A 70-year-old gentleman with Crohn's disease presented with an incarcerated ventral hernia that required urgent surgical intervention. Following repair, he returned two weeks later with an acutely distended abdomen and early sepsis. Emergent laparotomy revealed a contaminated abdomen with a small bowel perforation in a segment of the bowel in Crohn's disease. He returned to the operating room for exploration and bowel resection and primary anastomosis. The incision was left open due to severe contamination. In the operating room, instillation therapy was initiated with NPWTi-d along with ROCF-CC with normal saline with a 20-minute dwell time and continuous negative pressure at -125 mmHg. ROCF-CC was chosen for the mechanism of action to "fracture" the necrotic debris and perhaps avoid the need for an additional operative intervention. Normal saline was chosen to reduce bacterial burden and contain the cost of care (Figures -).
Following three days of NPWTi-d with ROFC-CC, there was significant wound improvement with increasing granulation tissue and less necrotic debris (Figure ).
However, the patient developed a leak at the anastomosis requiring another emergent operation. During this operation, which was performed as "damage control", the general surgeon and colorectal surgeon agreed it would be best to avoid another anastomosis and the small bowel was delivered to the skin as a controlled fistula.
The wound team and plastic surgery were consulted to assist in managing a contaminated abdominal midline incision and wound with a high-output fistula in a patient who was now critically ill with early sepsis.
The team's approach to the patient was as integrated as the team's approach to the complex wound. "All Hands On Deck!" (Figure ).
The cornerstone of our management was NPWT. Instillation therapy was initiated with NPWTi-d along with ROCF-CC in the operating room with normal saline with a 20-minute dwell time and continuous negative pressure at -125 mmHg (Figures -).
Complex foam application, bridging, and innovative strategies to keep a grossly contaminated wound from becoming the final straw to a patient's demise appeared our greatest challenge. Ostomy paste, rings, colloid, and barriers were utilized. Other items such as infant bottle nipples and condom catheters were also required. The team worked side by side to create dressing strategies to deliver NPWTi in the face of a high-output fistula to control contamination and allow primary healing. Despite the high output, the wounds improved (Figure ).
NPWTi was the cornerstone of our management strategy, wherein every type of foam, bridge, and securement was needed to gain success. As the patient's clinical status improved, he was transitioned from total parenteral nutrition (TPN) to an oral diet. However, the high-output fistula resulted in an increasing wound size that required continued NPWT which was transitioned from NPWTi-d to NPWTi-d to NPWT. (Figures -).
Once his clinical status improved, he was returned to the operating room for closure (Figures -).
Despite a successful closure, the challenge of fistula contamination continued. The initial closure was complicated by the inversion and disruption of the mucocutaneous sutures causing severe contamination to the distal incision. Revision required local tissue rearrangement and fasciocutaneous flaps to create a flatter, more appropriate topography of the stoma such that the fistula contents could be above the skin level.
Following this procedure, it was thought that incisional management could not be instituted due to fear of leakage under the dressing with secondary contamination. Unfortunately, two days after closure, the local flap dehisced and revision was required. During the operation, the local tissue rearrangement was redone, and the distal incision was managed with NPT as incisional management at a continuous negative pressure of -125 mmHg.
The high-output fistula continued with leakage and contamination, resulting in recurrent break down of the distal incision. NPWT was reinstituted to assist with fistula management. Due to the continued high output, it was elected to hold on any further attempt at surgical closure and depend solely on wound and fistula management. Fortunately, the patient's clinical progress continued to improve. The wound bed continued to improve with a healthy granulating tissue filling in the defect (Figure ).
NPWT was discontinued. He was transitioned from the acute to post-acute care setting with advanced wound dressings that could ultimately be managed at home (Figures -).
This patient's progress and apparent success were achieved only because of the commitment and experience of a caring group of providers that was led by their knowledge and experience of NPWT in the most challenging circumstances.
This case illustrates the multidisciplinary team approach toward a complex patient with a complex wound, with the team having worked endlessly to create new strategies using evidence-based wound therapies with negative pressure as the cornerstone of treatment.


A 65-year-old African American male presented to the clinic with a painless hard palate mass that had slowly enlarged over a period of 7 months. The mass was associated with bleeding, dysphagia, and dysphonia. The patient's medical and family history were unremarkable. On physical exam, a pink exophytic lesion was easily visualized on the left maxillary alveolar ridge. The lesion measured nearly 10 cm in diameter and extended across the midline. The mass was friable, with a central area of ulceration and necrosis.
Panoramic radiograph showed erosion of the maxillary bone in the area of the lesion, and computed tomography (CT) demonstrated a 7.0 cm × 6.6 cm × 7.5 cm irregularly enhancing mass lesion centered on the left maxilla ().
A punch biopsy was performed at an outside institution at the anterior superior portion of the lesion, and pathologic examination revealed oral mucosa consistent with a malignant glandular epithelium neoplasm. The lesion was poorly demarcated and consisted of glandular cells, primarily a monomorphous population of optically clear cells with central hyperchromatic and pleomorphic nuclei surrounded by clear cytoplasm. The neoplastic clear cells were arranged in nests, cords, and anastomosing trabeculae embedded in hyalinized, acellular, predominantly basophilic stroma. The overlying squamous mucosa was intact keratinized, acanthotic squamous epithelium. The neoplastic cells were periodic acid-Schiff (PAS) positive, which was abolished by diastase and mucicarmine negative. These results suggested that the clear cytoplasm was due to glycogen accumulation, not mucin production. Neoplastic cells were positive for pancytokeratin AE1/AE3, cytokeratin 7, smooth muscle actin, S-100, and p-40, which is consistent with myoepithelial differentiation. The tumor demonstrated a nodular infiltrative growth pattern, lacked overt ductal differentiation, and showed several areas of necrosis, including nests with comedo type necrosis. Although the cells were relatively bland cytologically, the infiltrative growth pattern suggested the diagnosis of myoepithelial carcinoma over myoepithelioma.
At our institution, a near-total maxillectomy was performed which included the hard palate, soft palate, alveolar process, upper left maxilla, and nasal septum. Bilateral modified radical neck dissection, free tissue reconstruction, and tracheostomy were performed concurrently. The specimen size was 9.2 × 6.5 × 6.5 cm, and an exophytic tumor grossly involving the left hard palate invaded into the sinus cavities. Sectioning revealed a light tan, solid tumor, measuring 7.0 × 6.5 × 5.2 cm (). It appeared to replace the majority of the hard palate and was adjacent to the lateral maxillary bone.
Histologic examination revealed similar findings to those described by the outside hospital: a poorly demarcated lesion consisting of nests of pleomorphic and hyperchromatic clear cells (). Subsequent staining for p40, smooth muscle actin, CK7, EMA, and calponin confirmed a diagnosis of myoepithelial carcinoma, clear cell variant, moderately differentiated (). The surgical margins were focally positive for invasive carcinoma. No lymphovascular or perineural invasion was noted. Tumor invasion of nearby structures included the cortical mandibular and maxillary bone, deep extrinsic muscle of the tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus), maxillary sinus, and skin of the face. The lymph node dissection included 74 lymph nodes examined, and no metastatic disease was identified. These findings corresponded to a pT4aN0 pathologic staging.
Due to the advanced tumor stage (T4), the patient underwent postop radiation to the primary site and neck. Twelve weeks after radiation (seven months after the surgery), positron emission tomography/computed tomography (PET/CT) revealed mildly hypermetabolic bilateral pulmonary nodules that were concerning for metastatic disease (). The patient was lost to follow up after this visit.
At 17 months after resection of the neoplasm, the patient returned for follow-up. The patient denied any difficulty breathing, hemoptysis, or weight loss but was wearing a cervical collar due to report of a spine metastasis. Outside CT of the thorax showed bilateral pulmonary nodules of various sizes throughout all lung lobes (). In comparison to the CT that first showed lung nodules, the nodules have increased in size and number. The largest nodule in the right lung was located in the right middle lobe, measuring 1.7 × 2.0 cm, while the largest nodule in the left lung was located in the left lower lobe, measuring 2.6 × 4.2 cm. No pathologically enlarged lymph nodes were identified within the mediastinum. Outside repeat PET/CT and MRI of the spine also confirmed likely metastasis to the C2 body. Bronchoscopic biopsies of two lung nodules from the left lower lobe showed morphology consistent with metastatic CCMC ().


A 67-year-old female with NF1 presented with lumbago, cold sweats, and sudden onset weakness, which necessitated an emergency transfer to our institution. She had no significant past medical history, was negative for hypertension, and was on no regular medications. She was hypotensive (systolic blood pressure = 60 mmHg) and tachycardic on arrival. An abdominal contrast computed tomography (CT) scan showed a rupture of an abdominal aortic aneurysm (AAA) with communication between the aneurysm and the inferior vena cava (IVC) (Fig. a, b). The maximum dimensions of the ruptured AAA and IVC were 34 mm and 37 mm, respectively. The aortic rupture was located 7.5 cm distal to the renal artery and 2.5 cm proximal to the bifurcation of the aorta (Fig. c). Due to the difficulty of primarily closing the ruptured IVC, we planned an endovascular treatment to control the bleeding from the IVC by exclusion of the ruptured AAA. The diameter of normal proximal aorta was 16 mm, which was too narrow to place a normal Y-shaped graft. Moreover, there was insufficient time to prepare another stent in emergency. Therefore, we instead deployed an ENDURANTII (Medtronic Vascular, Santa Rosa, CA, USA) iliac extension proximal to the terminal aorta that was long enough to insert three or more stents (Fig. d). As the bleeding from the AAA and the communication between the aneurysm and the IVC were not well controlled, we placed an EXCLUDER (W.L. Gore & Associates, Flagstaff, AZ, USA) cuff in the ENDURANTII iliac extension. Although a type IV endoleak was detected on angiography, the patient’s hemodynamics stabilized. We therefore decided to conclude the operation at this point and re-assess the endoleak in a few days.
An abdominal contrast CT performed 3 days after the operation showed a type Ib endoleak and injury to the distal abdominal aorta (Fig. a). This led to a redo-EVAR 4 days after operation. This included deploying an AFX (Endologix, Inc., Irvine, CA, USA) graft, as well as an infrarenal cuff, as the AFX head did not fit exactly within the stent placed in the primary operation. We also performed coil embolization treatment of the left internal iliac artery aneurysm (Fig. b), which was identified initially (Fig. b). We confirmed no endoleak at the final angiography. An abdominal contrast CT performed 18 days after the primary operation showed two new sequential aneurysms of the LCA, which were not previously detected. Coil embolization was planned to address these new aneurysms.
Twenty-two days after primary operation, however, the patient presented with new onset nausea, left abdominal pain, and hypotension. Her systolic blood pressure was 50 mmHg. She was resuscitated and required vasopressor support. Laboratory tests, including leukocyte count and electrolytes, were normal. The serum C-reactive protein and D-dimer were elevated to 0.37 mg/dl (normal range 0.01–0.30) and 6.8 μg/ml (normal range 0.0–1.0), respectively. We considered potential bleeding from nearby arteries, including the inferior mesenteric artery (IMA) and lumbar artery [, ]. An abdominal contrast CT showed enlargement of LCA aneurysms and surrounding hematoma (Fig. a–c), establishing the diagnosis of rupture of the LCA aneurysms. Emergency exploratory surgery was performed.
We gained access through a midline abdominal incision. Active bleeding was encountered intraperitoneally and controlled with compression. As a result of the patient’s initial AAA rupture, residual hematoma was present, which extended along the entire left abdomen and retroperitoneum (Fig. a). In addition, the AAA stent endograft had resulted in a left laterally displaced aorta, narrowing our operative field. Due to her distorted anatomy, active bleeding, and clinical condition, we elected to perform a left hemicolectomy. We divided the inferior mesenteric artery (IMA) 3 cm distal to the IMA root to not to injure the recently repaired aorta. We divided the colon at the rectosigmoid junction. Proximally, we divided the colon at the middle of the transverse colon (Fig. b). The mesentery was divided to include the LCA aneurysms. Given her clinical condition, we elected to not perform a colorectal anastomosis, but instead performed a Hartmann’s procedure with an end transverse colon colostomy. The surgery took 145 min, and the estimated blood loss was 4.5 L. Packed red blood cell transfusion volume was approximately 1.96 L, and fresh frozen plasma volume was 1.44 L.
In reviewing the specimens, a 2-cm aneurysmal sac and 1-cm aneurysmal sac were identified in the LCA. No thrombus was identified (Fig. a, b). No ischemic changes and no tumor were observed in the excised colon (Fig. c). Interestingly, fibrous tissue around the left colic artery stained positive for S-100 protein, suggesting that neurofibroma from NF1 might have been associated with the rupture of these aneurysms due to weakened integrity of the vascular walls (Fig. a–e). A follow-up abdominal CT showed no recurrence of the endoleak. The patient was discharged 37 days after the last operation without any other post-operative complications.


