A 65-year-old woman with a history of LSPAF (> 15 years) was referred for thoracoscopic left atrial posterior wall and pulmonary vein isolation combined with left atrial appendage resection. After being treated with amiodarone, digoxin, and beta-blockers for several years, her electrocardiogram remained abnormal. Electrical cardioversions eight and six years before the admission were unsuccessful. Anticoagulant (Rivaroxaban) use was stopped after intestinal bleeding two years before the surgery.
Brain natriuretic peptide on admission was elevated to 1621 pg/mL, while troponin I was negative. Echocardiography showed moderate mitral and tricuspid regurgitation, pulmonary hypertension (mean arterial pressure 41 mmHg at rest), moderate impairment of left ventricular systolic motion, a left ventricular ejection fraction of 50%, and atrial dilatation, with a left atrial diameter of 43 mm. Coronary angiography showed arteries without any sign of obstructive atherosclerosis. Preoperative chest computed tomography (CT) is a part of the protocol for patients undergoing video-assisted thoracoscopic procedures at our institution and it revealed a mass in the superior segment (S6) of the inferior lobe of the right lung ().
In order to follow the institutional protocol for cancer patients and minimize the operative trauma, we performed a totally thoracoscopic resection of the lung lesion and left atrial posterior wall and pulmonary vein isolation. Catheter ablation of atrial fibrillation was not performed because of its controversial efficacy in patients with LSPAF[.
The operation was carried out under general anesthesia with single lung ventilation. The patient was positioned supine with 45° rotation toward the left decubitus position. External pads for emergency defibrillation were placed on the chest wall. The surgeon stood in the right side of the patient to perform segmentectomy first.
Three ports were made, including a 1-cm thoracoscopic port in the 6th intercostal space (ICS) on the scapular line, a 2-cm incision on the middle axillary line in the 4th ICS, and a 2-cm incision in the 5th ICS on the anterior axillary line for resection of the superior segment of the right inferior pulmonary lobe using a thoracoscopic linear stapler (EndoGIA, Medtronic). The tumor had dark grey appearance and was completely included in the S6. The diagnosis of the lesion was confirmed by intraoperative frozen section.
After that, the patient was positioned in supine position on the table to perform left atrial posterior wall and pulmonary vein isolation combined with left atrial appendage resection (also known as GALAXY procedure[). At our institution, the modified GALAXY procedure is routinely used. We increased the number of ablations to 20 for each side (the total number of ablations is 40) with frequent position changing of the device and change of device angulation after 10 ablations (technique described below).
Briefly, the procedure is performed through three thoracic ports with pericardial reflection and sequential single lung ventilation. Soft grey and blue rubber catheters are passed behind the left atrium, above and below the superior and inferior pulmonary veins, respectively, to guide the device advancement while avoiding trauma.
The curved device is firstly inserted into the pericardial cavity from the left side, guided by the soft rubber catheters, up to the patient's spine. Once appropriately positioned, it is clamped over the left half of the left atrium. Lesions are applied guided by impedance drop to confirm transmurality. After each application, the device is adjusted a little to get overlapping lesions. The process is repeated on the right side to obtain isolation of the pulmonary veins as well as a large portion of the left atrial posterior wall ().
The final portion of the procedure is removal of the left atrial appendage with use of a thoracoscopic stapling device (EndoGIA, Medtronic).
After the surgery, the patient was transferred to the intensive care unit and recovered well. Sinus rhythm was restored 12 hours later, after amiodarone infusion and electrical cardioversion.
A perioperative red blood cell transfusion was not necessary. The patient’s postoperative mechanical ventilation time was 12 hours. Postoperative transthoracic echocardiography showed normal ejection fraction and heart chamber. Pathologic examination of the lung lesion showed a well differentiated primary pulmonary mucinous adenocarcinoma. Patient was discharged on the 6th postoperative day.
Three-month, 6-month, and 1-year follow-ups (24-hour Holter monitoring) revealed no sign of recurrence of atrial fibrillation or other supraventricular arrhythmia.
Postoperative therapy included amiodarone, warfarin (canceled after three months), and bisoprolol (the only medicine continued in this patient after the 3-month follow-up).
Chest CT at 3-month and 1-year follow-ups showed no sign of tumor recurrence and good expansion of the residual right lower lobe with no consolidation. No chemotherapy or radiotherapy was needed.


We present a clinical report of a 55-year-old male patient with a past medical history of four open-heart surgeries for aortic and mitral valve replacement. His first cardiac surgery was performed in 2009 and consisted in mitral valve replacement using a bioprosthesis due to symptomatic severe mitral regurgitation related to an anterior leaflet prolapse []. Due to regular sports practice and fearing major bleedings related to anticoagulant therapy the patient refused to receive a mechanical prosthesis at this point.
A year later, he received biological mitral prosthesis replacement for symptomatic severe paraprosthetic leak, with a good postoperative outcome []. In March 2013, he presented to the emergency department with a 2-week history of daily fever. Serial blood cultures were positive for Candida parapsilosis and transesophageal echocardiography showed multiple vegetations attached to the mitral prosthesis and native aortic valve. Given the diagnosis of fungal infective endocarditis, another cardiac surgical approach was necessary, consisting of combined mitral and aortic valve replacement using biological prostheses []. After a 6-week antifungal treatment with liposomal amphotericin-B, the patient was discharged from hospital on suppressive antifungal therapy with oral fluconazole for a year. After 3 years, the patient searched for emergency medical care with a 1-week history of high fever (39 °C). Once again, Candida parapsilosis was isolated from blood cultures and intravenous antifungal treatment with liposomal amphotericin-B was started. Candida endocarditis relapse was confirmed by transesophageal echocardiography, revealing mitral and aortic prosthesis with leaflet thickening and large vegetations with extension into the left atrium (Fig. , panels a, b). Then, the patient underwent his fourth operation: mitral and aortic prosthesis replacement (Fig. ) []. Transient inotrope dependence resulted in a prolonged postoperative intensive care unit period, related to left ventricular dysfunction (ejection fraction of 40%). Once again, a new 6-week liposomal amphotericin-B cycle was performed. This time, the patient definitely remained on suppressive antifungal therapy with oral fluconazole.
During the follow-up period, there was a worsening of the left ventricular ejection fraction up to 25%. Hospitalizations for acute decompensated heart failure became recurrent despite optimized pharmacological treatment and cardiac resynchronization therapy.
Due to clinical deterioration he was admitted to the cardiology unit of our institution with acute decompensated heart failure, requiring inotropic support with dobutamine in addition to intravenous diuretic therapy. After multidisciplinary evaluation, he was included in the national heart transplantation waiting list with priority criteria (inotrope dependence) []. After 3 months of waiting, he finally underwent orthotopic heart transplantation. The initial postoperative period was marked by acute kidney injury, requiring continuous venovenous hemofiltration and hemodialysis. Fortunately, there was a favorable outcome, with effective weaning of vasoactive drugs and recovery of kidney function. Between the 10th and 12th postoperative days, a persistent massive chylous fluid, with a typical “milky” appearance, started to drain from the pericardial tube. The high triglyceride level in the aspirated pericardium fluid (800 mg/dl) was compatible with chylopericardium diagnosis. Initially, clinical treatment with total parenteral nutrition and intravenous infusion of octreotide was attempted. However, after 1 week of treatment, the maintenance of high chylous pericardial drainage configured a clinical therapeutic failure. After a muldisciplinary discussion, invasive lymphangiography was proposed.
Lymphangiography and thoracic duct embolization were performed in a dedicated interventional radiology suit, according to the following steps: (1) inguinal lymph nodes guided puncture followed by microbubble contrast infusion for regional lymphatic ducts anatomic evaluation; (2) lymphangiography with lipiodol infusion (Guerbet, Villepint, France); (3) the lack of contrast impregnation into the upper abdomen and cisterna chyli led to a retrograde access approach; (4) left upper limb phlebography allowed the thoracic duct ostium identification and its retrograde catheterization; (5) thoracic duct lymphangiography showed a lymphopericardial fistula with lipiodol leakage into the pericardical sac; (6) thoracic duct embolization using micro coils and n-butyl-cyanoacrilate glue was performed (Fig. , panel a). The amount of contrast (lipiodol) used was 50 ml and the duration of the procedure was 3 h.
In the first postoperative day, there was a significant reduction in the drainage flow (160 ml). However, in the subsequent days, there was a progressive increase in the daily drainage volume. A new approach was then performed by transhepatic percutaneous direct puncture of the cisterna chyli, using 50 ml of lipiodol contrast. Another thoracic duct embolization with liquid agent n-butyl-2-cyanoacrylate was achieved, taking 3 h of procedure (see Additional file to watch the thoracic duct lymphangiography video confirming the lymphopericardial fistula). In the immediate postoperative period, there was a marked reduction in drainage flow, sustained in the subsequent days. (Fig. , panels b, c).
Finally, after a prolonged period of hospitalization, the patient was discharged in excellent clinical conditions. Table presents a timeline with the main reported events in this case (see Additional file to access a slide set containing details of the case presentation). At the 6-months follow-up, the patient was in good clinical condition and pleased to have recovered his quality of life, without cardiovascular symptoms.


