Helicobacter pylori Infection and Complications of Cirrhosis.

INTRODUCTION: Helicobacter pylori is a significant contributor to conditions such as peptic ulcer disease, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and colorectal cancer. Recent studies have suggested a potential link between H. pylori and cirrhosis. However, the impact of H. pylori on cirrhosis-related mortality, inpatient outcomes, and decompensating events remains unclear. Considering the widespread availability of H. pylori testing and effective treatment options, there is a potential rationale for eradicating H. pylori in cirrhotic patients to mitigate the morbidity and mortality associated with cirrhosis. This study aims to investigate the association between H. pylori and inpatient outcomes and complications related to cirrhosis. METHODS: The National Inpatient Sample (NIS) database, a part of the Healthcare Cost & Utilization Project, was utilized for this study. Inpatient data from the years 2016 through 2019 were extracted for patients with a primary discharge diagnosis of cirrhosis and a concurrent diagnosis of H. pylori infection. The primary outcomes included inpatient mortality, length of stay, and cost of care. Secondary outcomes involved cirrhosis-related complications during hospitalization, such as gastrointestinal bleeding, hepatic encephalopathy, and hepatorenal syndrome. RESULTS: Over the years 2016 to 2019, 416,410 patients received a primary discharge diagnosis of cirrhosis. Among them, 990 patients (0.2%) had a secondary diagnosis of H. pylori infection. Those with both cirrhosis and H. pylori tended to be younger on average (mean age 54.25 vs. 57.18 years, p=0.01) and more frequently fell within the age range of 18-49 (33.84% vs. 24.71%, P=0.01). H. pylori-infected patients were also more likely to be male (70.71% vs. 63.11%, P<0.028), of Hispanic race (36.4% vs. 18.6%, p< 0.1), and of Black race (20.2% vs. 8.1%, p< 0.1). While H. pylori-exposed patients had lower in-hospital mortality (0.51% vs. 4.44%, p=0.007), their mean length of stay was higher (6.97 days vs. 5.75, p=0.002). The overall cost of care was comparable between the H. pylori-exposed and non-exposed groups (mean USD18,106.18 vs. $16,543.49, P=0.160). H. pylori-exposed patients had a higher overall rate of cirrhosis-related complications (84.85% vs. 67.59%, p< 0.001), gastrointestinal bleeding (48.48% vs. 27.34%, p< 0.001), and hepatorenal syndrome (70.71% vs. 46.99%, p< 0.001), and these differences persisted in multivariable analysis. Initially, rates of hepatic encephalopathy were higher in H. pylori non-exposed patients (21.57% vs. 15.66%, p=0.04), but this discrepancy was corrected after adjusting for potential confounders. CONCLUSION: While patients in this study were diagnosed with both H. pylori and cirrhosis by discharge, it cannot be definitively concluded that H. pylori was the direct cause of cirrhosis complications. Recognizing this uncertainty, further studies are needed better to understand the associations between cirrhosis and H. pylori complications. Distinguishing the causes of cirrhosis and its relationship with H. pylori may offer deeper insights into whether H. pylori is a causative factor or merely correlated in its effects on patients with cirrhosis.

hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-κB p50.

The anti-cancer target hRpn13 is a proteasome substrate receptor. However, hRpn13-targeting molecules do not impair its interaction with proteasomes or ubiquitin, suggesting other critical cellular activities. We find that hRpn13 depletion causes correlated proteomic and transcriptomic changes, with pronounced effects in myeloma cells for cytoskeletal and immune response proteins and bone-marrow-specific arginine deiminase PADI4. Moreover, a PROTAC against hRpn13 co-depletes PADI4, histone deacetylase HDAC8, and DNA methyltransferase MGMT. PADI4 binds and citrullinates hRpn13 and proteasomes, and proteasomes from PADI4-inhibited myeloma cells exhibit reduced peptidase activity. When off proteasomes, hRpn13 can bind HDAC8, and this interaction inhibits HDAC8 activity. Further linking hRpn13 to transcription, its loss reduces nuclear factor κB (NF-κB) transcription factor p50, which proteasomes generate by cleaving its precursor protein. NF-κB inhibition depletes hRpn13 interactors PADI4 and HDAC8. Altogether, we find that hRpn13 acts dually in protein degradation and expression and that proteasome constituency and, in turn, regulation varies by cell type.

Differences in treatment and outcomes among patients with ST-segment elevation myocardial infarction with and without standard modifiable risk factors: a systematic review and meta-analysis.

