The patient, Ms. A, was a 55-year-old woman of Caribbean descent with a history of type 2 diabetes mellitus and hypertension with no past psychiatric history. Before admission, she had not been on any medications for her diabetes or hypertension. Ms. A initially presented to the hospital with shortness of breath, intermittent productive cough with white sputum, chest tightness, chills, sporadic headaches, anosmia, loss of taste, and malaise for one week in the context of receiving the first dose of Moderna coronavirus disease 2019 (COVID-19) vaccine (Moderna, Inc, Cambridge, MA) nine days ago. She reported a gradual worsening of the symptoms mentioned above and denied any recent travel or sick contact. On arrival to the emergency room, the patient tested positive for COVID-19 and was noted to have hypoxia with oxygen saturation of 87% and tachypnea with a respiratory rate of 24 bpm. On physical examination, the patient was alert and oriented, in distress, with normal heart rate and regular rhythm with the presence of rhonchi. Motor strength and sensations were intact with no focal neurological deficits.
Laboratory evaluation showed positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and chest X-ray showed ill-defined bibasilar opacities. EKG showed normal sinus rhythm. She was subsequently admitted and treated for acute hypoxic respiratory failure secondary to COVID-19 pneumonia. During the hospital course, she was noted to have elevated potassium of 5.1 mEq/L (improved to 4.2 mEq/L with Kayexalate), elevated lactate dehydrogenase of 563 U/L, ferritin of 212 ng/mL, and C-reactive protein of 27.2 mg/L. Also noted were elevated prothrombin time of 13.5 seconds, normal activated partial thromboplastin time (aPTT), normal d-dimer levels of 193 ng/mL, low to normal calcium levels from 8.2 to 8.6 mg/dL, elevated glucose of 113 mg/dL, and normal sodium, magnesium, phosphorous, and kidney and liver function tests. White blood cell count was 4.2 x x 109/L with a hemoglobin of 12.5 g/dl, and tests were negative for the respiratory syncytial and influenza viruses. On day one, Ms. A was treated with 3-6 L of oxygen supplementation, dexamethasone 6 mg IV for seven days, remdesivir 100 mg for five days, and deep vein thrombosis (DVT) prophylaxis with enoxaparin 40 mg. She was hemodynamically stable and discharged from the hospital after 11 days of admission on 4 L/minute of supplemental oxygen via nasal cannula. She did not have any psychiatric symptoms during this hospital course.
Two weeks after the initial hospital admission and three days after discharge, Ms. A presented to the hospital with complaints of a one-day history of bizarre abnormal behavior. While in the emergency room, the patient showed agitated behavior, pressured speech, and paranoid grandiose religious delusions. She refused to take medications by mouth given by the hospital and only wanted to take medications brought from home and complained that these were taken away from her by the hospital staff. She reported that she only wanted to take a blood thinner and did not want to take any medications by mouth, as per the wish of Jesus Christ. She said that Jesus Christ would cure her COVID-19 and that Jesus was her savior. On physical exam, Ms. A was alert and oriented to time, place, and person, with normal motor strength and normal heart rhythm and breath sounds. EKG showed sinus tachycardia with a ventricular rate of 120 bpm with premature atrial complexes and voltage criteria for left ventricular hypertrophy with repolarization abnormality. Chest X-ray showed hazy bilateral lung infiltrates, cardiomegaly, and mildly increased pulmonary vascularity. While in the emergency room, she removed the monitoring wires, threw oil on hospital staff, and was given intravenous diphenhydramine 25 mg, haloperidol 5 mg, and lorazepam 2 mg.
Ms. A was then admitted to the inpatient psychiatric unit. MRI of the brain was performed, which was unremarkable. Vitamin B12, rapid plasma reagin (RPR), and HIV tests were also unremarkable, and there were no electrolyte abnormalities. Physical exam findings were unremarkable for infectious cause or focal neurological deficits. During this hospital course, Ms. A showed paranoid behavior with delusions, poor insight and judgment, poor impulse control, and hyperverbal and pressured speech; she was very theatrical, noted to be hugging the TV, religiously preoccupied, delusional, and difficult to redirect. There were also episodes of the patient pacing back and forth, being loud, and yelling and screaming in the hallways.
Ms. A stated that God continued to speak to her in Gospels and that she had the blood of Jesus and that she did not have COVID-19. She reported not sleeping at all for the last three days. Ms. A complained that she had been poisoned about 10 years ago by her sister-in-law and admitted to a hospital; however, her husband denied this. There were no diurnal or nocturnal fluctuations in her paranoid behavior, and she was alert and oriented throughout the hospital course. She denied suicidal or homicidal ideation, intention, plan, auditory or visual hallucinations, or any history of self-harming behavior.
The patient used to work as a certified nursing assistant and worked with hospice patients. The last time she had worked was three weeks ago. Ms. A had been married for about 10 years and had four adult children from her previous marriage. Her brother had also been diagnosed with steroid-induced mania and psychosis a few days ago. There was no other family history of mental health diagnosis. There was also no prior psychiatric history or abnormal behavior as per family members and the patient's pastor.
Ms. A was treated with oral haloperidol 5 mg twice daily for psychosis, sodium valproate 500 mg twice daily for mood stabilization, acetylcholine 1 mg orally twice daily to prevent extrapyramidal symptoms, and clonazepam 1 mg twice daily for anxiety and insomnia. She responded well to milieu therapy and medication management. Her hygiene and grooming improved, and the patient reported feeling better, tolerating the meals, and sleeping better. She denied any active psychotic, manic, or depressive symptoms, and was less religiously preoccupied but continued to pray for humankind to get cured of COVID-19.
Ms. A’s insight and judgment improved, and haloperidol was discontinued and switched to aripiprazole since it had a lesser side effect profile. She was then discharged after four days of hospital stay on oral aripiprazole 10 mg once daily and sodium valproate 500 mg twice daily. Three weeks after discharge, she reported feeling better and did not want to continue these medications. She stopped taking both medications and exhibited no mood changes or psychosis during monthly outpatient follow-ups for three months.


A 48-year-old female presented to the emergency department due to concern for fatigue, weakness, and delayed reactions. Her mother was her primary caregiver and described that the patient had been functioning at a level lower than her baseline status. She was unable to participate as usual in physical therapy the day prior due to “lifelessness” and appeared more tired than normal. The patient’s past medical and surgical history was complicated. She had a history of complex partial seizures sometimes with secondary generalization since age three. Etiology remained unknown, as there was no known history of brain injury or trauma, the patient met all of her developmental milestones on time, and was mainstreamed throughout her schooling years with infrequent seizures. During her late teenage years, she was seizure-free on phenobarbital and phenytoin and graduated from high school on time and without difficulty. However, her seizures returned a few years later, and they became increasingly resistant to multiple medications as she aged, requiring placement of a VNS at age 32 in addition to her medication regimen of four anti-epileptic drugs (AEDs). For a short time, the patient's seizure frequency improved, but by age 34, the frequency had increased so much despite maximal medical therapy and trialing more than 10 AEDs that the patient underwent right anterior temporal lobectomy. At ages 39 and 44, she underwent an uncomplicated replacement of her VNS battery. At age 46, her seizure frequency increased again, with multiple nocturnal seizures. Approximately one year later, at age 47, she underwent craniotomy for invasive EEG monitoring with subdural grid placement, followed by residual anterior-superior temporal lobectomy and frontal corticectomies. Her hospital course was complicated by a perioperative ischemic stroke in the right MCA territory, with scattered foci of infarct in the right frontal lobe and right posterior parietal lobe seen on MRI (Figure ). This manifested as increased somnolence, left-sided hemiplegia, including left facial weakness, left-sided hypoesthesia, left-sided hemineglect, and left-sided hemianopsia. The etiology of her stroke was felt to be due to arterial thrombosis in the right MCA territory secondary to operative cortical vessel injury. Her clinical status improved substantially over the next two weeks but, on discharge, the patient required 24/7 care as she had a residual left-sided flaccid weakness that necessitated a wheelchair for ambulation. On the day of presentation, the patient's mother confirmed that the patient had been participating in routine physical therapy since her stroke 1.5 years prior and was receiving botulinum toxin therapy at regularly scheduled neurology appointments for left upper extremity spasticity. Her vision deficits had resolved, with no evidence of visual field deficits or hemineglect on subsequent exams. She had remained seizure-free since her last procedure. The inpatient neurology service was consulted to evaluate her for the decreased functional status.
The patient stated that although she was tired the day prior to the presentation, she was now back to her baseline. Her mother reported that the patient had seen her neurologist in the clinic two days before this visit; her escitalopram was discontinued and duloxetine started instead for migraine headaches and depression. The remainder of her medications were unchanged, including her nortriptyline for headache prevention and her antiepileptic drugs (lacosamide 250 mg bid, clobazam 15 mg bid, brivaracetam 100 mg bid, gabapentin 100 mg bid, lorazepam 1 mg tid as needed for two breakthrough seizures within a 24 hour period. bid: bis in die or twice a day, tid: ter in die or thrice a day). A complete review of systems was performed and was negative. On examination, she was alert and oriented with no evidence of change in her mental status from baseline. Her strength was 4+/5 in the right upper and right lower extremity. Her strength was 0/5 in her left upper and left lower extremity, with spasticity present in her left upper extremity, unchanged from her baseline.
However, one new finding was present; she was noted to have abnormal, fast conjugate eye movements to the left that were associated with each blink (Video ). These eye movements continued to be present even after the patient’s ability to fixate on an object was removed with the use of Frenzel goggles (Video ). The patient denied any subjective changes in her vision. Her pupillary responses were intact and she had normal visual acuity. She exhibited normal extraocular movements. It was unclear how long this finding had been present as the patient and her mother were unaware that these eye movements were happening and had not noticed them previously.
The patient's laboratory workup was normal. Review of her most recent MRI of the brain completed 10 months prior (eight months post-stroke) showed encephalomalacia and surrounding gliosis in the right MCA territory, including the right corona radiata, with right temporal laminar necrosis, microhemorrhages in the right basal ganglia and right parietal lobe, ex vacuo dilatation of the right lateral ventricle with Wallerian degeneration of the right cerebral peduncle, and interval development of a rightward midline shift secondary to the chronic right cerebral convexity volume loss (Figure ). The change in functional status the day prior was attributed to the patient's recent medication changes. Ultimately, she was deemed safe for discharge home with no changes to her medications. Since this consult, the patient has been examined numerous times at follow-up visits for management of her epilepsy and spasticity and continues to demonstrate the same abnormal blink-associated conjugate eye movements despite discontinuation of her duloxetine.


