in the north of Germany. Two days before disease onset, she had eaten poultry liver for lunch and grilled swine meat at an evening barbecue. Other family members also consumed the swine meat, but did not develop any symptoms. The patient's medical history was significant for diabetes mellitus, but no other risk factors. A mild diet led to recovery after 2 days. After shifting to a normal diet, she felt sick again with developing watery diarrhoea. Replacement of diet and symptomatic treatment did not lead to any improvement, and during the next few days she produced mucous stool and suffered from abdominal pain, tenesmus and fatigue.
After 1 week of disease, the patient visited a medical practitioner and a stool sample was analysed in the laboratory. An initial rapid test using the Verigene EP assay (Luminex, purchased from Thermo Fisher) showed a positive result for stx. The test was negative for stx, Salmonella spp., Shigella spp., Campylobacter spp., Yersinia enterocolitica, Vibrio spp., norovirus and rotavirus.Clostridiumdifficile tested negative by single PCR (BD Max; BD). For culture, the stool sample was streaked onto Salmonella–
Shigella-agar, Hektoen agar, Butzler agar, CIN agar and Brilliance E. coli/coliform chromogenic agar (all plates were purchased from Oxoid, Thermo Fisher Scientific). For enrichment of pathogenic bacteria, Gram-negative (GN) broth and selenite broth (BD) were inoculated. On one hand, culture confirmed the negative results of the Verigene assay; on the other hand, E. coli colonies isolated on chromogenic agar did not agglutinate with polyspecific antibody reagents directed against frequent serotypes (Sifin Diagnostics) and tested negative for stx
2 using the RIDAGENE EHEC/EPEC real time multiplex PCR (R-Biopharm). Agglutination and PCR were also performed from the inoculum site using a mixture of colonies. Brilliance E. coli/coliform agar was inoculated again with stool and GN broth samples, and on the following day testing of colonies for stx
2 by PCR was positive for the original stool specimen and GN broth. stx
1 and eae genes were not detected. Agglutination with polyclonal antisera covering 22 O serotypes (O25, O26, O44, O55, O78, O86, O91, O103, O111, O114, O118, O119, O124, O125, O126, O127, O128, O142, O145, O157, O158 and O164) also remained negative. Species identification was performed by MALDI-TOF MS (Vitek-MS) and biochemistry (Vitek-2). The strain was positive for β-galactosidase, β-glucuronidase and sorbitol fermentation. The patient was treated with azithromycin (500 mg day−1) for 3 days and recovered after 2 days without any relapse.


Our case is of a 52-year-old gentleman who presented with restricted tongue movement, dysarthria, and dysphagia that developed progressively over several months. He mentioned this at the Ear Nose and Throat clinic during follow-up of surgical drainage of a mucocele from the pterygopalatine fossa six months before. He also reported 15 kg of weight loss in the preceding four months. He is a nonsmoker with no medical history except for osteomyelitis following a meniscal knee repair four years before.
An MRI showed a 37 × 34 × 42 mm mass in the base of tongue extending to the geniohyoid muscle as well as the genioglossus muscle that was most concerning for squamous cell carcinoma as shown in .
His PET/CT scan showed a large intensely FDG avid tongue mass arising in the posterior of the tongue within the body of the tongue and extrinsic muscles and extending posterosuperiorly into the region of the lingual tonsils and midline tongue superiorly. There was moderate FDG uptake in adjacent nodes consistent with metastases.
Multiple bilateral rounded pulmonary nodules were present within the lungs bilaterally, the largest of which measured 5 mm. These showed no significant FDG uptake and were below the resolution of the PET/CT to accurately characterise.
The lung lesions were too small for biopsy to confirm metastasis; however, it was judged to be metastatic given the rapidly progressive disease and bilateral neck metastases. The tumour was staged as T4N2cM1.