The patient was a 23-year-old Japanese man who was a medical student and belonged to a boating club. Two days before admission, he developed back pain after performing several repetitions of lifting 30-kg weight in a semicrouched position during a training session with the club. The pain was initially mild. On the day before admission, although he had mild back pain, he participated in both morning and evening training sessions. After the evening session, the pain gradually intensified. He waited to see whether the pain would resolve, but he was transported to a nearby hospital by ambulance at midnight because the back pain had worsened, and he found it difficult to move.
Because of the combined symptoms of back pain at rest, hematuria, and a calculus detected in the ureter by computed tomography (CT), he was diagnosed with a urinary calculus and treated with fluids and rest. However, his pain persisted without relief. The following morning, because blood tests revealed elevated creatine kinase (CK) (46,190 U/L) and lactate dehydrogenase (LDH) (1815 U/L) levels, CS was suspected. He was then transferred to our hospital.
Upon admission to our hospital, his condition was as follows: blood pressure, 131/81 mmHg; pulse, 88 beats/minute; oxygen saturation, 100% in room air; respiratory rate, 22 breaths/minute; and consciousness level on the Glasgow Coma Scale, E4V5M6. His abdomen was flat and soft, and no tenderness was observed. The erector spinae muscles were tense, with especially severe spontaneous pain and tenderness in the lumbar region. The skin in the lumbar region was free from blistering or other superficial lesions. No neurological abnormalities, such as muscle weakness or impaired sensation, were observed in the lower limbs. There were no other findings suggestive of CS in the limbs.
Blood tests (Table ) revealed increases in the serum levels of aspartate aminotransferase, 619 U/L; alanine aminotransferase, 157 U/L; LDH, 2050 U/L; creatine phosphokinase (CPK), 53,984 U/L; and myoglobin, 3756 mg/dl. Urinalysis revealed 3+ occult blood and an increased myoglobin level of 6500 mg/dl. Blood gas analysis (Table ) revealed favorable oxygenation, and acidemia was not observed. Because the patient had a history of food allergy, plain CT was performed without contrast media. CT findings revealed swelling of the erector spinae muscles (Fig. ). Although magnetic resonance imaging (MRI) revealed edematous lesions in the erector spinae muscles and low-intensity regions in the lumbar multifidus, there were no clear findings that indicated muscle necrosis (Fig. ). Because paravertebral CS was suspected, compartment pressure was measured in the erector spinae muscles at the fourth and fifth lumbar levels, where the pain was severe. The pressure in the erector spinae muscles, measured at 3, 7, and 12 cm from the iliac crest, was elevated to 105 mmHg on the right side and 64 mmHg on the left side at 3 cm, and 95 mmHg and 48 mmHg, respectively, at 7 cm (Table ). On the basis of these findings, paravertebral CS was diagnosed. A volume load of saline was administered, including 250 ml of 7% sodium bicarbonate, to alkalinize the urine and prevent progression to renal failure due to elevated urine myoglobin levels. After the infusion of sufficient external fluid, administration of D-mannitol was started. Although nonsteroidal anti-inflammatory drugs (NSAIDs) were initially used for pain control, the pain could not be controlled, and continuous infusion of a fentanyl citrate injectable solution was initiated. Urine output was maintained at 1 ml/kg/hour with sufficient infusion (Fig. ); no deterioration of renal function was observed, and pain was controlled by continuous infusion of a fentanyl citrate injectable solution. Thus, conservative management was selected.
The patient’s compartment pressure gradually decreased, and his CPK levels peaked on the first day of admission to the hospital (Fig. ). The infusion of fentanyl citrate was subsequently discontinued and replaced with oral NSAIDs. Infusion was performed only with external fluid. The patient was able to get out of bed on hospital day 3 and returned to attending classes on hospital day 7. MRI performed on hospital day 7 revealed muscle necrosis in the right multifidus muscle and a reduction in edema in the left multifidus muscle. The area of high-intensity change in the right multifidus decreased on T2-weighted images (Fig. ). On hospital day 10, the patient was able to perform activities of daily living without difficulty, despite discomfort in the right lumbar region, and was independently ambulatory. He was therefore discharged. MRI performed 12 weeks after onset revealed no signal intensity changes in the muscles (Fig. ). Mild discomfort persisted in the marked lumbar region, as shown in Fig. . The patient was allowed to resume light sport activities at 24 weeks after onset because he did not feel any pain during his daily activities. Twelve months later, he could play tennis without pain. He reported mild discomfort in the lower back, the area of which decreased over time. The patient was scheduled to report for a follow-up at 24 months after the surgery. He consented to the publication of this case report.


In August 2019, a six-year-old male patient manifested right eye (RE) excessive tearing, conjunctival injection and pain. Family history was unremarkable. The child was born after uncomplicated twin pregnancy, in 37th gestational week, but ultrasound assessment was consistent with 34th maturity week. Birth weight was 2100 g and Apgar score 9/10. Photographs before the event depicted isocoria without anterior segment asymmetry.
On examination, RE demonstrated visual acuity of light perception and intraocular pressure (IOP) of 36 mmHg. Left eye showed no abnormalities. The diagnoses of neovascular glaucoma, CRVO and CRAO were established as affirmed with fluorescein angiography (FA). Extensive systemic work-up was performed. Neurological and cardiologic examinations were unremarkable. Laboratory tests for tuberculosis, Epstein-Barr virus, cytomegalovirus, Toxoplasma gondii, rubella, herpes simplex virus type 1 and 2, and HIV were negative, as well as factor V Leiden (FVL) mutation, MTHFR gene, anticardiolipin antibodies, and lupus anticoagulant. PHA was not reported in any of the findings. The child’s condition was perceived as idiopathic CRAO and CRVO, which led to the development of neovascular glaucoma. The patient was treated with antiglaucoma drugs topically (dorzolamide + timolol 20 mg/L + 5 mg/L drops b.i.d., latanoprost 50 μg/mL drops q.d., and acetazolamide 250 mg q.d.), panretinal photocoagulation, ranibizumab intravitreally and cyclophotocoagulation.
In December 2019, the child was referred to our Centre for second opinion. Clinical examination showed no light perception. The slit-lamp indirect lateral illumination revealed fully dilated, non-reactive RE pupil (Fig. a). Retroillumination verified blood cells in the HA lumen and anterior vitreous (Fig. b). RE IOP was 38 mmHg. Brückner’s transillumination revealed dim red reflex and tubular remnant of HA freely rotating in the anterior vitreous (Additional file 1). Closed angle and clear lens were depicted using ultrasound biomicroscopy (Fig. c). Extensive subhyaloid and intravitreal haemorrhages obscured visualization of fundus periphery and posterior pole (Fig. d). Thus, RE optical coherence tomography (OCT) angiography could not be performed. Ultrasound B-scan affirmed low reflective membranous tubular structure of the persistent hyaloid artery extending freely into the vitreous demonstrating substantial after-movements (Fig. e). It originated within the optic nerve head measuring 4.92 × 1.08 mm (Fig. f).
Vascular occlusion incident was discerned as a consequence of the existence of patent HA in the highly mobile Cloquet’s canal. No therapeutic intervention was currently indicated, but only close follow-up because the patient did not complain of any eye pain.


A 71-year-old woman diagnosed with acute myeloid leukemia underwent, while in complete remission, a nonmyeloablative allogeneic hematopoietic stem cell transplantation with HLA-compatible unrelated donor. Conditioning regimen consisted in fludarabine and total body irradiation; graft-versus-host disease (GvHD) prophylaxis consisted of mycophenolate mofetil and ciclosporine. Following transplantation, the patient presented multiple complications such as a reactivation of CMV disease (CMV serostatus: D−, R+). Ganciclovir was administered without effect on the viral load of CMV. Hence, based on in vitro documentation of resistance of CMV to ganciclovir, the patient was switched to foscarnet. Phosphonoformate crystalluria (proven by infrared spectrometry) was observed 14 days after the onset of foscarnet therapy and associated with a nonglomerular hematuria and renal tubular epithelial cells in urine sediment. Progressive elevation of serum creatinine concentration occurred (AKI Kidney Disease: Improving Global Outcomes [KDIGO] stage 3), despite adaptation of foscarnet doses to kidney function. The patient died after probable fungal bronchopneumonia and septicemia while still on foscarnet.


A 35-year-old man diagnosed with acute lymphoblastic leukemia achieved a second complete remission following salvage chemotherapy after a first relapse. Stem cell transplantation from an HLA-matched unrelated donor was performed following myeloablative conditioning. CMV serostatus was D−, R−. To prevent GvHD, cyclosporine with a short course of methotrexate was administered. Numerous complications occurred after transplantation, including an human herpesvirus 6 encephalitis. For the latter, ganciclovir was started and replaced after 24 hours by foscarnet because of concerns about known associated myelotoxicity with high doses of ganciclovir. Phosphonoformate crystalluria (proven by infrared spectrometry) was observed 7 days after onset of foscarnet associated with a nonglomerular hematuria but without renal tubular epithelial cells in urine sediment. Because of a stable kidney function, foscarnet administration was maintained at unchanged doses. Despite the human herpesvirus 6 encephalitis resolution, the patient died from acute respiratory failure due to uncontrolled bleeding.


A 59-year-old woman diagnosed with acute myeloid leukemia received successfully an allogeneic hematopoietic stem cell transplantation from an HLA-compatible unrelated donor following a reduced-intensity conditioning. The GvHD prophylaxis regimen was mycophenolate mofetil and cyclosporine. In the post-transplantation phase, the patient presented several complications, such as reactivation of CMV disease (CMV serostatus: D+, R+). Foscarnet was initiated and phosphonoformate crystalluria (proven by infrared spectrometry) was observed 7 days after onset of therapy associated with renal tubular epithelial cells in urine sediment. No hematuria was observed. The patient developed AKI KDIGO stage 1 24 days after foscarnet initiation.


This patient was a 63-year-old man who underwent liver transplantation for alcohol-induced cirrhosis. Despite anti-CMV (serostatus D+, R−) prophylaxis, the patient developed CMV infection against what he first received valganciclovir. The viral load of CMV further increasing, the patient was switched to foscarnet; however, phosphonoformate crystalluria (proven by infrared spectrometry) was observed 1 month after onset of the treatment with foscarnet and was accompanied by glomerular haematuria, leukocyturia, and renal tubular epithelial cells in urine sediment. The patient developed AKI KDIGO stage 1 47 days after onset of the treatment with foscarnet. CMV viral load decreased but remained present under bitherapy (foscarnet/ganciclovir, then ganciclovir/letermovir). Elevated creatinine persisted despite discontinuation of foscarnet.


A 73-year-old man, previously diagnosed with myelodysplastic syndrome, underwent hematopoietic stem cell transplantation from an HLA-haploidentical donor. CMV serostatus: D−, R−. GvHD prophylaxis consisted of post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil. In the post-transplantation phase, the patient presented several complications, including oral herpes (HSV1) infection. Because of proven in vitro valaciclovir resistance, foscarnet was introduced: phosphonoformate crystalluria was observed at day 11 after onset of therapy. Neither red blood cells nor any other cells were seen in the urine sediment. The patient developed AKI KDIGO stage 2 at day 12. The viral infection was effectively treated, but the patient died 2 months later due to an invasive fungal infection.


This patient was a 70-year-old woman, diagnosed with high-grade myelodysplastic syndrome. After having achieved remission with systemic chemotherapy, she underwent a haploidentical stem cell transplantation. For GvHD prevention, she received post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil. CMV serostatus: D−, R+. Despite anti-CMV prophylaxis with letermovir, CMV viral load increased from month 3 on, and a preemptive treatment with valganciclovir was introduced. Given a further increment of the viral load despite this treatment, foscarnet was subsequently started. Phosphonoformate crystalluria (proven by infrared spectrometry) was observed at day 9 after onset of foscarnet associated with a nonglomerular hematuria and renal tubular epithelial cells in urine sediment. The patient developed AKI KDIGO stage 1 at day 14.