A 49-year-old woman with no past medical or psychiatric history was admitted to the inpatient psychiatric unit with suicidal ideation. For the past two weeks, the patient's family members reported that the patient expressed thoughts that the world was ending. She was not sleeping, was increasingly agitated and not eating, and had an 8-pound weight loss. She had expressed thoughts of wanting to jump in front of the train, feeling morbidly guilty and hopeless. She also reported feeling helpless with multiple deaths in the city due to COVID-19, and the situation reminded her of her grandmother's death due to cancer. She also had paranoid delusions with nightmares and felt responsible for her grandmother's death due to cancer about 40 years ago.
She was a high school graduate and worked as a hairdresser and cleaner in a hair salon for 15 years. She stopped working a month ago due to COVID-19 and reported being stressed about this. She lived in an apartment with her three children, a 25-year-old son, a 22-year-old son, and a 12-year-old daughter. She had periodic contact with the father of her children, who lives in a different state. She also broke off a one-year romantic relationship with her boyfriend about two months ago. She denied a history of sexual or physical abuse as a child. She had no past psychiatric history or suicide attempts or substance use or criminal history and no family history of depression.
She also had a three-week history of on and off cough with a reduced appetite and anosmia but denied fever, malaise, and body aches. On examination, she was guarded, withdrawn, disheveled, and depressed with constricted affect. She was alert and oriented to time, place, and person with no focal neurological deficits. Besides, her memory and concentration were intact with a goal-directed thought process, however, with limited insight and judgment. Bloodwork showed normal white cell and platelet count, hemoglobin and hematocrit, and normal glucose and electrolytes, kidney, liver, and thyroid function tests. Urinalysis showed moderate leucocytes, trace blood, trace protein, positive for ketones and negative for nitrite and glucose. Urine microscopy showed few bacteria, 25-50 white cells, 5-10 red cells, moderate epithelial cells, and moderate mucus threads. Drug toxicology screen and lithium, carbamazepine, and valproic acid levels were negative. She tested positive for SARS-CoV-2 on admission. Oral aripiprazole 5 mg was started for psychotic symptoms, and the dose was titrated up to 7 mg. She was also started on oral escitalopram 10 mg for depressed mood, lorazepam 2 mg for anxiety, and oral mirtazapine 15 mg for poor sleep and poor appetite. Oral azithromycin and oral Hydroxychloroquine were started for SARS-CoV-2 infection for five days. Chest x-ray, EKG, and CT head were unremarkable.
On day four of hospital admission, she continued to express suicidal ideation and wanted to starve herself. She remained withdrawn, guarded, with poor appetite and sleep. She also had a brief catatonic episode of muteness for less than a minute. Subsequently, she got up from her bed, was agitated, and tried to run out of her isolation room. Repeat blood work showed normal white count, normal hemoglobin, platelets, electrolytes, and renal and liver function tests. She was given haloperidol, diphenhydramine, and lorazepam. Aripiprazole was discontinued and she was started on oral metoprolol for hypertension and oral olanzapine 7.5 mg for psychosis, poor sleep, and poor appetite, and the dose was slowly titrated up to 20 mg. With this regimen, clinical improvement was noted from admission days four to 15, and the patient’s depression, appetite, and behavior improved, with no suicidal ideation. There was a plan to send the patient home on day 16. However, on the scheduled discharge day, she reported a loss of appetite with paranoid behavior and she complained that she would be investigated and arrested if she left the hospital because she had COVID-19, so she did not want to leave the hospital. On examination, the patient was alert and oriented but showed guarded behavior and limited judgment. Subsequently, the olanzapine dose was increased to 25 mg, and oral aripiprazole 2 mg was re-started. From days 17 to 21, she showed clinical improvement, mood improvement, and improvement in her thoughts with no more paranoid behavior and no suicidal or homicidal ideation. She was subsequently discharged home on day 21 on olanzapine 25 mg, escitalopram 20 mg, and mirtazapine 15 mg, and metoprolol 25 mg. She had outpatient follow-ups with a psychiatrist after discharge and did not exhibit paranoid behavior or manic episodes. Olanzapine was stopped two months later due to akathisia as an adverse effect. Eight months after initial hospitalization, she was re-admitted to the inpatient psychiatric unit for grandiose, erratic, disorganized behavior at home, verbal aggression at work, and violently confronting strangers on the street. She was treated for 20 days in the inpatient psychiatric unit and diagnosed with bipolar disorder (current episode manic) with psychosis. She was then discharged on oral risperidone 3 mg twice daily, valproate 500 mg twice daily for mood, and metoprolol 25 mg once daily for hypertension.


A 56-year-old African American woman with a history of hypertension and not on any medications at home with no past psychiatric history was admitted to the hospital with acute hypoxic respiratory failure secondary to COVID-19 pneumonia.
On arrival to the emergency room, she was noted to be hypoxic on room air and required high flow oxygen therapy, and tested positive for SARS-CoV-2 infection. She reported symptoms of shortness of breath, chills, cough for two weeks. Her husband was sick at home for two weeks, and her boss was also ill at work. Physical examination revealed the patient was in acute distress with labored breathing and was speaking in short sentences. She was alert and oriented with a normal neurological exam with no focal neurological deficits. Urinalysis was not performed. Inflammatory markers including ferritin, C-reactive protein, sedimentation rate, and D-dimer were elevated. Chest x-ray showed extensive airspace consolidation throughout both lungs, consistent with extensive bilateral pneumonia. Chest CT angiogram revealed bilateral diffuse pulmonary infiltrate with mild cardiomegaly, no pulmonary embolus, and no pleural effusion.
She was then admitted to the inpatient unit for acute hypoxic respiratory failure and treated with vitamin C, vitamin D, zinc, one dose of monoclonal antibody, tocilizumab, dexamethasone for 10 days, and remdesivir for five days. In addition, she was treated with full-dose of enoxaparin for elevated D-dimer levels. She was also diagnosed with new-onset type 2 diabetes mellitus with a hemoglobin A1C of 14.4 and was started on insulin. Throughout this hospital admission, her oxygen requirement progressively decreased as she was weaned off from high flow nasal cannula to nasal cannula and then room air.
She exhibited altered mental status with bizarre delusions and agitated behavior during this hospital admission. She claimed that her boss had poisoned her and that the blood work would prove it. Her son provided collateral history and mentioned that her boss gave her antibiotics, possibly azithromycin and ivermectin, supposedly obtained from Tanzania. She took the antibiotics for a week and stopped a few days ago. Few days before the hospital admission, she experienced hallucinations and bizarre delusions and talked about "numbers on the wall." There was no prior history of psychiatric illness, no history of similar complaints in the past, no history of suicidal/homicidal ideations, no family history of mental illness, no family history of suicide, no drug use, and no other instances of paranoid behavior. She is a teacher at a daycare and the primary caregiver for her boyfriend and lives with her boyfriend and has three children, two sons and one daughter.
She mentioned that the board of education sent her as an undercover to observe and investigate and shut down this hospital. She also reported visual and auditory hallucinations, seeing numbers all over the walls, and the spirit of God was talking to her. She also reported mania-like symptoms with inflated self-esteem, easy distractibility, circumstantial thought process, rapid speech, racing thoughts, poor sleep at night, and despite minimally sleeping, she felt energetic before coming to the hospital. The plan was to start the patient on antipsychotics for her acute psychosis; however, these were initially placed on hold due to a prolonged QT interval of 550 milliseconds on EKG on admission. Urine drug screen, rapid plasma reagin (RPR) test for syphilis, and HIV testing were negative. Two samples of blood culture showed no growth after five days of incubation. CT head was normal. She exhibited paranoid behavior, believing that she was raped during this hospital stay. She thought the hospital had killed the patient next to her bed, and the staff was laughing at her. She was given oral aripiprazole 5 mg and intramuscular olanzapine 5 mg and was then discharged to an outside facility for further psychiatric management due to COVID-19. There was no follow-up after discharge.


We report the case of a 37-year-old male with a past medical history of essential hypertension and hyperlipidemia who was transferred to our hospital for further ongoing care for colitis and hematochezia in settings of possible bleeding disorder. The patient was initially presented to another hospital with a one-week history of diffuse abdominal pain, bloating, and a three-day history of bright red blood per rectum. He also reported multiple episodes of vomiting and one episode of gross hematuria. The patient also reported a six-month history of fatigue, generalized body weakness, cold intolerance, swelling in his arms and legs, easy bruising, and unintentional weight loss of 20 pounds over six months duration. In October 2020, he had an episode of profuse gum bleeding after a dental procedure, and he has been currently being worked up by hematology as an outpatient for von Willebrand disease (VWD) versus hemophilia. He had a remote history of proteinuria and was following by nephrology outpatient, but a biopsy was not pursued in the setting of bleeding disorder workup. We were consulted as he was found to have nephrotic range proteinuria with a 24 hr urine protein of 4.61 gm.
On examination, he was afebrile with a blood pressure of 105/64, tachycardia with a heart rate of 112, and normal oxygen saturation on room air. He was in no acute distress. His cardiac and pulmonary exam was unremarkable. Abdominal examination revealed mild diffuse tenderness and dullness on percussion. He had +2 non-pitting edema in the lower extremities. The skin was dry, and no rash was noted. Ultrasound abdomen was done, which showed hepatomegaly with findings of portal hypertension with the slow flow in the main portal veins, recanalized umbilical vein, pericholecystic edema, reversal flow within the splenic vein at pancreas, splenic siderosis, splenic varices, and moderate ascites.
Laboratory workup (Table ) revealed acute kidney injury (AKI) with serum creatinine of 1.88 mg/dl (baseline creatinine around 1 mg/dl), hyponatremia, hypoalbuminemia, and hyperlipidemia. Hepatitis and human immunodeficiency virus (HIV) serology were negative. Autoimmune workup showed negative antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), and anti-glomerular basement membrane antibody (anti-GBM), normal complement C3, high complement C4, and elevated beta-2 microglobulin. Urine analysis and microscopy showed no white blood cells (WBC) or red blood cells (RBC), random urine protein above 500. 24-hour urine protein showed 4.61-gram proteins, urine protein to creatinine ration of 5.54, and normal serum immunofixation pattern. No monoclonal immunoglobulins were detected. Serum protein electrophoresis (SPEP) report showed increased alpha proteins. No monoclonal immunoglobulins were detected. A urine immunofixation report identifies a free lambda monoclonal immunoglobulin representing less than 10% of total urine protein. The free kappa level was high, and the free lambda level was high; however, the kappa to lambda ratio was low.
A renal biopsy was performed. The tissue process for light microscopy is a single length of renal cortical tissue with a total of 11 glomeruli, four of which are globally sclerotic. The remaining glomeruli revealed a diffuse and global non-nodular increase in eosinophilic extra-cellular mesangial metrical material. The material was weakly PAS positive, silver negative, Congo red positive, and demonstrated apple-green birefringence when examined under polarized light (Figure ). There were occasional sheaf-like projections perpendicular to the glomerular basement membrane that were highlighted with the Jones silver stain. Tubule demonstrates PAS positive cytoplasmic protein droplets. There is no significant interstitial inflammation. There is mild interstitial fibrosis/tubular atrophy. The mesangial material demonstrated monotypic immunoreactivity for lambda light chains without dominant immunoglobulin expression. Ultrastructural examination confirmed the presence of fine randomly oriented fibrils consistent with amyloid of approximately 10 nm (Figure ). The kidney biopsy sample was sent to Mayo clinic for liquid chromatography-tandem mass spectrometry (LC-MS/MS): Liquid chromatography-tandem mass spectrometry (LC-MS/MS) detected a peptide profile consistent with AL (lambda)-type amyloid deposition. These findings support the diagnosis of amyloidosis and indicate AL (lambda)-type amyloid deposition.
Bone marrow biopsy revealed a plasma cell neoplasm, favor plasma cell myeloma (Figure ). Flow cytometry immunotyping showing CD (cluster differentiation) 19-, CD56-, CD117 +, lambda light chain restricted monotypic plasma cells consistent with plasma cell neoplasm. Echocardiography was done and showed an EF of 70%. The patient was started on CyBorD (Cyclophosphamide, bortezomib and dexamethasone) induction chemotherapy. Workup for bleeding disorders revealed that the patient has Type 2A von Willebrand Disease, likely secondary to the AL amyloidosis.