A 20-year-old right-hand-dominant and otherwise healthy female student presented with protrusion of the left upper back and left periscapular pain that occurred after sport activities. Ten months previously, the patient had been seated in the left rear passenger seat in a car that was hit in the left side by another car. Further details such as the posture and the arm position of the patient at the time of the accident were uncertain. At the time of the car accident, the patient visited an orthopedic clinic where a surgeon diagnosed left shoulder contusion without any abnormal radiographic findings. The left arm was kept in a sling for 2 months, as left arm elevation caused severe pain in the upper back. After sling removal, the patient returned to basketball, which generated continuous dull pain around the left scapula. She presented at our clinic because her mother had noticed the deformity of her back.
The patient had no relevant family or medical history. There was no neurological deficit in the left shoulder and arm. The left scapula was slightly higher than the contralateral scapula and exhibited atypical medial winging with the arm at the side. The distance between the spinal process and medial scapular border was shorter on the left side than the right side at the inferior angle level, but these distances were almost the same at the scapular spine level (). Contraction of the scapular stabilizing muscles was good. There was a palpable bony protuberance without tenderness on the ventral side of the ISA. The limitations of the active ranges of motion of the left shoulder compared with the right shoulder were 25° for total elevation, 15° for external rotation, and none for internal rotation and horizontal adduction; however, there were no limitations of the passive ranges of motion. The winged scapula became prominent at 0–45° of active flexion, while it disappeared when the patient flexed the left arm while consciously attempting to depress the scapula (). The winged scapula did not emerge when the patient pushed on a wall at chest level. Radiographs showed a small bony fragment in the ventral side of the ISA, with a narrow space between the fragment and the scapular body (). Computed tomography revealed a bony protrusion extending from the medial scapular border to the bony fragment, with a narrow gap between the protrusion and the fragment (Figures –).
The patient was instructed to avoid elevating the left arm for 2 months and then performed reinforcement exercises of the SA such as the scapular push-up and the bear hug using an elastic band for 2 months. At examination 4 months later, the periscapular pain and the winging of the scapula with the arm at the side and in active flexion had resolved. The push-on-the-wall test at waist level was negative, and the range of motion of the left arm was the same as the unaffected side, except for a 15° limitation in external rotation. Although the radiographic findings were the same as at the first visit, computed tomography demonstrated bony union (Figures and ). The patient was permitted to use the left arm without restrictions.
At the time of the final follow-up 10 years of postinjury, the patient reported that there was an occasional painless click and a sporadic floating feeling of the scapula with initial active flexion of the arm. However, there was no pain or any disturbance to the patient's activities of daily life and work as a physical therapist. The patient's colleague confirmed the disappearance of the winged scapula associated with shoulder movement. The DASH score was 0, and the Constant score ratio compared with the right shoulder was 100% [, ].


A 30-year-old nulligravida presented herself in our institution because of the inability to conceive for four years. She was healthy, with no history of previous surgeries. Menarche had occurred at age 14. She had used oral contraceptives for nine years, having stopped taking them four years ago, followed by regular menses. No one in her family had history of infertility or any type of gynecologic cancer.
General examination and body mass index were normal. Analytically she had normal blood count and hormonal assay [FSH, LH, TSH, free T4, testosterone, and dehydroepiandrosterone (DHEA)]. A transvaginal ultrasonography was performed revealing a normed uterus and ovaries slightly enlarged and polycystic with a small echogenic mass in the right ovary of 15 millimeters. The hysterosalpingography was normal.
Her husband was healthy and had no relevant past medical history and his semen analysis was normal.
She was proposed for a diagnostic laparoscopy and ovarian drilling. In the surgery, both ovaries were polycystic and a yellowish nodular solid and hardened formation of about two centimeters, vascular and friable to touch, was observed in the right ovary. That mass was removed, without rupture, and removed in an endoscopic bag. Tubal patency test confirmed bilateral permeability.
The removed mass was sent to histological examination. Macroscopically, it was a yellow-colored tumor measuring two centimeters in greatest diameter, with a smooth and well-limited surface. Microscopically, the ovarian parenchyma was almost entirely occupied by a tumor lesion, represented by large polyhedral cells with small nuclei and vacuolated eosinophilic cytoplasm, without mitosis and nuclear atypia. Hemorrhage and necrotic areas were absent (). Immunohistochemical study revealed diffuse marking for calretinin, vimentin, and melan-A (). These features were consistent with ovarian steroid cell tumor NOS.
In the postoperative period, the woman is followed up with serial measurements of serum testosterone levels and transvaginal ultrasound. At 24 months, she had no evidence of recurrence and began follow-up in reproductive medicine consultation. She was proposed to in vitro fertilization treatment, but despite gonadotropin therapy (in high doses, 300U) for ovarian stimulation, she had no response. At 36 months postoperatively, she is still not pregnant and no evidence of recurrence too.


A 30-year-old male presented with unproductive cough and multiple cervical lymphadenopathy in December 2016. The pathology of the cervical lymph node biopsy revealed T-LBL. Positron emission tomography-computed tomography (PET-CT) revealed multiple lymph node involvements in the neck, mediastinum, bilateral parasternum, and abdomen, the Ann-Arbor stage of the lymphoma reached stage III. The following treatment plan was implemented: 1 cycle of VDLP (vincristine + daunorubicin + L-asparaginase + prednisone) induction chemotherapy, followed by 2 cycles of CAM (cyclophosphamide + A-cytarabine + methotrexate) chemotherapy. After the induction chemotherapy and total body irradiation (TBI)/cyclophosphamide protocol, the patient underwent allo-HSCT with the patient's brothers as donors in July 2017. On the 12th day after transplantation, the CD34+ cell count was 8.33 × 106/kg, the mononuclear cell (MNC) count was 10.15 × 108/kg; the process was uneventful. Forty days after transplantation, the patient developed abdominal pain, diarrhea, and rash across his body. Acute grade three GVHD was considered. The symptoms were relieved after the intravenous administration of methylprednisolone, cyclosporine, and mesenchymal cells. The patient experienced fever during this period, and then the temperature returned to normal after treatment with broad-spectrum antimicrobials, including meropenem and voriconazole. Patients who showed transient BKV, CMV, and hepatitis B virus (HBV) expression levels after transplantation demonstrated improvements after antiviral treatment. The BK DNA level was checked on August 7, 2017, and the result was 4.07 × 107 (copy/ml). The BK DNA level was 1.05 × 105 (copy/ml). A chest CT scan showed diffuse ground-glass opacities (Figs. and ). An abdominal CT scan revealed enlargement of the spleen (Fig. ).
The patient underwent tracheoscopy and CMV-DNA was 3 × 106 in BALF and 6 × 103 in blood. The patient also carried out enteroscopy at the same time and his immunohistochemical CMV antigen was positive Then, the patient was diagnosed with CMV pneumonia and enteritis and treated with intravenous ganciclovir (500 mg/d) and high-dose glucocorticoids (80 mg/d). However, the patient continued to have high fever, progressive shortness of breath, and gastrointestinal bleeding. Intubation and invasive mechanical ventilation support were performed. Unfortunately, the condition continued to deteriorate. After 3 weeks, the patient died because of severe hypoxemia and hemorrhagic shock.
Informed consent for the collection of his medical history and blood samples was obtained in compliance with the Declaration of Helsinki and approved by the local ethical committee, and the patient provided informed consent for publication of the case.