Patient 1, a 28-year-old male, intravenous drug-dependent patient, presented with an infected aortic graft with recurrent pulmonary bleeding and esophagus fistula. Five years before, he underwent thoracic aorta resection and replacement with a synthetic graft due to aortic coarctation. Over the 5 years, the graft became infected and a paraprosthetic cavity connected to the esophagus with a fistula of 8 mm in diameter was formed (
). Additionally, there were multiple fistulas connecting the paraprosthetic cavity to the left lung parenchyma, which allowed for pulmonary bleeding.
The patient underwent the following 11-hour surgical procedure. After the PSM and gastric mobilization were finished, a right-sided thoracotomy was performed. The esophagus was mobilized and transected 2-cm proximal to the fistula. An en block resection of the upper part of the DAZ, including the graft, the infected paraprosthetic fibrous capsule, and the esophagus was done (
). The pulmonary fistulas were stitched with reverse U-shaped pledget sutures. Ivor–Lewis type esophagoplasty was performed. The zone of the paraprosthetic cavity and lung fistulas was filled with the omentum.
The postoperative period was complicated by stroke causing right-sided hemiparesis. The patient was transferred to the neurology department on the postoperative day 12. The patient was followed up for 7 years (
). Neurology deficit is completely resolved, and patient has returned to his work and stop narcotic use.


Patient 2, a 44-year-old male presented with left-sided pulmonary central adenocarcinoma, T3N0M0, and midthoracic esophageal squamous cell cancer, T3N1M0, with para-aortic metastatic invasion into the thoracic aorta (
). He underwent surgery that lasted 10 hours. After PSM and gastric mobilization were finished, left-sided thoracotomy and combined pneumonectomy with esophageal and DAZ, resection to the inferior pulmonary vein level were performed. Ivor–Lewis type esophagoplasty was done (
).
The postoperative period was uneventful. The patient was discharged on postoperative day 14. Three courses of adjuvant chemotherapy were performed. The patient was followed up for 6, 12, 18, 24, 32, and 40 months (
). Radiological computed tomography (CT) follow-up did not reveal any signs of recurrent tumors in the tumor bed. The patient's condition was stable with very good social activity. CT after 40 months disclosed numerous metastases. The patient died 44 months after our operation due to lung cancer progression.


A multipara 61-year-old postmenopausal woman presented with abnormal vaginal bleeding for 3 months. There was no associated pain or weight loss. She experienced the last menstruation at the age of 53 years. She had regular menstruation from menarche to menopause and never took hormonal replacement therapy. The patient was a known diabetic on oral medication (metformin) with no previous history of surgery and no family history of malignancy. Physical and pelvic examination did not show any abnormality. No abnormalities were observed in the laboratory findings including liver function, hepatitis B surface antigen, hepatitis C antibody, and tumor markers (CEA, CA19-9, and AFP). Cervical cytology was normal, too. Assessment by ultrasound and magnetic resonance imaging (MRI) revealed a hyperechoic mass in the uterine corpus. Furthermore, during radiologic investigation, there was an incidental isoechoic mass in the left lobe of the liver. The patient underwent total abdominal hysterectomy (TAH), right-sided salpingo-oophorectomy, and left lateral liver segmentectomy. During gross pathologic evaluation, dissection of the uterine corpus showed an intramural well-demarcated mass with a greasy yellow cut surface measuring 4 × 4 × 4 cm (). On microscopic examination, the mass was entirely composed of mature adipose tissue with bundles of smooth muscle at periphery, and the histology confirmed pure uterine lipoma (). Endometrium was atrophic, and the right adnexa showed no pathologic abnormality.
Although the radiologic and pathologic findings of the liver mass were in favor of a classic FNH, measuring 8 × 5 × 4 cm, immunohistochemistry (IHC) was done for complete ruling out of hepatocellular adenoma. Glutamine synthetase (GS) stained the hepatocytes in a map-like pattern and confirmed the diagnosis of FNH ().


A 30 years old male patient presented to the hospital with a 2-day history of high-grade fever and headache. Headache was diffuse, moderate to severe in intensity, associated with pain and stiffness in neck, photophobia and vomiting. Condition was not associated with blurring of vision, double vision, vomiting, loss of consciousness or convulsions. There was no history of sore throat, cough, ear pain, ear discharge, motor weakness, sensory weakness, hearing difficulty, altered level of consciousness, abnormal jerky movements or skin rashes. Patient also reported persistent colorless discharge from nose and postnasal drip for 4 months. There was no history of ear fullness, persistent headache or head trauma. Patient was non-smoker and there was no history of alcohol use.
6 weeks ago, patient was discharged from hospital after being treated as bacterial meningitis. The CSF examination for viral PCR and bacterial gram stain/culture was negative. He was treated with a 14-day course of intravenous (IV) ceftriaxone. He had complete recovery of symptoms without any neurological sequalae. During hospital stay at that time, he underwent MRI head which showed large bony defect in the sellar floor with soft tissue in the anterior aspect of the sella with infrasellar extension into the left sphenoid sinus ). Neurosurgery and otorhinolaryngology teams were consulted, and an elective endoscopic endonasal/open repair of the skull base defect was planned as outpatient after resolution of meningitis. Patient still had persistent rhinorrhea during this presentation as he did not undergo repair of bony defect of sellar floor.
Physical examination revealed a young adult well oriented to time, place and person. He was febrile with temperature of 38.9 degrees Celsius. Pulse, blood pressure and respiratory rate was normal. There were no skin rashes or scratch marks. GCS was 15/15. He had normal cranial nerves, motor and sensory examination. Neck stiffness, Kernig’s and Brudzinski’s signs were positive. Cardiovascular, chest and abdominal examination was normal.
Complete blood count revealed neutrophilic leukocytosis with raised C reactive protein. Urea, creatinine, electrolytes and liver function tests were normal. Lumbar puncture was performed and cerebrospinal fluid (CSF) examination showed high white blood cell count with predominance of neutrophils, high protein and low glucose (). Viral PCR of CSF was negative. CSF culture showed gram negative coccobacilli () identified as Pasteurella multocida sensitive to ceftriaxone, ampicillin and penicillin. Blood cultures were negative. After confirmation of the organism, a retrospective history of contact with dogs, cats or other animals was taken which revealed that he often used to feed stray cats who lived around his house. However, there was no history of cat scratches, bites, licks or kisses on any part of the body. Patient was treated with IV ceftriaxone 2 g twice a day for 14 days with complete resolution of his symptoms. He was offered surgical correction of his skull defect, but he preferred to do it in his home country. He was discharged with advice to avoid contact with dogs and cats till surgical correction of bony defect of skull.


A 49-year-old Japanese man was referred to our hospital with dysphagia for solids and food impaction around the neck for several years. His medical history was otherwise unremarkable, and he had not continuously taken any medications for an extended period. A physical examination revealed no abnormalities, and the results of laboratory tests were within normal ranges. Upper intestinal endoscopy revealed a diverticulum on the left side of the cervical esophagus below the piriform recess (Fig. a). There were no mucosal abnormalities or neoplastic lesions in the diverticulum. Barium esophagography showed a left-sided outpouching sac just below the cricopharyngeal bar. This outpouching sac from the cervical esophagus was conspicuous on the front view (Fig. b). Contrast-enhanced computed tomography revealed a 35-mm-diameter diverticulum containing gas and food debris behind the left thyroid lobe, connecting to the cervical esophagus at the level of the cricothyroid cartilage (Fig. c). Based on these findings, the patient was diagnosed as having a KJD. Transcervical diverticulectomy was performed under general anesthesia. An 8-cm collar skin incision was made two fingers above the sternoclavicular joint with a scalpel. After elevation of the skin flap, the left sternohyoid muscles were preserved. The thyroid gland was exposed, and posterior and lower dissection of the left thyroid lobe was performed. The lower border of the left thyroid lobe was mobilized, and the diverticulum was exposed. The thickened diverticulum was identified without difficulty; however, there was adhesion at the base of the diverticulum. The left RLN was identified and marked for monitoring. The diverticulum was carefully dissected from the surrounding tissue using an IONM system (Nerve Integrity Monitoring Response 3.0 system; Medtronic Japan, Tokyo, Japan) (Fig. a). The left RLN is typically located in the tracheoesophageal groove. A handheld probe, which was used to avoid mechanical or thermal injury, revealed that the left RLN was active at the base of the diverticulum. Therefore, it was considered possible to preserve the RLN with a high degree of certainty. The base of the diverticulum was below the cricopharyngeal muscle and lateral to the longitudinal esophageal muscle and was diagnosed as a KJD (Fig. b). In definitive diverticulectomy, a partial cricopharyngeal myotomy was performed to expose the cranial side of the base of the diverticulum. The transection line was selected under the guidance of intraoperative upper intestinal endoscopy to ensure both appropriate dissection of the diverticulum and an adequate caliber of the cervical esophageal lumen. The diverticulum was transected transversally using a linear stapler (Fig. ). Because of the proximity of the RLN course to the diverticulum stump, the staple line was not buried with sutures. To reinforce the staple line, a TGF was prepared. The TGF was directly supplied by the superior thyroid artery and harvested from the superior aspect of the designated thyroid lobe (Fig. a). The size of the left thyroid gland was adjusted to fit and then placed on the area of the partial cricopharyngeal myotomy (Fig. b). The TGF was fixed so that it completely covered the staple line on the cut surface of the thyroid gland (Fig. 4c). Thus, this weakened area was completely covered with the TGF, which had a rich blood flow from the superior thyroid artery. The total blood loss was 79 mL, and the total surgical time was 153 min. Histopathological examination showed a pseudodiverticulum with a defect of the muscle layer, which was compatible with a KJD. The postoperative course was uneventful, without vocal cord paralysis. Postoperative barium esophagography confirmed that there was no leakage or remnant diverticulum (Fig. c). Enhanced computed tomography showed that the TGF was accurately located corresponding to the defect (Fig. d). Oral intake was resumed on postoperative day 3, and the patient was discharged on postoperative day 8. He developed no findings suggestive of recurrence or other complications.


