Search

Huzefa Bhopalwala,1 Nakeya Dewaswala,2 Sandhya Kolagatla,1 Lauren Wisnieski,3 Jonathan Piercy,1 Adnan Bhopalwala,1 Nagabhishek Moka1 1Department of Internal Medicine, Appalachian Regional Healthcare, Whitesburg, KY, USA; 2Department of Cardiovascular Disease, University of Kentucky, Lexington, KY, USA; 3Department of Public Health and Research, Lincoln Memorial University, Harrogate, TN, USACorrespondence: Nakeya Dewaswala, Department of Cardiovascular Disease, University of Kentucky, 900 South Limestone Street, Charles T. Wethington Building Rm. 326, Lexington, KY, 40536-0200, USA, Tel +1 4252136401, Email nakeya52@gmail.comBackground: The prevalence and outcome of coronavirus disease 2019 (COVID-19) in rural areas is unknown.Methods: This is a multi-center retrospective cohort study of hospitalized patients diagnosed with COVID-19 from April 5, 2020 to December 31, 2020. The data were extracted from 13 facilities in the Appalachian Regional Healthcare system that share the same electronic health record using ICD-10-CM codes.Results: The number of patients diagnosed with COVID-19 per facility ranged from 5 to 535 with a median of 106 patients. Total mortality was 11.4% and ranged from 0% to 22.6% by facility (median: 9.0%). Non-survivors had a greater prevalence of congestive heart failure (CHF), hypertension, type 2 diabetes mellitus, stroke, transient ischemic attack (TIA), and pulmonary embolism. Patients who died were also more likely to have had chronic obstructive pulmonary disease (COPD), acute respiratory failure (ARF), liver cirrhosis, chronic kidney disease (CKD), dementia, cancer, anemia, and opiate dependence.Conclusion: The aging population, multiple co-morbidities, and health-related behaviors make rural patients vulnerable to COVID-19. A better understanding of the disease in rural areas is crucial, given its heightened vulnerability to adverse outcomes.Keywords: coronavirus, COVID-19, SARS-CoV-2, cohort, mortality, survival

Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant inherited condition, significantly impacts lung and liver functions, with mutations in the SERPINA1 gene, notably the Z allele, playing a pivotal role in disease susceptibility. This retrospective descriptive study from a rural Eastern Kentucky pulmonary clinic aimed to characterize patients with AAT deficiency, focusing on demographic, clinical, and laboratory parameters extracted from electronic health records (EHR) of Appalachian Regional Healthcare (ARH). Among 100 patient encounters, 56 were analyzed, revealing notable sex-based differences in smoking rates and co-existing conditions, with males showing higher rates of black lung and chronic obstructive pulmonary disease. In comparison, females exhibited higher rates of asthma, COVID-19, pneumothorax, and obstructive sleep apnea. The study emphasizes the importance of understanding genotype-phenotype correlations and demographic factors in assessing AAT deficiency, advocating for further research to refine management strategies and elucidate causal relationships., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kolagatla et al.)

Background: There has been little to no characterization of the pandemic's effects on rural Central Appalachia, in which health disparities in the pre-COVID-19 era have historically plagued. This is the first study to compare wave-based differences in outcomes of hospitalized patients with COVID-19 in the rural Appalachian region. This study aims to provide a more comprehensive understanding of the effects of the COVID-19 pandemic on large rural communities and Appalachia., Methods: This is a retrospective cohort study of hospitalized patients with COVID-19 between April 2020 and June 2022, which includes 13 Appalachian Regional Healthcare (ARH) hospitals. The primary outcome of the study was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) stay, need for mechanical ventilation, length of hospital stay, 1-30-day re-admittance, 30-60-day re-admittance, and thromboembolism incidence risk., Results: The second wave of infections during the pandemic demonstrated the highest mortality with higher odds of affecting younger patients. The third wave demonstrated similar mortality to the first wave. Elderly patients and patients with chronic morbidities demonstrated the highest mortality and morbidity and the highest requirement for mechanical ventilation across the three waves. Vaccination lowered the odds of mechanical ventilation and ICU stay., Conclusions: This study comprehensively characterizes the impact of the COVID-19 pandemic in rural regions of Appalachian Kentucky and West Virginia. Future studies comparing differences between rural and urban geographies may be able to distinguish whether the disparities in these regions played a role in the impact on residents., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kolagatla et al.)

