Fibrosis-4 (FIB-4) index as a predictor for mechanical ventilation and 30-day mortality across COVID-19 variants.

Background: The Fibrosis-4 (FIB-4) index, a simple index that includes age, liver enzymes, and platelet count has been studied as a tool to identify patients at a risk of requiring mechanical ventilation due to its high negative predictive value. It is unknown if FIB-4 remains useful to predict the severity of respiratory disease requiring mechanical ventilation amongst new Coronavirus disease 2019 (COVID-19) variants and whether a relationship also exists between FIB-4 and 30-day mortality. The main objective was to determine if FIB-4 can predict mechanical ventilation requirements and 30-day mortality from COVID-19 across variants including Alpha, Delta, and Omicron. Methods: This was a population-based, retrospective cohort analysis of 232,364 hospitalized patients in the National COVID-19 Cohort Collaborative between the age of 18-90 who tested positive for COVID-19 between April 27, 2020 and June 25, 2022. The primary outcome was association between FIB-4 and need for mechanical ventilation. Secondary measures included the association of FIB-4 with 30-day mortality. Results: A FIB-4 > 2.67 had 1.8 times higher odds of requiring mechanical ventilation across all variants of COVID-19 (OR 1.81; 95% CI: [1.76, 1.86]). The area under the ROC curve showed high diagnostic accuracy with values ranging between 0.79 (Omicron wave) and 0.97 (delta wave). Increased FIB-4 was associated with 30-day mortality across the variates. Conclusion: The FIB-4 was consistently associated with both increased utilization of mechanical ventilation and 30-day mortality among COVID-19 patients across all waves in both adjusted and unadjusted models. This provides a simple tool for risk-stratification for front-line health care professionals.

Prediction of Recurrence of Atrial Fibrillation Post-ablation Based on Atrial Fibrosis Seen on Late Gadolinium Enhancement MRI: A Metaanalysis.

OBJECTIVES: This meta-analysis aims to investigate the recurrence of atrial fibrillation (AF) post-ablation based on the various stages of fibrosis seen in the late gadolinium enhancement magnetic resonance imaging (LGE-MRI). METHODS: Electronic databases were searched using specific terms and identified nine studies that met the inclusion criteria. A total of 1,787 patients underwent LGE-MRI to assess atrial fibrosis before catheter ablation for AF. We performed three analyses: first, we compared stage IV versus stage I (reference group). The second set examined the combined stages III and IV versus stages I and II (reference group). The third set compared stage IV versus combined stages I, II, and III. The metanalysis relied on a random-effects model to pool the odds ratios (OR) and 95% confidence intervals (CI) using the DerSimonian and Laird method. The data was analyzed using StatsDirect software in England. RESULTS: The study showed a higher rate of AF recurrence after ablation in stage IV atrial fibrosis than in stage I (OR, 9.54; 95% CI, 3.81 to 28.89; P<00001). Also, in patients with combined stages III & IV of atrial fibrosis, AF recurrence was significantly higher after ablation than in stages I & II groups (OR, 2.37; 95% CI, 1.61 to 3.50; P<00001). Similarly, compared to combined stages I, II, and III, patients with stage IV have higher odds of recurrence post-ablation (OR, 4.24; 95% CI, 2.39- 7.52, P < 0.001). CONCLUSION: This metanalysis demonstrates the strong association between left atrial fibrosis in LGE-MRI and AF post-ablation recurrence. The finding of this study will further assist clinicians in predicting the recurrence rate of AF based on the amount of fibrosis and tailor therapeutic decisions for further management.

An assessment of race and gender-based biases among readmission predicting tools (HOSPITAL, LACE, and RAHF) in heart failure population.

BACKGROUND: The objective of our study is to retrospectively investigate if the HOSPITAL score, LACE index, and RAHF scale exhibit any bias based on gender and race in heart failure readmissions. METHODS: This is a retrospective cohort study with all adult medical patients discharged with congestive heart failure from 2016 to 2018 from Southern Illinois University School of Medicine Hospitalist service. The receiver operating characteristic (ROC) curve was constructed comparing prediction tools (HOSPITAL score, LACE index, and RAHF scale) performance based on gender and race by measuring the area under the curve (AUC). Absolute Between-ROC Area (ABROCA) values were calculated. All statistical analyses were performed using R version 3.6.2. RESULTS: The performance of the HOSPITAL score in the majority and minority population showed a statistically significant difference between AUCs (0.714 and 0.633, p = 0.029) and an ABROCA of 0.081 indicating superior performance in predicting hospital readmissions in the majority group vs. the minority. The performance of RAHF score in females and males showed statistically significant differences between AUCs (0.567 and 0.527, p = 0.04) and an ABROCA of 0.04 indicating the superior performance of the RAHF score in females compared with males. CONCLUSIONS: Our study demonstrated that the HOSPITAL score and the RAHF scale showed significant differences in predicting 30-day readmissions risk based on race and gender, respectively, in heart failure patients, whereas the LACE index did not show any significant difference.