A 58-year-old woman, without any past and family history of psychiatric illnesses, presented with symptoms of catatonia (e.g., extreme forward inclined posture, grim expression, extremely low volume of voice, and limited speech). She appeared to have acoustic hyperesthesia because loud conversations with individuals around her hurt her feelings. Hypopraxia resulted in some pressure sores on her hips. Subsequently, she developed additional depressive symptoms, including depressed mood, inhibition of thoughts, fatigue, low self-esteem, appetite loss, and sleep disturbances with marked psychosocial dysfunction. Her family informed the medical team that her catatonic symptoms were initially observed 7 months earlier and gradually worsened. She reported sharp pain in various parts of her body (mainly, the back), without any causes of the pain that directed her to consult us.
At the time of admission to our hospital, she had been receiving loxoprofen (prescribed by her family practitioner); however, she had discontinued treatment due to the absence of analgesic effects. Blood testing did not reveal signs of infection. Also, she did not show any signs of Parkinsonism other than the tonus enhancement of muscles and extreme forward inclined posture. Computed tomography and magnetic resonance imaging of her brain did not show any albocinereous or cerebrovascular abnormalities. These findings initially suggested that her catatonic symptoms may have been caused by major depressive disorder.
However, her family had not been aware of her depressive symptoms until the catatonic symptoms became obvious. In addition, we simultaneously noticed that her eyes and mouth were extremely dry. She did not present with any specific dermatological and mucosal symptoms of SLE. Pleuritis and pericarditis were excluded using ultrasonography of the heart. Urinalysis did not demonstrate proteinuria or cellular cast. She had leukopenia (1,500/mm3), but not anaemia, lymphopenia, or thrombocytopenia. Antiphospholipid antibodies, antibodies against native DNA, antinuclear antibodies, or antibodies against the Sm nuclear antigen were not detected. However, antibodies against Ro (SSA) were detected in her serum sample (128 U/mL). Schirmer's test showed positive hypolacrimation (2 mm in 5 min). Labial gland tissue biopsy showed several foci of lymphocytic sialoadenitis. According to the American College of Rheumatology Classification Criteria for SS [] and Classification Criteria for SS of the American-European Consensus Group [], we diagnosed this patient with SS.
Because of the presence of pressure sores, we were not able to perform lumbar puncture for the identification of inflammatory pathologies in the CNS. Single-photon emission computed tomography of the head showed multifocal hypoperfused areas (). It has been reported that patchy diffuse hypoperfusion, as a manifestation of abacterial encephalitis, is commonly observed in patients with NPSLE []. Thus, we considered she had an autoimmune pathology in CNS and hypothesised that her catatonia was probably caused by SS rather than major depressive disorder. Subsequently, we performed modified electroconvulsive therapy (ECT) to treat her catatonia.
She received a 20-session course of ECT within a period of 10 weeks. There were no adverse effects that interfered with the treatment, except for minor temporal delirium. Her catatonia was obviously improved along with the other depressive symptoms, including appetite loss and decline in locomotor activity. One week after the final ECT session, her pressure sores had completely resolved, and we were able to collect cerebrospinal fluid through a lumbar puncture for cytological examination. The results showed an increased cell count (10/μL), elevated IgG levels (14.3 mg/dL), and elevated interleukin-6 levels (5.14 pg/mL). The specific gravity and protein levels were within the normal limits. Based on these observations, we confirmed the diagnosis of neuropsychiatric SS.
Following steroid pulse therapy, she has not experienced catatonia for more than 5 years without the need for psychiatric treatments (e.g., antidepressants and ECT).
We obtained written informed consent for publication from the patient.


A 30-year-old female patient was brought to our emergency department 4 h after she developed right-sided hemiparesis, aphasia, right homonymous hemianopia, right central facial paralysis and reduced sensation in the right side of the body while she was at the gym (NIHSS 22). A month earlier, she presented to her local general practitioner (GP) with symptoms including sore throat, lethargy and general malaise. Her GP found no specific abnormalities on thorough general examination. CT of the brain showed already established changes in the left middle cerebral artery territory with an Alberta stroke program early CT score (ASPECTS) of 6. CT angiography of the brain showed a thrombus in the terminal segment of the left internal carotid artery (ICA). Thrombolysis was not performed because of the low ASPECT score on the CT brain. Mechanical thrombectomy was performed using a combination of aspiration and stent retriever, and partial recanalization was obtained (TICI 2a). A day later, the CT of the brain showed haemorrhagic transformation with an intraparenchymal haematoma centred in the left lentiform nucleus and her NIHSS was unchanged. At the same time, she developed rising fever and elevated CRP (145 mg/L). On day 4 of her admission, transthoracic echocardiogram showed vegetation on the aortic valve with associated severe aortic regurgitation. Left ventricular function was unimpaired. Blood cultures were positive for Gram-negative diplococcus, identified as Neisseria gonorrhoeae. She was therefore treated with ceftriaxone and azithromycin. After 3 months, her mRS was 3.


A 67-year-old male patient was transferred from a local hospital to our emergency department 3 h after sudden onset of left sided weakness, sensory disturbance and dysarthria. His NIHSS was 17. The patient was initially admitted for infective endocarditis of his native mitral valve and he was supposed to valve replacement surgery soon. Blood culture was positive for Gemella morbillorum. Computer tomography (CT) with CT angiography showed an occlusion of the M1 segment of the right middle cerebral artery. ASPECT score was 8 (Fig. ). Because of the evidence of endocarditis, intravenous thrombolysis was not considered an option. However, based on the large vessel occlusion, mechanical thrombectomy was performed under local anaesthetic with sedation. Endovascular thrombectomy was then performed with successful aspiration of the clot (TICI 3) (Fig. ). No immediate complications were recorded after the procedure. After 24 h, his NIHSS dropped to 13. Mitral valve replacement surgery was successfully performed 1 month later. At neurological follow-up after 3 months, the patient showed no neurological deficits (NIHSS 0) and mRS score of 0.


A 65-year-old female patient with staphylococcal native mitral valve infective endocarditis had a witnessed onset of right-sided hemiparesis and aphasia (NIHSS 18). The patient was initially admitted in a local hospital for infective endocarditis and treated with teicoplanin and gentamicin. The patient was brought to our emergency department 3 h and 45 min after she developed her stroke symptoms. Her past medical history included also liver cirrhosis, type 2 diabetes, hypertension and breast cancer. CT angiography showed an occlusion of both M2 divisional branches. Intravenous thrombolysis was contraindicated because of the evidence of endocarditis. Mechanical thrombectomy was considered due to the large vessel occlusion. Despite several attempts at aspiration, the clot remained in situ with the final angiography demonstrating a subtotal occlusion of both the M2 divisional branches (TICI 1). After 24 h, her NIHSS was 21 and the CT showed no haemorrhagic transformation. At neurological follow-up after 3 months, her mRS score was 4.


A 38-year-old Filipino patient, G3P2+0 presented to the emergency department on the 18th of October 2019 complaining of acute onset of lower abdominal pain associated with a history of amenorrhea for three months. She was unsure of the date of her last menstrual period and had no previous antenatal follow-up. She was medically free and her past obstetric history included a normal uncomplicated vaginal delivery, followed by a cesarean section which was performed four years back. She had no allergies and was not taking any medication or contraception. Upon presentation, she complained of generalized lower abdominal pain which was of a sudden onset, continuous, not radiating, and not relieved by oral analgesia. The pain was associated with nausea and symptoms of anemia such as dizziness and shortness of breath, but there was no history of loss of consciousness, gastrointestinal or urinary tract symptoms. There was no history of fever or symptoms suggestive of pelvic inflammatory disease.
Upon clinical examination, the patient looked pale and distressed. Her blood pressure was 90/42 mmHg, with a pulse rate of 110 beats per minute. Her abdomen was generally distended and tender on both superficial and deep palpation, with signs suggestive of peritonitis. The digital vaginal examination was positive for cervical motion tenderness and her BhCG Level measured 113000 IU/ml. The examination was complemented by a bedside pelvic ultrasound, which showed an empty uterine cavity as well as a live fetus floating in a moderate amount of free fluid in the pouch of Douglas (Figure ). Her hemoglobin count measured 3.2 g/L, and her total white cell count was 7.5 g/L. Blood grouping and cross-matching of four blood units were immediately sent.
The possibility of a ruptured ectopic pregnancy was explained to the patient, and she consented to an emergency laparotomy with possible salpingectomy. During the laparotomy, a total of 4 liters of intra-abdominal blood was suctioned while blood transfusion was ongoing. A live 13-week fetus was found and removed from the pelvic cavity, and the remains of the ectopic pregnancy (gestational sac and placenta) were found along a ruptured right fallopian tube. The right tube was successfully resected, and the specimen was sent to histopathology. Both the right and left ovaries looked normal. Peritoneal lavage was completed, and a large pelvic drain was inserted. The histopathology report revealed chorionic villi within the lumen of the right tube, which was consistent with tubal ectopic pregnancy (Figure ).
Intra-operatively, the patient received a total of five units of packed red blood cells plus three units of fresh frozen plasma. She was transferred to the Surgical Intensive Care Unit where she was observed for two days. During her ICU stay, she remained hemodynamically stable. Her oxygen saturation was maintained with a 6L O2 face mask. Her chest was clear with bilateral equal air entry. Her abdomen was soft and lax, and the surgical wound was covered with a dressing. The pelvic drain contained hemoserous fluid measuring around 450cc and urine output was adequate. Repeated hemoglobin level post-transfusion was 10 g/L, and her white blood cell count was 15 g/L. Electrolytes were balanced and double antibiotic coverage was initiated along with and anti-stress medications. On post-op day 3, the patient was transferred back to the Gyne ward. She was discharged home in a stable condition five days after surgery.


A 33-year-old healthy male was referred to the emergency department due to blurred vision in his left eye for the past month, accompanied by flashes of light without any accompanying neurological symptoms.
Further investigation ruled out any medical details such as hypertension, obstructive sleep apnea, obesity or known hypercoagulability state. The patient reported a three-week period of fatigue, dry cough, and shortness of breath ended about 2 weeks prior to the ocular symptoms. He was not tested for COVID-19 at the time of his respiratory complaints. Familial and social history were noncontributory. The patient denied smoking or past use of drugs.
At presentation uncorrected visual acuity was 20/20 OD and 20/25 OS. Pupils were equal, round, and reactive to light with an afferent defect OS. Motility and confrontational visual fields were normal OU. He was able to identify 24/24 Ishihara color plates.
On Slit-lamp examination, the anterior segment was within normal limits, including intraocular pressure (IOP). Dilated fundus exam was within normal limits in the right eye. As for the left eye, fundoscopy showed tortuosity and dilatation of all branches of the central retinal vein, dot, blot and flame-shaped hemorrhages throughout all four quadrants, and optic disc edema (A).
Laboratory evaluation was unremarkable with no evidence of hypercoagulability markers such as aPTT (Activated partial thromboplastin time), PT (Pothrombin time), INR (International normalized ratio), LAC RVVT (Lupus anticoagulant Russell's Viper Venom Time), LAC SCT screen (Lupus anticoagulant Silica Clotting Time), Anti-Thrombin-III, LAC SCT ratio (Lupus anticoagulant Silica Clotting Time ratio), Protein C activity, Protein-S antigen, Anti Cardiolipin IgM and IgG, B2 Glycoprotein IgM and IgG, Fibrinogen and D-dimer were performed and were only slightly abnormal.
Neurological examination did not reveal focal neurological deficit. Computed tomography (CT) of the brain and orbits, CT angiography and CT venography showed no pathological findings.
Optical Coherence Tomography (OCT) of the macula was within normal limits (B), and Goldmann Perimetry showed normal visual fields OU.
Fluorescein angiography showed marked delay in arteriovenous transit time, staining of dilated tortuous veins and masking by retinal hemorrhages. All well fit with non ischemic CRVO (A and B).
During admission, a real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 from a nasopharyngeal swab was performed and was found to be negative, however, an IgG/IgM Rapid Test (Inzek International Trading, the Netherlands) was performed and was found to be IgM negative and IgG Positive for SARS-CoV-2, confirming recovery from COVID-19.
The patient was reevaluated at monthly follow-ups up to complete resolution of symptoms and gradually improvement of the retinal vascular appearance.