A 2-year-and-8-month-old Swiss girl presented to a pediatric office with fever of 38.8°C, vomiting, and refusal to eat for 3 days. Prior to admission, according to the parents, the patient had drunk ca. 500 ml of fluids. This was a response to a reviewers remark concerning signs of thirst. Blood analysis demonstrated severe hypernatremia (196 mmol/l), prompting urgent hospital admission.
The patient was born at term (40 + 1 weeks of gestation) and had a birth weight of 3390 g. She was delivered through a C-Section due to pathological cardiotocography (CTG) and green amniotic fluid. The APGAR score was 6/8/10. On the second day of life, she developed bilateral parenchymal and intraventricular grade III brain hemorrhage diagnosed by ultrasound. Additionally, she had recurring seizures, which were successfully treated with phenobarbital (3 mg/kg/d). cMRI at two weeks of age showed hydrocephalus with intraventricular hemorrhage in the caudothalamic groove displacing, but not including the thalamus, as well as a small intraparenchymal hemorrhage of the right parietal side and subarachnoid hemorrhage of the left occipital side, along the tentorium and the cisterna cerebellomedullaris, with signs for slight hypoxia.
Postnatally, the patient also had hypernatremia of 180 mmol/l, which was treated with infusion therapy (glucose 5%). We are not aware of any further urine or serum measurements (e.g. osmolality). Neonatal ultrasound showed, slight hyperplasia and no adrenal hemorrhage and tumor. She was discharged with a sodium level of 160 mmol/l. A “central dysregulation” etiology was hypothesized. Sodium levels in the first year were normal (or slightly elevated) and ranged from 136 to 154 mmol/l.
After birth, fT3 and fT4 serum levels were decreased; thus, thyroxine substitution was initiated. The therapy was ended after 1 month because of a hyperthyroid metabolic state (differential diagnosis at that time was euthyroid sick syndrome). Neonatal screening was unremarkable. Two weeks later, at the age of 6 weeks, fT4 was decreased again to 15.6 pmol/l (normal values 17–32), and thyroxine substitution was restarted.
At the age of 1 year, growth arrest (<3rd percentile, before 25–50%) as well as reduced oral intake were observed. IGF1 was reduced to 1.8 nmol/l (normal values 3.67–20.4), IGFBP3 was normal (1.07 mg/l), with no adrenal insufficiency (ACTH, cortisol, aldosterone, renin, FSH, LH, and prolactin normal), sodium was 136 mmol/l, no celiac disease, and bone age was normal. After re-evaluation of cMRI at 2 weeks of age, retrospective diagnosis of pituitary hypoplasia was carried out (ca 60 mm3, normal values 148 ± 37). Growth hormone deficiency was postulated followed by substitution with Norditropin. At the age of 12 months, cMRI was performed again, which showed partial pituitary dysgenesis and hydrocephalus malresorptivus.
The patient was regularly seen in endocrinological and neurological offices. She showed motor development delay which improved partially until the age of 2 years. At this age, a general development delay of 3–4 months and strabismus divergens/alternans on the left side were observed. She had one seizure at 18 months of age lasting 30–40 minutes with postictal paresis of the right arm and facial nerve paresis on the right side; cMRI at that time was unremarkable.
The patient was referred to our hospital in a reduced general condition. On presentation, the skin color was pale and turgor slightly reduced. She had symmetric limb movements with good muscle tonus but appeared tired. The pupils were equal and reacted promptly to light. The percentiles for weight (10.4 kg), length (93 cm), and head circumference (46 cm) were all below the 3rd percentile. Body temperature was 37.6°C, blood pressure was 97/65 mmHg, and heart rate was 102/min. The remainder of the physical examination was normal.
The patient was admitted to the pediatric intensive care unit. Blood gas analysis showed excessive hypernatremia (187 mmol/l) and hyperchloremia (148 mmol/l) with normal pH and base excess (). Osmolality was 362 mmol/kg (normal values 280–300 mmol/kg).
Infusion with isotonic glucose-electrolyte solution (sodium 140 mmol/l and glucose 5%) was initiated. Potassium chloride (7.46%) was added due to mild hypokalemia of 3.02 mmol/l. Blood gas analysis was performed hourly, revealing a slow decrease of sodium to a minimum of 143 mmol/l (), decreasing by an average of 0.5 mmol/l per hour.
Blood glucose on admission was 11.1 mmol/l and normalized with rehydration, suggesting the high blood glucose on admission was due to stress hyperglycemia. Supplementation of thyroid and growth hormones was continued. On the day of admission, urinary excretion was slightly reduced (ca. 2.4 ml/kg/h), and on the second day, the excretion increased (ca. 4 ml/kg/h). There was no fever or edema, vital parameters were stable, and other laboratory tests showed no abnormalities.
The following values were measured on admission: Urine osmolality was 876 mosmol/kg (normal values 50–1200 mosmol/kg), urine antidiuretic hormone (ADH) level was 23.70 ng/l (normal values 1.3–42.4 ng/l), plasma aldosterone level was 7.0 ng/dl (normal values < 9.0 ng/dl), and copeptin pro-arginine-vasopressin (AVP) was 4.4 pmol/l (normal values 1.70–11.25 pmol/l []) The cortisol level was slightly elevated to 32.72 µg/dl (normal values 5–25 µg/dl).
After normalization of serum electrolytes on day 4 of hospitalization, the child developed tremors, particularly while standing, and a general reduction of movement was observed. A slight bilateral rigor of both arms and ataxia were observed. The rest of the neurological evaluation was normal.
A 10/20-electroencephalography (EEG) was normal. MRI of the head showed vague, nonischemic diffusion impairment in the basal ganglia, corpus callosum, and subcortical regions on both sides (), with only discrete signal modulation in the T2 fluid-attenuated inversion recovery (FLAIR) sequence (). No signs for hemorrhage were observed. Slightly dilated lateral ventricles with no active hydrocephalus or indication of increase in pressure were observed. The pons was unremarkable (). The findings were interpreted as meningoencephalitis, so lumbar puncture was performed.
The results of cell count, protein, and glucose in the cerebrospinal fluid (CSF) were normal. Cefotaxime and aciclovir intravenous were initiated. Multiplex polymerase chain reaction (PCR) of the CSF was negative for cytomegalovirus (CMV), Cryptococcus neoformans, Escherichia coli, Enterovirus, Haemophilus influenzae B, human herpesvirus 6 (HHV-6), human parechovirus, herpes simplex virus (HSV) 1/2, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae (group B streptococcus (GBS)), Streptococcus pneumoniae, and varicella zoster virus (VZV). Additional PCR for Mycoplasma and Rotavirus was negative. The antibody specificity index (ASI) for mumps, measles, rubella, varicella, CMV, Epstein–Barr virus (EBV), herpes simplex and Borrelia, as well as tick-borne encephalitis (TBE) antibodies was normal. CSF examination showed an absence of oligoclonal bands, and only a slight increase of immunoglobulin M (IgM) of 2.4 mg/l (normal up to 1.3 mg/l) and a slight increase in albumin quotient of 8.5 (normal up to 4.2) were noted.
Creatine kinase (CK) was extremely elevated (12794 U/l), with normal values for other muscle enzymes (aspartate transaminase (AST), alanine transaminase (ALT)). Although CK-isoenzyme analysis was not performed, the elevated CK levels were assumed to be mostly brain creatine kinase (CK-BB). Rhabdomyolysis due to excessive hypernatremia remains a possible explanation. No seizures, as a possible explanation, were observed throughout the hospitalization.
After 5 days, the child was transferred by plane to Switzerland, where the family resides.
At the accepting hospital, the neurological symptoms remained. Rehydration was continued and slowly tapered over time. Brain computed tomography (CT) scan was performed to rule out sinus vein thrombosis. Antibacterial and antiviral therapy were stopped. Central dysregulation was discussed again concerning the origin of the hypernatremia. A retrospective review of the MRI was interpreted as extrapontine myelinolysis following extreme hypernatremia. After hospitalization for nearly 2 weeks, the child recovered completely.


A 13-years-old mentally impaired girl (since birth due to perinatal asphyxia) presented to the emergency department (ED) with a severe abdominal pain and signs of acute abdomen, fever, and hypovolemic shock. She was unconscious, febrile, with a blood pressure of 80/40 mmHg, pulse rate of 160/min, and a respiratory rate of 34/min. Physical examination revealed a diffuse tenderness and a muscular rigidity. The abdomen was distended and bowel sounds were absent. The abdominal X-ray obtained in a supine position showed a massive free air within the peritoneal cavity and undigested remains of food along the alimentary tract imitating the contrasting liquid (). At hospital admission, a medical audit accompanying the girl described a 4-days history of food rejection, frequent vomiting and progressive deterioration of her general condition. Her anamnesis was negative for traumatic events but was suggestive for PA due to a characteristic appearance of air swelling and abdominal distension that rapidly progressed during the day and caused the flatus during sleep.
Laboratory investigations revealed the following results: White blood cell count: 7.100/uL; mean platelet volume: 11.8 fL; platelet count: 220 × 103/uL; hemoglobin: 11.1 g/dL; hematocrit: 35.2%; serum proteins: 5.7 g/dL; serum albumin: 2.9 g/dL; serum globulin: 2.8 g/dL; aspartate aminotransferase: 107 IU/L; alanine aminotransferase: 30 IU/l; creatinine: 0.9 mg/dl; serum sodium: 135 mEq/L; serum potassium: 5.4 mEq/L; serum chloride: 101 mEq/L; C-reactive protein: 367.4 mg/L; serum lactate dehydrogenase: 401 IU/L; serum creatine kinase: 4,086 IU/L; serum glucose: 107 mg/dL; arterial blood pH: 7.07 nmol/L; PaCO2: 4.93 kPa; pO2: 5.59 kPa; HCO3: 10.5 mmol/L; base excess: 18.8 mEq/L.
Following an aggressive resuscitation with intravenous hydration, decompression of the stomach, a correction of metabolic abnormalities, and administration of empiric antibiotic therapy (amikacin, metronidazole, and meropenem), an emergency laparotomy was performed. It revealed a massively distended and partially necrotic stomach. Huge amounts of free peritoneal fluid (about four liters) with food particles due to perforation of the necrotic gastric wall were removed. The size of the perforation measured 7 × 3 cm affecting the greater curvature on the posterior wall of the stomach ().
A free peritoneal fluid with food particles was washed out from the abdominal cavity. The gastric perforation was treated by debridement of necrotic tissue and a primary closure with additional using an omental patch. The debrided necrotic gastric tissue was submitted to the pathologist for the examination. The pathology assessment of the gastric wall showed a multiple areas of massive, transmural necrosis ().
Post-operatively, the patient was transferred to the pediatric intensive care unit (PICU) on mechanical ventilation and treated with inotropes, cefotaxime, metronidazole, gentamicin, and fluconazole. A fourth day of admission, abdominal cultures taken at the laparotomy as well as a blood culture showed Enterococcus faecalis and Candida glabrata infections.
In the following days, despite an extensive medical support, her clinical condition rapidly deteriorated and she eventually died on day 26 after admission due to overwhelming infections and progressive multisystem failure.


A 69-year-old woman presented to the ED with painless vision loss in her left eye. She stated that over the course of minutes, she completely lost vision in that eye, with onset approximately six hours prior to evaluation. Initially, there was concern for posterior circulation arterial stroke, as the patient had elected to stop taking her antihypertensive medications one year prior. A computed tomography (CT) of the head showed no evidence of intracranial hemorrhage, and a magnetic resonance imaging (MRI) evaluation of the brain showed no evidence of acute stroke. The patient’s fundoscopic exam was limited by constricted pupils, and she was transferred to a tertiary care academic medical center for ophthalmologic evaluation.
On arrival to the tertiary care center, the ED team performed a POCUS, linear probe, 12 MegaHertz (MHz) of the patient’s eye to evaluate for retinal detachment. No evidence of retinal detachment, vitreous detachment, or massive vitreous hemorrhage was found. However, the study demonstrated a widened and irregular optic nerve sheath, which measured over the normal limit of five millimeters (mm). Additionally, an area of hyperechoic signal was noted in the distal aspect of the optic nerve, raising concern for embolic event (). Additional radiologist review of the patient’s MRI showed no evidence of embolism in that area. Ophthalmology was consulted and performed a dilated fundoscopic exam, with direct visualization of a pale, occlusive object within the central retinal artery.
The patient was admitted to the neurology service for monitoring of permissive hypertension initially, and then resumption of an antihypertensive medication regimen. The timing of symptom onset was a contraindication for thrombolytic treatment. Rapid stroke-risk stratification demonstrated no echocardiographic evidence of cardiac source of her embolus, no right-to-left cardiac shunt, and no significant carotid stenosis on CT angiography. She was re-initiated on her outpatient antihypertensive medications, and on two-month follow-up she had no significant return of vision in her left eye and had no evidence of further embolic events.