A 51-year-old undoctored male with no known past medical history presented with weakness and jaundice. Approximately one week prior to presentation, the patient developed intermittent fevers and confusion. Two days prior to presentation, he developed fatigue, jaundice, and dark urine. He had one episode of non-bloody emesis but denied hematemesis, melena, hematochezia, or pain. He denied personal or family history of sickle cell disease, thalassemia, or malignancies.
On arrival, he was afebrile with heart rate of 114, blood pressure 110/61, respiratory rate 18, oxygen saturation 97% on 5 liters via nasal cannula. Initial workup revealed white blood cells 41.4 thousand cells/MCL, hemoglobin 3.1 g/dL, MCV 124.1 FL, platelets 343 thousand cells/mL, creatinine 1.4 mg/dL, total bilirubin 5.3 mg/dL, direct bilirubin 1.6 mg/dL, and COVID-19 positive by reverse transcription-polymerase chain reaction testing. Electrocardiogram (EKG) revealed supraventricular tachycardia with nonspecific ST segment and T wave changes (Figure ). A chest radiograph showed no focal evidence of airspace disease (Figure ) and CT abdomen and pelvis revealed hepatic steatosis and mild splenomegaly (Figure ). Four units of packed red blood cells were transfused with response in hemoglobin to 6.8.
Peripheral blood smear found primarily nucleated red blood cells, no abnormal white blood cells, and no increase in lymphocyte quantity. Further workup showed iron studies, B12, and folate within normal ranges. COVID-19 severity labs included lactate dehydrogenase (LDH) 1460 U/L, fibrinogen 488 mg/dL, d-dimer 1780 ng/mL, erythrocyte sedimentation rate (ESR) 130 mm/hr, C-reactive protein (CRP) 4.44 mg/dL, and procalcitonin 1.43 ng/dL (Table ). Initial hematologic analysis from hospital day 1 showed blood type A+, Rh+. Direct antiglobulin test (DAT) was positive for IgG and C3 complement antibodies, consistent with warm AIHA. Hematopathologist review also revealed agglutination on immediate spin reactivity consistent with cold AIHA. On hospital day 2, hemoglobin returned at 6.6 and he was given the fifth unit of blood. His creatinine normalized to 0.8 with fluids. Infectious workup including hepatitis B, hepatitis C, and HIV returned negative. Repeat chest x-ray showed bibasilar opacities worse throughout the right lobes (Figure ). Flow cytometry found 0.4% circulating myeloblasts without evidence for malignancy. He was started on the empiric treatment of AIHA with prednisone 1 mg/kg daily (100 mg daily).
His platelet count decreased throughout his admission with a low of 65 on hospital day 6. Heparin antibody and serotonin release assay both returned negative for heparin-induced thrombocytopenia. On hospital day 3, CT chest with pulmonary embolus protocol showed multiple segmental and subsegmental pulmonary emboli in all lobes, few occlusive but mostly nonocclusive with moderate clot burden. He was started on apixaban.
He was discharged on hospital day 8 on prednisone 100 mg daily. Repeat flow cytometry performed two weeks after discharge was normal. His hemolysis labs including hemoglobin, bilirubin, haptoglobin, and LDH normalized by his two-week follow-up appointment. Prednisone was decreased to 80 mg daily at one month post-discharge and 60 mg daily at two-month follow-up. At his most recent follow-up 70 days since admission, DAT for IgG and anti-complement remained positive and prednisone was decreased to 50 mg daily.


We present the case of a 33-year-old female patient, working as a nurse in the medicine department. She was admitted to the emergency unit on 15 November 2020 for oppressive chest pain, fever, cough, tachycardia and fatigue. A PCR test was positive on 10 November with a cycle threshold (CT) of 18. The severe symptomatology started 24 h before presenting to the emergency department. She also noted having some chills and generalized fatigue within the previous 72 h. The patient was conscious and oriented in space, time and toward people. Blood pressure on admission was 140/80 mmHg, heart rate was 100 beats/min. Patient respiratory rate was 16 breaths/min and SPO2 was 94% on room oxygen. The patient had fever with a body temperature of 38.8°C.
The patient does not have any known or documented cardiovascular risk factor: no history of tobacco consumption, dyslipidemia, diabetes or cardiac problems. She is allergic to amoxicillin, with an allergic reaction of a cutaneous rash and angioedema. She also has an intolerance to butylscopolamine, resulting in agitation and irritability. She cannot take metoclopramide as it once resulted in hypotension.
A blood test performed on 15 November showed slightly increased C-reactive protein (CRP) and d-dimer levels. Full results are shown in .
A thoracic computed tomography (CT) scan performed on 15 November 2020 showed right inferior lobar pneumonia and typical COVID-19 ground glass pattern (). No adenomegaly was noted in the mediastinum and no pleural or pericardial effusion was found.
The patient did not require hospitalization due to the absence of comorbidities, a moderate lung inflammation on the scan and stable vital signs without a supplementary need of oxygen. She was released and a medical home treatment was started. It included oral corticosteroid therapy (deflazacort 15 mg per day for 10 days), anti-coagulation (fondaparinux 2.5 mg per day for 1 month), prophylactic antiplatelet dose (acetylsalicylic acid 100 mg per day for 2 months), an analgesic and antipyretic (paracetamol 1000 mg per 8 h) and supplements (vitamin C, vitamin D, zinc).
The onset of COVID-19 infection was on 10 November 2020, and involved the skin rather than respiratory system or general state. The skin lesions presented with an uncommon pattern starting with small vesicles on the forearms and the left sub clavicular area on 10 November 2020. On this day, a COVID-19 PCR test was positive with a CT value of 18. This was the first symptom of the infection and other symptoms occurred 24 h later. The skin vesicles evolved into itchy, painful, red, swollen maculopapular lesions ( & ) with progressive regression and complete resolution in one week ().
After this atypical presentation, the patient gave us further information about her personal medical history, mentioning severe childhood viral infections, varicella infection despite vaccination (during childhood), mumps infection despite vaccination (during childhood), and severe H1N1 infection (in 2017). The patient had no history of personal or family auto-immune disease, no chronic or intermittent arthralgia or myalgia.
A complete blood analysis was done on 25 November 2020 and the results are shown in . CRP and d-dimer levels were normalized. Two PCR tests were done systematically on 24 and 27 November 2020, and were negative. The patient noted an improvement of COVID-19 symptoms. d-dimers were decreasing.
After recovering from COVID-19, the patient noted many episodes of sinus tachycardia treated with betaloc 25 mg (½ pill/day). She also had episodes of bronchoconstriction and wheezing treated with symbicort (budesonide/formoterol fumarate) 160 (2 times/day) and ventolin (albuterol) when needed. A COVID-19 serology IgG test was done on 2 February 2021 and showed: IgG = 19.58.
On 25 February 2021, and after 3 months already passed since the infection, the patient received the first dose of Pfizer-BioNTech vaccine for COVID-19. After 12 h of receiving the vaccine, she noted fever, chills, myalgia, vertigo, nausea and emesis. Forty-eight hours later, these symptoms resolved completely.
After 24 h of the first dose, an oral ulceration developed, with multiple maculopapular skin lesions, this time on the dorsal part of the hands. These lesions had the same evolution pattern as the skin lesions that appeared during the onset of the COVID-19 infection, and they disappeared quickly. On 28 February 2021, the patient noted four big maculo-papular lesions on the posterior side of the right forearm, these lesions started as small vesicles () and progressed into red, painful, and itchy maculopapular lesions (). She presented at the ED on 2 March 2021, with these lesions, as they became swollen. A central vesicle was visible in each lesion. The pattern of evolution of the forearm lesions, progressing from small vesicles into maculopapular lesions, then regressing before they disappear (–).
On day 5 postvaccination (), the patient came to the emergency department, we assessed the clinical status of the patient and ordered biological and microbiological investigations. A PCR test was made along with a serology IgG COVID-19 test to assess the immune status of the patient. A sample was taken from the lesions site for microbiological culture. Intravenous corticosteroid therapy was given (Solu-MEDROL 40 mg/12 h), with empiric antibiotic therapy (clindamycin 100 mg/6 h). The patient was admitted for 72-h surveillance at the hospital, during which she had a palpitation episode with a normal EKG. A hypotension episode was noted. No other complications occurred during the surveillance period. The evolution of skin lesions was favorable as they regressed and inflammatory signs disappeared.
Follow-up tests were performed: a SARS-CoV-2 PCR test performed on 27 February 2021 was negative. A serology of anti-SARS-CoV-2 antibodies performed on 2 March 2021 showed a value greater than 100. The lesion's bacterial culture was negative. More tests were done on the following day, showing normal values of complements C3 (128) and C4 (20). CRP and thyroid stimulating hormone (TSH) values were normal. Diagrams summarizing patient’s clinical presentation and management during COVID-19 infection and after COVID-19 vaccination are shown in & , respectively.


An 11-year-old Malagasy female patient was referred to our hospital for investigation of productive cough with hemoptysis of bloody streaks. She had a 10-day history of fever and shortness of breath. In her detailed medical history, the patient was unaware of her accidental aspiration of the foreign body. Nevertheless, she had been diagnosed with prolonged and recurrent pneumonia symptom not responding to standard medical therapy. Clinically, the patient’s oxygen saturation was 96%, and she was spontaneously breathing (23 breaths/minute). Her heart rate was 90 beats/minute, with a stable hemodynamic status not presenting an altered level of consciousness (Glasgow score 15). Asymmetric chest wall movement was noted on physical examination. On auscultation, there were decreased breath sounds and signs of consolidation suggesting collapse of the pulmonary parenchyma of the left hemithorax. Chest X-ray showed changes consistent with bronchiectasis. Chest computed tomography showed localized bronchiectasis in the left upper lobe and atelectasis in the lower lobe, and revealed a foreign body obstructing the lumen of the left main bronchus with virtual bronchoscopy as well as a hernia of the right lung that invaded the left part, with a displacement of the mediastinal structures into the left hemithorax (Fig. ). Based on hemoptysis and the left lung almost destroyed by the presence of an occlusive lesion within, a left pneumonectomy was decided, and she underwent a posterolateral thoracotomy. Intraoperatively, we could complete left pneumonectomy despite dense pleuropulmonary adherence. The patient was extubated safely after the surgery, and her oxygen saturation improved considerably. The postoperative period was uneventful with negative conversion of the clinicobiological inflammatory reaction. Our patient was discharged on the fifth postoperative day. The permanent pathologic result revealed, on sectioning the specimen, a red pen cap obstructing the left main bronchus, with distal bronchiectasis (Fig. ). During a retrospective interrogation, she confessed about a choking episode in elementary school after she sucked the blind cap of her pen and involuntarily aspirated it 4 years ago. Two years after the pneumonectomy, our patient was doing well and was asymptomatic.


