Granulocyte-colony stimulating factor in decompensated liver cirrhosis: a meta-analysis of four randomized controlled trials.

BACKGROUND: Decompensated liver cirrhosis (DC) has high mortality, but liver transplantation is limited due to organ scarcity and contraindications for transplantation. Granulocyte-colony stimulating factor (GCSF) shows potential for liver disease treatment with its regenerative and immunomodulatory properties. To assess the controversial use of GCSF in DC, a meta-analysis of randomized controlled trials (RCTs) compared survival benefits in patients receiving GCSF plus standard medical therapy (SMT) versus SMT alone. METHODS: A literature search was performed in four databases from data inception up to December 2022, and all registered randomized controlled (RCTs) evaluating GCSF-based therapies for cirrhotic patients were included. RESULTS: A study combining four RCTs assessed the impact of GCSF with SMT in 595 patients with decompensated cirrhosis. The results indicated that GCSF + SMT led to higher odds of survival compared to SMT alone [risk ratio 1.28, 95% CI (1.08-1.5)]. Heterogeneity existed among the studies, but overall, GCSF showed potential in improving survival. The intervention group exhibited improved Child-Pugh-Turcotte scores [-2.51, CI (-4.33 to -0.70)], and increased CD34 levels, but no significant improvement in MELD scores. These findings suggest GCSF may benefit patients with decompensated cirrhosis in terms of survival and liver function. CONCLUSION: These results suggest that the combination of GCSF and SMT may have a positive impact on the survival rate and improvement in CPT score in patients with DC. Further RCTs are needed to shed more light on this promising modality in end-stage liver disease.

Outcomes of Patients with Monoclonal Gammopathy of Undetermined Significance with and without Atrial Fibrillation: A Retrospective Cohort Analysis of the Nationwide Inpatient Sample Database.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant precursor of multiple myeloma (MM). MGUS has been suggested to be associated with a higher risk of cardiovascular diseases, including AFIB, but it is still unclear whether this association is real. Studies are lacking on the impact of atrial fibrillation on health outcomes in this population. The association of AFIB in this population is lagging and merits further investigation. METHODS: The study conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) for 2018, including adult patients with primary diagnoses of MGUS and AFIB. Patients were divided into two groups based on AFIB presence. Outcomes assessed included complications, length of stay, mortality, hospital charges, and discharge disposition. RESULTS: The study included 9007 patients with MGUS of whom 2404 had AFIB. Patients with both MGUS and AFIB had higher rates of acute kidney injury [AKI] (31.5% vs. 27.5%; p = 0.002) and pericarditis (2% vs. 1.2%; p = 0.029). They also had longer hospital stays (5 vs. 4 days; p < 0.001) and higher hospitalization costs ($43,729 vs. $41,169; p < 0.001). CONCLUSIONS: The study showed that the prevalence of AFIB in MGUS patients is high. Patients with AFIB had increased rates of complications (AKI and pericarditis) and higher mortality compared to patients without AFIB. Further studies screening for AFIB in this patient population are warranted.

Heparin-Induced Thrombocytopenia in Chronic Hemodialysis Patients.

Heparin-induced thrombocytopenia (HIT) is a disorder originating from exposure to heparin and has a spectrum of presentation ranging from asymptomatic positive antibodies to thrombotic complications. When symptomatic, it is associated with morbidity and mortality. The incidence of HIT in the ESRD population is yet to be defined. End-stage renal disease (ESRD) patients are at particular risk due to constant exposure to heparin. The main treatment of HIT is to avoid heparin and pursue alternative anticoagulants. Since 1 of the main advantages of heparin in ESRD patients is the ease of its use due to non-renal clearance, the use of alternative anticoagulants poses yet another challenge for this population due to cost, availability, and adverse effects on ESRD patients. Argatroban seems like the best alternative to heparin in hemodialysis (HD) patients due to its liver clearance. Despite having limited studies in HIT, direct oral anticoagulants (DOACs) were added as a potential treatment for HIT, with apixaban favored in kidney dysfunction as it is the least dependent on kidney clearance. Other treatment modalities exist but are still being studied in ESRD patients. The presence of HIT antibodies is not always associated with clinical syndrome, and some studies suggested that heparin antibodies are transient, and the reintroduction of heparin is still being evaluated as a treatment option. Hence, HIT is a challenging diagnosis in ESRD patients, a population that has frequent exposure to anticoagulants, and a risk/benefit ratio should be weighed between the risk of progression to symptomatic HIT and the benefit of switching to a non-heparin anticoagulant bearing in mind the difficulties associated with the latter.

