Outcomes in patients with COVID-19 and new onset heart blocks: Insight from the National Inpatient Sample database.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a worldwide health crisis since it first appeared. Numerous studies demonstrated the virus's predilection to cardiomyocytes; however, the effects that COVID-19 has on the cardiac conduction system still need to be fully understood. AIM: To analyze the impact that COVID-19 has on the odds of major cardiovascular complications in patients with new onset heart blocks or bundle branch blocks (BBB). METHODS: The 2020 National Inpatient Sample (NIS) database was used to identify patients admitted for COVID-19 pneumonia with and without high-degree atrioventricular blocks (HDAVB) and right or left BBB utilizing ICD-10 codes. The patients with pre-existing pacemakers, suggestive of a prior diagnosis of HDAVB or BBB, were excluded from the study. The primary outcome was inpatient mortality. Secondary outcomes included total hospital charges (THC), the length of hospital stay (LOS), and other major cardiac outcomes detailed in the Results section. Univariate and multivariate regression analyses were used to adjust for confounders with Stata version 17. RESULTS: A total of 1058815 COVID-19 hospitalizations were identified within the 2020 NIS database, of which 3210 (0.4%) and 17365 (1.6%) patients were newly diagnosed with HDAVB and BBB, respectively. We observed a significantly higher odds of in-hospital mortality, cardiac arrest, cardiogenic shock, sepsis, arrythmias, and acute kidney injury in the COVID-19 and HDAVB group. There was no statistically significant difference in the odds of cerebral infarction or pulmonary embolism. Encounters with COVID-19 pneumonia and newly diagnosed BBB had a higher odds of arrythmias, acute kidney injury, sepsis, need for mechanical ventilation, and cardiogenic shock than those without BBB. However, unlike HDAVB, COVID-19 pneumonia and BBB had no significant impact on mortality compared to patients without BBB. CONCLUSION: In conclusion, there is a significantly higher odds of inpatient mortality, cardiac arrest, cardiogenic shock, sepsis, acute kidney injury, supraventricular tachycardia, ventricular tachycardia, THC, and LOS in patients with COVID-19 pneumonia and HDAVB as compared to patients without HDAVB. Likewise, patients with COVID-19 pneumonia in the BBB group similarly have a higher odds of supraventricular tachycardia, atrial fibrillation, atrial flutter, ventricular tachycardia, acute kidney injury, sepsis, need for mechanical ventilation, and cardiogenic shock as compared to those without BBB. Therefore, it is essential for healthcare providers to be aware of the possible worse predicted outcomes that patients with new-onset HDAVB or BBB may experience following SARS-CoV-2 infection.

Impact of Hospital Readmissions Reduction Program Policy on 30-Day and 90-Day Readmissions in Patients With Acute Myocardial Infarction: A 10-Year Trend From the National Readmissions Database.

Hospital readmissions following acute myocardial infarction (AMI) pose a significant economic burden on health care utilization. The hospital readmission reduction program (HRRP) enacted in 2012 focused on reducing readmissions by penalizing Centers for Medicare & Medicaid Services (CMS) Medicare hospitals. We aim to assess the trend of readmissions after AMI hospitalization between 2010 and 2019 and assess the impact of HRRP. The National Readmission Database was queried to identify AMI hospitalizations between 2010 and 2019. In the primary analysis, trends of 30-day and 90-day all-cause and AMI specific readmissions were assessed from 2010 to 2019. In the secondary analysis, trend of readmission means length of stay and mean adjusted total cost were calculated. There were a total of 592,015 30-day readmissions and 787,008 90-day readmissions after an index hospitalization for AMI between 2010 and 2019. The rates of 30-day and 90-day all-cause readmissions decreased significantly from 12.8% to 11.6%, (P = 0.0001) and 20.6 to 18.8, (P = 0.0001) respectively in the decade under study. With regards to HRRP policy intervals, the pre-HRRP period from 2010 to 2012 showed a downward trend in all-cause readmission (12.8% to 11.6%) and similarly a downward trend was also seen in the post HRRP period (2013-2015:11.0%-8.2%, 2016-2019-12.3-11.7%). Secondary analysis showed a trend towards increase in mean length of stay (4.54-4.96 days, P = 0.0001) and adjusted total cost ($13,449-$16,938) in 30-day all-cause readmission for AMI in the decade under review. In our National Readmission Database-based analysis of patients readmitted to hospitals within 30-days and 90-days after AMI, the rate of all-cause readmissions down trended from 2010 to 2019.