Social Vulnerability Indices as a Risk Factor for Heart Failure Readmissions.

Objectives: The objective of our study was to use the parameters of social vulnerability index (SVI) to observe their association with the 30-day hospital readmissions in the heart failure population.Methods: Data required for analysis were extracted from the electronic medical record. The geographic SVI data was then merged with the clinical data. Qualitative variables and reported as frequency and quantitative variables and reported as the mean ± standard deviation. Variables from univariate analysis with a P value of ≤ 0.10 were evaluated using multivariate logistic regression with stepwise backward variable selection and receiver operating curve (ROC) analysis.Results: The odds ratio of readmission predicted by HOSPITAL score was 1.137 (P value = 0.004, 95% CI = 1.041-1.241). SVI parameter recording disability showed odds ratio of 1.521 (P value = 0.006, 95% CI = 1.125-2.058) and SVI parameter tracking vehicle ownership showed odds ratio of 15.355 (P value = 0.014, 95% CI = 1.755 - 134.383). The ROCs were generated for three scenarios: (i) HOSPITAL score only which had area under the curve (AUC) of 0.702 (P value = 0.015), (ii) SVI indicators tracking vehicle ownership and disability resulted in the AUC of 0.589 (P value = 0.016), and (iii) all of the above combined increased the AUC increased to 0.718 (P value = 0.015).Conclusions: Two social parameters (limited vehicle access and prevalence of disability) from the SVI showed a strong association with 30-day hospital readmissions.

Sequential dosing of convalescent COVID-19 plasma with significant temporal clinical improvements in a persistently SARS-COV-2 positive patient.

The current global pandemic, SARS-CoV-2 infection, is still extending across the world affecting millions of lives to the date. While new successful vaccines are available with promising outcomes to minimize the spread and to reduce the severity of the disease, optimal therapeutic options still remain elusive. COVID-19 convalescent plasma (CCP) is an investigational treatment option which studies suggesting signals of efficacy and favorable outcomes only for patients treated very early in course of the disease. Benefits of the use of CCP later in the disease remain highly debated and therefore are not common practice. We hereby report a case of severe SARS-CoV-2 infection in a young male patient with prolonged COVID-19 positivity who received repeat doses of CCP treatments later in the disease with temporal clinical improvement. This patient's case highlights the need of further studies evaluating efficacy of repeated dosing of CCP. This also suggests a potential of successful use of CCP later in the disease in selected COVID-19 patients.

Comprehensive evaluation of cardiovascular efficacy and safety outcomes of SGLT2 inhibitors in high risk patients of cardiovascular disease: systematic review and meta-analysis.

OBJECTIVES: To demonstrate a magnitude of the cardiovascular benefits, concomitantly analyzing the safety outcomes of sodium-glucose cotransporter 2 inhibitor (SGLT2-I) comprehensively, as a class effect in a larger sample size combined from recent randomized control trials. METHODS: We searched electronic databases using specific terms and evaluated 6 efficacy and 10 safety outcomes. Odds ratios (ORs) and 95% confidence interval (CI) were used to compare two interventions. RESULTS: Five studies (n = 41 267) were included, among which 23 539 received SGLT2-I. The SGLT2-I group favored reduction in major adverse cardiovascular events (OR, 0.78; 95% CI, 0.62-0.98; P = 0.03), cardiovascular death (CVD) or heart failure hospitalization (OR, 0.60; 95% CI, 0.46-0.80; P = 0.0004), rate of hospitalization for heart failure (OR, 0.56; 95% CI, 0.44-0.72; P < 0.00001), CVD (OR, 0.68; 95% CI, 0.50-0.93; P = 0.01), all-cause mortality (OR, 0.67; 95% CI, 0.48-0.93; P = 0.02) and myocardial infarction (OR, 0.79; 95% CI, 0.64-0.99; P = 0.04) when compared to the placebo group. Safety analysis showed higher diabetic ketoacidosis (DKA) rate in SGLT2-I group (OR, 2.33; 95% CI, 1.40-3.90; P = 0.001); in contrast, major hypoglycemic events were significantly lower (OR, 0.79; 95% CI, 0.73-0.87; P < 0.00001). AKI was significantly higher in the placebo group (OR, 0.76; 95% CI, 0.65-0.88; P = 0.0004). There were no statistically significant effects on other outcomes. CONCLUSION: In selected high-risk patients of cardiovascular disease, the SGLT2-I is a potential effective class of drugs for improving cardiovascular outcomes and all-cause mortality without an increased risk of all other major complications except DKA on this meta-analysis.