Purpose: Major adverse cardiac events (MACEs) because of immune checkpoint inhibitors (ICIs) are infrequent immune-related adverse events (irAEs) that comprise a spectrum of cardiac toxicities with variable manifestations. ICI-related MACEs can lead to significant morbidity and mortality, hence the need to better define presentations of MACEs and their association with noncardiac irAEs in ICI-treated patients., Methods: We conducted a retrospective pooled analysis of MACE captured in the serious adverse events reporting database of the National Cancer Institute-Cancer Therapy Evaluation Program for National Cancer Institute-sponsored investigational clinical trials between June 2015 and December 2019. Patients were eligible if they had been treated with anti-programmed cell death protein-1 (anti-PD-1)/programmed cell death-ligand 1 (anti-PD-L1) alone or with additional anticancer therapies., Results: A total of 6,925 participants received anti-PD-(L)1-based therapies; 48% (n = 3,354) were treated with single-agent anti-PD-(L)1 therapy. Of 6,925 patients, 0.6% (n = 40) qualified as ICI-related MACE, with 77.5% (n = 31 of 40) being ≥ grade 3. Myocarditis accounted for 45% (n = 18 of 40) of total ICI-MACEs. Concurrent multisystem involvement with other noncardiac irAEs was seen in 65% (n = 26 of 40). Most patients with myocarditis (83%, n = 15 of 18) had one or more noncardiac irAEs associated. Incidence of MACE was higher with anti-PD-(L)1 + targeted therapies compared with anti-PD-(L)1 + anti-cytotoxic T-cell lymphocyte-4 combinations (2.1% v 0.9%, P = .08). There was a higher incidence of myocarditis with anti-PD-(L)1-based combination therapies versus single-agent anti-PD-(L)1 therapies (0.36%, n = 13 of 3,571 v 0.15%, n = 5 of 3,354, P = .08). Deaths related to myocarditis were identified in 22.5% (n = 4 of 18). All four patients who died had concurrent myositis., Conclusion: Increasing patient and prescriber awareness in understanding patterns of ICI-MACE and associated noncardiac irAEs should be emphasized. Better characterization of the risk of MACE with the concurrent use of non-ICI-based anticancer therapies with anti-PD-(L)1 treatments is needed.

Background: The Southeastern rural areas of the USA have a higher prevalence of heart failure (HF). Coronavirus disease 2019 (COVID-19) infection is associated with poor outcomes in patients with HF. Our study aimed to compare the outcomes of hospitalized HF patients with and without COVID-19 infection specifically in rural parts of the USA., Methods: We conducted a retrospective cohort study of HF patients with and without COVID-19 hospitalized in Southeastern rural parts of the USA by using the Appalachian Regional Healthcare System. Analyses were stratified by waves from April 1, 2020 to May 31, 2021, and from June 1, 2021 to October 19, 2021., Results: Of the 14,379 patients hospitalized with HF, 6% had concomitant COVID-19 infection. We found that HF patients with COVID-19 had higher mortality rate compared to those without COVID-19 (21.8% versus 3.8%, respectively, P < 0.01). Additionally, hospital resource utilization was significantly higher in HF patients with COVID-19 compared to HF patients without COVID-19 with intensive care unit (ICU) utilization of 21.6% versus 13.8%, P < 0.01, mechanical ventilation use of 17.3% versus 6.2%, P < 0.01, and vasopressor/inotrope use of 16.8% versus 7.9%, P < 0.01. A lower percentage of those with COVID-19 were discharged home compared to those without a COVID-19 diagnosis (63.4% versus 72.0%, respectively). There was a six-fold greater odds of dying in the first wave and seven-fold greater odds of dying in the second wave., Conclusions: Our study confirms previous findings of poor outcome in HF patients with COVID-19. There is a need for review of healthcare resources in rural hospitals which already face numerous healthcare challenges., Competing Interests: The authors declare that they have no conflict of interest., (Copyright 2022, Bhopalwala et al.)