A 63-year-old male with a past medical history significant for dementia and HIV presented to the emergency room with confusion, frequent falls, and productive cough. He was found on the floor by his mother on the day of the presentation. On arrival to the emergency room, he was found to be tachycardic with a heart rate of 109, blood pressure of 133/89, and respiratory rate of 26, saturating 98% on room air. His physical exam was significant for a 5 cm x 5 cm area of ecchymoses over the right parietal scalp and chest wall tenderness to palpation. He was alert and oriented to place, time, and self and was moving all of his extremities spontaneously without overt abnormal neurological findings. He stated that he was diagnosed with HIV in 2014. His HIV risk factors included sexual encounters with multiple female and male partners. He took efavirenz-emtricitabine-tenofovir from 2014 to 2015 but then self-discontinued the therapy as he had to travel for work.  He was not able to provide additional information about his HIV. He was found to be anemic with a hemoglobin of 8.5 g/dL (13.2-17.1) and had an elevated serum creatinine kinase of 856 µ/L (30-223). During workup, the patient was noted to have a CD-4 count of <35 cells/µL (255-2496), viral load of 658,000 copies/mL (undetectable), and corrected calcium of 11 mg/dL (8.6-10.3).
Infectious disease was consulted for productive cough with abnormal CT imaging findings in the setting of a new diagnosis of AIDS (given CD-4 count <200 cells/µL). Sputum cultures were obtained on day 4 and day 6 of hospitalization which grew Mycobacterium avium. He was started on HAART therapy with bictegravir, emtricitabine, tenofovir, and alafenamide regimen on day 8. On day 27, the patient’s corrected calcium was noted to suddenly increase to 14.1 mg/dL. Further testing revealed a TSH of 1.18 IU/mL (0.45-4.12), PTH 4.0 pg/mL (12-88), and a 25-hydroxy vitamin D level of 54.1 ng/mL (30-100). He was given calcitonin 280 IU twice a day subcutaneously for hypercalcemia. MAC treatment was initiated with rifabutin, ethambutol, clarithromycin, and azithromycin. In addition, his HAART therapy was switched to emtricitabine, tenofovir, alafenamide, and dolutegravir given concern for medication interactions. Despite these interventions, no improvement in hypercalcemia was noted. Therefore, endocrinology was consulted on day 30 to assist with the management of hypercalcemia. On day 30, IV Pamidronate 90 mg was given but the patient’s hypercalcemia persisted (Figure ). On day 31, consideration was given to the possibility of IRIS-induced hypercalcemia in the setting of a patient with an underlying MAC infection. HAART therapy was, thus, discontinued at that time. He was ultimately found to have a negative PTH-rP and elevated calcitriol of 115 pg/mL (19.9-79.3). On day 33, he was initiated on prednisone 60 mg to treat IRIS and was noted to have normalized corrected calcium of 8.8 mg/dL by day 36. The prednisone was initiated at 60 mg for five days then tapered to 40 mg for five days, 20 mg for five days, followed by 10 mg for five days. HAART was reinitiated on day 37 after resolution of hypercalcemia and calcium levels remained stable thereafter.


A 49-year-old woman presented with diarrhea approximately once every 30 min for two days prior to her visit. On arrival, she had a fever of 39.0°C with chills. The patient had persistent diarrhea and fever and had trouble moving; hence she required emergency assistance and was brought to our hospital. She was a current smoker, who smoked 10 cigarettes/day for 29 years and consumed 1,500 mL of cocktails per day. She owned a pet cat, and the cat licked her body surface regularly. She had a history of depression; however, she had not consulted a doctor for five years. She had no other medical history and was not taking any medications, including any over-the-counter medications.
Her height and body weight were 162 cm and 60 kg, respectively. On admission, consciousness was assessed using the Glasgow Coma Scale (score, 14) (E4V4M6), her body temperature was 38.0℃, pulse was 132 beats/min, blood pressure was 88/51 mmHg, respiratory rate was 24 breaths/min, and the peripheral arterial oxygen saturation was 94% (nasal cannula, 1 L). Physical examination revealed livedo reticularis on the lower limbs. There was no site of soft tissue infection with redness, heat, or swelling throughout the body. The blood tests that were performed are shown in Table . Arterial blood gas analysis showed mixed alkalosis and hyperlactatemia (serum lactate, 8.4 mg/dL). Conventional abdominal computed tomography revealed mild enlargement and a diffuse low-density area of the liver.
The patient was admitted to the intensive care unit in a state of septic shock with alcoholic cirrhosis, hypokalemia (serum potassium, 1.9 mEq/L) with frequent diarrhea, and disseminated intravascular coagulation syndrome. The clinical course of the patients is shown in Figure . Blood, urine, and spinal fluid specimens were cultured, and piperacillin-tazobactam (4.5 g) was administered as an empiric therapy with the initiation of potassium replacement through a central vein. On the same day, the antibacterial agents were changed to meropenem (1 g every 12 h) and vancomycin (1.5 g every 24 h) due to deteriorating clinical conditions. Artificial respiration was started on the same day as the patient's respiratory condition worsened. After admission, she did not have frequent diarrhea. On the second day of admission, the patient’s renal function (serum creatinine, 2.6 mg/dL) and liver function (prothrombin time, 35.6%; total bilirubin, 6.0 mg/dL) worsened, thereby requiring continuous hemodiafiltration (CHDF), plasma exchange therapy, and coagulation factor replacement. In addition, venoglobulin and amikacin 400 mg were administered for sepsis. The dosage of meropenem was changed to a severe dose of 2 g every 12 h considering the worsening clinical condition and the dosage of vancomycin was changed to 1 g every 24 h as the renal function worsened and CHDF was initiated. However, metabolic acidosis and hyperlactatemia progressed, and the patient died in the early hours of the third sick day. On the third day of admission, blood culture yielded P. multocida, which was susceptible to piperacillin-tazobactam and meropenem.


A 79-year-old woman, 145 cm in height and 37 kg in weight, presented with a pelvic fracture due after falling from a standing height when walking in her room. She was unable to walk with low back pain. The patient was moderately healthy with some comorbidities (hypertension, cerebral infarction). The paralysis of the cerebral infarction was slight, and she was able to walk independently before this injury). Her American Society of Anesthesiologists physical status classification [] was III.
X-ray and CT taken in the previous hospital showed few dislocations of the sacral fracture (). After that, bed rest/conservative treatment and administration of PTH injection were performed in the previous hospital, but the pain did not improve over some weeks and walking was difficult. She was referred to our hospital because the pain persisted and the treatment was unsuccessful. CT taken at our hospital showed that the dislocation of the sacral fracture had worsened (). The diagnosis of type IVb FFPs, displaced sacral fracture, was made from CT. In CT, a sacral corridor for inserting the transiliac transsacral (TITS) screw existed, but the TITS bar was not be approved to be used in Japan, and in this osteoporotic case with dislocation of the sacrum, there was concern about fixation with the TITS screw. On the other hand, in this case, L5 and S1 were bonny fused, and we decided to perform SIRF with inserting a pedicle screw into L5 and S1, fixing the fractured bone directly, and connecting it to the iliac screw. The operation was performed 2 months after the injury and 4 days after the transfer to our hospital under general anesthesia with the patient in the prone position.
About 5 cm incisions were made to the skin bilaterally placed medial to both the posterior superior iliac spines (PSIS). The fascia was peeled away from the surfaces of the PSIS to develop sufficient space for manipulation of the iliac screws (IS) and S1 pedicle screws (S1PS). First, the bilateral S1PS were aimed at the promontory. The right L5 pedicle screw was inserted (left L5 pedicle screw was not inserted this time because it was inserted from the fractured site in the case). The entry point of the IS was set 2–3 cm distal to the head of the S1PS. With image intensifier position for the “teepee” view, a guidewire was placed from the PSIS toward the anterior inferior iliac spines (AIIS). Iliac screws (φ9.5-90 mm) were inserted []. Constructs were made using spinal instruments (Solera, Medtronic Co., Dublin, Ireland) (). The surgery time was 2 h and 56 min, and intraoperative blood loss was 95 g. Immediate weight bearing as tolerated was allowed postoperatively.
The patient continued PTH injection treatment after the surgery. CT examinations (postoperative 6 months) were performed to determine the progress of bone union (). The patient experienced no pain waking with a walking stick and returned to most social activities including living independently within 6 months of the operation. The modified Majeed score was 94 (except sexual intercourse, which was 4 points out of a possible 96) at the visit of 6 months after operation. No particular implant-related complications such as skin irritation, screw loosening, or buck out have occurred.