A 21-year-old woman presented to the ED with complaint of chest pain and shortness of breath. Prior to arrival to the ED she had an episode of near syncope. Her previous medical history included development of diffuse erythematous rash following a course of minocycline prescribed for acne three months prior to ED presentation. The minocycline was discontinued, and she was treated with 30 milligrams (mg) daily oral prednisone with improvement of the rash. Initial vitals included blood pressure of 81/68 millimeters of mercury (mmHg), heart rate of 121 beats per minute (bpm), and respiratory rate of 18 breaths per minute. She was afebrile (36.7ºC oral temperature) and had pulse oximetry (SpO2) of 100% on room air. Physical exam was within normal limits. Electrocardiogram (ECG) showed right bundle branch block and normal ST-T segments, but no previous ECG was available.
While in the ED the patient had an episode of syncope during peripheral venous catheter placement, and intravenous (IV) fluids were administered due to concern of vasovagal event. She was also administered 5 mg IV dexamethasone due to possibility of adrenal suppression from steroid use. Her systolic pressure improved. However, the patient complained of worsening chest pain and then became unresponsive with pulseless electrical activity arrest (PEA). Cardiopulmonary resuscitation (CPR) and Advanced Cardiac Life Support were initiated. She received two doses of 1 mg IV epinephrine with return of spontaneous circulation (ROSC) in normal sinus rhythm of 70 bpm and blood pressure of 72/48 mmHg. Due to persistent hypotension, norepinephrine infusion was administered with improvement of blood pressure to 88/56 mmHg. She was intubated for airway protection.
Due to concern for massive pulmonary embolus, computed tomography chest angiography was performed but was unremarkable. Point-of-care echocardiogram demonstrated no right heart strain and grossly reduced heart function. Telemetry demonstrated QRS widening and increasing bradycardia to 41 bpm. The patient then developed a second PEA arrest with ROSC after CPR and one dose of 1 mg IV epinephrine. She remained hypotensive with blood pressure of 60/40 mmHg despite norepinephrine infusion. Initial troponin-T measured was 8.56 nanograms/milliliter (ng/mL) (reference range 0.0–0.02 ng/mL) and complete blood count with differential showed leukocytosis of 17.5 × 103 cells/mL (reference range 4.0–10.0 × 103 cells/mL) and eosinophilia of 1.6 × 103 cells/mL r (reference range 0.0–0.4 × 103 cells/mL). The cardiology service was consulted and a formal echocardiogram demonstrated a severely reduced ejection fraction of 15% (normal range 55–70%).
The dermatology service was also consulted at bedside in the ED; concern for ANEM in setting of DRESS given the rapidity of onset of her cardiac dysfunction was discussed. Also, the differential diagnoses included coronary vasculitis, viral myocarditis, infiltrative cardiomyopathy, and sepsis. (She was administered 4.5 g piperacillin/tazobactam and 20 milligrams/kilogram (mg/kg) vancomycin, and 500 mg azithromycin IV.)
While in the ED the patient developed further hypotension with blood pressure of 61/40 mmHg despite multiple vasopressors (IV vasopressin and norepinephrine infusions) and had severe acidemia and hypoxemia despite high ventilator support. Ventilator settings were tidal volume of 360mL, positive end-expiratory pressure of 20 centimeters of water (cmH2O), and fraction of inspired oxygen of 100%, and respiratory rate of 28 breaths per minute. Arterial blood gas (ABG) revealed respiratory acidosis with pH of 7.06, carbon dioxide partial pressure (pCO2) of 78 mmHg (reference range 33–43 mmHg), low arterial oxygen (PaO2) of 61 mmHg (reference range 80–100 mmHg), and normal bicarbonate. Basal metabolic panel was within normal limits. Due to continued decline, she received cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) within the ED. ECMO cannulation occurred within three hours of initial cardiac arrest. Once placed on ECMO she had significant improvement in her acidosis and hypoxemia on repeat ABG (pH 7.39, pCO2 41 mmHg, PaO2 135 mmHg) and was rapidly weaned from her vasopressors.
The patient was admitted to the cardiac intensive care unit (ICU) for further management. Due to concern of DRESS-induced myocarditis, dexamethasone with a dose of 1 mg/kg/day was administered intravenously. On hospital day (HD) eight, cardiac biopsy demonstrated diffuse active myocarditis with coagulative myocyte necrosis and mixed infiltrate including eosinophils consistent with DRESS myocarditis. She was decannulated from ECMO on HD 16. She was eventually discharged after 20 days in the ICU and 62 total days in the hospital with a life vest and continued cardiac follow-up. An echocardiogram performed three months later demonstrated improved ejection fraction of 34%.


In this article, we present the case of a 54-year-old woman suffering from severe obesity with a body mass index (BMI) of 47.5 kg / m2 (weight: 104 kg, height 148 m). In anamnesis, chronic bronchopathy treated with corticosteroids and laparoscopic cholecystectomy, no family history of cancer.
She contacted our institute for bariatric surgery. The cross-disciplinary pre-operative assessment included clinical psychology interview, dietary evaluation, oesophagogastroduodenoscopy with biopsy, H. pylori identification and abdominal ultrasound. All the tests were negative for pathologies and, in agreement with the patient and the cross-disciplinary team, a surgical recommendation was given. A gastric bypass with fundectomy was performed laparoscopically.
At one and three postoperative months the patient showed a good weight loss: 95 kg at one month with 18.3% excess weight loss (%EWL) and 8.7% total body weight loss; 84 kg at 3 months with a 40.6% EWL and 19.2% total body weight loss.
At nine months she had an excellent weight loss: 72 kg with a 64.9%EWL and 30.8% total body weight loss, but she reported sporadic episodes of vomiting, asthenia and poor appetite.
The latter symptoms are common after bariatric procedures and are compatible with the normal outcome of the bypass procedure. For this reason, the patient was scheduled for the normal follow-up at one year.
One year after surgery, the patient contacted the department because of a worsening of her symptoms with vomiting and asthenia. Blood tests and X-ray with Gastrografin were carried out. Blood tests revealed slight anaemia (haemoglobin: 10.5 g/dl), and the X-ray with Gastrografin showed a regular progression of the contrast medium through the gastro-jejunal anastomosis and an absence of pathological findings ().
In the context of initial uncertainty, it was possible to subject the patient to a full gastroscopy, thanks to this technique which allows for an easy exploration of the bypassed stomach. It showed the presence of a 6 mm antral ulcer on which biopsies were performed. The results indicated that it was an intestinal type G3 gastric adenocarcinoma. After this diagnosis, preoperative staging was performed with abdominal and thoracic CT scan with contrast dye, which resulted in negative metastasis and the gastric lesion was not visible. Cancer markers tested were in the normal range (CEA, Ca19.9 and alphafetoprotein).
The patient underwent laparoscopic degastroresection with D2 lymphadenectomy. The operation lasted 230 min, with no intraoperative complications. The post-operative period was normal and the patient was discharged on the fifth day.
The definitive histological analysis documented the presence of a gastric adenocarcinoma of the antrum pT1bN0M0 with 22 negative lymph nodes removed. After an oncological evaluation, the patient underwent standard follow-up without chemotherapy or radiotherapy.
The follow-up at two years showed no recurrence of disease.


In our initial case report [], we described the case of a 57-year-old man diagnosed with stage IIA cutaneous melanoma in November 2007 following biopsy of a melanocytic lesion on the left posterior arm that revealed ulcerated primary melanoma with Breslow thickness 1.75 mm and a mitotic index of 1/mm2.
He underwent wide excision of the primary lesion followed by completion lymph node dissection (LND) of the left axillary basin following what was initially deemed a positive sentinel lymph node biopsy, although histology from the LND favored a diagnosis of capsular nevi within several regional lymph nodes (LNs) (ie, pathologic stage IIA, T2b melanoma). The patient remained disease-free for three years, when an in-transit metastasis was detected near the primary site. Following excision of the lymphatic metastasis, he was treated with adjuvant radiotherapy of 50 Gy in 20 fractions to the left posterior arm, followed by one month of adjuvant systemic therapy with high-dose interferon (IFN). One year later, he experienced a second local in-transit recurrence, with positron emission tomography–computed tomography (PET-CT) imaging and tissue confirmation of two to three metastatic melanoma lesions in the liver. BRAF testing on the hepatic metastasis was negative for the V600 mutation.
To induce an anti-tumor immune response that could mediate systemic tumor regression (abscopal effect), planned treatment for the patient included four doses of ipilimumab (anti-CTLA-4) at 3 mg per kilogram of body weight every three weeks, with radiation to begin after two doses. After two cycles of ipilimumab alone, a PET-CT scan showed progression of liver metastases with enlargement of the two previous liver lesions and development of five new hypermetabolic foci in the liver, the largest measuring 2.3 x 2.5 cm (Figure ). He then was treated with stereotactic body radiotherapy (SBRT) to two of the liver metastases with a total dose of 54 Gy in three fractions (Figure ). During cycle 3 of ipilimumab, he developed another in-transit melanoma recurrence in his left upper arm, which later completely resolved following initial enlargement consistent with “pseudoprogression.” He also developed hypophysitis that was treated with prednisone. Our previous report concluded at one-year follow-up, in August 2012, with complete resolution of the hypermetabolic lesion in the left arm and all seven hypermetabolic lesions in the liver and no evidence of local or distant disease progression.
Follow-up
Six and a half years after completing treatment, the patient remains disease-free. He continues to be followed every six months, and as of June 2018, he has no clinical or radiologic evidence of disease recurrence. His most recent PET-CT and maximum intensity projection (MIP) scans were performed in 2016 and showed no evidence of disease (Figure ). His dual-energy X-ray absorptiometry (DEXA) scan T-score was -2.0, which is consistent with osteopenia, a secondary effect of prolonged prednisone use for chronic hypophysitis that he developed from ipilimumab. Symptoms of hypophysitis recurred when he attempted to wean off the prednisone. He therefore remains on a regimen of 3 mg per day. Bisphoshosphonate therapy was recommended, which the patient declined, though he continues to take calcium and vitamin D supplements to manage the osteopenia.


