Check Point SOS! A Case of Cemiplimab-Associated Sinusoidal Obstruction Syndrome

Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).

The Effect Of Rhabdomyomas On Underlying Cardiomyopathy: A Case Report

Case Presentation: Term male infant born to SARS-CoV-2 positive mother with infant testing negative. ECG for perinatal bradycardia revealed ventricular pre-excitation. Echocardiogram showed asymmetric LV hypertrophy with prominent trabeculations, subaortic narrowing with no pressure gradient, and normal biventricular systolic function. Rapid increase in RV pressure estimates and NT-proBNP in first week if life concerning for diastolic dysfunction. Anti-arrhythmic therapy initiated for SVT with subsequent resolution. Later, developed progressive LV dilation and systolic dysfunction. Myocardium showed regions resembling non-compaction and others concerning for infiltrative process. Cardiac MRI showed no obvious tumors, but rhabdomyomas could not be ruled out given similar appearance to myocardium. Due to worsening heart failure, everolimus therapy initiated to target potential rhabdomyomas while awaiting genetic testing for tuberous sclerosis. Subaortic narrowing and LV hypertrophy improved within days, and LV appearance became more consistent with non-compaction. Genetic testing revealed a TSC2 gene variant consistent with tuberous sclerosis. Systolic function improved, and patient discharged on afterload reduction. Echocardiogram 6 months post-discharge shows continued LV dilation and mild systolic dysfunction. Discussion(s): Although outflow obstruction and arrhythmias are common with cardiac rhabdomyomas and can cause dysfunction, our patient developed progressive dysfunction in the absence of outflow tract gradient or prolonged arrhythmia. As rhabdomyomas subsided, it became clearer that he had an underlying cardiomyopathy. We suspect that rhabdomyomas in the setting of abnormal myocardium led to abnormalities in myocardial contractility and compliance causing combined systolic and diastolic dysfunction. After complete resolution of rhabdomyomas, cardiac function has improved. However, he continues to have ventricular dilation and mild dysfunction attributable to cardiomyopathy. It is unlikely that mother's SARS-CoV-2 infection played a role as infant tested negative and clinical picture was not consistent with myocarditis.

High efficacy of activated carbon fabric filters and masks developed to prevent the inhalation of microorganisms and particles associated with respiratory tract infections

As a major international public health emergency, COVID-19 has posed many challenges for healthcare professionals who have been heavily exposed to contamination. This article describes the development of a high-filtration capacity mask consisting of filter-element layers interspersed with super-activated carbon fiber fabric, non-woven polypropylene for dental–medical–hospital use and antiviral polyamide with nanostructured SiO2 thin film coating. The study found 98.18% particle filtration efficiency and determined 2.11 mmH2O/cm2 differential pressure, while fluid repellency complied with Brazilian standard NBR ABNT 15052:2004. © The Author(s) 2022.

Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

NHS GRAMPIAN REVIEW OF NEW GUIDANCE FOR VARICEAL SCREENING

Introduction Covid-19 pandemic caused significant disruption to elective endoscopy services nationally. This paved way to endoscopy minimised management pathways for patients with liver cirrhosis. Standard pathway pre-COVID19 was as set out in Baveno VI consensus guidelines and involved variceal screening endoscopy for all patients with clinically significant portal hypertension. We adopted the new pathway as suggested by the national clinical forum, endorsed by the Scottish Government, which proposes the use of Carvedilol in patients with clinically significant portal hypertension and endoscopy reserved for patients who are intolerant of carvedilol or have contraindications to beta-blocker use. The rationale behind new guidance is the improvement in survival with Carvedilol and its efficacy in reducing hepatic venous pressure gradient and preventing decompensation. The recent Baveno VII consensus also suggests patients established on Carvedilol therapy do not need endoscopy as it is unlikely to change clinical management. We aim to assess the impact of applying the new guidance on the variceal screening/surveillance endoscopy waiting list. Methods 243 patients were identified on our variceal endoscopy waiting list who were due an endoscopy between 2019 and 2024. Patients on variceal banding programme have been excluded from this analysis. Data collected included their Childs Pugh score, fibroscan score, medications, platelet count and previous endoscopy results if applicable. Patients were then categorised into three groups. 1. Clinical monitoring of blood tests and fibroscan yearly without endoscopy 2. Carvedilol therapy indicated 3. To continue with endoscopic screening. Results 26/243 (10.6%) patients were removed from the waiting list with plan for yearly monitoring. 10/243 (4%) patients were to continue with endoscopic screening due to Carvedilol intolerance. 207 patients met the criteria to commence Carvedilol without the need for endoscopy. Therefore, 207/233 (88%) patients could be removed from the waiting list by applying the new guidance. This would free up approximately 29 endoscopy lists which can be utilised to address other areas within gastroenterology and hepatology service with longer waiting times. Conclusions The impact on variceal endoscopy waiting times by adopting the new guidance is significant. It provides opportunity to utilise the resources more effectively. From patient's perspective, endoscopy is an invasive procedure and anxiety provoking to some patients resulting in failure to attend endoscopy appointments. As the requirement for endoscopy is considerably low, the new guidance may be more acceptable to patients who prefer to avoid endoscopy. Patient compliance and tolerance to Carvedilol will be recorded prospectively to assess the overall impact on the service.