Two tongue biopsies performed were inconclusive; however, the third biopsy a month later showed an infiltrating biphasic tumour with solid nests composed of epithelial and myoepithelial cells as shown in . The tumour cells also demonstrated perineural invasion as shown in . There was nuclear atypia and prominent mitoses present. Tumour cells were positive for SMA, p40, p63, CK5/6, EMA (patchy and luminal), CEA (luminal), and CD43. Ki-67 reveals a high proliferation index (60%). The diagnosis was epithelial-myoepithelial carcinoma with myoepithelial anaplasia.
Subsequently, the patient was offered radical local treatment with radiotherapy and chemotherapy. The patient declined these so as to maximise his quality of life. He was referred to the palliative care service for continued care and over a year later required a percutaneous endoscopic gastrostomy (PEG) tube for feeding. Approximately 18 months after the diagnosis, the patient passed away from obstruction of the airway.


A 48-year-old previously healthy Caucasian female presented with progressive shortness of breath on exertion, right upper quadrant abdominal pain, and left lower extremity pain and swelling. On presentation, the patient was afebrile; however, she was borderline hypotensive, tachycardic, and tachypneic. Laboratory results showed marked leukocytosis (37.3 × 109/L) with predominant neutrophilia and mild thrombocytopenia, as well as acute kidney injury, elevated transaminases with hyperbilirubinemia, and metabolic acidosis. summarizes the relevant laboratory findings. Initial differential diagnosis included sepsis, cholecystitis, or pulmonary embolism. Empiric broad-spectrum antibiotics were initiated immediately. Imaging studies did not show any venous thromboembolism or cholecystitis but revealed hepatomegaly, small lung nodules, and mild axillary lymphadenopathy.
Extensive infectious workup studies including urine culture, blood culture, respiratory virus panel, hepatitis, and HIV were all negative. The peripheral blood smear showed severe neutrophilia with toxic granulation and a small number of atypical lymphocytes (). These atypical cells have an irregular nuclear contour and prominent nucleoli and vacuoles. Hematolymphoid malignancies were added to the differential diagnosis list. Flow cytometric analysis of peripheral blood () revealed a small population of abnormal T-cells, which was positive for CD45 and CD7, but negative for CD2, CD3, CD4, CD5, CD8, CD16, CD56, and CD57. In addition, aberrant CD13 expression was also detected (data not shown). These cells featured increased forward scatter and side scatter, when compared with immunophenotypically normal lymphocytes. While pathological evaluation of the bone marrow was in process, the patient's leukocytosis rapidly worsened and peaked at 110.6 billion/L. She developed multiorgan failure requiring ventilator support, continuous renal replacement therapy, and multiple vasopressors. Her laboratory parameters along her clinical course are shown in . Despite maximum supportive therapy, her condition continued to decline. After extensive discussion, her family decided to pursue comfort care and she expired approximately 80 hours after initial presentation.
The flow cytometric analysis of the bone marrow aspirate () showed a small T-cell population (3.7% of marrow nucleated cells) with identical immunophenotypic features to those in peripheral blood. Bone marrow core biopsy revealed hypercellularity with loose clusters of small to medium sized neoplastic cells, accounting for 5–10% of the marrow cellularity (Figures and ). The immunohistochemistry studies of the core biopsy revealed that lymphoma cells expressed CD30 (strong), CD7 (strong), and ALK (cytoplasmic) (). The expression of epithelial membrane antigen (EMA) appeared to be equivocal. Autopsy showed diffuse microscopic lymphoma infiltration of the spleen (Figures and ), lung (Figures and ), and liver. Intravascular lymphoma involvement was present in both brain and lung (Figures and ). Bone marrow cytogenetic evaluation identified an unusual chromosome 2 inversion [inv(2)(p23q22)] resulting in ALK gene rearrangement, as well as a translocation involving the inv(2) chromosome with chromosome 22q (); however, fluorescence in situ hybridization (FISH) studies demonstrated that the ALK gene was not involved in the translocation with chromosome 22 (). These findings are consistent with small-cell variant of ALCL.