A 12-year-old female presented to the local emergency room with persistent intense left flank pain. Dipstick showed large blood and abdominal CT showed 4 mm obstructing calculus in the proximal left ureter, nephrolithiasis with minimal scarring in the upper pole of left kidney, multiple bilateral renal cysts with the dominant on the left kidney at 2.8 mm. Non-calcified 2 mm right lower lobe pulmonary nodules was also identified. Renal function was preserved with the BUN of 11 mg/dl and creatinine of 0.6 mg/dl, electrolytes were within normal range. The patient was treated with pain control medications and hydration with improvement and was referred to a nephrologist. At the nephrology clinic, urine was collected over 24 h for a “stone risk study” and renal ultrasound (RUS) was performed. RUS showed multiple bilateral cysts and renal calculi in the kidneys (). The right kidney measured 10.5 cm × 4.9 cm × 4.8 cm and the left kidney measured 9.8 cm × 4.7 cm × 5.0 cm. Renal cysts were present bilaterally with some displaying thick internal septation (Bosniak type II renal cyst). The largest cyst was present in the left kidney, measuring 3.3 mm. There were no solid masses present. An extrarenal pelvis was present on the left. There was no caliectasis present.
Twenty-four hours urine “stone study” showed elevated levels of calcium oxalate, brushite, and monosodium urate. Because of strong family history, both the father and paternal grandmother had a history of never genetically tested ADPKD, and radiological and clinical finding the patient underwent genetic testing for PKD1, PKD2, GANAB, and HNF1B. Using genomic DNA from the submitted specimens, the exonic regions and flanking splice junctions of the genome were captured and sequenced by next-generation sequencing (NGS) on an Illumina sequencing system and compared to the human genome build of non-mutated genes of interest. The results returned positive mutations for GANAB and PKD1. The GANAB mutation was classified as the pathogenic variant and the PKD1 mutation was classified as a variant of uncertain significance.
GANAB is vital for Polycystin-1 and Polycystin-2 maturation (). The three genes, GANAB, PKD1, and PKD2 are characterized by a high number of exons, 26, 50 and 16 exons, respectively. We identified dual mutations in GANAB and PKD1genes, which are mapped on the reverse strands on long and short arms of chromosomes 11 and 16, respectively (; ). The identified GANAB mutation resulted in generating nonsense codon that terminates transcription (CGA > TGA) of GANAB mRNA. The mutation located in exon 3 of GANAB mRNA NM_198335.3 (). shows the position of the mutated nucleotide C > T in the CGA codon generating nonsense codon TGA at position 308 of GANAB mRNA NM_198335.3. The site of mutation is equivalent to the nucleotide site 181 in the CDS sequence, c.181C > T (). The GANAB-CDS occupies a region of 2900 nucleotides (nts) located at 128–3028 in the GANAB mRNA NM_198335.3. The mutation is predicted to stop transcription of the amino acid arginine (R) coded by CGA at position 61 of the glucosidase II alpha subunit polypeptide, p.Arg(R)61Ter () and causes loss of normal protein function. It is possible to interpret the GANAB variant as a pathogenic variant, which is not reported in large population cohorts ().
Mutations in the PKD1 gene are linked to renal cystic dysplasia and renal tubulogenesis (). The detected PKD1 mutation p.Pro(P)61Leu(L): c.182C > T mapped at nucleotide site 391 in the exon1 of the PKD1-mRNA transcript NM_001009944.2 () equivalent to position 182 of the CDS sequence (). The mutation is of missense type. The CTC codon is generated from base pair substitution of the middle letter of the CCC codon, CCC>CTC. The triplet CCC codes for proline (P), the mutated codon, CTC, codes for leucine (L) and is predicted to replace proline in the polycystin-1 polypeptide sequence ().
Missense mutations are either silent or mild mutations unless they occur at critical sites along the polypeptide chain. Although, the identified PKD1 missense mutation (p.Pro(P)61Leu(L) is likely of uncertain clinical significance. The finding that showed about 15% of human codons are dual-use codons (duons) specify both amino acids and transcription factor (TF) recognition sites (), motivated us to investigate the exon 1 for “duons”. Our analysis showed the PKD1-exon 1 untranslated and translated regions host motifs for eight types of transcription factors ( and ). Intriguingly, the site of the detected missense mutation showed three overlapping TFs motifs. Also, we identified motifs for two types of genomic structural regulators CTCF and YY1.


An 80-year-old Caucasian female was referred for left renal mass and multiple expansile bone lesions resulting in back and chest wall pain in September 2016. She had a history of in situ high-grade papillary transitional cell carcinoma of the urinary bladder, status post radical cystectomy and pelvic lymph node dissection in May 2012. She underwent left renal mass biopsy which revealed invasive urothelial carcinoma. She received first-line palliative chemotherapy with gemcitabine and carboplatin along with palliative radiation therapy for pain control. Subsequently she also received denosumab, a bone modifying agent, for symptomatic bone metastases after dental evaluation. Due to progressive disease, she started second-line systemic treatment from December 2016 with atezolizumab 1200 mg intravenously over 60 min every 3 weeks, an inhibitor of programmed cell death ligand 1 []. She tolerated atezolizumab well but developed progressive disease in May 2017. At the end of atezolizumab treatment course, she developed clinically significant hypothyroidism with cold intolerance, insomnia, constipation and extreme fatigue in the setting of elevated thyroid stimulating hormone (TSH) level to 21 uIU/mL (reference range 0.8–7.7 uIU/mL). Therefore, she was started on levothyroxine, and her symptoms resolved with normalization of TSH.
Afterwards she was enrolled to a phase II study (ClinicalTrials.gov Identifier: NCT02465060) and underwent tumor biopsy at sternum for next-generation sequencing assay which revealed an actionable mutation at FGFR3. She received AZD4547 80 mg orally twice a day from June 2017 on clinical trial. After 2 months of AZD4547 treatment, she experienced recurrent hypothyroidism symptoms, and was hospitalized twice for small bowel obstruction responding to medical treatment. Her TSH level at that time was significantly increased to 2957 uIU/mL, and daily levothyroxine dose was increased from 50 to 100 mcg accordingly. Her thyroid function returned to normal 1 month afterwards, and she did not experience recurrence of small bowel obstruction.
She achieved stable disease on AZD4547 for approximately 6 months prior to development of progressive disease. She progressed through subsequent lines of treatment with cisplatin and docetaxel and finally pemetrexed before succumbing to disease in June 2018.


A 48 years old diabetic male complained of intermittent high fever associated with chills and rigor, abdominal discomfort and generalized body ache for more than a year. He had visited several hospitals with these complaints and had already been treated with several antimicrobial agents that included antitubercular and antimalarial drugs. However, his symptoms persisted.
He had also visited our hospital six months ago when he was diagnosed as Brucellosis (based on Brucella abortus antibody titre > 1:320) with splenic abscess. He was then treated with doxycycline and rifampicin for three weeks. It should be noted that aminoglycoside was not preferred due to deranged renal function test. Eventually, fever subsided and patient remained asymptomatic for three months. Unexpectedly, the patient re-developed high fever and visited our center again. This time he complained of accompanying pain in the right elbow that was consecutive for five days. A thorough examination revealed that he was anemic but his respiratory and gastrointestinal findings were normal. The lateral aspect of right elbow was tender; however, no swelling or redness was noticeable. In addition, blood examination revealed normocytic normochromic anemia, raised inflammatory markers like ESR and C-reactive protein, deranged renal function test, raised random blood sugar (32 mmol/L) and raised Brucella Ab titre (both IgG and IgM). His chest radiography showed infiltration in left upper and middle zone of lung whereas the ultrasonography of abdomen showed splenomegaly. The patient was treated with ceftriaxone and flucloxacillin and his blood sugar level was maintained to normal by intravenous insulin. But fever didn’t subside instead an abscess developed in lateral part of his right elbow which was drained and pus was sent for evaluation in microbiology laboratory.
The patient’s condition had begun to deteriorate after fifth day of admission, which accompanied high fever (5 spikes with maximum 104 °F), tachycardia, tachypnoea and decreased oxygen saturation below 60%. Therefore, he was immediately shifted to intensive care unit and managed.
Meanwhile, the pus sample showed gram negative bipolar bacilli in the gram stain. The organism formed off white wrinkled colony on blood agar and pinkish wrinkled colony on MacConkey agar at 48 h of incubation. Various biochemical tests were performed that suggested the organism to be Burkholderia pseudomallei which was susceptible to ceftazidime, meropenem and doxycycline but resistant to amoxicillin with clavulanic acid, polymyxin B, colistin and aminoglycoside.
The patient had traveled to Malaysia ten years ago for employment and stayed there for four years, after which he returned to Nepal and indulged in farming. His travel and occupational history accord with the diagnosis of melioidosis. Thus, the patient was treated with intravenous meropenem for the next 28 days. For eradication phase, oral cotrimoxazole and oral doxycycline was prescribed for three months.


A 29-year-old woman with a history of asthma (on intermittent inhaler use) came in with one episode of unarousable loss of consciousness. She was noted to have irregular breathing that alarmed the mother who was sleeping next to her. She called for help and the brother then tried to wake her up but she was not arousable. According to the account, she was sweating profusely and had labored breathing. She spontaneously started breathing normally and started coming around. At this point, she felt very weak, experienced nausea and vomiting, and felt like her “stomach was upset”. Her post-event recovery was less than five minutes. She was brought to the hospital. She is a nurse by profession and was doing her normal ward duties and reports no remarkable event in her history that would have suggested volume loss or prolonged hemodynamic stress. Her examination was unremarkable and there was no postural drop in blood pressure (BP). She was admitted under neurology; her blood and electrolyte work-up was normal and she underwent a complete neurological work-up. She was then referred to cardiology at which point it was noted that she had pre-excitation on the electrocardiogram (ECG). She was taken to the catheterization lab where she underwent an electrophysiological (EP) study that induced an orthodromic atrioventricular tachycardia. Atrial fibrillation was induced through rapid atrial pacing but could not be sustained and no ventricular arrhythmias were inducible without or with dobutamine provocation. Ablation of a left posteroseptal pathway was carried out. The earliest ventricular signal was tracked during tachycardia and ventricular pacing but ablation at the earliest position suppressed accessory pathway conduction only to recur every time. After extensively mapping the right side and the coronary sinus, the ablation was stopped. She was put on flecainide and calcium channel blockers and was discharged. After a few weeks, she had a similar episode and was brought to the hospital. She then underwent a head-up tilt (HUT) test on suspicion of vasovagal mechanism of syncope, which came out positive with nitrate provocation. Her post-ictal phase was reported by her to be an exact replication of her clinical symptoms. The flecainide and calcium channel blockers were discontinued as the mechanism of her fainting was identified to be vasovagal and not a cardiac arrhythmia. She was prescribed hydration, counter-maneuvers (which she practiced inconsistently), and preventive measures. Since the last episode, she has done well but experiences recurrences.