Comparative analysis of acute on chronic liver failure related to herbs and anti-tubercular drugs

Objectives: Liver injury precipitated by drugs and herbal medicines( DHMs) can have variable presentations and outcomes. In Indian subcontinent, drug induced liver injury due to Anti-tubercular drugs( ATDs) and inadvertent herbs induced liver injury (HILI) are common. Comparative natural history and outcome of acute-onchronic liver failure(ACLF) due to common DHMs is largely unknown. Materials and Methods: Consecutive in-patients with ACLF precipitated by herbs or ATDs(year 2010-2021) were compared for baseline clinical profile, disease severity, histological features and organ failures. Treatment outcomes and predictors of in-hospital mortality were also analyzed. Results: 529 patients presented with ACLF related to HILI(ACLF-H, n = 430) and ATDs(ACLF-D, n = 99) [Mean Age-47.6 - 14 years, mean MELD score and HVPG were 29.1 - 5.4 and 15.5 - 3.4 mmHg respectively]. 61.4% patients had underlying histological cirrhosis. 21.2% patients had additional superadded acute insult [severe alcoholic hepatitis(n = 66), acute hepatitis E or A(n = 24/15)]. Twelve percent ACLF-H patients presented with clinical cholestasis, autoimmune hepatitis(n = 18) and hypersensitivity reactions(n = 4). Most common recognizable agent associated with ACLF-H was Tinospora cordifolia (n = 35,8.1%), inadvertently used in Indian households during the COVID-19 pandemics. Patients with ACLF-H as compared to ACLF-D had higher male preponderance (70.9% vs. 54.5%;p-0.002) and peripheral eosinophilia (6.4% vs. 1%;p-0.03), clinical cholestasis (19.6% vs 10.8%;p-0.05) and acute kidney injury (44.4% vs. 28.3%;p-0.003) at presentation. Use of plasma exchange(18.5%) had no impact on outcomes. None of the patients underwent liver transplantation. In-hospital mortality(19.2%) was higher in ACLF-D compared to HILI ACLF-H (31.3% vs. 17.2%;p-0.002). Presence of AKI [HR:5.5 (95%CI:2.78 to 11.1)], hepatic encephalopathy[HR:4.4(95%CI:1.76 to 11)] and pneumonia[ HR:7.2(95%CI: 3.59 to 14.65)] were independent predictors of mortality. Conclusion: Herbs and anti-tubercular drugs are common precipitants of ACLF in India and have high in-hospital mortality resulting from sepsis and organ(s) failure. In the absence of specific treatment options, prevention and early and careful monitoring of liver functions is of utmost importance.

Using CONTAM to Design Ventilation Strategy of Negative Pressure Isolation Ward considering Different Height of Door Gaps

Infectious disease departments in hospitals require pressure gradient to create unidirectional airflow to prevent the spread of contaminants, typically by creating active air infiltration through the difference between supply and exhaust air volumes. The door gap is the channel of air flow between rooms, so its height has an important influence on the pressure difference and infiltration air volume of the room. There is still a lack of research on setting reasonable ventilation strategies according to the different height of door gaps at different positions in the building. In this study, model of a set of isolation ward was established and analyzed using the multi-zone simulation software CONTAM, and the ventilation strategies with different height of door gaps were applied to the actual infection diseases department. The results show that in a building with ventilation system divided by functional area, the difference in the height of the door gaps requires different active infiltration air volumes. Pressure fluctuations in the medical and patient corridors are greater than in other rooms. The significance of this study is to understand the active infiltration of air to guide the design and operation of ventilation systems in infectious disease hospitals or building remodeled to isolate close contacts of Covid-19 patients. It is also instructive for the design of pressure gradients in clean workshops, biological laboratories, and other similar buildings.

Cerebral Venous Sinus Thrombosisin the Setting of an AVMWhile on Anticoagulation: A Case Report

Objective: To increase the awareness of neurological complications of arteriovenous malformation (AVM) due to obstruction of the venous drainage despite being on anticoagulants. Background: Cerebral AVMs are high-flow intracranial vascular malformation comprised of feeding arteries, a nidus of vessels with intervening brain parenchyma through which arteriovenous shunting occurs and dilated draining veins allowing significant hemodynamic gradient without an interposed resistance. Venous drainage stenosis or occlusion will increase the hemodynamic pressure gradient within the AVM compartments and potentially lead to redistribution of flow resulting in cerebral venous sinus thrombosis or hemorrhagic stroke from nidus rupture. This effect might be worsened in the presence of a generalized hypercoagulable state causing microvascular injury and thrombosis;despite adequate anticoagulation therapy. Design/Methods: N/A Results: 66-year-old obese woman with history of atrial fibrillation, coronary artery disease, diabetes, hypertension, hyperlipidemia, prior stroke, small left frontal AVM diagnosed on conventional angiogram and recent COVID-19 infection presented to our comprehensive stroke center with seizures and right hemiparesis. MRI brain showed T2/FLAIR hyperintense lesion in the left frontal/parasagittal region with an extensive vasogenic edema, heterogeneous diffusion restriction, and gyriform contrast enhancement. Conventional angiogram showed AVM without nidus opacification but with an associated mass effect correlating with parenchyma edema and early venous shunting. Patient was initially misdiagnosed as low-grade neoplasm although accurate diagnosis of left parasagittal frontal venous infarct in the setting of spontaneous venous thrombosis of left frontal AVM was made with conventional angiogram. Conclusions: Venous infarct due to CVST is a devastating complication of AVM. The hemodynamic pressure gradient within the AVM might play a larger role in contributing to hypercoagulable state within the venous system leading to cerebral venous sinus thrombosis despite patient being on therapeutic anticoagulation.