Man vs. man-made marijuana: A case of drug-induced posterior reversible encephalopathy syndrome (PRES) due to K2, a ynthetic cannabinoid (SCB).

Synthetic Cannabinoids (SCB) are engineered chemical compounds that share a similar chemical structure with the active ingredient of marijuana, delta-9-tetrahydrocanabinol. Although the FDA has not approved the use of SCB without a prescription from a licensed health-care provider, the cost effectiveness and availability of SCB has made it a popular choice among recreational drug users. Manufacture of SCB as a street drug is not regulated. These SCB are highly potent chemicals that cause various severe toxicities. In this case report, we describe an adult who suffered from PRES after consuming K2, a synthetic cannabinoid.

Immunotherapies and Combination Strategies for Immuno-Oncology.

The advent of novel immunotherapies in the treatment of cancers has dramatically changed the landscape of the oncology field. Recent developments in checkpoint inhibition therapies, tumor-infiltrating lymphocyte therapies, chimeric antigen receptor T cell therapies, and cancer vaccines have shown immense promise for significant advancements in cancer treatments. Immunotherapies act on distinct steps of immune response to augment the body's natural ability to recognize, target, and destroy cancerous cells. Combination treatments with immunotherapies and other modalities intend to activate immune response, decrease immunosuppression, and target signaling and resistance pathways to offer a more durable, long-lasting treatment compared to traditional therapies and immunotherapies as monotherapies for cancers. This review aims to briefly describe the rationale, mechanisms of action, and clinical efficacy of common immunotherapies and highlight promising combination strategies currently approved or under clinical development. Additionally, we will discuss the benefits and limitations of these immunotherapy approaches as monotherapies as well as in combination with other treatments.

Heart Failure Drug Class Effects on 30-Day Readmission Rates in Patients with Heart Failure with Preserved Ejection Fraction: A Retrospective Single Center Study.

Background: The pharmacologic management of heart failure with preserved ejection fraction (HFpEF) involves far fewer options with demonstrated additional benefit. Therefore, we examined the effect of combination of multiple classes of HF medication in the 30-day hospital readmission in patients with HFpEF. Methods: All adult patients discharged with a diagnosis of HFpEF and a left ventricular ejection fraction (LVEF) of ≥ 50% reported during the admission or within the previous six months from our institution were retrospectively studied for a 30-day hospital readmission risk. Individual as well as combination drug therapy at the time of hospital discharge were evaluated using Pearson chi2 test and multivariate logistic regression. Results: The overall 30-day readmission rate in this HFpEF cohort of 445 discharges was 29%. Therapy with loop diuretics (p = 0.011), loop diuretics and angiotensin receptor blocker (p = 0.043) and loop diuretics and beta blockers (p = 0.049) were associated with a lower risk of 30-day hospital readmission. Multivariate logistic regression revealed only loop diuretics to be associated with a lower risk of hospital readmission in patients with HFpEF (OR 0.59; 95% CI, 0.39-0.90; p = 0.013). Conclusions: Our study revealed that loop diuretics at discharge decreases early readmission in patients with HFpEF. Further, our study highlights the implication of a lack of guidelines and treatment challenges in HFpEF patients and emphasizes the importance of a conservative approach in preventing early readmission in patients with HFpEF.

Heart Failure with Preserved Ejection Fraction and 30-Day Readmission.