Factor Xa inhibitors versus vitamin K antagonist in morbidly obese patients with venous thromboembolism: a systematic review and meta-analysis.

INTRODUCTION: Guidelines have endorsed non-vitamin K antagonist oral anticoagulants (NOACs), consisting of factor Xa inhibitors (xabans) and direct thrombin inhibitors, as the first line of treatment in venous thromboembolism (VTE) and atrial fibrillation. However, morbidly obese patients were under-represented in landmark trials of NOACs. Therefore, this study aimed to systematically review and perform a meta-analysis of studies on xabans versus vitamin K antagonist (VKA) in this high-risk population with VTE. METHODS: PubMed, Embase, Medline, Cochrane library, and Google Scholar databases were searched to identify studies that compared xabans and VKA in treating morbidly obese patients with VTE. Morbid obesity was defined as body weight ≥ 120 kg or BMI ≥ 40 kg/m2. Outcomes of interest included recurrent VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB). RESULTS: Eight studies comprising 30,895 patients were included. A total of 12,755 patients received xabans while 18,140 received VKAs. No significant difference in the odds of recurrent VTE (OR 0.75, 95% CI 0.55-1.01) and CRNMB (OR 0.69, 95% CI 0.44-1.09) was observed between the xabans group and the VKA group. However, the xabans group was associated with lower odds of major bleeding (OR 0.70, 95% CI 0.59-0.83). CONCLUSION: Xabans have lower odds of major bleeding but similar odds of recurrent VTE when compared with VKAs in treating VTE in morbidly obese patients. Large registry analyses or future randomized controlled trials will be helpful in confirming these findings.

Trends and Outcomes of Transcatheter Aortic Valve Implantation in Patients With Peripheral Arterial Disease: Insights From the National Readmissions Database.

Due to shared risk factors, many patients with severe aortic stenosis (AS) also have concomitant peripheral arterial disease (PAD). The readmission rates and long term clinical outcomes of these patients following transcatheter aortic valve implantation (TAVI) in a large sample has not been well defined. The National Readmissions Database (NRD) (2015-2019) was used to identify patients undergoing TAVI. TAVI in patients with PAD was compared with those without PAD using a propensity score matched (PSM) analysis to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI) of net adverse clinical events (NACE), and its components. A total of 189,216 patients were identified, of which 14,925 patients (7386 with PAD, 7539 without PAD) were selected for adjusted analysis. Using PSM, patients with PAD undergoing TAVI had significantly higher in-hospital adjusted odds of NACE (aOR 1.60, 95% CI 1.36-1.88), and mortality (aOR 4.10, 95% CI 2.88-5.83). However, rates of other in-hospital peri procedural complications (stroke, major bleeding, paravalvular leak, cardiogenic shock) were not significantly different. There was no significant difference in the incidence of NACE, mortality, or other complications between the 2 groups at 30- and 180 days follow-up. Patients with PAD undergoing TAVI have an increased risk of mortality and NACE during the periprocedural period. However, following discharge, there was no statistically significant difference in 30 days and 6 month outcomes of TAVI in this population compared to those without significant PAD.

Readmission and In-Hospital Outcomes After Transcatheter Aortic Valve Replacement in Patients With Dementia.

BACKGROUND/PURPOSE: The prevalence of dementia and aortic stenosis (AS) increases with each decade of age. Transcatheter aortic valve replacement (TAVR) is a definitive treatment for AS, but there are scarce data on morbidity, mortality, and readmission risk after TAVR in patients with dementia. METHODS/MATERIALS: We identified all admissions for TAVR in patients with AS in the National Readmissions Database in 2017-2018 and stratified them according to the presence or absence of a secondary diagnosis of dementia. Inpatient outcomes were compared using logistic regression. Cox proportional-hazards models were used to compare 30-, 60-, and 90-day readmissions. RESULTS: A total of 48,923 index hospitalizations for TAVR were identified, of which 2192 (4.5 %) had a secondary diagnosis of dementia. Presence of dementia was associated with higher odds of delirium, pacemaker placement, acute kidney injury, and fall in hospital. The hazard of 30-day readmission was not significantly different between patients with and without dementia, but patients with dementia experienced a higher hazard of 60-day readmission (HR 1.15, 95 % CI 1.03-1.26, p = 0.011) in the unadjusted model and higher hazard of 90-day readmission in both unadjusted (HR 1.18, 95 % CI 1.08-1.30, p < 0.001) and adjusted models (aHR 1.14, 95 % CI 1.04-1.25, p = 0.004). CONCLUSIONS: Patients with dementia who undergo TAVR are at higher risk of in-hospital adverse outcomes and 60- and 90-day readmissions compared with patients without dementia. These estimates should be integrated into shared decision-making discussions with patients and families.