A 47-year-old male patient with neck mass for 3 years, progressive dysphagia lasting over 6 months and difficulty breathing after exercise for more than 1 month was referred to our department. Ultrasound examination detected a tumor (7 cm × 6 cm × 3 cm) located behind the right thyroid lobe. Preoperative biopsy indicated a spindle cell tumor. Contrast-enhanced computed tomography scan revealed that the tumor was located between the cervical esophagus and trachea, and compressed these structures (Fig. ).
Tracheal intubation and general anesthesia were performed. A U-shaped skin flap was elevated to the level of hyoid bone and the right carotid sheath was exposed and pulled outward. The tumor (7 cm × 6 cm × 3 cm) originated from the right recurrent laryngeal nerve and invaded the esophageal mucosa (Fig. A, B). The tumor, partial right recurrent laryngeal nerve, partial cervical and upper thoracic esophagus were resected. Rapid intraoperative pathological examination indicated a spindle cell tumor. Meanwhile, the tumor-free margins were confirmed by intraoperative frozen section pathology analysis. The semi-circumference defect of the esophagus was about 7 cm in length after complete tumor resection (Fig. C).
Passing through the hypopharynx and down into the distal esophagus, a nasogastric tube was inserted. A FPTAPF with the size of 7 cm × 4 cm, was designed and harvested to reconstruct the esophageal window defect (Fig. A). Once the cervical recipient vessels (including superior thyroid artery, superior thyroid vein, and external jugular vein) were prepared, the FPTAPF was transferred to the defect site. As shown in Fig. B, C, and D, the flap was initially sutured to the residual esophageal mucosa. Microvascular anastomosis, during which 1 artery and 2 veins were anastomosed, was then performed. In addition, the part of right recurrent laryngeal nerve entering larynx was identified. The right ansa cervicalis was used to restore the continuity of the right recurrent laryngeal nerve. A tracheotomy was carried out before skin closure.
The operative time of the procedure was about 3 hours. The flap survived well postoperatively with no operation-related complication observed. Postoperative pathological examination results showed that the tumor was a recurrent laryngeal nerve schwannoma, and invaded the esophageal mucosa. Oral feeding and normal diet were resumed on postoperative day 22 and day 35, respectively. Satisfactory recovery of swallowing function was gained. The patient was weaned from tracheostomy on postoperative day 60. An excellent function of the reconstructed esophagus was observed by esophagography on postoperative day 90 (Fig. A) and no local tumor relapse was indicated by computed tomography during the 2-year postoperative follow-up (Fig. B). Voice hoarseness existed postoperatively but relieved significantly within 3 months after operation.
The report was approved by the Institutional Review Board of West China Hospital. Written informed consent was obtained from the patient for publication of this case report and accompanying images.


A 69-year-old man was referred to our hospital for evaluation of a painless abdominal mass within his left abdomen that was incidentally discovered during assessment for ureterolithiasis. However, according to the patient's medical documents, there was no abdominal mass 4 years ago on computed tomography (CT) scan. He had no history of pancreatitis, trauma, or abdominal surgery. The physical examination did not reveal any abdominal tenderness or a palpable mass. Laboratory tests were normal, including hepatobiliary function, renal function, inflammatory response, and urinalysis. CT scan showed a round and encapsulated 4 × 4 cm mass without any contrast enhancement in the upper left abdomen (Figure ). There was no evidence of lymphadenopathy or distant metastasis of liver and lungs. Magnetic resonance imaging showed that the tumor on the descending mesocolon had high-intensity (SI) portions on T1-weighted images (WIs) and iso-intense portions on T2-WIs compared to the fat. Comparison of iso-SI to the fat showed fat suppression on T2-weighted short tau inversion recovery images. There was a thin rim at the periphery of the mass showing low SI on both T1- and T2-WIs and revealing contrast enhancement (Figure ). Imaging findings could not positively suspect malignant signs, but a 4-cm-sized tumor that suddenly occurred during the last 4 years with no history of pancreatitis, trauma, or abdominal surgery could not completely rule out liposarcoma. Close follow-up was also offered to patients as an alternative to surgeries; however, liposarcoma was undeniable and the surgery was conducted for definitive diagnosis and treatment. The tumor on the descending mesocolon was removed laparoscopically (Figure ). The adhesion around the tumor was peeled and removed without breaking the capsule. There were no adhesion and inflammation in the appendix, appendices epiploicae, omentum, and retroperitoneum around the kidney and ureter. Histopathological findings revealed that the tumor wall comprised hyalinized fibrous connective tissue and the inside of the tumor consisted of degenerated and necrotic fatty tissue of the same size; it was diagnosed as encapsulated fat necrosis (Figures and ). The patient's postoperative course was uneventful, and he was discharged 5 days later. Presently, about 1 year after surgery, the patient remains healthy and has no signs of recurrence or complications.


A 26-year-old female with CF (genotype F508del/F508del), with a baseline forced expiratory volume in 1 s (FEV1) of 21% predicted and a 6-l home oxygen requirement, was undergoing evaluation for bilateral lung transplantation. Her medical history included recurrent respiratory infections with multi-drug resistant pathogens, pancreatic insufficiency, malnutrition requiring percutaneous gastrostomy feeds, atrioventricular nodal reentry tachycardia status post ablation, and the recent delivery of a healthy baby. She had no history of biliary tract stones, cirrhosis, hepatitis B, or hepatitis C. As part of the lung transplantation workup a CT scan of the chest, abdomen, and pelvis revealed a new peripherally enhancing 6.3 cm mass in the right lobe of her liver, and subsequent MRI suggested intrahepatic cholangiocarcinoma. At this time, the patient reported feeling a hard mass under her right ribs along with intermittent right upper quadrant pain and fullness, anorexia, weight loss, and daily subjective fevers for several weeks.
Ultrasound-guided biopsy identified the mass as an adenocarcinoma, with positive staining for cytokeratin 7 (CK7), GATA-3, a transcription factor important in the regulation of certain genes, and p40, a marker of squamous differentiation. Notably, the tumor was negative for estrogen receptor (ER), thyroid transcription factor 1 (TTF-1), cytokeratin 20 (CK20), and high risk human papillomavirus ribonucleic acid in situ hybridization (HR HPV RNA ISH), and therefore did not support tumor origin of breast or gynecologic, lung, lower gastrointestinal, or cervical or head/neck, respectively. Serum tumor markers demonstrated normal alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels, but a markedly elevated carbohydrate antigen (CA)19–9 level of 5949.5 U/mL (0–36 U/mL), which can be elevated in pancreatic, gastric, hepatobiliary, and colonic malignancies. Given the tumor location, serum markers, and pathology findings, the tumor was thought to be most consistent with a primary cholangiocarcinoma.
The patient underwent complete staging following hospital discharge, where radiation therapy with curative intent was recommended. Ultimately her poor performance status, chronic pulmonary disease, and risk of severe life-threatening infection influenced the decision not to pursue systemic chemotherapy or surgery as the initial treatment modality. However, prior to starting treatment, she developed pneumonia leading to acute respiratory failure requiring intubation. A second CT of the chest, abdomen, and pelvis (4 weeks from the initial CT) revealed the liver mass had grown to 13.6 × 10 cm and there were patchy pulmonary consolidations concerning for both pneumonia and metastatic disease. Positron emission tomography (PET) scan demonstrated uptake in the lungs bilaterally, mediastinal lymph nodes, right iliac, and right femur, consistent with metastatic disease. Given her critical condition, it was decided she was no longer a candidate for treatment of her cancer. She was transitioned to home hospice where she passed away approximately 10 weeks after the initial CT.
Autopsy revealed a 20 × 17 × 23 cm tan mass in the right lobe of the liver (Fig. a and b), consistent with intrahepatic cholangiocarcinoma (Fig. c), along with metastatic deposits in the heart/epicardium (Fig. d), bilateral lungs (Fig. e), anterior/posterior cul-de-sacs, left ovary, vaginal adventitia, spleen, diaphragm and bone marrow (Fig. f).
Intrahepatic cholangiocarcinoma can resemble adenocarcinomas from other sites, and because there are no histologic markers that can reliably make the distinction, it is often difficult to distinguish them from metastatic tumors []. Due to a lack of a dominant tumor at other possible primary sites at autopsy, and a morphology showing anastomosing glands in a fibrotic stroma with focal squamous differentiation, cholangiocarcinoma was favored in this case.


A 78 year-old-man with a past medical history of essential hypertension (HTN) presented to his primary care physician with chest pain for one week, retrosternal, radiating to the left arm, dull in nature, brought by walking half a block and alleviated by rest. The patient denied any associating symptoms. He provided us with a treadmill nuclear stress test report that revealed downsloping ST-segment depressions in leads I, II, V4-6, and had to stop after five minutes and 24 seconds due to chest pain and dyspnea. The nuclear imaging did not show perfusion defects. He was referred to our cardiology clinic for further management. He was observed to have profound shortness of breath and clenched his chest upon walking a few steps in our facility. Given his history and stress test result, he was rushed to the emergency department (ED) for urgent coronary angiography.
On arrival to the ED, he was afebrile, had heart rate (HR) 92 beats/min, respiratory rate (RR) 19/min, blood pressure (BP) 145/94, and was saturating 94% on room air. Serum troponin I was elevated to 0.04 ng/mL (normal value is 0.00 - 0.02 ng/ml). Urgent cardiac catheterization revealed 40% stenosis in the left main coronary, 50% stenosis in the proximal and distal right coronary artery. The third obtuse marginal artery had 99% stenosis, which was revascularized using a drug-eluting stent (Figure ). His symptoms were out of proportion to the angiographic findings; hence we sent d-dimer, which was significantly elevated - 3257 (normal value 0 - 500). He remained dyspneic on ambulation; therefore, we obtained an urgent chest CTA, which revealed saddle pulmonary embolus extending into bilateral upper, bilateral lower, and right middle lobe pulmonary arteries and their branches, without infarct. Bilateral lower extremity venous duplex scan revealed acute deep vein thrombus (DVT) in the Left popliteal vein.
Furthermore, transthoracic echocardiogram (TTE) revealed normal left ventricular ejection fraction, increased pulmonary artery systolic pressure (46 mmHg), and moderately enlarged right ventricle with reduced systolic function. Despite optimal anticoagulation therapy initiation, the patient continued to exhibit shortness of breath on minimal exertion and had occasional de-saturations on room air; therefore, he underwent pulmonary angiography and catheter-directed thrombectomy. Pulmonary artery angiography revealed a moderate clot burden in the right pulmonary artery (Figure ).
The patient’s shortness of breath resolved post thrombectomy. He was discharged home on aspirin, clopidogrel, and oral apixaban therapy for anticoagulation.