Importance: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden., Objective: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019., Evidence Review: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs)., Findings: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles., Conclusions and Relevance: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Metastatic prostate cancer remains lethal with a 5-year survival rate of about 30%, indicating the need for better treatment options. Novel antiandrogens (NAA)-enzalutamide and abiraterone-have been the mainstay of treatment for advanced disease since 2011. In patients who progress on the first NAA, responses to the second NAA are infrequent (25-30%) and short-lasting (median PFS ~3 months). With the growing adoption of NAA therapy in pre-metastatic castration-resistant settings, finding better treatment options for first-line mCRPC has become an urgent clinical need. The regulatory approval of two PARP inhibitors in 2020-rucaparib and olaparib-has provided the first targeted therapy option for patients harboring defects in selected DNA damage response and repair (DDR) pathway genes. However, a growing body of preclinical and clinical data shows that co-inhibition of AR and PARP induces synthetic lethality and could be a promising therapy for patients without any DDR alterations. In this review article, we will investigate the limitations of NAA monotherapy, the mechanistic rationale for synthetic lethality induced by co-inhibition of AR and PARP, the clinical data that have led to the global development of a number of these AR and PARP combination therapies, and how this may impact patient care in the next 2-10 years.

Hepatitis B Virus (HBV) reactivation is a known complication of intense immunosuppression with B-cell depleting monoclonal antibody therapy and transplantation immunosuppression. HBV reactivation has occurred following treatment with chemotherapy regimens for hematologic malignancies and solid tumors. There are 2 prior case reports of HBV reactivation following cisplatin monotherapy for head and neck squamous cell carcinoma (HNSCC). Here, we present a case of a 49-year-old Caucasian male with a past medical history of laryngeal squamous cell carcinoma (SCC). There are no consensus guidelines on how to define hepatitis B reactivation. There are guidelines on when to initiate prophylaxis with Entecavir while on immunosuppressive therapy with risk according to medication category and hepatitis B surface antigen/hepatitis B core antibody IgG serology. CDC recommends screening everyone. American Society of Clinical Oncology (ASCO) now with a recent update in 2020 recommends screening everyone. There is a definite role of immunosuppression in HBV reactivation, however, there is also direct enhancement by cisplatin of viral replication by creating endoplasmic reticulum stress which increases HBV DNA indirectly. Finally, cytotoxicity enhances HBV reactivation and immune reconstitution post withdrawing immunosuppressive treatment. Because of the effects of chemotherapy, aka cisplatin goes beyond immunosuppression-related reactivation of HBV, our recommendations are in line with CDC and ASCO to screen all patients for HBV before onset of chemotherapy and start Entecavir/Tenofovir Disoproxil Fumarate before the onset of chemotherapy for HBV-positive patients.

Extramedullary myeloma (EMM) is an infrequent but well-established manifestation of multiple myeloma (MM), defined as a soft tissue plasma cell neoplasm without bone marrow involvement. Gallbladder involvement in EMM, however, is a very rare occurrence, with only 8 cases found in the English medical literature. Here, we present a case of an older adult male with a gallbladder mass in the presence of increasing serum kappa light chains after a normal bone marrow biopsy confirmed the complete remission of a previous MM diagnosis. Histopathologic evaluation of a biopsied sample confirmed the mass as an atypical plasma cell neoplasm. Later in his treatment, he developed several firm, smooth, violaceous skin nodules on the torso, which histopathology confirmed as also being atypical plasma cell neoplasms. We aim to contribute to the medical literature by expanding the pool of information regarding EMM of the gallbladder to support future diagnostic and treatment recommendations.