A 72-year-old male was transferred from a local hospital on 18 March 2020, due to severe hypoxia and hypercapnia. The patient was taking medication for hypertension and dyslipidemia and was a nonsmoker. He developed upper respiratory symptoms such as headache, fever, chilling sensation, and cough 8 days before being transferred to our hospital. A real-time reverse transcriptase-polymerase chain reaction test for COVID-19 was done which confirmed COVID-19 infection 5 days prior to being transferred to our hospital. He was an inpatient at a local medical institution and was treated with antibiotics (levofloxacin) and antiviral agent (lopinavir/ritonavir) 2 days before being transferred to our hospital. However, the patient's chest X-ray haziness was aggravated, fever was sustained, and hypoxia worsened despite the symptomatic treatment. His initial vital signs were blood pressure of 136/63 mm Hg, heart rate of 79 beats/min, body temperature of 37.3℃, respiratory rate of 40 breaths/min, and peripheral O2 saturation of 90% on non-rebreather mask of 15 L/min. The pH, pO2, pCO2, and O2 saturation were 7.318, 78.1 mm Hg, 50.7 mm Hg, and 93.8%, respectively, in the arterial blood gas analysis. Chest X-ray demonstrated diffuse ground-glass opacities in the left middle and both lower lobes (Figure ). Initial electrocardiogram (ECG) revealed normal sinus rhythm with a heart rate of 90 beats/min, normal PR (172 ms) and QRS (92 ms) intervals, and normal QT (350 ms) and QTc (428 ms) intervals (Figure ). The patient underwent intubation and was started on mechanical ventilator care 1 hour after admission. Medical treatment was administered with antibiotics (levofloxacin) and antiviral agent (darunavir/cobicistat). A mechanical ventilator was applied, and midazolam and fentanyl citrate were used for sedation initially. The heart rate was stably maintained at 60-70 beats/min, and cardiac arrhythmia was not observed. On day 2 of hospitalization, antibiotics was changed from levofloxacin to piperacillin/tazobactam due to persistent fever. On day 4 of admission, the antiviral agent was stopped due to liver enzyme elevation. In addition, antibiotics (azithromycin) was added on day 6 of hospitalization because chest radiography demonstrated deteriorating pulmonary consolidation (Figure ). On day 9 of admission, a paroxysmal complete atrioventricular (AV) block was observed on the ECG monitor (Figure ). Paroxysmal complete AV block lasted for 5-10 seconds at the time of occurrence and developed one to two times per hour. Changes in consciousness, such as syncope, were not observed because the patient was in the sedation state at the time of paroxysmal complete AV block onset. Accordingly, we first identified and discontinued medication that could induce cardiac arrhythmia. The antibiotics piperacillin/tazobactam and azithromycin were discontinued and were changed to a different class of antibiotics. In addition, the mechanical ventilator setting value was adjusted in consideration of the possibility of AV block due to vagal overstimulation due to an increase in intrathoracic pressure and hyperinflation of the lungs. At the time, the patient's mechanical ventilator was set to assisted/controlled mandatory ventilation—volume controlled ventilation mode with 340 mL per inspiration of tidal volume (TV), 10 cmH2O of positive end-expiratory pressure (PEEP), 28 breaths/min of respiratory rate, and 50% fraction of inspiration oxygen.
TV and PEEP were adjusted from 340 to 320 mL per inspiration and from 10 to 8 cmH2O, respectively. Paroxysmal complete AV block did not occur 2 hours after adjusting the mechanical ventilator, and follow-up ECG revealed normal sinus rhythm with a heart rate of 68 beats/min (Figure ). Thereafter, cardiac arrhythmia including paroxysmal complete AV block was not observed during the hospitalization period. Fortunately, the patient gradually recovered from acute respiratory distress syndrome. On day 13 of hospitalization, mechanical ventilation was stopped and extubation was performed. Finally, the patient was discharged 49 days after admission.


We present a case of a 29-year-old woman G2 P2 with fetal IUGR. The pregnancy was uncomplicated and the fetus’s growth was normal for the gestational age. The prenatal test performed in the first trimester showed a low genetic risk. The investigation of the fetus at 34 gestational weeks was carried out at the Clinic of Obstetrics and Gynecology of Vilnius University Hospital Santaros Clinics. The biometry showed an estimated fetal weight (EFW) of 1778 g (11.8 percentile), an abdominal circumference (AC) below the 5th percentile with normal Doppler findings and normal NST. The fetal monitoring performed from 35 to 37 pregnancy weeks involved NST and Doppler examination of the fetal arteries (tibial, umbilical and middle cerebral), the ductus venosus and uterine arteries (). NST and Doppler parameters for all the observed arteries were normal until 36 weeks and 5 days. The first pathological change was registered at this time, the tibial artery PI registering >95th percentile (). At 37 weeks and 0 days, a pathological decrease of MCA-PI <5th percentile was registered. UA-PI remained normal. The tibial artery PI remained >95th percentile (). At 37 weeks and 2 days, a male newborn was delivered, weighing 2070 g (<3 percentile), with a height of 48 cm, 9/9 Apgar points and the amniotic fluid clear with a pH of 7.4. In conclusion, this was a case of fetal growth restriction monitored by supplementary evaluation of the peripheral artery (the tibial artery) Doppler, which appeared to be the first indicator of the deteriorating condition of the fetus.


A 43-year-old male, sport coach, presented him-self at the Emergency unit of a local hospital for epigastric pain, myalgia pain, severe headache and brown urine. He claimed having used for some days a combination of GW1516 (4 days, 20 mg per day) and MK2866 (1 day, 20 mg) to gain muscle mass. This occurred 10 days before he went to the hospital. Both products were bought on the Internet (10 g of GW1516 and 46 g of MK2866 for a total of 200 euros). The day before he went to the hospital, he cycled 120 km. Vital signs included a blood pressure of 135/70 mmHg and a heart rate of 76 beats per minute and no respiratory distress (SpO2 at 99%). The ECG was normal. The abdomen was supple but painful. Initial laboratory tests showed serum creatinine of 109 µmol/L (clearance at 76 mL/min), elevated liver enzymes (alanine aminotransferase or ALT 966 UI/L, aspartate aminotransferase or AST 1000 UI/L), normal bilirubin and creatine phosphokinase or CPK elevated at 10,000 UI/L. Blood (green Vacutainer), urine without preservative and hair (2 cm in length, brown in colour) were immediately collected and sent to the laboratory for toxicological investigations. Some hours later, rhabdomyolysis worsened with a rise of CPK at 57,000 UI/L. Treatment consisted of intra-venous (IV) re-hydrating at 3 L per 24 hours. The next day, biochemical tests included CPK at 86435 UI/L, ALT at 922 UI/L and AST at 2558 UI/L. No kidney insufficiency was noticed and urine started to become clearer. Muscle pain remained but abdominal pain was gone. The subject was allowed to turn home, despite the installation of an asthenia that lasted for 15 days. Five days later, during a control, CPK were at 1765 UI/L, ALT at 726 UI/L and AST at 331 UI/L. Normal values were obtained after 2 weeks. Six weeks after the event, the subject totally recovered. Both white powders used by the subject were also submitted to the laboratory for confirmation of identity and determination of purity.


A 53-year-old woman presented at the emergency room with a 4-day history of fever, headache, fatigue, dizziness and productive cough. She had a medical history of type 2 diabetes mellitus, asthma, chronic kidney disease, grade I obesity (BMI = 32.87 kg/m2), Hashimoto thyroiditis, ischemic heart disease, severe pulmonary hypertension, and mitral valve stenosis post prosthetic mitral valve implantation. Her treatment consisted of: spironolactonum/furosemidum, nebivololum, insulinum glargine, levothyroxinum, beclometasonum/formoterolum, acenocumarolum. Her husband was COVID-19 positive and she claimed a close household contact with him.
Rapid antigen testing for SARS-CoV-2 was positive at admission. To confirm the SARS-CoV-2 infection, a nasopharyngeal swab sample was collected in order to perform the molecular testing using RT-PCR.
At admission, physical examination showed a hemodynamically and respiratory stable patient with the following parameters: blood pressure = 139/79 mmHg, heart rate = 69 beats per minute, SaO2 = 88% on room air, body temperature = 36.4 °C.
Thoracic radiography revealed sternal threads after valve replacement surgery, no pleural collections, no pulmonary condensation, grade II venous stasis, cardiomegaly and metal prosthesis in mitral position.
Abdominal, thyroid and cardiac ultrasounds were performed on the 3rd day of hospitalization. The abdominal ultrasound showed dilatation of the inferior vena cava and suprahepatic veins, the gallbladder with a hyperechoic image. The cardiac ultrasound revealed a normofunctioning prosthetic valve, left atrium dilatation (50 mm), mild interventricular septal dyskinesia, severe secondary pulmonary hypertension, normal ejection fraction and monophasic mitral flow. The thyroid ultrasound detected a 1 cm/1.3 cm hypoechoic thyroid nodule for which we recommended further endocrinological evaluation.
A native thoraco-pulmonary CT exam revealed the image of a typical viral pneumonia with a degree of lung damage of approximately 10%. This was interpreted as a mild form of SARS-CoV-2 pneumonia. Because the RT-PCR from the nasopharyngeal swab was positive for SARS-CoV-2, we established the main diagnosis of bilateral COVID-19 pneumonia and acute respiratory failure. We initiated antiviral treatment with Remdesivir (Veklury®) 200 mg on the first day, and 100 mg over the next four days. The summary of medication used in the hospital is presented in .
Although initial ECG showed sinusal rhythm with 60 beats/min without other modifications, 24 h after the admission ECG exploration revealed atrial fibrillation with 208 beats/min for which we initiated the treatment following the guidelines with 1200 mg/24 h of amiodarone. Unfortunately, we could not convert this to normal sinus rhythm. We continued the administration of amiodarone during hospitalization.
The evolution of the laboratory tests and the general presentation of the patient management is presented in .
On the 5th day of hospitalization, microbiologic results from the sputum sample collected on the 1st day came back negative for bacteria. However, macroscopic examination of the fungal culture on Sabouraud agar shows several wide, flat, floccose colonies with a yellow-green color. In order to ensure the isolation and identification of the fungi, aspergilli were subculture from the primary culture on Sabouraud chloramphenicol gentamicin agar (Bio-Rad, Marnes-la-Coquette, France) (). Microscopic examination, using the lactophenol cotton blue method, revealed vesiculated conidiophores with large, round and smooth conidia, roughened stalks, phialides arising directly from the entire surface of the vesicle in some heads, and produced on metulae in others (). These findings concluded in the identification of Aspergillus spp. most likely Aspergillus section Flavi. The antifungal susceptibility testing, using the concentration gradient strip Etest method, revealed that this strain was susceptible to voriconazole. We collected another sputum sample and initiated intravenous specific antifungal treatment with voriconazole: 2 × 400 mg at first day, 2 × 200 mg the next days. After 5 days, the antiviral therapy with Remdesivir was stopped.
On the 8th day of hospitalization, we repeated the native thoraco-pulmonary CT examination (), which showed unsystematized central and peripheral pulmonary infiltrates and ground-glass opacities with a degree of damage of around 50–60%. These findings were suggestive of a severe form of SARS-CoV-2 pneumonia. There were also several mediastinal lymph node images, enlarged heart, the valvuloplasty in the mitral position and trachea-bronchial malformations. Pulmonary condensation foci were described in upper right lobe, upper left lobe and lower left lobe. Also, at the level of the upper abdomen included in the examination, a 15/23 mm nodular lesion was highlighted in the left adrenal gland.
On the 10th day of hospitalization, the microbiological report from the sputum sample collected on the 5th day came back negative for bacteria and positive for fungi. Macroscopic examination of the fungal culture on Sabouraud agar showed a flat, powdery colony with a blue-green color. In order to ensure the isolation and identification of the fungi, aspergilli were subcultured from the primary culture on Sabouraud chloramphenicol gentamicin agar (Bio-Rad, Marnes-la-Coquette, France) (). Microscopic examination, using lactophenol cotton blue method, revealed vesiculated conidiophores with small, round and slightly roughened conidia, short stalks, pear-shaped vesicles, crowded phialides arising from the upper two-thirds of the vesicles only with no metulae (). These findings concluded the diagnostic of Aspergillus spp., most likely Aspergillus section Fumigati. The antifungal susceptibility testing, using the concentration gradient strip Etest method, revealed that this strain was also susceptible to voriconazole. Before we again started the intravenous treatment with voriconazole, we collected blood to determine the level of galactomannan, which is the serological test with the best sensitivity used for demonstrating the presence of Aspergillus antigen. Galactomannan’s index was 0.65 which according to the product specifications it was reactive for Aspergillus antigen [,,].
On the 13th day of hospitalization, we have repeated the RT-PCR test from a nasopharyngeal swab. The result was negative for SARS-CoV-2 and the patient was discharged the next day with the following recommendations: continuing voriconazole therapy for 5 weeks more, maintaining physical distance, wearing the mask at home and at work for another 10 days after the end of the isolation period, avoiding close contact with other people in the house and, if possible, isolation in a separate room with separate bathroom, washing hands with soap and water for at least 20 s and frequent use of disinfectants.