A 33-year-old woman, married with four children, presented to the clinic with a history of four episodes of unresponsiveness. Two were in an upright posture in the morning hours while she was preparing breakfast for her children. The other two were while she was sleeping and her husband discovered that her breathing pattern had become irregular. He tried to arouse her but could not do so. He reported that she was sweating profusely. She recovered in less than five minutes but was too weak to move and had abdominal cramps and a desire to defecate. The first such episode was short and she had not sought medical help. After the second episode, she was seen at a cardiology tertiary care center. Her exam and basic laboratory work were unremarkable. She did not have a postural drop in BP. Her ECG showed normal sinus rhythm with frequent ventricular ectopy of the right ventricular outflow tract origin. An echocardiogram revealed structurally normal heart with preserved left and right ventricular functions. In view of ventricular tachycardia as a cause of her syncope, she was offered an EP study and ablation. She was brought to the EP laboratory, where her rhythm was normal sinus rhythm and no ectopy could be induced despite isoprenaline provocation. She was then discharged on calcium channel blockers. At the time of her visit, she was doing well and had no ventricular ectopy. She underwent a HUT test which was positive with nitrate provocation. She stated that her symptoms on the HUT table were consistent with the ones that she had been experiencing during the episodes. She was prescribed hydration, counter-maneuvers and preventive measures. Since the last episode, she has not had any recurrence.


A 43-year-old man who is a hospital worker came to the clinic with three successive syncopal attacks, all in the morning hours. One was noted while he was supine and got up from sleep. He was sweating profusely according to him and it was witnessed by his wife. He felt nauseous and had an abdominal gripe and passed out while in bed. He recovered spontaneously after a few minutes while his wife tried to revive him. On examination, he did not have a postural drop in BP. His ECG was within normal limits and an echocardiogram was conducted which was normal. His blood and biochemical work-up were normal. He underwent a HUT test which was positive with nitrate provocation. He was reassured and sent home with advice to remain hydrated, apply counter-maneuvers and exercise. After his clinic visit, he had another episode of supine fainting and this time his wife raised his legs and he reports that despite experiencing the same symptoms, the duration of the episode was abbreviated. He has done well since the institution of regular hydration and exercising the counter-maneuvers, though he still experiences recurrent episodes.


A 51-year-old man presented to us with three episodes of loss of consciousness. He had an aortic valve replacement with a metallic valve a few years ago and did not have any other cardiac risk factors and was fairly active. He took warfarin and his international normalized ratio (INR) was within therapeutic range. The day of the admission, he has been out the whole day and had not eaten or taken the usual amount of liquids; the initiating event took place at a funeral, where he felt nauseous and dizzy. This was in the evening time. At night, he went to operate the water pump and had an unheralded fall and recovered spontaneously. He was brought up to his room where he lay with head propped up. At that time, he felt a griping pain in the abdomen and experienced nausea and passed out. According to the wife, he came around with sprinkling of water. He complained of worsening of the gripe and felt like vomiting. By this time he was totally lying flat in bed. The wife witnessed his eyes rolling up and he had myoclonic jerks. He came around in a couple of minutes and was rushed to the hospital. On examination, he has normal range pulse and BP, while the rest of the exam was unremarkable. His ECG (sinus rhythm with right bundle-branch block), blood work-up and echocardiogram were normal. His ejection fraction (EF) was 55% and the prosthetic aortic valve was functioning normally. His neurological assessment, electroencephalogram (EEG) and scan ruled out a neurologic cause (hemorrhage or thromboembolic event). He then underwent a HUT test, which came out positive at three minutes post nitrate provocation with a cardio-inhibitory response, where the ECG showed severe sinus bradycardia and sinoatrial (SA) exit block. He reproduced and confirmed all the clinical symptoms of an abdominal gripe, nausea, and sweating. He also felt like moving his bowel at the time. He was prescribed hydration, counter-maneuvers and walking. He did not have any recurrence in the follow-up period.


A 67-year-old man who was functionally very active, presented with a history of fainting while in bed lying flat. He had similar multiple episodes. The episodes were noted during sleep, where his breathing would become labored and he had difficulty being aroused from sleep. These episodes were during the period when he had “stomach flu”. The five noted episodes were spread over months. The last one was prolonged with longer recovery time, necessitating a hospital visit. He did give a history of upright syncope in his youth. He had a history of hypertension for which he was well controlled on calcium channel blockers and low dose hydrochlorothiazide. On admission, his pulse and BP were in range and there was no postural drop. His ECG, blood work-up and echocardiogram were normal. He also had a 24 hours Holter monitoring, which showed normal diurnal variation and appropriate nocturnal slowing and there was no episode of blocks or pauses. The neurologic clinical assessment and workup were normal for age. He underwent a HUT test, which revealed a sinus arrest with pause (nine seconds) after five minutes of nitrate provocation. He experienced sweating, nausea, and abdominal pain prior to syncope on the HUT test; during his phase, he showed sinus bradycardia. He was prescribed hydration and measures to take care of the trigger in time as well as counter-maneuvers (leg crossing and muscle tensing) and walking. He has been followed-up without recurrence.


A 25-year-old female was admitted into a partial psychiatric hospital program after a short stay in the behavioral health unit of a community hospital. She initially presented to the emergency department due to recurrent depression, mood swings, anxiety, and suicidal thoughts/intent. Upon initial evaluation, she reported suicidal thoughts, sad mood, a low energy level, anhedonia, and feelings of worthlessness, helplessness, and hopelessness. She also admitted poor sleep, poor appetite, poor concentration, and recurrent episodes of self-harm. She denied any symptoms of hypomania or mania. However, she did admit to a history of mood swings and anxiety. She had several superficial lacerations on her forearms in multiple stages of healing consistent with self-mutilation. She told staff that she had been “cutting” since she was a teenager and had also tried to intentionally overdose as a teen. The patient had a long history of psychiatric conditions and had multiple prior psychiatric hospitalizations. She denied any history of physical or sexual abuse. She reported a family history of substance abuse, bipolar disorder, and borderline personality disorder. The patient was also diagnosed with Ehlers-Danlos syndrome with symptoms beginning in early childhood.


Our patient was a 33-year-old man with congenitally corrected transposition of the great arteries and ventricular septal defect (VSD). Cardiac MRI showed a dilated right ventricle with an indexed end-diastolic volume of 165 mL/m2 on the left side, and moderate systolic dysfunction, having an ejection fraction (EF) of 36%. In addition, morphologically, left subpulmonary ventricle was observed on the right side with moderate depression (EF of 37%). The VSD was subpulmonary and presented a pulmonary/systemic flow rate (Qp/Qs) of 1.8. Right cardiac catheterization showed severe pulmonary hypertension (mean pulmonary arterial pressure of 92 mm Hg, systolic pulmonary arterial pressure of 109 mm Hg, and diastolic pulmonary arterial pressure of 70 mm Hg). Considering these findings, an implantable cardioverter defibrillator (ICD) was provided as the primary prevention for the sudden death, and treatment with bosentan was started. One year later the patient’s functional condition worsened; the maximal oxygen uptake in the exercise testing was 41% of the theoretical. Bosentan was replaced by sildenafil, but due to poor tolerance to sildenafil, Ambrisentan was prescribed.
Five months later, the patient was hospitalized for atrial flutter. During electrophysiological study, atrial fibrillation (AF) was induced, and cavotricuspid isthmus ablation and isolation of pulmonary veins were performed. The patient was then discharged in sinus rhythm and anticoagulated with 110 mg of dabigatran every 12 hours. Nevertheless, his clinical status progressively worsened in the following months, with limiting dyspnea and symptoms of low cardiac output. An upgrade from ICD to cardiac resynchronization therapy was performed, since the patient presented a high percentage of ventricular stimulation and reduced ejection fraction. A risk assessment study for heart and lung transplantation (HLT) was carried out. The echocardiogram showed severe biventricular dysfunction with severe tricuspid regurgitation. Right cardiac catheterization confirmed pulmonary hypertension; he had a mean pulmonary arterial pressure of 90 mm Hg, systolic pulmonary arterial pressure of 104 mm Hg, diastolic pulmonary arterial pressure of 72 mm Hg, pulmonary capillary wedge pressure of 36 mm Hg, pulmonary vascular resistance of 9 Wood units, and cardiac output of 2.92 L/min. No absolute contraindications for HLT were detected. The patient was included in the waiting list for transplantation and was discharged with anticoagulation therapy (dabigatran), after checking idarucizumab was available.
In October 2016, an optimal donor was found. The patient was admitted to the hospital 7 hours after the last dose of dabigatran (110 mg). Two ampoules of intravenous idarucizumab 2.5 mg were given over 5 minutes each, with an interval of 15 minutes between the first and second doses. Since the antidote is a non-competitive inhibitor, the onset of inhibition of the anticoagulant action of dabigatran is practically instantaneous. Therefore, the drug was administered once it was confirmed the donor was suitable and the transplant could be performed. Dabigatran mainly prolongs the activated partial thromboplastin time (APTT) and, to a lesser extent, the prothrombin time (PT). However, idarucizumab routine monitoring is not necessary due to its stable and predictable pharmacokinetics []. The patient’s APTT and PT before CPT was 41 and 14.3 seconds, respectively. HLT was performed without hemorrhagic, intra-operative or post-operative complications.