A 57-year-old female with past ocular history of an eight-cut radial keratotomy (RK) with two transverse incision astigmatic keratotomy (AK) in both eyes and subsequent recurrent corneal erosions (RCE) presented to our ophthalmology clinic complaining of sharp pain and photophobia in the left eye. Notably, she experienced five episodes within the last 12 months of RCEs secondary to the temporal AK of the left eye (OS). Prior treatment for RCEs included bandage contact lenses (BCLs), moxifloxacin, sodium chloride hypertonicity solution, artificial tears, cyclosporine, and most recently anterior stromal puncture.
Screening was within normal limits, with the exception of best-corrected visual acuity (BCVA) being diminished during acute events but returning to 20/20 between episodes. On slit-lamp examination, the patient was noted to have a recurrent corneal erosion with underlying gaping AK inferotemporally of the left cornea. Dilated fundoscopic examination was unremarkable. Initial therapy included BCL, moxifloxacin, sodium chloride hypertonicity solution, and continuation of cyclosporine.
During follow-up over the next several months, the patient reported fluctuating symptoms, denied any subjective improvement, and continued to demonstrate unresolved edema surrounding the temporal AK OS despite management with antibiotics, steroids, topical cyclosporine, artificial tears, sodium chloride ointment, BCLs, and even anterior stromal puncture. Significantly, underlying the area of erosion was a gaping AK incision as seen in image one of Figure .
Due to the persistent nature of the patient’s subjective complaints and increasing frequency of recurrent corneal erosions secondary to gaping AK incision, the patient was counseled and offered a re-approximation of the AK incision using 11-0 suture followed by collagen cross-linking in order to reduce further surgical trauma and promote corneal stromal healing. The epithelium was debrided over the AK incision with alcohol and an 11-0 suture was placed through the AK incision to appose wound edges. Shortly after suture placement, trace aqueous humor was noted leaking from the suture track, however the globe was noted to be stable. Cross-linking was carried out with riboflavin and ultraviolet (UV) light application for 30 minutes in accordance with FDA approved collagen cross-linking Dresden protocol. Repeat images were obtained immediately following the procedure as seen in image two of Figure .
Initial post-operative exam again demonstrated trace fluid leaking around the suture, which was then removed, with subsequent application of ReSure (Ocular Therapeutix, Bedford, MA) and a BCL. Routine post-operative drops prescribed included antibiotics, artificial tears, topical steroid, and promethazine with oral vitamin C 500 mg twice a day.
On post-operative day (POD) #1, visual acuity OS was 20/400 (pinhole to 20/60-2) and fluorescein exam demonstrated wounds were Seidel negative. Trace eyelid edema, conjunctival injection, corneal edema, and anterior chamber reaction were present. POD#1 images reveal a gaping AK wound with ReSure in place, as seen in image three of Figure .
The remainder of her post-op course was notable for repeat ReSure application POD#4. Complete epithelium closure was noted at post-operative week (POW) #2 and remained closed throughout follow-up. Images four through seven of Figure demonstrate continued resolution of corneal edema, epithelialization of the wound, and narrowing over the gaping AK.
Upon final examination at post-operative month (POM) #5, complete AK incision closure with intact overlying epithelium was noted as shown in image eight of Figure . The patient is currently only on artificial tears with uncorrected visual acuity (UCVA) 20/40-1 and BCVA 20/20+2 and remains free from RCE.


We present a case of a 48-year-old female who presented to the clinic for established care. The patient had just been discharged from hospice care due to chronic pain secondary to Dercum's disease. Upon chart review, the patient had a medical history of type 2 diabetes, Hashimoto's disease, migraines, and obesity. Regarding her diagnosis of Dercum's disease, a chart review revealed that the patient began having episodic bouts of generalized pain starting at the age of 40. The pain rate was 7–10/10 during her episodes and could last minutes to days, with the longest episode of generalized pain lasting for 32 days. She also began experiencing migraines along with the pain, accompanied by auras as well as blurry vision and photophobia. Her episodes of pain became more frequent, and she began noticing tender lumps around her abdomen. During one episode, she went to the emergency room due to severe pain. Although her medical records could not be obtained, according to her husband, her lab tests were unremarkable; however, a CT scan of her abdomen revealed many small masses in her subcutaneous tissue. Attempts to obtain the CT scan images were not successful as her husband could not recall the specific emergency room she went to. Subsequent biopsies of the masses revealed histopathologic characteristics of lipomas. The patient's clinical picture was in favor of the diagnosis of Dercum's disease. The patient was discharged and was told to follow-up with her primary care doctor, as well as she was given an appointment with an endocrinologist. The patient saw the endocrinologist for further evaluation, and the patient was diagnosed as having both type I and type II Dercum's disease as she initially had widespread pain in her adipose tissue and then developed painful lipomas. She was referred to physical therapy and was managed in an outpatient setting for years for her pain control which included oxycodone 10 mg BID, ibuprofen 800 mg TID, and alprazolam 0.5 mg TID PRN for anxiety. Upon presentation at the clinic, the patient was accompanied by her husband for established care. The patient reported severe constant diffuse pain, poor appetite, and difficulty sleeping because of the pain. A physical exam revealed multiple mobile, tender masses on her neck, arms, chest, and abdomen. The patient was referred to pain management and hospice care for further evaluation and management. Eventually, the patient was lost to follow-up, and means of communication went unanswered


A 58-year-old female patient presented to the outpatient clinic complaining of a gradual onset of constant left knee pain of a 9-week duration after several visits to her primary care provider as well as an orthopaedic surgeon without improvement. No history of trauma was noted, and her pain was localized to the medial and anterior aspects of the knee. On examination, the patient walked with antalgic gait. Localized medial tenderness was elicited. No swelling nor signs of internal derangement were noted. She was able to extend to 0° and flex to 135°. Knee radiographs were negative with maintained joint space and without evidence of fracture or notable osteoarthritis (Figure , A). The patient was presumed to have mild degenerative joint disease; therefore, she was prescribed naproxen and was sent to physical therapy for 4 weeks. On the follow-up, the pain did not improve, and she started to complain of similar pain affecting her right knee. MRI of the left knee was done that showed a large area of acute bone marrow edema with abnormal signal intensity in the medial tibial plateau measuring 6.5 × 5.2 cm, suggestive of insufficiency fracture (Figure , A and B). The knee was placed in a hinged brace, and the patient started to use a walker for protected weight-bearing. Medial history and medications were reviewed. She had hypothyroidism, hypertension, depression, and allergic rhinitis. Her medication included levothyroxine, escitalopram, hydrochlorothiazide, and intranasal corticosteroids (fluticasone propionate [Flonase] two puffs each nostril twice a day) for several years. She never smoked and often drank 1 to 2 glasses of wine a day.
Because of persistent pain of the right knee, MRI of the right knee was done that showed similar findings but more extensive compared to the left knee with partial collapse of the medial tibial plateau (Figure , C and D). A linear T2-hyperintense signal was identified in the medical and lateral meniscus as well but without definite articular surface tear. At that time, hip radiographs were done that showed no evidence of ON, and new knee radiographs showed bilateral subchondral sclerotic lesions, with collapse of the medial tibial plateau more severe in the right knee (Figure , B). She was treated conservatively with ibuprofen, gabapentin, diphosphonate (alendronate 70 mg once a week), and physical therapy. At 8 weeks of follow-up, her knee pain had become less intense, but she started to experience disabling pain in her left ankle. Ankle radiographs were negative. She was thought to have L5/S1 left radiculopathy; therefore, she underwent left L5/S1 transforaminal epidural steroid injection under fluoroscopy, which did not provide any benefit. Because of continuing pain, MRI of the left ankle was done that showed extensive ON involving the talus and navicular bones (Figure ). The patient received additional tests including connective tissue disease workup (complete blood count, erythrocyte sedimentation rate, C-reactive protein, urine analysis, serum creatinine, rheumatoid factor, antinuclear antibody, antidouble stranded DNA, lupus anticoagulant, and anticardiolipin antibodies), coagulation profile (prothrombin time, international normalized ratio, activated partial thromboplastin time, and fibrinogen), and thrombophilia workup (antithrombin, protein C, protein S, factor V Leiden, and factor VIII) to exclude underlying diseases that were negative.
Follow-up knee radiographs showed progressive collapse of the medial tibial plateau with varus malalignment and secondary osteoarthritis bilaterally. The disease progressed to stage IV according to the Ficat and Arlet classification (Figure ) over 2 years. Staged bilateral total knee arthroplasty (TKA) was performed because of progressively worsening knee pain recalcitrant to conservative treatment (Figure ). Bone histopathology confirmed bone ON. The patient recovered well after TKA, with great improvement of pain and function at the 6-month follow-up. The mean knee injury and osteoarthritis outcome score (KOOS) pain scale improved from 38 before surgery to 83. Similarly, the mean KOOS function in daily living (ADL) scale improved from 37 before surgery to 85. The patient achieved an active range of knee motion from 0 to 128° of flexion, with no extension lag. The left ankle was treated conservatively with solid ankle-foot orthosis to provide some comfort and to postpone the ankle surgery until she recovers from the TKA. The ankle ON progressed with talar collapse and secondary degenerative arthritis of the tibiotalar and subtalar joints (Figure ).


A 77-year-old female with a history of atrial fibrillation on apixaban, non-ST-elevation myocardial infarction (NSTEMI), congestive heart failure with preserved ejection fraction, and hypertension presented to the emergency department (ED) with chest pain. The patient described non-exertional, sudden-onset and severe left-sided chest pain radiating to her left shoulder. Review of systems was positive for shortness of breath, nausea, and diaphoresis. Vital signs were notable for an elevated heart rate and respiratory rate. Physical exam revealed jugular venous distension, irregular rate and rhythm, and 2+ lower extremity edema. Electrocardiogram revealed atrial fibrillation, and labs were significant for an elevated high-sensitivity troponin.
Point-of-care ultrasound (POCUS) in parasternal long view of the heart revealed left atrial enlargement, left ventricular hypertrophy, mitral valve regurgitation, and a hyperechoic structure on the posterior leaflet of the mitral valve representing moderate mitral annular calcification (MAC) with posterior shadowing ( and ). The patient was admitted to cardiology for atrial fibrillation with NSTEMI and further management.