Pembrolizumab-Induced Myasthenia Gravis and Myositis: Literature Review on Neurological Toxicities of Programmed Death Protein 1 Inhibitors.

We present herein the case of an elderly male patient, who was receiving immunotherapy for his urothelial cancer and who presented to our facility with lower extremity weakness. The patient was diagnosed with myasthenia gravis, thyroiditis, myositis and myocarditis, which were considered as immune adverse events of pembrolizumab therapy. The patient received pyridostigmine, intravenous immunoglobulin, plasmapheresis, corticosteroids, and rituximab with mild improvement of his symptoms. The patient had some neurological recovery, was discharged to a nursing facility, however he was ventilator dependent. Of importance, our case is followed by review and discussion of the literature related to immunotherapy and its side effects.

Intraparenchymal Hemorrhage: A Fatal Presentation of Undiagnosed Acute Myelogenous Leukemia.

We present the case of a 73-year-old patient who was admitted to the neurocritical care unit with spontaneous intracerebral hemorrhage (ICH). Upon further investigation, she was found to have hyperleukocytosis and thrombocytopenia due to acute myelogenous leukemia (AML), likely resulting in coagulopathy, vessel friability, and consequential intraparenchymal bleed. Prior reports of AML presenting with ICH are scant in the literature. As such, a heightened awareness of such a phenomenon is recommended for rapid detection and appropriate tailored management. This hopefully would, in turn, optimize outcomes.

Duodenocaval Fistula: A Spontaneous Complication of Chemoradiation Therapy in Stage III Ovarian Cancer.

Duodenocaval fistula (DCF) is a rare entity which is sparsely described in the literature. Few etiologies have been listed including chemoradiation therapy. Early recognition may reduce the high mortality rate. We describe the case of a 63-year-old woman with a history of stage III ovarian cancer treated with cytoreductive surgery and adjuvant chemotherapy, including bevacizumab, who presented to the hospital because of fresh blood per rectum. One month earlier, the patient was admitted to the intensive care unit because of hemorrhagic shock secondary to a necrotic duodenal ulcer and was treated with cauterization. The patient was stable when discharged home, however, she was readmitted to the hospital because of hematemesis and hematochezia and was again in hemorrhagic shock for which the patient was urgently transfused. An abdominal computerized tomography (CT) angiography demonstrated locules of air within the intrahepatic and infrahepatic inferior vena cava (IVC), as well as evidence of communication with the duodenal lumen, and a thrombus within the IVC. The patient was evaluated by the surgical oncology and vascular teams, who deemed the patient inoperable. Our case describes ovarian malignancy, treated by radiation, leading to duodenitis, with subsequent ulcer formation. The co-administration of bevacizumab delayed gastric healing and promoted ulcer perforation favoring fistula formation.

A Case of Primary Sternomanubrial Osteomyelitis With Oxacillin-Resistant Staphylococcus aureus (ORSA) Bacteremia.

We herein report the case of a previously healthy 26-year-old male patient who presented to our hospital with chest pain and fevers. Investigations revealed oxacillin-resistant Staphylococcus aureus (ORSA) osteomyelitis of the manubrium, for which no inciting event or background was identified, classifying it as primary sternomanubrial osteomyelitis (PSO). The patient was appropriately treated with intravenous antibiotics, resulting in clinical improvement. The sternomanubrial site without trauma has rarely been described in the literature.

Predictors of Deep Venous Thrombosis in Hospitalized Patients With Liver Cirrhosis in the US.