Causes and predictors of immediate and short-term readmissions following percutaneous left atrial appendage closure procedure.

INTRODUCTION: Percutaneous left atrial appendage device closure has been offered as an alternative to anticoagulation for high-risk patients with nonvalvular atrial fibrillation. Given the relative novelty of the procedure, we aimed to analyze the rates and causes of immediate (30 days) and short-term (90 days) readmission after the procedure. METHODS: We performed a retrospective observational study using the Nationwide Readmissions Database for 2018. We studied 29 449 hospitalizations for percutaneous left atrial appendage (LAA) device closure. RESULTS: In both the 30- and 90-day cohorts, the most common causes of readmissions were gastrointestinal bleeding (16.1% and 14.8%), heart failure exacerbation (11.1% and 11.6%), and atrial fibrillation (6.2% and 7.2%). Female sex, liver disease, chronic kidney disease, chronic pulmonary disease, presence of heart failure, human immunodeficiency virus/acquired immunodeficiency syndrome status, and diabetes mellitus were independently associated with higher odds of readmission in both cohorts. CONCLUSION: Our study highlights the need for further deliberation on the choice and duration of anticoagulation periprocedurally after percutaneous LAA closure, especially among those with high bleeding risk. It also highlights the need for optimization of heart failure status periprocedurally to avoid readmissions for exacerbations.

Safety and efficacy of ultrafiltration versus diuretics in patients with decompensated heart failure: A systematic review and meta-analysis.

BACKGROUND: Ultrafiltration (UF) is used for fluid removal patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) refractory to diuretics. However, data on the relative merits of UF and diuretics are limited. METHODS: Online databases were queried to identify clinical trials on the comparison of UF and diuretics. The major adverse cardiovascular (MACE) and its components (mortality and re-hospitalizations) were compared using the random-effects model to calculate the unadjusted odds ratio (OR) with its 95% confidence interval (CI). RESULTS: A total of 10 clinical trials comprising 838 patients (413 UF, 425 diuretics) were included in the analysis. At a median follow-up of 90 days, there was no significant difference in the odds of MACE (OR 0.71, 95% CI 0.47-1.07) and all-cause mortality (OR 1.08, 95% CI 0.77-1.52) between patients undergoing UF compared with those receiving diuretics therapy. The need for emergency department visits (OR 1.05, 95% CI 0.38-2.90), all-cause admissions (OR 0.97, 95% CI 0.72-1.30) and heart failure-related re-hospitalization (OR 0.47, 95% CI 0.21-1.02) was also similar between the two groups. The in-hospital risk for hypotension (OR 0.49, 0.23-1.04) and post-therapy creatinine rise>0.3 mg/dL (OR 1.18, 95% CI 0.74-1.89) was also not significantly different between the UF and diuretics arms. A sensitivity analysis of MACE and mortality did not show any deviation from the pooled outcomes. CONCLUSIONS: In patients with HFrEF, UF appears to be safe but might not provide significant benefits in terms of reducing the risk of mortality or readmission rates compared with those treated with diuretics.

Electrolyte Abnormalities Associated With the Use of Atezolizumab - A Systematic Review.