There are limited data available on outcomes and pathophysiology behind ST-segment elevation myocardial infarction (STEMI) in populations without standard modifiable risk factors (SMuRFs). The authors carried out this meta-analysis to understand the differences in treatment and outcomes of STEMI patients with and without SMuRFs. Methods: A systematic database search was performed for relevant studies. Studies reporting desired outcomes among STEMI patients with and without SMuRFs were selected based on predefined criteria in the study protocol (PROSPERO: CRD42022341389). Two reviewers independently screened titles and abstracts using Covidence. Full texts of the selected studies were independently reviewed to confirm eligibility. Data were extracted from all eligible studies via a full-text review of the primary article for qualitative and quantitative analysis. In-hospital mortality following the first episode of STEMI was the primary outcome, with major adverse cardiovascular events (MACE), repeat myocardial infarction (MI), cardiogenic shock, heart failure, and stroke as secondary outcomes of interest. Odds ratio (OR) with a 95% CI was used to estimate the effect. Results: A total of 2135 studies were identified from database search, six studies with 521 150 patients with the first STEMI episode were included in the analysis. The authors found higher in-hospital mortality (OR: 1.43; CI: 1.40-1.47) and cardiogenic shock (OR: 1.59; 95% CI: 1.55-1.63) in the SMuRF-less group with no differences in MACE, recurrent MI, major bleeding, heart failure, and stroke. There were lower prescriptions of statin (OR: 0.62; CI: 0.42-0.91) and Angiotensin converting enzyme inhibitor /Angiotensin II receptor blocker (OR: 0.49; CI: 0.28-0.87) at discharge in SMuRF-less patients. There was no difference in procedures like coronary artery bypass graft, percutaneous coronary intervention, and thrombolysis. Conclusion: In the SMuRF-less STEMI patients, higher in-hospital mortality and treatment discrepancies were noted at discharge.

Pericardial Mesothelioma Presenting as Constrictive Pericarditis.

This case report presents a 60-year-old gentleman with a significant smoking history and possible asbestos exposure who was referred to the emergency department for atrial fibrillation with a rapid ventricular rate and symptoms of heart failure. Labs showed normal brain natriuretic peptide and troponin I. His echocardiography finding suggested constrictive pericarditis with an ejection fraction of 60%. A computed tomography scan was concerning for a pericardial mass. Left and right heart catheterization hinted more toward constrictive physiology; however, some findings were concerning for restrictive physiology. Hence, cardiac magnetic resonance imaging was done, which established the diagnosis of constrictive pericarditis. Pericardiectomy was planned with a maze procedure for atrial fibrillation. However, a malignant neoplasm was seen on a frozen biopsy. Hence, surgery was limited to partial pericardiectomy, as the patient had advanced infiltrative neoplasm that had resulted in constrictive pericarditis. The final pathology report confirmed the diagnosis of malignant pericardial mesothelioma mixed type. Malignancy is usually diagnosed in an advanced stage, like in our case, due to nonspecific initial presentation. A literature review suggests that there is a lack of established consensus on treatment. The response to therapy also seems to be poor and results only in palliation of symptoms, with a median survival of six months from diagnosis despite optimum medical management.

Pseudohyperkalemia Associated With Leukemia.

Elevated potassium levels can be a life-threatening emergency. We describe a case of falsely elevated serum potassium level in a patient with leukemia, which was suspected to be falsely elevated because the patient was asymptomatic with a normal electrocardiogram (EKG). Common reasons behind such a discrepancy in leukemia patients are the use of a tourniquet before collection, use of vacuum/pneumatic tubes for transportation, prolonged periods of incubation, use of heparin for sample collection, and processing of samples via centrifugation. Since the process is related to the method of collection and processing, we recommend using rapid point of care testing in such cases to differentiate between false and true potassium elevation, as it is a well-validated tool. Moreover, there is a good correlation between potassium measured with the blood gas, point of care, and central laboratory analyzers when the concentration of potassium is above 3 mEq/L.

A Challenging Case of Mechanical Mitral Valve Obstruction.

Prosthetic valve thrombosis (PVT) is a frequent complication with a mechanical valve that presents with symptoms of heart failure or thromboembolic episodes. A 45-year-old lady with antiphospholipid syndrome (APS) complicated by a previous history of native mitral valve thrombus and mechanical mitral valve replacement maintained on warfarin presented with complaints of chest pain and shortness of breath (NYHA class 2). The initial lab showed a subtherapeutic international normalized ratio (INR) of 1.8. Transthoracic echo (TTE) showed severe mitral stenosis with a normal ejection fraction of 65%, elevated peak gradient of 34.5 mmHg, mean gradient of 23.7 mmHg, and pressure half time of 214 ms. Cine-fluoroscopic images revealed an immobile posterior mitral valve leaflet. She failed two trials of low-dose alteplase therapy during the hospitalization. Hence cardiac CT with contrast was done, which showed a small degree of pannus formation on the ventricular surface of the mitral valve ring and a small thrombus. Due to persistent immobility of the post mitral valve after two doses of alteplase and a cardiac CT scan concerning pannus formation, a multi-departmental decision was made to proceed with mechanical mitral valve replacement, following which she had a good recovery. Our case report depicts the importance of imaging study, like cardiac CT scan that can help distinguish thrombus (which has a lower Hounsfield unit, HU of <90) vs. pannus (higher HU of more than 145).