A Real Circuit Breaker: Hyperhemolysis Syndrome Related to the VA-ECMO Circuit?

Introduction: Myocarditis is an inflammatory disease of cardiac muscle caused by a variety of infectious and non-infectious conditions. Viral infection is the most frequent cause of myocarditis;however, herpes simplex virus 1 (HSV-1) infection causing myocarditis has been rarely described. We present a case of a young woman with HSV-1 viremia and fulminant myocarditis presenting with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO), complicated by hyperhemolysis. Case Report: A 35 year-old immunocompetent woman with moderate alcohol consumption presented to hospital with a 4-day history of fever and flu-like symptoms. She was fully vaccinated for COVID-19 two months prior to symptom onset. Her COVID-19 testing was negative and she was discharged home. She returned to hospital 4 days later in cardiogenic shock. Transthoracic echocardiogram demonstrated LVEF of 30% with a small pericardial effusion. Coronary angiogram revealed normal coronaries. She was placed on peripheral VA-ECMO for worsening cardiogenic shock. Due to inadequate LV unloading, she underwent atrial septostomy. Five days after VA-ECMO cannulation, HSV-1 was detected in the blood and she was started on intravenous acyclovir. Her ECMO course was complicated by acute kidney injury requiring dialysis, and hyperhemolysis with a peak LDH of 12,000 U/L. The mechanism of hemolysis was attributed to an intravascular process (plasma free hemoglobin 7487 mg/L, normal < 150 mg/L) likely from a combination cold agglutinins and the mechanical circuit. Interestingly the membrane pressure gradient was within normal. The patient received treatment with plasmapheresis (Table 1), and was eventually decannulated after 12 days following hemodynamic improvement. This case report highlights a rare viral cause of fulminant myocarditis and emphasizes the need for collaboration among various specialists in the management of complex cases.

Cardiac function is normal in most patients recovered from COVID-19

Background: There are conflicting results regarding impaired cardiac function in patients that have recovered from COVID-19. Cardiovascular magnetic resonance (CMR) studies have revealed a very high frequency of cardiac involvement (78%) and ongoing myocardial inflammation (60%) in patients recently recovered from COVID-19. Findings are advocating further investigation of the long-term myocardial consequences of COVID-19 disease. Purpose: We aimed to investigate left ventricular (LV) and right ventricular (RV) function by a comprehensive echocardiographic study in patients recovered from COVID-19 infection 3 months after admission to hospital. Methods: All patients (n=92) had been hospitalized for COVID-19 and were examined with echocardiography three months after hospitalization. They were 59±13 years, and 43% were women. LV function was assessed by ejection fraction (EF) and global longitudinal strain (GLS) and RV function was measured by fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE) and RV GLS free wall. Tricuspid regurgitation pressure gradient was measured to estimate pulmonary artery pressure. Results: LV EF was 63±6% and LV GLS was -18.6±2.2%. All patients had normal EF >53%, but 10 showed signs of subtle impaired LV function by LV GLS (≥ -16%). Only two of these did not have hypertension, LV hypertrophy, diabetes or other preexisting diagnosis of heart disease explaining subtle LV dysfunction. All had normal RV FAC (48±7%) and TAPSE (2.3±0.3 cm). We found modestly impaired RV longitudinal function (RV GLS free wall >-25%) in 30% patients, but none had RV GLS worse than -20%. One-third of all patients with reduced RV GLS had signs of elevated pulmonary arterial pressures, which might impact the assessment of RV function. Conclusions: Traditional echocardiographic parameters showed normal function in all hospitalized COVID-19 patients three months after hospital admittance. Approximately one-third had subtle ventricular dysfunction detected by sensitive echocardiographic methods, but these findings could mostly be explained by systemic or pulmonary hypertension. We cannot, however, exclude that a slight reduction in cardiac function in a minority of our patients was caused by the COVID-19 infection.

Outcome of Conservative Therapy in Coronavirus disease-2019 Patients Presenting With Gastrointestinal Bleeding.

BACKGROUND/OBJECTIVE: There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with Coronavirus disease -2019 (COVID-19) amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. METHODS: In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22nd April to 22nd July 2020, were included. RESULTS: The mean age of patients was 45.8 ± 12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis- 21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma (FFPs) and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. CONCLUSION: Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient's condition, response to treatment, resources and the risks involved, on a case to case basis.