Background and objectives: In recent years, immune-checkpoint inhibitors (ICIs) particularly atezolizumab is on the rise in treating advanced malignancies. With its increased clinical use, various electrolyte abnormalities have been reported in the literature. In this review, we have addressed the question of significant electrolyte abnormalities associated with atezolizumab. Materials and methods: Following PRISMA guidelines, we performed a thorough literature search in four databases including PubMed, Cochrane Library, Embase, and Clinicaltrials.gov. We included only randomized controlled trials from 2010 till March 2021. After a comprehensive screening of 1587 articles, we selected 14 articles for our review and tabulated the results. Following MeSH terms were used: "electrolyte abnormalities", "immune checkpoint inhibitors", "atezolizumab". Results: Non-small cell lung cancer (n = 1270) and metastatic urothelial carcinoma (n = 1164) were the most common malignancies among 3160 patients. The most common electrolyte abnormality was hypomagnesemia (4.7%). Hyponatremia, hypophosphatemia, hypercalcemia and hypokalemia were found in 2.3%, 0.63%, 0.25% and 0.06% patients respectively. For patients taking atezolizumab, hypomagnesemia was most frequently found in non-small cell lung carcinoma patients (9.4%), while urothelial metastatic carcinoma patients most commonly had hyponatremia (5.15%). Hypokalemia though insignificant was observed only in patients with metastatic renal cell carcinoma (2.85%). Conclusion: Since the use of atezolizumab is on the rise for the treatment of various cancers, more studies need to be conducted to better understand its safety and toxicity profile.

Efficacy and Safety of Regimens Used for the Treatment of POEMS Syndrome- A Systematic Review.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy/edema, monoclonal plasma protein [M protein], and skin changes) is a rare paraneoplastic disorder associated with underlying plasma cell neoplasia. Although limited-stage disease can be treated with radiotherapy, treatment for the more advanced disease remains unclear. The most commonly used therapies for POEMS syndrome include alkylators and steroids, high-dose chemotherapy with autologos stem cell transplantation, lenalidomide, and bortezomib. In general, patients tend to have excellent prognosis if the diagnosis is made early and appropriate therapy is used. Here we present a systematic review of the efficacy and safety of treatment regimens used to treat POEMS syndrome in the adult population. Combinations of immunomodulatory agents with corticosteroids were most frequently utilized regimens with durable hematological and neurological responses. Combinations of proteasome inhibitors and alkylating agents with corticosteroids, although less frequently utilized, appear to have reasonable safety and efficacy profiles.

Efficacy and Safety of Daratumumab-based Regimens in Pretreated Light Chain (AL) Amyloidosis: A Systematic Review.

With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50%-90% and 50%-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT.

Efficacy and Toxicity Profile of Carfilzomib-Based Regimens for Treatment of Newly Diagnosed Multiple Myeloma: A Systematic Review.

Carfilzomib (CFZ) is a proteasome inhibitor currently approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Multiple trials are ongoing to evaluate its efficacy and safety in newly diagnosed multiple myeloma (NDMM). The use of CFZ-based two- or three-drug combination regimens as induction for the management of NDMM is an emerging approach. CFZ-based regimens include combinations of immunomodulators, alkylating agents, and monoclonal antibodies along with dexamethasone. In this review, we assess the efficacy and toxicity of CFZ-based regimens in NDMM. We reviewed a total of 27 studies (n=4538 patients) with overall response rates (ORR) ranging between 80% and 100%. Studies evaluating the combination of CFZ with daratumumab reported an ORR of approximately 100%. Achievement of minimal residual disease (MRD) negativity, measured by multi-parameter flow cytometry (MPFC), ranged between 60% and 95% in 4 (n=251) out of 6 studies that measured MRD-negativity. The interim results of the ENDURANCE trial failed to show superior efficacy and progression-free survival (PFS) of carfilzomib-lenalidomide when compared to bortezomib-lenalidomide combination, albeit with a lower incidence of neuropathy. Hematological toxicity was the most common adverse event observed with these regimens, and the most common non-hematological adverse events were related to cardiovascular and electrolyte disturbances. We need to further evaluate the role of CFZ in NDMM by conducting more Phase III trials with different combinations.

Role of Venetoclax in the Treatment of Relapsed and Refractory Multiple Myeloma.

Biomarker-driven targeted therapies have been an area of exploration for innovative therapeutic options in oncology. B-cell lymphoma-2 (BCL-2) protein is an anti-apoptotic protein expressed on the clonal plasma cells in patients with multiple myeloma (MM). MM subsets with t (11;14) have overexpression of BCL-2 and can benefit from venetoclax (VEN) when used either alone or in combination with other chemotherapeutic agents with an overall response rate (ORR) ranging from 40% to 100%. The most commonly reported grade ≥ 3 adverse effects include cytopenias and gastrointestinal side effects. This review highlights the meaningful efficacy and tolerable safety of VEN monotherapy and its combination regimens in the treatment of relapsed refractory MM.