An 83-year-old man with a history of gangrenous cholecystitis requiring cholecystectomy, partial gastrectomy, and Roux-en-Y gastrojejunostomy presented to an outside hospital with severe sepsis and recurrent unstable monomorphic ventricular tachycardia (requiring synchronized cardioversion) secondary to non-ST segment elevation myocardial infarction (NSTEMI). On examination, he was febrile (102.4°F) and hypotensive (systolic blood pressure of 85 mmHg), with generalized abdominal pain, nausea, and vomiting. Labs were notable for troponin, 1.31 ng/mL; total bilirubin, 4.0 mg/dL; aspartate aminotransferase (AST), 157 U/L; and alanine aminotransferase (ALT), 122 U/L. He was intubated and started on vasopressors. The following day, he was taken emergently to the cardiac catheterization lab during which a drug-eluting stent was placed for a coronary occlusion, and the patient was started on dual antiplatelet therapy. Following stabilization of the patient, a magnetic resonance cholangiopancreatography (MRCP) was obtained due to concerns for cholangitis, which demonstrated two large obstructing stones in the common bile duct (larger stone measuring 25 mm in diameter). He was formally diagnosed with severe acute cholangitis, grade 3, according to the Tokyo Guidelines []. He then underwent two unsuccessful ERCPs at an outside hospital (due to an inaccessible major papilla in the setting of SAGA) complicated by an additional cardiac arrest requiring life vest placement. On arrival to Wake Forest, he was noted to be febrile (102°F) and hemodynamically stable. After discussion with the patient and family regarding therapeutic options for choledocholithiasis and cholangitis including PTBD or EUS-HG, the patient elected to proceed with EUS-HG due to less morbidity and patient preference to avoid percutaneous drains. Given the patient's recent NSTEMI, cardiology was consulted and recommended holding dual antiplatelet therapy for no more than 3 days prior to the procedure to minimize the risk of stent thrombosis with immediate resolution 6 hours after procedure.
Upper GI endoscopy revealed a gastric pouch with a patent Roux-en-Y gastrojejunostomy anastomosis (). EUS was then performed using a linear echoendoscope (GF-UCT140-AL5; Olympus Medical Systems, Tokyo, Japan) connected to an ultrasound processor (Aloka Prosound Alpha 10; Hitachi, Tokyo, Japan). With the scope positioned in the gastric pouch, a dilated segment 3 branch was identified in the left lobe of the liver (). The biliary radicle was punctured with a 19-gauge fine needle aspiration (FNA) needle (EchoTip Ultra HD, Cook Medical, Winston-Salem, NC). Following aspiration of the bile, contrast was injected through the needle for cholangiography. Cholangiogram showed diffuse intrahepatic ductal dilation and a dilated common bile duct measuring 18 mm in diameter with two large filling defects consistent with stones (). A 0.025 inch in diameter and 450 cm in length straight tip VisiGlide 2 guidewire (Olympus, Tokyo, Japan) was then advanced through the needle into the biliary tree and past the major papilla into the duodenum. The hepaticogastrostomy tract was subsequently dilated using a 4 mm × 4 cm Hurricane biliary dilation balloon (Boston Scientific, Marlborough, MA, USA) (). An 8 mm × 80 mm GORE VIABIL biliary stent (W. L. Gore Associates, Flagstaff, AZ) was placed in the left hepatic duct with the distal end in the gastric pouch. The metal stent was anchored by a plastic double pigtail stent (7 Fr × 18 cm) with the distal end of the plastic stent placed past the major papilla and the proximal end placed in the stomach (). This procedure permitted decompression of the biliary tract while allowing the patient to recover from his acute infection.
The patient returned for ERCP 3 months after resolution of cholangitis and improvement of his cardiac function. Dual antiplatelet therapy was not held before procedure. Following removable of the plastic stent with a snare from the gastric pouch, the biliary tree was accessed via the left hepaticogastrostomy using a sphincterotome preloaded with a 0.025 inch × 450 cm VisiGlide 2 guidewire. Successful balloon sphincteroplasty was performed using a CRE (controlled radial expansion) wire-guided balloon (Boston Scientific, Marlborough, MA), and the diameter was gradually increased to 15 mm (). Cholangioscopy was then performed using a SpyScope DS (Boston Scientific, Marlborough, MA) with visualization of two large stones in the common bile duct which were fragmented using EHL (). The biliary tree was then swept with a 15 mm stone extraction balloon (Cook Medical, Winston-Salem, NC) with antegrade advancement of stone fragments past the ampulla into the duodenum with subsequent duct clearance (). The patient was followed up in clinic 4 weeks later, and repeat LFTs were normal.


Students were asked to break in to groups of three or four to discuss the vignette of a 14-month-old afebrile male with respiratory distress, copious nasal secretions, with coarse breath sounds, but without wheezing. Students generated a list of differential diagnoses, initial diagnostic, and management plan. The vignette was developed with the intended diagnosis of bronchiolitis, but allowed for the suggestion of alternate diagnoses, such as reactive airway disease or pneumonia. Because students were not initially told that the topic of the session was HVC, we suggested an alternate title for the presentation, such as “Management of the Pediatric Patient,” or another option that does not allude to HVC. The suggested time for this initial activity is no more than 10 minutes.


A 29-year-old systemically healthy non-smoking female reported to the Department of Oral Surgery of the University of Valencia (Valencia, Spain) with mild pain and purulent discharge in relation to the lower left posterior tooth region during the last month. At intraoral examination, the gingival tissue attached to the vestibular surface of the first lower left molar showed the presence of an abscess (Fig. A). The patient reported no history of trauma to the tooth. The first lower left molar had undergone root canal treatment three years ago. From the periodontal perspective, the dentition was sTable and clinically healthy, but tooth 3.6. presented a localized deep probing depth of 9 mm along the vestibular surface of the mesial root. Intraoral periapical radiography of the affected tooth revealed the presence of bone destruction around the roots of the lower molar (Fig. B). An ill-defined radiolucency was observed surrounding the three-thirds of the roots, and compromising the molar furcation.
Cone-beam computed tomography (CBCT)(Planmeca®, Helsinki, Finland) revealed the presence of localized periapical bone loss with loss of vestibular bone cortex and marginal alveolar bone around the mesial root, compromising the furrow of molar 3.6. (Fig. C,D). Based on the CBCT findings, a diagnosis of apicomarginal bone defect was established. The clinical and radiographic examination confirmed persistent chronic apical periodontitis caused by lower left first molar 3.6.
The patient signed the informed consent to treatment and the use of data for scientific purposes. Periapical surgery was performed, with regeneration of the apicomarginal defect with vestibular cortical block autograft and A-PRF + membrane coating.
For A-PRF+ preparation, the median cubital vein was punctured to collect three 10-ml glass tubes without additives (Plain Vacuum Tube, A-PRFTM+, Process for PRF, Nice, France). The tubes were centrifuged at 1300 rpm for 8 min (A-PRFTM DUO centrifuge, Process for PRF, Nice, France). The fibrin clots obtained were extracted with special tweezers and scissors, avoiding the red blood component below the buffy coat, and were further processed to obtain a standardized membrane thickness in a sterile container (PRF-BOX, Process for PRF, Nice, France).
Periapical surgery began with anesthetic infiltration at the bottom of the vestibule of 3.6. using two 4% articaine carpules with 1: 100,000 epinephrine (Inibsa®, Lliça de Vall, Barcelona, Spain). A sulcular incision was performed, with mesial release of 3.5 and another distal to 3.7., with raising of a full thickness trapezoidal flap (Fig. A).
Ostectomy of the vestibular cortex was performed with ultrasound tips (Piezomed®, W&H, Bürmoos, Austria), and a vestibular cortex block with was obtained chisel and hammer (Fig. B).
The margins of the vestibular bone cortex lesion were profiled with a tungsten carbide burr mounted on a handpiece with abundant irrigation of physiological saline solution, allowing visualization of the entire lesion. Then, the periapical inflammatory tissue was removed and the apicoectomies of the two roots of the lower left first molar were performed.
Once root integrity of the first lower left molar was checked, the retrograde obturation box was performed with ultrasound tips (Piezomed®, W&H, Bürmoos, Austria). After proper control of hemostasis with polytetrafluoroethylene strips (Fig. C), it was retrogradely sealed with mineral trioxide aggregate (MTA) (ProRoot®, Dentsply, PA, USA). The MTA was compacted in the retrograde cavity and, after waiting 7 minutes for initial setting, it was polished with a red ring burr (Fig. D). Retrograde filling of the two mesial root canals (Figure 2E) and distal root canal (Fig. F) was checked with an endoscope (Karl Storz®, Tuttlingen, Germany) (Fig. E,F).
Regeneration of the apicomarginal defect was performed with replacement of the vestibular cortex, fixed in the coronal third of the tooth root, which was fixed with a screw (Bone Management® System Master-Pin-Control, Meisinger, USA) (Fig. G), and the buccal cortical autograft and bone defect were covered with A-PRF + membranes (Fig. H).
Suturing was performed with non-reabsorbable 5/0 multifilament suture (Tevdek®, Teleflex®, PA, USA) (Fig. I). The patient was prescribed 500 mg of amoxicillin three times a day for 7 days, 600 mg of ibuprofen three times a day for three days, and 0.12% chlorhexidine rinses during 7 days. The sutures were removed one week later.
One year after surgery, the patient underwent clinical (Fig. A) and radiological evaluation (Fig. B). There were no clinical symptoms, and the tomographic study showed radiological healing of the lesion together with the formation of bone around the furcation of the lower left first molar (Fig. C,D).


This is a case of a 57-year-old Caucasian female who, in September 2019, presented for her annual screening mammogram, which revealed grouped 35 mm x 23 mm x 17 mm coarse heterogenous calcifications in the left breast. Ultrasound-guided biopsy of the mass revealed pleomorphic invasive lobular carcinoma with a signet cell component, which was estrogen receptor (ER) (5%), progesterone receptor (PR) (0%), and HER2neu 3+ positivity by immunohistochemistry (IHC) as seen in Figures - and Figures -. The patient also underwent genetic screening, which was negative. She went on to receive neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab for six cycles followed by surgical resection. She tolerated chemotherapy well with expected toxicities and did not require hospitalization during treatment. After completion of neoadjuvant chemotherapy, she underwent a segmental mastectomy of the left breast with sentinel lymph node mapping of the left axilla and oncoplastic reconstruction with axillary nodal dissection. The entire tumor was measured to be 2.4 x 1.2 cm and was composed of invasive and in-situ lobular carcinoma foci that involved 4% of the tumor bed, as seen in Figures -. Treatment-related changes were seen with a definite response as per the College of American Pathologists (CAP) guidelines. Margins were negative for invasive carcinoma and no lymphovascular invasion was identified. Of the three sentinel lymph nodes removed, macrometastatic (5 mm) lobular carcinoma was identified in one sentinel node and five isolated tumor cells were identified in the third sentinel node. The remaining 15 lymph nodes dissected from the axilla were all negative for metastatic carcinoma. Pathological staging was noted as ypT1a(m) ypN1a pMNA. Due to the residual invasive pleomorphic lobular carcinoma, the patient is currently undergoing trastuzumab emtansine (Kadcyla) for 14 cycles adjuvantly per the KATHERINE trial [].