An 11-year-old boy was referred to our pediatric endocrinology department for suspect PP (onset of pubic hair at the age of 8.5). The patient’s weight was 49 kg (75–90p), height was 156.3 cm (97p) (Tanner’s target height 165.6–176.6 cm) and testicular volumes were 15 mL (Tanner stage 4 puberty). The bone age was three years older than the chronological age (14 years old according to Greulich Pyle Atlas). Laboratory work up revealed basal LH 2.94 mUI/mL (normal range < 0.3) FSH 3.58 mUI/mL (normal range 0.51–2.82), testosterone 4.23 ng/mL (normal range 0.026–0.055), free testosterone 23.15 pg/mL (normal range 0.82–15.4). After LH-FSH-releasing hormone test, a peak LH value of 35.1 mUI/mL and a peak FSH value of 9.01 mUI/mL (after 4 h) were detected. ACTH stimulation test was performed: 17 OH-P rose from a basal value 1.56 ng/mL to 6.25 ng/mL at 60 min; levels of DHEA-S, delta-4 androstenedione and cortisol remained within normal range. Late onset (non-classic) 21-hydroxylase deficiency was excluded by genetic analysis. Plasma thyroxin, thyroid-stimulating hormone, serum beta-hCG and alfa-fetoprotein concentrations were within normal range for age. One month after pediatric endocrinology consultation, brain MRI detected a mixed solid and microcystic left hemispheric cerebellar lesion growing into the cerebellomedullary and cerebellopontine cisterns, partly infiltrating the middle cerebellar peduncle, with a small extension into the jugular foramen. The solid component showed an inhomogeneous hyperintensity on T2-weighted turbo spin echo (TSE) and fluid attenuated inversion recovery (FLAIR) sequences. T1-weighted contrast-enhanced sequences showed two foci of centimetric nodular enhancement in the posterior lobe. Hydrocephalus was absent. Sagittal post-contrast T1-weighted images of the spine showed no leptomeningeal spread ().
The patient was diagnosed with CPP and started gonadotropin releasing hormone (GnRH) agonist treatment (triptorelin acetate 3.75 mg every 90 days). He was referred to the pediatric oncology department for preoperative evaluation.
The patient did not complain of neurological symptoms and neurological examination was unremarkable.
Chest x-ray, abdomen and testicular ultrasound, cardiological, neuropsychiatric and genetic consultation did not reveal any abnormality. A minimal left hypoacusia was detected by otolaryngologists. The patient was operated on via a left retrosigmoid approach on lateral position. Intraoperative neuromonitoring (IONM) was performed recording brain stem auditory evoked potentials (BAEPs), motor and somatosensory evoked potentials and V VII, IX, X, XI cranial nerve monitoring. Baseline BAEPs showed a decreased function on the left. During and after surgery no further changes were recorded. Early postoperative MRI showed a small tumor residue in the middle cerebellar peduncle, hyperintense on T2-weighted TSE and FLAIR sequences, with no contrast enhancement on T1-weighted images ().
Postoperative neurological examination reported a mild sensorineural left hearing loss and a transient diplopia. The boy was discharged on postoperative day 8.
Histopathological features were consistent with a combination of aggregates and nests of neuronal elements, that were comprised in a background of neuropil containing benign glial elements, set in a reticulin containing stroma. Ganglion cells were large with multiple processes, nuclei were large, rounded and appeared somewhat hyperchromatic, with large nucleoli, without binucleate forms, cytomegaly, pleomorphism, mitoses and necrosis. Tumor margins were well-circumscribed, without leptomeningeal infiltration. Immunostaining for glial-fibrillar acid protein and chromogranin A were strongly positive in ganglion cells, but not in neuronal cells, which were strongly positive for synaptophysin. Ki67/MIB-1 labelling involved only glial component and was 1.0% (). Final diagnosis was GG, grade I WHO 2016 [].
Progression of puberty was clinically restrained, testicular volume decreased from 15 mL to 10 mL and GnRH treatment was maintained, with the indication to further evaluate biochemical response. Diplopia improved, but the auditory brainstem response confirmed left central auditory tract dysfunction. Brain MRI revealed stable findings with no evidence of tumor relapse.
We conducted a qualitative systematic review following the ENTREQ [] (enhancing transparency in reporting the synthesis of qualitative research) framework. This methodology was chosen as it better describes qualitative research according to the guidelines for reporting systemic reviews at: (accessed on 4 May 2021). A case-based literature search of pediatric cases of CPP associated with posterior fossa tumor was performed. The main search was conducted through PubMed and MeSH Database and the terms used were “precocious puberty” AND “brain tumor” OR “posterior fossa tumor” OR “cerebellar tumor” OR “infratentorial tumor”. Only full text papers (case series, reviews and research studies) published between 2001 and 2021 in peer-reviewed journals were included in the study. A systematic approach to the collected data and a collegial discussion between the authors led to a final version of the manuscript.
We identified a total of 191 records through database searching according to our selection criteria. All publications were obtained through MEDLINE/PubMed. Twenty-four studies were duplicate and were excluded from our review. A total of 167 peer-reviewed papers were screened based on this review’s focus (CPP in pediatric patients with posterior fossa tumor). Five papers describing cases of pediatric patients with infratentorial tumors and CPP were included for the qualitative analysis; 162 were found not relevant and were excluded ().
Four out of five tumors were in the cerebellum, two medulloblastomas [,] and two pilocytic astrocytomas [,]. All those patients received surgery as the main tumor treatment; only one patient needed both radiotherapy and chemotherapy [], while one needed chemotherapy only []. Additional treatment with GnRH-agonist was administered in one case [], whereas surgery resolved precocious puberty in all the other cases. Gass et al. [] reported a glioma of the quadrigeminal plate with symptoms of PP and hydrocephalus, successfully treated with endoscopic third ventriculostomy (ETV), given the infiltration of the dorsal midbrain ().


A 27-year-old woman presented to the Emergency Department complaining of asthenia, adynamia and weight loss associated with lower urinary tract symptoms and subfebrile temperature. Ten years before, she had undergone a pediatric en-bloc kidney transplant because of end-stage kidney disease secondary to perinatal asphyxia syndrome. Asphyxia can lead to multi-organ dysfunction and a redistribution of cardiac output to maintain cerebral, cardiac and adrenal perfusion while potentially compromising renal, gastrointestinal and skin perfusion as circulatory response.
One allograft was located in the right iliac fossa (upside-down implantation with ureteric anastomosis following Lich-Gregoir technique, violet in Fig. ) and the other in the right flank (end-to-side uretero-ureteral anastomosis with native right kidney, blue and orange in Fig. ). The en-bloc graft was made to rest on the right psoas muscle, and the graft vena cava was anastomosed terminolaterally to the recipient external iliac vein using 6–0 polypropylene suture. The graft aorta was also anastomosed terminolaterally to the right external iliac artery using 7–0 polypropylene suture.
Our patient presented other comorbidities as well such as hypertension, asymptomatic, bilateral cataracts, intellectual disability, sensorineural hearing loss and Wolff–Parkinson–White syndrome (WPW pattern or preexcitation consisting of a short PR interval and prolonged QRS with an initial slurring upstroke—“delta” wave—in the presence of sinus rhythm) with episodic palpitations and lightheadedness. Anthropometric features are : height 125 cm, weight 25 kg, BMI = 14.2. She reported 10 kg weight loss in the last 5 months due to depression symptoms associated with COVID-19 (coronavirus disease) quarantine. Her daily medication was: prednisone 4 mg, amlodipine 5 mg, atenolol 25 mg, enalapril 2.5 mg, mycophenolic acid 250 mg/250 mg and tacrolimus 2 mg/2 mg.
The main abnormalities in the laboratory data were white blood cells count 15,654/mm3, serum creatinine level 1 mg/dl (baseline: 0.6 mg/dl), lactate 3.6 mmol/l and pH 7.39.
Non-contrast computed tomography (NCCT) scan showed staghorn calculi in the kidney allograft implanted in the right iliac fossa composed of at least 3 stones of 12.5 mm, 13.7 mm and 10 mm located in superior, medium and inferior calyx, respectively (530 Hounsfield Units) (Fig. ). Moreover, both the right flank transplanted kidney and the right native kidney had severe pelvicalyceal dilation because of two ureteral stones of 6.7 mm and 5.9 mm impacted in the uretero-ureteral anastomosis (450 to 510 HU). Finally, a 7.2-mm stone was reported in the lower calyx of her right native kidney (457 HU).
Initial management consisted in hospital admission and empiric treatment with ceftriaxone. After 24 h of empiric ceftriaxone and following our COVID19 protocol, an attempt to perform primary URS of the ureteral stones was carried out. Nevertheless, once the guidewire (Sensor™ PTFE-Nitinol Guidewire with Hydrophilic Tip, Boston Scientific®) passed through the ureteral stones, purulent material came out from the ureteral meatus. Due to this finding, we decided to take an upper urinary tract urine sample for culture, place a double pig-tail stent and a bladder catheter, and stop the procedure. She stayed 9 days in-hospital for management of postobstructive polyuria and was discharged with oral antimicrobial agents (ciprofloxacin and fluconazole) and without the bladder catheter.
Definitive operative treatment of urolithiasis was performed three weeks thereafter. The traditional lithotomy position, in this unprecedented patient, allowed both antegrade and retrograde access. After removing ureteral stent, semirigid ureteroscopy (8Fr, Richard Wolf, Germany®) and Holmium-YAG laser lithotripsy of the ureteral stones (120 W, Lumenis®) were carried out. Retrograde intrarenal surgery (RIRS) (Flex X2, Karl Storz®) was required to treat the stone located in the inferior calyx of the native kidney. Fragmentation of the stones was executed using these laser settings: 0.8 J and 10 Hz. Fragments were removed using a nitinol stone-retrieval frontal basket (NGage, Cook Medical®).
At the meantime, upper pole puncture of the right iliac fossa allograft was performed under ultrasound (US) guidance by a second endourologist. Endovision puncture was not attempted in order to protect the reusable flexible ureteroscope from an extreme proximal ureteral kinking loop (Fig. B).
Tract dilation was accomplished using one-shot dilator to establish a 21-Fr working channel over the guidewire. Mini-PNL (MIP Storz 12 Fr Nephroscope ®) was performed with Holmium-YAG laser dusting of the stones (settings: 0.5 J and 50 Hz). Stone fragments and dust were flushed out through the sheath by vortex effect. After most of the stone fragments had been removed, antegrade flexible nephroscopy (Flexible Fiber-Cystoscope 15Fr, Richard Wolf, Germany®) was conducted to search for residual stones in locations that were inaccessible with the rigid nephroscope (Fig. C). A 14-Fr 100% silicon nephrostomy tube and a bladder catheter were left in place. Operating time was 120 min. Estimated blood loss was approximately 50 cc.
Postoperative NCCT scan, performed 12 h postoperatively, showed neither residual fragments nor suggestive signs of immediate postoperative complications (Fig. ). Both the nephrostomy and the bladder catheter were removed the following day. The patient remained in hospital for 3 days because of tacrolimus blood levels fluctuation. Neither early nor late onset postoperative complications occurred.
After 10 months from discharge, the patient remains stone-free. She is now under magnesium supplement and nitrofurantoin 100 mg daily prophylaxis since crystallographic analysis showed ammonium magnesium phosphate as the main component of the stones. Every six months ultrasound will be performed as follow-up.