Langerhans cell histiocytosis (LCH) is a rare disorder involving the proliferation of myeloid-derived dendritic cells. It most commonly affects children aged less than 1 to 2 years old. Langerhans cell histiocytosis in adults is more uncommon with an estimated incidence of 1 to 2 cases per 1 million. Langerhans cell histiocytosis can present as a multisystem or single-system disease involving bone, skin, lymph nodes, and various other organ systems. The spectrum of symptoms can range from asymptomatic disease, localized skeletal or dermatologic manifestations, or systemic symptoms of weight loss, fever, and other organ-specific manifestations. Langerhans cell histiocytosis with isolated involvement of the gastrointestinal tract is exceedingly rare with only approximately 14 cases reported in the English medical literature. Here, we report an additional case of LCH presenting as an isolated colonic polyp. This patient was also followed for a 3-year period after initial diagnosis to provide valuable follow-up data. With this case, we aim to contribute to the literature by further characterizing the presentation, treatment, and disease course of this rare phenomenon and provide valuable data to guide future screening guidelines for isolated LCH polyps in the colon.

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare intracranial tumor that arises from pericytes surrounding the blood vessels. Solitary fibrous tumor/hemangiopericytoma accounts for less than 1% of primary brain tumors and is classified as grades I, II, or III based on mitotic count. These tumors often masquerade as meningiomas. Histologically, SFT/HPC is vascular with high cellularity and often surrounded by connective tissue. Immunohistochemistry is positive for stat 6, vimentin, and CD34. Although aggressive surgical resection is the mainstay of treatment, close long-term follow-up is necessary as recurrence or extra cranial metastasis can present several years after resection.

Heřmanský-Pudlák syndrome (HPS), a rare autosomal recessive disorder, manifests with oculocutaneous albinism and a bleeding diathesis. However, severity of disease can be variable and is typically related to the genetic subtype of HPS; HPS type 6 (HPS-6) is an uncommon subtype generally associated with mild disease. A Caucasian adult female presented with a history of severe bleeding; ophthalmologic examination indicated occult oculocutaneous albinism. The patient was diagnosed with a platelet storage pool disorder, and platelet whole mount electron microscopy demonstrated absent delta granules. Genome-wide SNP analysis showed regions of homozygosity that included the HPS1 and HPS6 genes. Full length HPS1 transcript was amplified by PCR of genomic DNA. Targeted next-generation sequencing identified a novel homozygous missense variant in HPS6 (c.383 T > C; p.V128A); this was associated with significantly reduced HPS6 mRNA and protein expression in the patient's fibroblasts compared to control cells. These findings highlight the variable severity of disease manifestations in patients with HPS, and illustrate that HPS can be diagnosed in patients with excessive bleeding and occult oculocutaneous albinism. Genetic analysis and platelet electron microscopy are useful diagnostic tests in evaluating patients with suspected HPS. Clinical Trial registration: Registrar: ClinicalTrials.gov Website: www.clinicaltrials.gov Registration Numbers: NCT00001456 and NCT00084305., (© 2018 Wiley Periodicals, Inc.)

A 56-year-old man presented as an acute coronary syndrome. A transthoracic echocardiography (TTE) performed to assess left ventricular (LV) function revealed multiple hydatid cysts in the right ventricular cavity compressing the interventricular septum. CT scan for chest and abdomen revealed similar cysts in right-lung apex and left lobe of liver. A polyvisceral involvement in the setting of multiple cardiac cysts suggested cardiac hydatidosis as the most probable diagnosis. CT coronary angiography was normal. A preoperative oral albendazole therapy was initiated. Later the patient underwent elective surgery, 'Evaculation of RV Hydatid Cysts and Obliteration of Cavity with Bovine Pericardium'. His postoperative recovery was good. Regular exercise, chest physiotherapy, a life-long anticoagulation therapy and antibiotic prophylaxis for invasive procedures were recommended. Patient was scheduled for regular follow-up, to check for any recurrences or late complications.