Background Patients with liver cirrhosis were previously considered as anticoagulated; thus, their risk of developing venous thromboembolism (VTE) is lower. Recently, several studies showed contradicting results regarding deep venous thrombosis (DVT) occurrence in cirrhotic patients. The aim of this study is to evaluate the prevalence and risk associated with developing DVT in hospitalized cirrhotic patients in a large US population. Methods We queried the commercial database Explorys (IMB Inc., Armonk, New York), an aggregate of electronic health record data from 26 US healthcare systems. After excluding patients under 20 years old, a cohort of patients with a Systematized Nomenclature of Medicine - Clinical Terms of "cirrhosis of the liver" and "inpatient care" between 2015-2019 were identified, and prevalence of DVT was calculated in the exposure and the control groups. Statistical analysis for a multivariable model was performed. Factors adjusted for include gender, race, obesity, hypoalbuminemia, diabetes mellitus, viral hepatitis, and liver malignancy. Results Among 9,990,290 patients who were hospitalized between 2015 and 2019, 157,400 patients had a diagnosis of liver cirrhosis. The prevalence of DVT in hospitalized patients with liver cirrhosis was 3.29% compared to 3.18% in non-cirrhotic patients. Using the multivariate analysis model, DVT was inversely associated with cirrhosis in hospitalized patients [OR: 0.921; p<0.0001] compared to patients without liver cirrhosis. Predictors of developing DVT among patients with cirrhosis were non-Caucasian race, obesity (BMI>30), liver malignancy, hypoalbuminemia, and diabetes mellitus. Cirrhotic patients due to viral hepatitis were less likely to develop DVT [OR: 0.775; p<0.001] compared to non-cirrhotic patients. Conclusion In this database, although the prevalence of DVT in cirrhotic hospitalized patients was slightly higher than in non-cirrhotic patients (3.29% vs. 3.18%, respectively), cirrhosis as an independent factor was associated with less risk of DVT during hospitalization. This poses a question regarding DVT prophylaxis necessity in this group of patients. Further studies are needed to clarify the benefit and risks of DVT prophylaxis in cirrhotic patients.

Statin Use in Patients With Chronic Liver Disease and Cirrhosis: Current Evidence and Future Directions.

Chronic liver disease (CLD) and its complications constitute a significant cause of mortality and morbidity worldwide. Most deaths are secondary to the decompensation of cirrhosis and evolution of portal hypertension (PHTN). Since disease progression reversal is hardly attainable after decompensated cirrhosis develops, it is essential to intervene early with a therapeutic agent or regimen that could prevent or slow disease evolution. Thus far, there has been no agreed-upon medication to help in the fight against the development of cirrhosis or its decompensation. While early data depicted statins as harmful agents for the liver, current evidence from preclinical and clinical studies suggests that they might have positive impact on CLD. Low-quality evidence supports the fact that statins reduce mortality in CLD. Moderate-quality evidence suggests that statins reduce the risk of hepatic decompensation, variceal bleeding, and mortality, especially among patients with compensated cirrhosis. Combining this data with the long track-record of safety and tolerability of statins and their potential benefits in hepatocellular carcinoma (HCC) risk reduction, hepatologists might soon rely on statins to achieve better outcomes in their CLD and cirrhotic patients without significant additional costs. This review describes the rationale behind the use of statins in patients with CLD and cirrhosis. It sheds light on the current preclinical and clinical studies that reflect beneficial effects of the use of different types and doses of statins in the treatment of patients with different types and stages of CLD and cirrhosis. It also emphasizes the need for designing and developing additional large prospective interventional randomized control trials (RCTs) to better evaluate the association between statin exposure and the risk of fibrosis progression and development of cirrhosis in patients with non-cirrhotic CLDs, the risk of progression of PHTN in patients with cirrhosis, and the mortality rates in patients with cirrhotic or non-cirrhotic CLDs.

Clinical and Microbiologic Efficacy and Safety of Imipenem/Cilastatin/Relebactam in Complicated Infections: A Meta-analysis.

BACKGROUND: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP). MATERIALS AND METHODS: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I² statistic. RESULTS: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. CONCLUSION: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).

Bariatric venous thromboembolism prophylaxis: an update on the literature.

Introduction: Rates of obesity have been increasing worldwide and with the current situation obesity now represents an epidemic. Bariatric surgery is one the most effective ways to help reduce weight and sustain weight loss. Venous thromboembolism is a major cause of morbidity and mortality among bariatric surgery patients with no clearly established guidelines on prophylaxis. Areas covered: In this review the authors summarize clinical studies evaluating unfractionated heparin (UFH) and low molecular weight heparins (LMWH) in bariatric surgery patients. The authors present studies that assessed venous thromboembolic (VTE)-related risk stratification but also various dosing regimens of heparin products in this population of patients. Moreover, the authors will also present the feasibility of using direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prevention along with providing a summary of few current guidelines for VTE prevention in bariatric surgery patients. Expert opinion: Based on the data presented in this review, the authors conclude that LMWHs may be better options than UFH for VTE prophylaxis in bariatric surgery patients. We also conclude that risk stratifying bariatric patients may be a better approach when deciding on the best thromboprophylaxis modality, dose and duration.