Case 1: A 66-year-old woman presented with chronic bloody nasal discharge, sero-mucous otitis and acute arthritis of the right elbow. With the onset of episcleritis and the finding of cANCA-PR3, a diagnosis of GPA was made. The patient was treated with prednisone and cyclophosphamide, subsequently replaced by mycophenolate mofetil because of hemorrhagic cystitis. The evolution was favorable. Due to weight loss of 10 kg a thoraco-abdominal CT was performed 10 years later revealing hyperdense spontaneous thickening with enhancement around the ascending and horizontal aorta. In addition pulmonary opacity of the right lower lobe was detected and a diagnosis of mononeuropathy with falling foot was made. A PET-CT showed hypermetabolism (SUV max 8.1) at the aortic arch and the ascending aorta. cANCA-PR3 were present at all times. In this context, immunosuppression by corticosteroids and mycophenolate mofetil was intensified. PET-CT scanning 18 months later showed a clear decrease in hypercaptation.


Case 2: A 52-year-old woman known for intracranial hypertension for 7 years, who was hospitalized for the investigation of headaches with tonic epileptic seizures. A brain MRI showed diffuse pachymeningitis. Due to unusual headaches located in the temporal area associated with hyperesthesia of the scalp and inflammatory syndrome, a temporal artery biopsy was performed and showed inflammatory lymphocytic infiltrate with intimal fibrosis, disappearance of the elastic lamina, and vasa vasorum granulomas. Nasal biopsy revealed mixed inflammation with rough granuloma. With MRI pansinusitis and positive cANCA-PR3, the diagnosis of GPA was made, and the patient was treated with corticosteroids and rituximab with an improvement in inflammatory syndrome and symptoms.


Case 3: A 76-year-old woman presented with progressive bilateral headaches and jaw claudication. The laboratory results revealed inflammation with a CRP of 120 mg/l and a sedimentation rate of 67 mm/h. A temporal biopsy showed a granulomatous and giant cell vasculitis (Fig. A). However, due to subglottic stenosis, nasal cartilage destruction, MRI pansinusitis, and persistent glomerular hematuria, a renal biopsy was performed showing segmental fibrous crescents compatible with pauciimmune extra-capillary glomerulonephritis (Fig. B). Perinuclear ANCAs were found, specifically anti-MPO. The perinuclear ANCAs remained positive over a 5-year follow-up whereas anti-MPO titers disappeared under treatment.


Case 5: A 46-year-old woman, known for GPA with nasal polyps, lower limb neuropathy, and optic neuritis with granulomatous ocular infiltration, presented with aortic dissection of type A (Fig. A). She benefited from an emergency operation with replacement of the ascending aorta. The pathological analysis showed a granulomatous vasculitis with chronic inflammation and multiple foci of collagenous necrosis without giant cells (Fig. B). The evolution was satisfactory after the operation under treatment with corticosteroids.
The clinical characteristics of the five AAV patients with LVV are summarized in Table .


The 48-year-old woman unintentionally felt a painless mass of about 2 cm × 1 cm in the upper outer quadrant of her left breast in March 2017, which gradually enlarged due to her neglect. In September 2017, the mass rapidly enlarged to 7cm × 6 cm, and there was infiltrated erythema and ulceration on the skin of the breast. In October 2017, she was admitted to our hospital and received mammary magnetic resonance imaging (MRI) (), which showed a 91 mm × 55 mm × 87 mm mass with ill-defined margins and a heterogeneous internal enhancement in the left breast; breast imaging reporting and data system (BI-RADS) category was identified as 5. Additionally, enlarged lymph nodes in her left axilla were observed. Laboratory examinations presented normal carcinoembryonic antigen (CEA) level (0.926 ng/ml) and high cancer antigen 15-3 (CA15-3) level (61.4 U/ml). Subsequently, core needle biopsy was performed on October 28, 2017, and invasive ductal carcinoma was pathologically diagnosed, histological grade 2, with estrogen receptor (ER) negative and progesterone receptor (PR) negative, overexpression of HER-2 (+++), and high proliferation index Ki-67 (70%) (). The patient was in good health without any medical history of hypertension or diabetes and without smoking, drinking, and other bad habits. She had menarche at 13 years old, and the last menstrual period was October 11, 2017. Before any treatment, we offered a thorough examination and excluded any distant metastases. The clinical stage was cT4N2aM0 according to the 7th edition of American Joint Committee on Cancer (AJCC) staging manual ().
As pertuzumab and T-DM1 had not been approved in China at that time, after obtaining informed consent, we adopted a TCbH regimen (docetaxel, 75 mg/m2 d1; carboplatin, AUC = 6 d1; trastuzumab, 8 mg/kg for the first cycle and 6 mg/kg thereafter d1, 21 days/cycle) as first-line treatment according to the National Comprehensive Cancer Network (NCCN) guidelines. After five cycles (November 6, 2017–January 30, 2018), reexamination of mammary MRI () showed the size of the mass shrank from 91 mm × 55 mm × 87 mm to 84 mm × 48 mm × 72 mm. According to the evaluation criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, we judged the therapeutic effect as stable disease (SD).
Based on the NOAH test (), limited cycles of joint application of trastuzumab and anthracycline were effective and had controllable cardiac toxicity. Therefore, we choose ECH (epirubicin, 90 mg/m2 d1; cycloposphamide, 600 mg/m2 d1; trastuzumab, 6 mg/kg d1, 21 days/cycle) regimen as second-line treatment (February 27, 2018–May 23, 2018). After four cycles, re-examined mammary MRI () showed that the tumor shrank from 84 mm × 48 mm × 72 mm to 66 mm × 29 mm × 56 mm. According to the evaluation criteria of RECIST v1.1, the therapeutic effect was still SD. There was no significant change in the appearance of the breast ().
As the efficacy still did not reach PR, the regimen was altered to nab-paclitaxel combined with trastuzmab. For metastatic breast cancer patients who had received prior taxanes, nab-paclitaxel plus still has the objective response rate of 54.2% (), and nab-paclitaxel plus traszumab to EC was superior to taxanes combined with trastuzumab to EC as neo-adjuvant therapy in GBG 69 trial (). Therefore, we choose nab-paclitaxel plus trastuzumab as the third-line treatment (nab-paclitaxel, 125 mg/m2 d1, d8; trastuzumab, 6 mg/kg d1, 21 days/cycle). The patient got PR after the first two cycles (), but two cycles later, the efficacy deteriorated to progressive disease (PD) ().
As the patient had developed acquired trastuzumab resistance after three lines of trastuzumab-based regimen, another regimen with distinct mechanism of anti-HER2 therapy was needed. To investigate the potential reason of drug resistance, a next-generation gene sequencing (NGS) of 425-gene panel was performed using the tissue repunctured from the tumor. According to the NGS report, persistent existence of ERBB2, CDK12, and MYC amplification with abundance of 15.7, 16.2, and 7.6 were detected, respectively. Meanwhile, there were mutations as p.R314H on IDH1 gene and p.H179R on TP53 gene. On ERBB2 gene, the patient had L755S () and K907R mutation. L755S mutation indicated resistance to trastuzumab and lapatinib (, ) and may be sensitive to neratinib (), an irreversible pan-HER TKI. At that time, neratinib had not been admitted to China, and a similar agent, pyrotinib, had just been approved by the China Food and Drug Administration (cFDA), whose phase II trial had indicated that for the treatment of advanced HER2-positive breast cancer patients, pyrotinib combined with capecitabine had better efficacy than lapatinib combined with capecitabine (). Thus, we selected pyrotinib plus capecitabine (pyrotinib, 400 mg/d d1–21; capecitabine, 1,250 mg/m2 bid d1–14, 21 days/cycle) as the fourth-line treatment regimen. After six cycles (August 28, 2018–December 29, 2018), the patient got PR (), and the surface of the breast almost completely healed ().
Left breast cancer mastectomy and local rotation skin flap grafting were performed on the patient in January 16, 2019, and postoperative pathology report showed an invasive ductal carcinoma with changes in Miller–Payne Grade 4 (), with a tumor size of 1.0 cm × 0.8 cm × 0.8 cm and lymph nodes negative (0/14). Immunohistochemistry indicated ER (−), PR (−), C-erbb-2 (+++), and ki-67 (70%+) ().
The patient continued to receive pyrotinib plus capecitabine (pyrotinib, 400 mg/day d1–21; capecitabine, 1,250 mg/m2 bid d1–14, 21 days/cycles) synchronous with radiotherapy (left chest wall plus left supraclavicular area, 5,000 cGy/25f), and pyrotinib plus capecitabine continued to be administrated for 1 year. There were no signs of metastasis or recurrence after an overall examination after 1 year of adjuvant therapy with pyrotinib plus capecitabine. The patient suspended capecitabin due to severe hand–foot syndrome and took pyrotinib as single agent for another 1 year (), partially referred to ExteNET clinical trial (). By the time of contribution, the second (June 2019) and last regular follow-ups (March 2021) showed no signs of metastasis or recurrence ().