A 45-year-old woman presented to West China Hospital with a 1-month history of coughing with abdominal pain. She had no shortness of breath, hemoptysis, chest pain, night sweats, or notable marasmus. She had no significant medical history. Chest CT revealed evidence of infectious disease in the right upper lung lobe and enlargement of a mediastinal lymph node (Fig. ). All laboratory findings were within the reference ranges with the exception of the cancer antigen 125 level, which was 482.8 U/L (reference range, 0–35 U/L). The results of a tuberculosis interferon-γ release assay and purified protein derivative test were considered positive. However, the purified protein derivative test may have a high risk of false-positive results.[ Additionally, because the sputum smear did not reveal acid-fast bacilli, tuberculosis could not be diagnosed and she did not undergo antituberculosis treatment.
One month later, the patient was admitted to our hospital for abdominal pain. No abnormalities were found in a physical gynecologic examination. B-scan ultrasound showed a 3.0- × 1.7- × 2.2-cm right adnexal cystic mass and a 1.5- × 1.3- × 1.2-cm plaque with weak echogenicity. Abdominopelvic CT demonstrated multiple solid-cystic nodules located on the surface of the bilateral adnexa, a small amount of abdominal effusion, and multiple nodules in the thickened omentum, fascia, and peritoneum. The pelvic mass was suspected to be either tuberculosis or ovarian cancer. Therefore, the patient was scheduled to undergo exploratory laparoscopy for a definitive diagnosis. Lumbar CT showed bulging of the lumbar discs at L3-4 and L4-5 without spinal tuberculosis or a cold abscess. After standard monitoring according to the American Society of Anesthesiologists guidelines, the patient was placed in the lateral decubitus position, and epidural anesthesia was established in one attempt by insertion of an 18-gauge Tuohy epidural needle into the L1-2 space. The epidural catheter was inserted smoothly. Next, 3 mL of 2% lidocaine was injected as a test dose. Five minutes later, 6 mL of 2% lidocaine was given via the epidural catheter. DEX was continuously infused by an intravenous pump with different speed capabilities. In the first 10 minutes, the total dosage was 1 μg/kg. The speed was thereafter maintained at 0.3 to 0.5 μg/kg per hour. After administration of a loading dose of DEX, 5 mL of 2% lidocaine was incrementally given via the epidural catheter to obtain a T8 sensory level. The DEX was adjusted to keep the Ramsay sedation score (RSS) at 3 to 4 during surgery. One 10-mm optic trocar was inserted above the umbilicus in the Trendelenburg position, and 2 working trocars were inserted through the left inferolateral abdominal wall. The carbon dioxide pneumoperitoneum pressure was maintained at 11 mm Hg. The patient complained of discomfort during exploration of the upper abdomen; her discomfort was resolved by administration of 1 mg of midazolam. Laparoscopic examination showed extensive gray tubercles on the surface of the liver, omentum, intestinal canal, abdominal wall, and internal genitalia (Fig. A and B). Adhesions and yellowish peritoneal fluid were present in the abdominopelvic cavity. During the operation, the patient's vital signs were stable and no hypotension was observed. The surgical operation lasted for 35 minutes, and her vital signs are shown in Figure . The RSS recovered to 2 approximately 15 minutes after stopping the DEX administration. No adverse effects, including psychological conditions, were observed during the surgery or 1-day follow-up. The pelvic tubercles were confirmed to be caseous necrotic tissue by pathologic examination.


A 65-year-old male farmer was admitted to the dermatology department of Lishui Central Hospital in April 2016 with the chief complaint of erythema, pruritus, and ulceration of the perianal skin combined with cough, which lasted for 1 year. One year ago, patient had perianal erythema, accompanied by pruritus, ulceration, exudation, and pain. Further questioning revealed that the patient had been coughing several times a day. The patient occasionally had white sputum, without any hemoptysis, chest pain, low grade fever, night sweats, or any other discomfort. The patient had applied a variety of ointments for external use, without improvement. The erythema gradually expanded, affecting half of the hip on both sides of the crissum; an ulcer developed at the center of the erythema. Past medical history included hepatitis B for more than 10 years, and hypertension for about 3 years. The patient had surgical history of cholecystectomy at 39 years of age and denied previous history of TB, tumor, being engaged in risky sexual behaviors, or similar family history. Physical examinations included body temperature of 36.9°C, blood pressure 133/86 mm Hg, pulse rate 86 beats/min, breathing 20 times/min, double pulmonary breath sounded rough without obvious rales. Physical examination by specialist showed a large erythematous plaque of about 20 cm × 15 cm around the anus, skin ulcers could be seen nearly 4 cm range at the perianal area, and the base could be seen with fresh granulation, and few purulent secretions (See Fig. ). Blood routine test, liver and kidney function tests, treponema pallidum particle agglutination assay (TPPA), toluidine red unheated serum test (TRUST), combined detection of human immunodeficiency virus (HIV) antibodies, and HIV antigens were all negative or within normal ranges. The detection and screening of alpha-fetoprotein (AFP) tumor marker, carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), total prostate specific antigen (TPSA), and free prostate-specific antigen (FPSA) were all normal. Blood sedimentation rate was 50.0 mm/h, TB DNA was positive, and TB antibody was positive. Acid-fast bacillus detection in sputum samples was ++++. Histological examination of perianal skin showed an ulcerative and necrotic area in the perianal skin, and peripheral epidermis had keratosis and hyperkeratosis. The stratum spinosum was proliferated, accompanied by intercellular edema. The whole dermis had epithelial-like cell mass, Langerhans giant cells could be seen, a large number of infiltrating lymphocytes were observed, and anti-acid staining was positive. Pathological diagnosis demonstrated (perianal skin) necrotic granulomatous lesions (TB). Special staining demonstrated acid-fast bacilli using acid-fast staining, periodic acid-Schiff stain (PAS) was negative (−), silver hexosamine stain was negative (−) (See Fig. ). Chest computed tomography (CT) scan showed symmetrical thorax, trachea moved to the right, and double lung marking increased and disordered. Diffuse nodular, flocculent, and striped high-density shadow could be seen in both the lungs, the edges were blurred, and the density was uneven. The partial lung tissues in both the upper lungs were consolidated and the cavity was formed. Hilus of the lung and mediastinal lymph nodes were not enlarged. The shape of the heart was not abnormal. There was no pleural effusion in the bilateral pleural cavity. Intrahepatic bile duct showed dilatation. Chest CT scan showed secondary pulmonary TB with cavitation in both upper lobes, and part of the right upper lung was damaged (See Fig. ). The results of abdominal enhanced CT showed intrahepatic bile duct dilatation and pneumobilia, gallbladder was not shown; splenomegaly, and multiple renal cysts in both the kidneys; possibility of duodenal descending diverticulum, and a little pneumatosis as a partial small intestinal obstruction. Admitting diagnosis showed perianal ulcerative skin TB, secondary bilateral pulmonary TB with possible cavity formation in the 2 upper lungs, TB bacillus was positive (+) in sputum smear. The patient was transferred to the infectious disease department for treatment, and was given with regular anti-TB treatment, which included isoniazid tablets 0.1 g/time, 3 times/day; rifampicin capsules 0.45 g/time, 1 time/day; ethambutol tablets 0.75 g/time, 1 time/day; pyrazinamide tablets 0.75 g/time, 2 times/day. The patient was discharged after 8 days of hospital treatment. M. tuberculosis in sputum smear was negative (−) at the time of discharge. Flushing and exudation of perianal skin were better than before. The patient was recommended to take regular anti-TB drugs for 6 months after discharge. After 6 months of discharge, the patient was followed up through telephone and replied that the ulcer had healed.


A 69-year-old Caucasian man presented with a dark-brown to black pigmented macula on the glans and foreskin of several years duration. The asymptomatic pigmented lesion had rapidly enlarged in the last few months (Fig. ). The patient came to the plastic surgical team after that the urologists performed excision of the foreskin and some biopsies on the glans to made the diagnosis of the lesion. Histological examination showed a diagnosis of MIS (Fig. ).
The surgical treatment consisted to excise the lesion with a healthy margin of 1 cm all over except close to the urethral meatus where it was impossible and where only 5 mm of free margin was excised. A full thickness mucosal graft from oral cavity was performed to repair the defect on the glans after the wide excision of MIS (Fig. ). At the sixth clinical follow-up the patient was alive and disease free at 50 months after surgery (Fig. ). Moreover, no lower urinary tract symptoms and erectile dysfunction were observed.


A 50-year-old Korean man presented with a keloid scar on his anterior chest wall, which had developed 1 year prior following trauma and had gradually enlarged beyond the original wound's boundaries. He complained about pain and itching sensations in the keloid scar. The keloid scar measured about 5 cm and was located on the sternal area; a cystic lesion with a pin-point-sized skin opening was present at the center of the keloid scar (Fig. A). The cystic lesion was absent before the traumatic event, and dermoscopic examination revealed an EC with a central skin opening (Fig. B). The patient was asked to choose which among the 2 treatment options to undergo: total excision of the scar tissue including the cyst or laser therapy for the keloid and cystic lesion; the patient chose the latter method. First, laser therapy using a 595-nm pulsed dye laser (Vbeam; Candela Corporation, Wayland, MA) with a 7-mm spot size at a fluency of 12 J/cm2 and a 20-ms pulse width was performed to manage the keloid scar. Adjacent, nonoverlapping laser pulses were applied to the entire surface of the keloid scar. Epidermal cooling was achieved using a cryogen spray cooling device, which had a spurt duration of 30 ms with a delay of 30 ms. These procedures were performed 3 times with 3-week intervals. Second, laser therapy using a carbon dioxide laser (Spectra SP carbon dioxide laser, 20 Hz, 250 μs pulse width, 17 mJ; Lutronic, Korea) to create multiple punctures, resulting in a 2 to 4 mm hole, was performed to manage the EC. Gentle pressure and squeezing led to the exudation of the cyst's internal contents through the hole, and the remaining visible cystic walls were cauterized using the carbon dioxide laser. We applied Steri-Strip skin closures (3 M, Maplewood, MN) to the wound without surgical sutures. There were no postoperative complications, such as infection or wound dehiscence. The EC healed completely following the carbon dioxide laser therapy. We performed 5 further pulsed dye laser cycles on the whole keloid scar (Fig. C and D). After completing the laser therapy, Mepiform dressing (Mölnlycke Health Care, Oakville, Ontario, Canada), which is a self-adherent soft silicone dressing designed for scar management, was used by the patient for 5 months (Fig. E and F). There were no EC recurrences or keloid overgrowth during the 2-year follow-up period, and the patient was satisfied with the final outcome (Fig. G).


A 43-year-old woman presented with post-Bacillus Calmette–Guérin vaccination keloid scars on both shoulders. A protruding lesion had developed at the center of the keloid scar on her right shoulder 3 months prior. The lesion had increased in size, and she had squeezed out the lesion's contents several times. However, the lesion had become swollen again and was painful. When she visited our clinic, the lesion had already ruptured, and inflammation had spread to the surrounding keloid scar tissue. The keloid scar on the patient's right shoulder measured about 9 × 7 cm, and the ruptured lesion measured 2 × 1.5 cm (Fig. A). We excised all the keloid tissue including the ruptured lesion, and repaired the wound using subdermal 3-0 PDS (Ethicon, Inc., Somerville, NJ) and interrupted 5-0 Ethilone (Ethicon, Inc.) sutures, primarily (Fig. B–D). Histopathologically, a large laminated keratin-filled cyst was present in the dermis surrounded with a dense collagenous keloid scar (Fig. E). The cyst wall consisted of stratified squamous epithelium with a granular layer, which was consistent with an EC. The adjacent dermis contained characteristic broad, eosinophilic, and homogeneous keloidal collagen bundles (Fig. F). There were no postoperative complications, such as an infection or wound dehiscence. The stitches were removed 14 days postoperatively, and Steri-Strip skin closures were applied for 1 month to prevent wound dehiscence and scar widening. Subsequently, the patient used Mepiform and applied a personalized compression garment for 5 months (Fig. G and H). There were no EC recurrences or keloid overgrowth during the 1-year follow-up period, and the patient was satisfied with the final outcome.