Safety and Efficacy of Renin-Angiotensin-Aldosterone System Inhibitors in COVID-19 Population.

INTRODUCTION: The safety of renin-angiotensin-aldosterone system inhibitors (RAASi) among COVID-19 patients has been controversial since the onset of the pandemic. METHODS: Digital databases were queried to study the safety of RAASi in COVID-19. The primary outcome of interest was mortality. The secondary outcome was seropositivity improvement/viral clearance, clinical manifestation progression, and progression to intensive care units. A random-effect model was used to compute an unadjusted odds ratio (OR). RESULTS: A total of 49 observational studies were included in the analysis consisting of 83,269 COVID-19 patients (RAASi n = 34,691; non-RAASi n = 48,578). The mean age of the sample was 64, and 56% were males. We found that RAASi was associated with similar mortality outcomes as compared to non-RAASi groups (OR 1.07; 95% CI 0.99-1.15; p > 0.05). RAASi was associated with seropositivity improvement including negative RT-PCR or antibodies, (OR 0.96; 95% CI 0.93-0.99; p < 0.05). There was no association between RAASi versus control with progression to ICU admission (OR 0.99; 95% CI 0.79-1.23; p > 0.05) or higher odds of worsening of clinical manifestations (OR 1.04; 95% CI 0.97-1.11; p > 0.05). Metaregression analysis did not change our outcomes for effect modifiers including age, sex, comorbidities, RAASi type, or study type on outcomes. CONCLUSIONS: COVID-19 is not a contraindication to hold or discontinue RAASi as they are not associated with higher mortality or worsening symptoms. Continuation of RAASi might be associated with favorable outcomes in COVID-19, including seropositivity/viral clearance.

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19.

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.

Relapsed breast cancer complicated by isolated brain metastasis.

The most common etiology of malignant brain tumors is metastatic lesions. They usually present as multiple lesions at the gray-white matter junction. However, they can unconventionally present as a single space-occupying lesion mimicking meningioma.

Omega 3 Fatty Acids and COVID-19: A Comprehensive Review.

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to "cytokine storm". This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.

Paraneoplastic syndromes in cholangiocarcinoma.

Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy, due to complex interactions between the body's immune system and malignant neoplasm. Cholangiocarcinoma (CCA) is an aggressive epithelial malignancy of hepatobiliary tree and it is found to be associated with various paraneoplastic syndromes. These syndromes can present as dermatological, neurological, renal, hematological, or multi-systemic manifestations. Clinical suspicion and timely recognition of these syndromes can lead to early diagnosis of covert malignancies like CCA. The management plan remains the removal of the underlying cause which in this case is CCA.

A Systematic Review of Transfusion-Transmissible Infections Among Blood Donors and Associated Safety Challenges in Pakistan.

The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly regulated transfusion practices. There is a considerable possibility that transfusion-transmissible infections (TTIs) are contributing to the current epidemic of hepatitis B virus (HBV) and hepatitis C virus (HCV) (affecting 7.4% of the general population) in the country. To study this issue, we conducted a systematic review to identify articles related to TTIs and transfusion safety in Pakistan from January 1, 2010 to January 31, 2020. A review of 33 articles met the final criteria for qualitative synthesis. Analysis of these studies showed a cumulative frequency of HBV 2.04%, HCV 2.44%, HIV 0.038%, syphilis 1.1% and malaria 0.11%. The frequency of coinfections among blood donors varied from 0.0099% to 0.35%. The highest number of coinfections were HCV and syphilis, followed by HCV and HBV infections. Syphilis and malaria were tested in only 38% and 46% of all the blood donations in one study. The rate of voluntary non-remunerated donations (VNRDs) was less than 13%, and male donors were 95% to 100% in these studies. There was a significant difference in the frequency of HBV and HCV in VNRDs (0.48%) as compared to replacement donors (RDs) (4.15%). In short, this review shows a high frequency of TTIs, especially HBV, HCV and syphilis in the blood donor population in Pakistan. There is a high dependency on RDs, minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods and limited knowledge of donor health. Without standardized safe transfusion practices, there will be an ongoing increase in transmission of TTIs, especially HBV, HCV, syphilis, and HIV leading to a significant adverse public health impact.