A 63-year-old man was admitted to the hospital with “persistent lower abdominal pain for one day”. Physical examination: flat abdomen, plate-shaped abdomen, the tension of abdominal muscles, tenderness of the right lower abdomen, obvious rebound pain, negative mobile voiced sound, weak bowel sounds, one time/min. Imaging examination: abdominal CT examination: a small amount of free gas in the abdominal cavity, ascites, gastrointestinal perforation (). Laboratory examination: white blood cell (WBC): 6.6*10E9/l, neutrophil (%): 90.8%, red blood cell (RBC): 3.49*10E12/l, hemoglobin: 70g/l, and C-reactive protein (CRP): 235.4 mg/l; direct bilirubin (DB) 7.8 μmol/l, total protein (TP): 35.9g/l, albumin (ALB): 22.1g/l, globulin13.8 g/l, sodium:135.2 mmol/l, amylase: 246U/l, procalcitonin (PCT) > 100.0 ng/ml. Previous history: the patient had a history of anemia, and the patients were treated with iron intermittently, and no obvious abnormality was found in the rest.
The patient was admitted to the hospital for emergency surgery, and the right side was dissected into the abdominal cavity through a rectus abdominis incision. During the operation, the end of the right lower abdominal ileum was found to be conglutinated and twisted into a mass (). Local intestinal dilatation and obstruction were found, the local intestinal wall was black, and gangrene and fecal effusion were observed. The adhesions were separated with an electric knife and scissors, and a gangrene rupture of the ileum was found about 50 cm from the ileocecal area (). The intestinal tube in the necrotic area was resected, about 20 cm long, and the distal and proximal small intestines were anastomosed side-to-side with a linear cutting closure device. Postoperative pathology: acute and chronic inflammatory cell infiltration, focal mucosal degeneration and necrosis, granulation tissue formation was found in the whole layer of the intestinal wall, immunohistochemistry: type IV collagen (+). Anti-infection and parenteral nutrition were given symptomatic treatment after operation. On the third day postoperation, the patient developed anal exhaust and was instructed to drink water properly. On the seventh day postoperation, the patient had anal defecation, and the patient was on a complete liquid diet, the gastrointestinal angiography showed that there was no leakage of contrast agent in the abdominal cavity (). WBC:5.2*10E9/l, neutrophils (%): 71.6%, RBC: 3.82*10E12/l, hemoglobin: 91g/l, CRP: 15.6mg/l, TP: 57.5g/l, ALB: 34.8g/l, on the 10th day postoperation, the patients returned to their normal diet without abdominal pain and abdominal distension, and were discharged 12 days postoperation.


A 66-year-old male initially presented with an elevated PSA of 6.0 ng/ml. Multi-parametric 3 T pelvic phased-array coil prostate MRI (Siemens, Erlangen, Germany), including multi-planar T2WI, 3D T2WI SPACE, DWI (with a calculated b-1500 image set), and DCE images were performed. Prostate MRI demonstrated an 18 × 11 mm right peripheral zone lesion assigned a PI-RADS assessment score of 5, with associated extra-prostatic extension. MRI-ultrasound fusion targeted biopsy demonstrated Gleason score 3 + 4 tumor. The patient decided to undergo prostatectomy. Image segmentation of the prostate, lesion, urethra and bladder neck, neurovascular bundles, and rectal wall was performed using the T2WI SPACE sequence. Image post processing was completed in 3-matic and the AR model was built in the Unity software. In this case, the model helped the patient to better understand the size of his cancer and the surgeon to fully appreciate the extent of extra-prostatic extension (EPE) (Fig. ).


A 74-year-old man presented with a PSA of 5.3 ng/ml. Prostate MRI was performed as above; and it demonstrated a 14 × 10 mm posteromedial midgland-to-apex peripheral zone lesion that was assigned a PI-RADS score of 4. MRI-ultrasound fusion targeted biopsy demonstrated Gleason score 4 + 3 tumor. The patient elected to undergo radical prostatectomy. In order to create the AR model, image segmentation and post-processing were performed. The lesion was manually segmented on the DWI images and the remaining structures were segmented on the SPACE images. The segmented anatomy was co-registered using a 3D rigid registration method consisting of translation and rotation. 3D meshes were generated and the contours were generated onto the original source images to verify accuracy. The AR model was created in the Unity software and was used to plan the procedure (Fig. ). In addition, visualizing the AR model helped the patient to understand why the nerve could not be preserved in this case.


A 39-year-old female presented to a regional Australian hospital with a three-day history of polydipsia, polyuria and fatigue. This was on a background of a previous stroke suffered 11 years ago, resulting in left-sided hemiplegia and epilepsy. Patient was not a known diabetic.
Vital signs on initial presentation included tachycardia to 160 beats per minute and mild hypotension of 110/80 mmHg. Abdomen was soft non-tender. Patient also had a strong ketotic breath. Venous blood gas was done which showed a pH of 7.36, lactate of 2.5, blood glucose of 44, and ketones of 6.5. Urine microscopy was also performed which showed 500 leukocytes, 80 erythrocytes and 10 epithelial cells. Impression of the patient at the time of admission was that the patient’s urinary tract infection had unmasked undiagnosed diabetes mellitus in the form of diabetic ketoacidosis (DKA).
Patient was commenced on intravenous fluid resuscitation, insulin infusion and intravenous antibiotics (piperacillin-tazobactum and gentamycin). Patient was admitted to the intensive care unit for ongoing care.
During the patient’s stay in intensive care, patient’s diabetic ketoacidosis resolved and insulin infusion was ceased on day 2 of admission. However, the patient remained tachycardiac to 116 beats per minute with an oxygen requirement of 4 litres on nasal prongs so a CT pulmonary angiogram was performed. An occlusive thrombus was found in the right lower lobar artery with CT evidence of right heart strain. Patient was then commenced on therapeutic anticoagulation (Figure ).
On day 4 of admission, patient remained tachycardic despite therapeutic anticoagulation and then became febrile. A computed tomography (CT) scan of abdomen and pelvis was done to rule out pyelonephritis given the known urinary tract infection (Figure ). CT found a large left staghorn calculus with an obstructed infected left kidney. An additional finding included emphysematous left pyelonephritis with soft tissue gas in the left retroperitoneum and left flank/posterolateral soft tissues in keeping with necrotising fasciitis.
Later that day the patient was reviewed by the local general surgery team. Abdomen was soft with significant left flank tenderness and oedema but no crepitus. There was also a skin tear and bruising at the left flank (Figure ).
Given the aetiology of the necrotising fasciitis, the patient was discussed with urology at a tertiary hospital. Discussions centred on whether debridement of necrotising fasciitis should occur at the current treating hospital or whether the patient should be transferred for definitive source control and wound debridement. Given the massive pulmonary embolism and that the patient was relatively stable, decision was made for patient to be transferred for definitive management rather than subject her to two general anaesthetics and procedures.
The patient was then urgently transferred to a tertiary hospital for ongoing care. On the day of transfer, patient underwent a left open nephrectomy with extensive debridement of left flank and groin. Findings included a large pus-filled retroperitoneal cavity extending to the left gluteal region, an atrophic friable left kidney filled with pus and calculus. Vac dressing was applied to the open wound. The patient was subsequently taken back to theatre the following day for further debridement of necrotising fasciitis. Day 2 post nephrectomy, the patient was again taken back to theatre for a relook and debridement and faeces was found in the abdominal cavity. Upon exploration, two colonic perforations were found near the splenic flexure where the kidney had been removed. An omental patch was performed and a loop ileostomy was formed. After this, a total of five relooks and debridements were performed. Eventually, edges of the flank wound were able to be closed with suture repair but a defect in the central portion of the wound remained. This was closed with a split-thickness skin graft performed by plastic surgery.
Approximately two months after the initial presentation, the patient was transferred back to the regional hospital for a two-week stint of rehabilitation after which she was discharged home.


A 71-year-old man with no remarkable medical history experienced sudden lower abdominal pain. Computed tomography (CT) performed at a neighboring hospital revealed a right IIIAA (6.7 cm in diameter) with small volumes of contrast medium extravasation and hematoma (Fig. ). He was referred to our hospital due to a suspected ruptured right IIIAA. On emergency room arrival, the patient's general physical condition was stable (blood pressure, 120/70 mmHg; heart rate, 120 bpm). He complained of lower abdominal tenderness upon palpation and had bilateral lower limb cyanosis. Blood gas analysis showed lactic acidosis (pH, 7.258; lactate, 6.5 mmol/L). He was diagnosed with a ruptured right IIIAA complicated by peripheral circulatory failure. Considering his pre-shock status and probable time-consuming preparation for endovascular devices, emergency open surgical aneurysm repair was scheduled.
Under general anesthesia, the abdominal cavity was entered through a lower midline skin incision. The intraperitoneal and retroperitoneal cavities were filled with large volumes of hematomas. After surgical hematoma evacuation, the large right IIIAA was easily identified in the pelvic cavity. The proximal neck of the right IIIAA was encircled carefully and ligated close to the right common iliac artery. Active bleeding from the aneurysmal surface was not observed. Encircling the distal IIA was considered difficult; therefore, we opened the aneurysm and removed a large mural thrombus and performed suture closure of distal IIA drainage sites (Fig. ). Circulatory status was stable throughout the operation. Perioperative hypotension was not observed.
The patient was weaned from the ventilator immediately after the operation. However, he was found to have motor dysfunction from the bilateral thighs to the toes (Manual Muscle Testing of 1/1) and sensory disturbance below the L5 region. Spinal magnetic resonance imaging (MRI) confirmed presence of SCI at T12-L1 (Fig. ). The patient was treated with cerebrospinal fluid drainage and continuous intravenous infusion of naloxone. Although SCI was intensively managed, he could not stand independently, and neurogenic bladder and rectal disorder remained. Thereafter, after 51 postoperative days, he was transferred to the rehabilitation center.


A 73-year-old woman was referred to our hospital to undergo an endoscopic ultrasonography (EUS) for a gastric SET that was covered with normal gastric mucosa, which was located on the greater curvature, at the lower part of the gastric body; it was found incidentally during screening endoscopy (Fig. A). EUS showed a heterogeneous hypoechoic lesion measuring 1.4 × 0.5 cm in the submucosal layer (Fig. B). Endoscopic forceps biopsies were inconclusive. An abdominal computed tomography showed a soft tissue density subepithelial tumor without lymph node enlargement. We decided to perform an endoscopic resection for diagnosis and treatment. ESD requires prolonged operative time and an experienced therapeutic endoscopist. Recently, UW-EMR has been described as an effective and safe treatment modality for SETs embedded in the submucosa. Therefore, UW-EMR (video) was performed using a 25-mm polypectomy snare (Endo-Flex GmbH, Germany) through a single channel endoscope (Olympus GIF-HQ290, Tokyo, Japan) using ENDO CUT Q current (effect 3, cut duration 2, cut interval 3), which was generated using the VIO 300 D electrosurgical unit (Erbe Elektromedizin GmbH, Tübingen, Germany) (Fig. A). En bloc resection was achieved and the operative time was 5 minutes. There were no signs of bowel perforation or residual lesions (Fig. B), and the resection margin was grossly tumor-free (Fig. A). The histological diagnosis was a grade I FL which measured 1.4 cm (Fig. B) with tumor-free margins. Follow-up endoscopic biopsy after 3 months revealed no residual tumor on the resection site. The patient was planned to undergo periodic surveillance using endoscopy and abdominal computed tomography without additional treatment. The patient provided informed consent for the publication of her clinical data accompanying images.


The patient was a 62-year-old man admitted to the hospital with dysphagia and ataxia. He was diagnosed with a dissecting aneurysm of the left vertebral artery using magnetic resonance imaging and angiography. Seven days later, he underwent trapping of the left vertebral artery and developed left Wallenberg syndrome. Twenty-six days later, he was transferred to a convalescent rehabilitation hospital. The patient agreed to the publication of his case by providing informed consent.