A 51-year-old woman was diagnosed with CVID since 2000. Diagnosis was reached after her having contracted two episodes of pneumonia and developing chronic diarrhea. IVIG treatment was delivered every 45 days (4 gr/kg). Patient's IgG levels reached normal blood levels (> 700 mg/dl) with good clinical conditions. Since 2012, due to patient's personal reasons, IgG levels were not correctly kept within normal ranges; in 2017, the patient developed bilateral laterocervical lymph nodes (1 subtributary lymph node of 6.5 mm), lymph nodes in the mediastinal space (3.5 mm), and splenomegaly. Histological examination on supraclavicular and abdominal lymph node biopsies was negative for neoplasm. Clinical signs of fatigue, fevers, and night sweats as well as anemia elevated CRP levels, and hepatosplenomegaly was present. The patient was diagnosed with MCD and referred to our clinical immunology unit due to severe hypogammaglobulinemia and splenomegaly.
Blood count detected hypochromic microcytic anemia, mild neutropenia, and thrombocytopenia. The study of lymphocyte subpopulations showed an inverted CD4/CD8 T-cell ratio due to the numerically expansion of CD8+ T-cells. Immunoglobulin levels were low: IgG 345, IgA 2, and IgM 4 mg/dl. Wright agglutination test, markers of hepatitis B, hepatitis C, HIV, HHV8, tumor markers, serum and urine immunofixation, and fecal antigen H. Pylori were normal.
IVIG treatment was started at 5 g/Kg maintaining IgG levels > 700 mg/dl as well as i.v. iron therapy.
A complete abdomen ultrasound detected hepatomegaly (large wing 22 cm), splenomegaly (greater than 30 cm), with a lesion at the splenic pole of 26 mm, increased portal vein (20 mm), thick gastric and mesenteric walls, and modest free spillage in the right and left iliac fossa. A thoracic-abdominal CT with contrast medium showed the presence in both lungs of numerous occurrences of parenchymal thickening with nodular appearance, some confluent, with irregular morphology, and contours. The examination also highlighted the presence of bronchiectasis. Numerous paraaortic and iliac-obturator lymph nodes with a short axis of about 12 mm were identified. Other lymph nodes were identified in the celiac site and along the small gastric curvature. The liver, increased in volume, did not show focal lesions. Port vein ectasia (24 mm) and splenic vein ectasia (25 mm) were highlighted ().
Surgical counselling recommended splenectomy. As it was not an emergency surgery, in order to prevent any infectious surgical complication, IgG levels were maintained over 700 mg/dl for 2 months before splenectomy ().
Spleen biopsies were performed, which showed a predominant lymphocytic infiltration ().
A further thoracic-abdominal CT scan was performed three months after surgery, which showed a reduced size of the numerous paraaortic and iliac-obturator lymph nodes with a short axis of about 8 mm.


A 37-year-old woman presented with gradually progressing weakness of the right arm. She had a medical history of asthma only in her childhood and no notable family history. On physical examination, she showed mild paralysis of the right arm. Although she felt palpitation and sweating at times, exophthalmic and enlarged thyroid lobes were not observed. Diffusion-weighted imaging (DWI) showed cortical and subcortical infarcts in the left MCA territory (Additional file : Figure S1), but magnetic resonance angiography (MRA) showed almost-normal cerebral arteries or very mild stenosis of the left ICA (Figs. a, a). The vessel wall seemed thicker in the left ICA than in the right on three-dimensional (3D)-T1WI, but the difference was not clear (Additional file : Figure S2A). Hyperthyroidism [levels of free T3, free T4, and thyroid stimulating hormone (TSH); 10.58 pg/mL, 2.70 ng/dL, and 0.01 μU/mL, respectively], and autoantibodies related to GD [anti-thyroid peroxidase antibody (anti-TPO Ab, 148.0 IU/mL), and TSH receptor antibody (TRAb, 8.3 IU/mL)] were identified (Fig. ). Other laboratory investigations showed unremarkable results except for leukopenia, anti-SS-A antibody (89.5 IU/mL; normal range, < 7.0 IU/mL), anti-SS-B antibody (12.4 IU/mL; normal range, < 7.0 IU/mL) and thrombin-antithrombin complex (TAT, 2.5 ng/mL; normal range, < 0.3 ng/mL). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were negative. She was diagnosed with GD, but not with Sjogren’s syndrome, based on the normal results of Schirmer’s test and a salivary flow-rate test. Rather than methimazole, she was treated with potassium iodide (150 mg/day) for GD due to leukopenia. MRA excludes over 50% stenosis of intracranial and extracranial cerebral arteries and we could not find any major risks of cardioembolic source of embolism, through electrocardiography, echocardiography, and cardiac rhythm monitoring for over 24 h, so heparin, then warfarin (4 mg/day) were administrated as treatments for stroke as unknown etiology. Mild weakness remained at discharge.
Five months later, she presented with intermittent transient weakness of the right arm and leg. DWI did not show new infarction. Stenosis of the left ICA progressed on MRA (Figs. b, b). Thyrotoxicity was exacerbated (Fig. ). Although argatroban was administered, attacks recurred 5 times. We started intravenous methylprednisolone (IVMP; 1000 mg/day on days 2–6), clopidogrel (300 mg on day 1, and 75 mg/day from day 2), and aspirin (300 mg on day 1, and 100 mg/day from day 2). The attacks subsequently stopped. Catheter angiography showed stenosis of the left ICA from the proximal to distal portion and CBN (Fig. a, b). High intensity lesion on T1 W1 in the distal portion of the left ICA was observed (Additional file : Fig. S2B). MMV associated with GD was diagnosed. She refused any surgery. Methimazole (15 mg/day) was started, but mild thyrotoxicity continued (Fig. ).
We subsequently identified gradual progression in the left ICA and middle cerebral artery (MCA) on MRA (Fig. b-d) and 3D computed tomographic angiography. Finally, we found smooth, circumferential, concentric wall thickening with diffuse gadolinium enhancement of the left ICA from the proximal to distal portion on 3D-T1WI (Fig. a, b). We considered the possibility of vasculitis of medium-to-large vessels and administered prednisolone (PSL; 1 mg/kg/day) and methotrexate (MTX; 4 mg/week). Subsequently, thyroid function normalized (Fig. ).
Six months later, PSL was reduced to 0.1 mg/kg/day, and MTX increased to 14 mg/week. Signal intensity in the left ICA and MCA increased on MRA. Catheter angiography showed development of net-like vessels, and incomplete occlusion of the ICA (Fig. c). By 18 months after recurrence, further improved flow in the left ICA and MCA on MRA was observed (Fig. e), but the vessel wall of the left ICA from the proximal to the distal portion still remained enhanced on CE 3D-T1WI in the same way as the previous one. Two years after recurrence, catheter angiography also showed improved blood flow in the left ACA, MCA and ICA, as well as mild improvement of stenosis of the terminal portion of the left ICA (Fig. d). We evaluated the polymorphism in c.14576 G > A (rs112735431) in the RNF-213 gene, a susceptibility gene for Moyamoya disease, using genomic DNA samples from the patient. Genetic analysis of RNF-213 showed wild type.


A 77-year-old man with hypertension, hyperlipidemia, and prior infrarenal aortic aneurysm repair presented with several months of worsening lower abdominal pain and a weight loss of 20 pounds (9 kilograms). The endovascular repair of his aortic aneurysm occurred two years prior and was prompted by expansion to 4.4 cm in diameter. He denied any fever or chills. He lived in the rural southeastern United States (Georgia), where he hunted deer and had exposure to livestock on a nearby farm. On exam, he was cachectic and had a temperature of 100.4°F (38°C). Abdominal exam showed tenderness to deep palpation in the epigastrium and bilateral lower quadrants. His white blood cell count was normal at 8.0 × 109/L (reference 4–11 × 109/L), hemoglobin 11.3 g/dL (reference 11.4–14.4 g/dL), and platelet count of 345 × 109/L (reference 150–400 × 109/L). Serum sodium, renal function, and aminotransferases were normal. The erythrocyte sedimentation rate and C-reactive protein were elevated at 100 mm/hr (reference 0–20 mm/hr) and 111.8 mg/dL (reference 0–7.5 mg/dL), respectively. A chest radiograph was unremarkable, and computed tomography (CT) scan of his abdomen and pelvis detected large (up to 2.6 cm × 2 cm) necrotic periaortic lymph nodes with normal appearance of the liver. CT-guided retroperitoneal lymph node biopsies were performed, and pathology was negative for malignancy but noted chronic inflammation and non-necrotizing granulomas. Lymph node aerobic and anaerobic Gram stain and cultures, acid fast bacillus (AFB) smear and culture, and fungal stain and cultures were negative. Aerobic and anaerobic blood cultures, AFB blood smear and culture, serum cryptococcal antigen, HIV antigen/antibody, purified protein derivative for tuberculosis exposure, and rapid plasma reagin (RPR) for syphilis were all negative. Positron emission tomography (PET) CT imaging was pursued for further evaluation of the intra-abdominal lymphadenopathy and revealed increased radiotracer activity and soft tissue stranding at the bifurcation of the aortoiliac stent, indicative of increased metabolic activity ().
Prior to hospital discharge, the patient's Coxiella burnetii titers were pending as well as the psoas fluid aspirate polymerase chain reaction (PCR) and culture. The psoas fluid aspirate was sent to the Centers for Disease Control and Prevention given negative infectious workup until this point. After discharge, his Coxiella burnetii (Q fever) titers resulted as follows: IgM Phase I: 1 : 64, IgG Phase I: 1 : 131,072, IgM Phase II: 1 : 16, IgG Phase II: 1 : 65,536. Polymerase chain reaction (PCR) testing of the psoas fluid aspirate was pursued, and aspirate PCR and cultures were positive for Coxiella burnetii. During outpatient infectious diseases management, the patient was started on therapy with hydroxychloroquine and doxycycline. Despite therapy, he had progressive decline in his functional and nutritional status, which limited monitoring of titers and drug levels. On a subsequent admission two months later, he was noted to have developed psoas abscesses bilaterally (left 1.9 × 1.8 × 4 cm and right 1.9 × 2.5 × 6 cm) () with aortitis of the posterior aspect of the aorta at the level of L2 and osteomyelitis of L2 and L3 vertebral bodies (). The patient declined despite therapy with doxycycline and hydroxychloroquine and fluoroscopy-guided drainage (with drain placement) of the psoas abscesses. The patient was deemed high-risk given need for revision of aneurysm repair, progression to bedbound status, failure to thrive, and poor nutritional status. After discussions with the patient, family, and the medical and surgical teams, it was decided to forego potential surgical interventions, such as removal of the infected graft, due to the high risk of intraoperative mortality. The patient and his family elected hospice care. He died at home five months after the diagnosis of chronic Q fever and four years after his abdominal pain began. The exact timing of his exposure to C. burnetii is uncertain, but he did recall that several years prior to the onset of symptoms, he assisted his neighbor with the difficult birth of a calf.