OBJECTIVE: Several studies identify heart failure (HF) as a potential risk for hospital readmission; however, studies on predictability of heart failure readmission is limited. The objective of this work was to investigate whether a specific type of heart failure (HFpEF or HFrEF) has a higher association to the rate of 30-day hospital readmission and compare their predictability with the two risk scores: HOSPITAL score and LACE index. DESIGN: Retrospective study from single academic center. METHODS: Sample size included adult patients from an academic hospital in a two-year period (2015 - 2017). Exclusion criteria included death, transfer to another hospital, and unadvised leave from hospital. Baseline characteristics, diagnosis-related group, and ICD diagnosis codes were obtained. Variables affecting HOSPITAL score and LACE index and types of heart failure present were also extracted. Qualitative variables were compared using Pearson chi2 or Fisher's exact test (reported as frequency) and quantitative variables using non-parametric Mann-Whitney U test (reported as mean ± standard deviation). Variables from univariate analysis with P values of 0.05 or less were further analyzed using multivariate logistic regression. Odds ratio was used to measure potential risk. RESULTS: The sample size of adult patients in the study period was 1,916. All eligible cohort of patients who were readmitted were analyzed. Cumulative score indicators of HOSPITAL Score, LACE index (including the Charlson Comorbidity Index) predicted 30-day readmissions with P values of <0.001. The P value of HFpEF was found to be significant in the readmitted group (P < 0.001) compared to HFrEF (P = 0.141). Multivariate logistic regression further demonstrated the association of HFpEF with higher risk of readmission with odds ratio of 1.77 (95% CI: 1.25 - 2.50) and P value of 0.001. CONCLUSIONS: Our data from an academic tertiary care center supports HFpEF as an independent risk factor for readmission. Multidisciplinary management of HFpEF may be an important target for interventions to reduce hospital readmissions.

Late Atrial Thrombus Formation After Percutaneous Patent Foramen Ovale Closure.

Late thrombus formation is a rare complication associated with patent foramen ovale (PFO) closure devices. We report the case of an incidental discovery of large thrombi in both atria 9 months after percutaneous PFO occlusion that required cardiac surgery for thrombi removal. (Level of Difficulty: Beginner.).

A Rare Case of Isolated and Idiopathic Spontaneous Renal Artery Dissection in a Female Patient on Multiple Medications.

Constituting less than 25% of all renal artery dissections (RAD), isolated spontaneous renal artery dissection (SRAD) is a rare diagnosis that can cause subsequent renal infarction with impairment. The majority of SRAD cases are idiopathic. Management ranges from conservative, medical to endovascular, and surgical repair. We report a case of a young female on multiple medications who presented with SRAD. She presented with acute abdominal pain and was found to have isolated spontaneous renal artery dissection. The etiology of this patient's isolated SRAD could possibly be pinned down to her multiple stimulant medications used after the major known causes were ruled out.

Trimethoprim-sulfamethoxazole Induced Pancytopenia: A Common Occurrence but A Rare Diagnosis.

Trimethoprim-sulfamethoxazole (TMP-SMX) is a bacteriostatic antimicrobial medication used for the treatment of a variety of infections and has many reported skin and hematologic side effects. Due to the easy availability and cost effectiveness, TMP-SMX is one of the medications commonly used for treatment of skin and soft tissue in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. One of the rare hematologic manifestations of TMP-SMX is pancytopenia, which is a reduction in all cell lines. In this case report, we are documenting a case of pancytopenia due to severe drug reaction to TMP-SMX in a 70-year-old female after two weeks of medication use. Upon initial stabilization she underwent a thorough workup and was subsequently diagnosed with severe drug-induced pancytopenia. Detailed history, early diagnosis, prompt discontinuation of the offending medication along with supportive care remain the mainstay of treatment in the management of TMP-SMX induced pancytopenia.

Novel Delivery Systems for Checkpoint Inhibitors.

Checkpoint inhibition (CPI) therapies have been proven to be powerful clinical tools in treating cancers. FDA approvals and ongoing clinical development of checkpoint inhibitors for treatment of various cancers highlight the immense potential of checkpoint inhibitors as anti-cancer therapeutics. The occurrence of immune-related adverse events, however, is a major hindrance to the efficacy and use of checkpoint inhibitors as systemic therapies in a wide range of patients. Hence, methods of sustained and tumor-targeted delivery of checkpoint inhibitors are likely to improve efficacy while also decreasing toxic side effects. In this review, we summarize the findings of the studies that evaluated methods of tumor-targeted delivery of checkpoint inhibitors, review their strengths and weaknesses, and discuss the outlook for therapeutic use of these delivery methods.