The patient is a 35-year-old man and a petroleum engineer. He was doing very well with no significant previous medical history of note. He had a history of contact with a COVID-19-positive campmate. There was no history of travel to tropical countries, no family history of heart block or sudden death, neither a previous history of jaundice nor a history of skin rashes. He sought medical advice four days before his referral to our cardiac center because of headache and fever. He was admitted into the coronary care unit into a single negative pressure room and under strict droplet isolation precaution measures. Clinical evaluation revealed a temperature of 38°C, which subsided with one dose of antipyretic. Otherwise, he had stable vital signs and hemodynamics. His oxygen saturation was 98% on room air. His body weight was 85 kg, with a height of 170 cm (body mass index, 29.4 kg/m2). He was found to have severe bradycardia with a heart rate of 33 beats per minute (BPM), with otherwise healthy vital signs and cardiac examination results. He had symptoms of COVID-19-fever and headache. Before initiation of hydroxychloroquine the patient has baseline ECG, which was normal and screened for glucose 6-phosphate dehydrogenase deficiency and it was normal. He was treated with a course of hydroxychloroquine 400 mg orally for the first dose, then 200 mg twice daily for seven days. He also received levofloxacin 200 mg orally for five days and vitamin C 500 mg orally twice daily. On the third day after admission, he developed a skin rash and diarrhea, but both conditions subsided spontaneously. Serial laboratory tests, including a complete blood count and blood differential counts, serum electrolytes, liver function test, renal function test, lipid profile, and arterial blood gas, were within reference ranges. His coagulation profile and cardiac enzymes were both within reference ranges during the first day of admission. Liver functions increased at five days of admission due to possible hydroxychloroquine side effect. Acute phase reactants showed mildly increased C-reactive protein of 2.27 mg/dl (reference range of 0-0.8 mg/dl), erythrocyte sedimentation rate of 42 mm/h, and ferritin level of 525 ng/ml (reference range of 30-400 ng/ml), with healthy low-density lipoprotein (LDL) in the absence of leukocytosis. Arterial blood gas confirmed neither absence of acidosis nor any other acid-base imbalance disorders. Three serial tests of COVID-19 were positive in the first 21 days. Laboratory investigations were performed, as shown in Table .
A chest x-ray revealed normal bronchovascular markings with free costophrenic angles (Figure ). Serial electrocardiograms with Holter monitoring and telemetry records revealed second-degree atrioventricular conduction block (AVB; Mobitz type 2), which progressed to complete AVB. His ventricular rate fluctuated between 32 and 42 BPM with evidence of sinus node dysfunction and left bundle branch block (Figures , ). A temporary pacemaker was implanted immediately to support circulation (Figure ). There were trials to examine the intrinsic heart rate and evaluate his conduction system status. Evaluation of intrinsic rate after five days of admission revealed scattered normally conducted sinus beats, which was interpreted as a possible recovery of the cardiac conduction system (Figure ). Cardiac catheterization revealed healthy coronary arteries (Figure ). As there is no clear-cut reference period in the current medical literature for the maximum time before implanting a permanent pacing system in a COVID-19-based heart block, we planned for a three-week waiting time. This is one week more than our reference waiting time after an atrioventricular (AV) block post cardiac surgery. After 18 days, the temporary system site was inflamed, causing pain and distress. The team decided to implant a permanent dual-chamber system on the same day (Figure ). During the third month after pacemaker implantation, the patient was still having complete AV block and was considered a stage four dependency (pacemaker-dependent).


The first patient was a 70-year-old woman with DCIS. During the MRgFUS treatment, each sonication was performed for 20 s followed by 1 min of cooling time to avoid skin burning. Sixty sonication applications were performed, which required a treatment time of 180 min. The average energy during the treatment was 842 J. Enhanced MRI after the treatment revealed a ring-like enhanced lesion that was caused by necrosis and edema related to the ablation (Fig. ). Histopathology revealed 100% necrosis of the targeted tumor in the post-MRgFUS biopsy specimens and 70% necrosis of the ablated area in the surgical specimens (Fig. ). This was attributed to increased temperature because of ultrasound reflection around the biopsy clip, which caused breast pain. Thus, inadequate sonication energy was presumably used to avoid patient complaint. No severe adverse events were observed after the MRgFUS treatment, such as skin redness or burns. The patient reported shoulder and breast pain that were related to remaining in the same posture throughout the treatment, as well as the excessive temperature that was caused by irregular ultrasound reflection near the biopsy clip (Table ). No breast deformation was observed and 12 scores were obtained by Sawai’s scoring method. The patient underwent adjuvant radiation therapy after surgical resection.


The second patient was a 69-year-old woman. During the MRgFUS treatment, 37 sonication applications were performed with an average energy of 1,625 J and a treatment time of 240 min. Enhanced MRI after the MRgFUS treatment revealed that the center of the ablated area had changed to a low-intensity lesion, which reflected tissue necrosis caused by the ablation (Fig. ). The histopathology findings revealed 100% necrosis of the ablated tumor in the post-MRgFUS biopsy specimens and 40% necrosis of the ablated area in the surgical specimens (Fig. ). The lower necrosis value in the surgical specimen was also presumably related to inadequate ablation energy that was related to increased temperature caused by ultrasound reflection around the biopsy clip. The patient did not experience skin redness or burns (Table ), had a good cosmetic outcome (12 scores by Sawai’s scoring method), and completed adjuvant radiation therapy after surgery.


A 9-year-old boy of Italian descent was referred to our Pediatric Department with a one-year history of abdominal pain, progressive poor scholastic performance and gait disturbance in absence of a clear diagnosis. At the age of 8 years and 2 months he had been hospitalized for severe abdominal pain of unknown origin. The stools were normal without history of constipation or diarrhea. All routine laboratory tests were normal. An abdominal ultrasonography, esophageal gastroduodenoscopy and colonoscopy with mucosal biopsies, and an abdominal CT-scan were sequentially performed, without evidences of any abnormality. Common causes of pediatric abdominal pain such as peritonitis, appendicitis, cholecystitis, pancreatitis, intra-abdominal abscesses, malignancy, inflammatory bowel disease, vasculitis and pleural abnormalities, malignancies, eosinophilic gastro-enterocolitis and inflammatory bowel disease were ruled out. Fecal cultures, parasitic examination and virus polymerase chain reaction test on stools all resulted negative. Family history was negative for psychiatric disorders, and absence of emotional or anxiety disorder was assessed by a pediatric psychiatrist.
After discharge the pain gradually and spontaneously remitted over the next 2 months. Six months before our evaluation he experienced learning difficulties with attention deficit and irritability, in addition, he developed difficulty in walking.
When he was admitted to our Department he presented with ataxic gait, difficulty in speaking and attention deficit. Physical examination was unremarkable except for bilateral patellar areflexia and sensory ataxia with positive Romberg sign. Routine laboratory values (including erythrocyte sedimentation rate, C-reactive protein level and white cell count) were normal. Nerve conduction studies of the lower limbs showed bilateral slowed conduction in the peroneal motor nerves. Brain and spine magnetic resonance imaging (MRI) showed a diffuse contrast enhancement of the leptomeninges and of the III, V and VII cranial nerves, as well as of the cauda equina nerve roots, with multiple bilateral T2-hyperintense lesions in periventricular white matter. CSF analysis showed lymphocytic pleocytosis (290 cells/mm3 – normal values < 5 cells/mm3), low glucose level (15 mg/dl - normal values > 50 mg/dl), hyperproteinorrachia (587 mg/dl - normal values < 45 mg/dl). Bacterial blood and CSF cultures were negative as well as a multiple molecular assay panel for meningitis and encephalitis (BIOFIRE® FILMARRAY® ME Panel, BioMerieux Italy) for the most common bacteria and viruses linked with encephalitis.
Angiotensin-converting enzyme (ACE) activity on serum and CSF was negative excluding neurosarcoidosis.
Antineuronal antibodies were negative (i.e. anti-NMDA-R, anti-AMPA-R, anti-GABA, anti-CASPR2, anti-Hu, anti-CV2, anti-RI, anti-Yo, anti-amphiphysin, anti-GAD, anti-Sox1). CSF oligoclonal IgG bands were found at immunofixation and Lyme neuroborreliosis was considered.
The Clinical Microbiology Laboratory used a cytospin slide centrifuge to prepare CSF Gram stains. Cytospin smears were prepared by centrifuging 0.2 mL of CSF at 2000 rpm for 10 min and staining it with conventional Gram staining, slides were examined by light microscopy at 100x magnification to allow quantitation of CSF cells: many activated mononuclear cells and some polymorphonuclear cells were identified, without evidence of bacteria or malignant cells (Fig. ).
Serum Borrelia burgdorferi-specific IgG were detected (enzyme-linked immunosorbent assay ELISA followed by Western Blot positive for anti-VIsE and anti-p14, 21, 30). Specific antibodies in CSF were tested in an enzyme immunoassay (IDEIA Lyme Neuroborreliosis). Borrelia burgdorferi IgG index was 12.6 (references: < 0.3) and B. burgdorferi IgM index was 10.1 (references: < 0.3) which indicate intrathecal production of specific antibodies consistent with neuroborreliosis. Diagnosis of LNB was thus confirmed. Detection of Borrelia burgdorferi-DNA PCR resulted negative in the CSF. Indeed, a thorough past medical history collection evidenced that the onset of abdominal pain started 2 weeks after a tick-bite episode occurred during a walk in the wood. Neither the patient nor his parents showed any skin rash. According to the latest European clinical guidelines for LNB, the boy was treated with a course of intravenous ceftriaxone (3 g daily for 3 weeks) []. Furthermore the treatment was prolonged with oral amoxicillin (2 g daily for 3 weeks) considering the disseminated and long-lasting illness []. Three months thereafter, CSF findings had remarkably improved (20 cells/mm3, proteins 127 mg/dl, glucose 70 mg/dl) (Table ). Similarly, we recorded a slight improvement in gait and better scholastic performances. At the one-year follow-up visit, complete neurological recovery was observed, without any recurrence of abdominal pain. The patient was considered completely healed, without specific signs and symptoms.