Aplastic anaemia is a rare side effect of terbinafine.Patients should be advised about this, and serial laboratory testing can be helpful for those who are on a long-term course of terbinafine.Early diagnosis and start of treatment can lead to a favourable outcome.

The use of adeno-associated virus (AAV)vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion-associated reactions (IARs)pose a significant challenge to the safety and efficacy of AAV-based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll-like receptor activation and subsequent production of pro-inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies (Nabs) and T-cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre-existing Nabs, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu-like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre- and postadministration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV-based gene therapy.

Abstract Introduction/Objective Primary pericardial angiosarcoma is an uncommon, aggressive cardiac neoplasm that arises from the endothelial cells of blood vessels. It typically affects middle-aged men and has a poor prognosis due to early metastasis. Unfortunately, there are currently no established guidelines or effective treatments for this rare malignancy. The purpose of this case study is to emphasize the significance of recognizing the unspecific presentations of pericardial angiosarcoma and ensuring timely diagnosis and appropriate treatment. Methods/Case Report A 56-year-old male presented with recurrent pericardial effusion and exudative pleural effusion. The radiologic studies showed a thickened pericardium with right-sided pericardial effusion and a large right- sided pleural effusion. Resected partial pericardium and parietal pleura showed the presence of epithelioid to spindled cells that formed solid sheets and vascular structures filled with numerous red blood cells. The tumor cells were cytologically malignant, with angulated shapes and hyperchromatic nuclei, and showed extensive invasion into the surrounding connective tissue. Mitotic figures were variably visualized, and there was abundant hemorrhage. Immunohistochemical analysis of the lesional cells showed positivity for ERG, CD31, Factor VIII, and retention of Methylthioadenosine phosphorylase (MTAP) and BRCA1-associated protein 1 (BAP1), while they were negative for WT1, calretinin, claudin-4, and p40. Based on the morphology and immunoprofile, a diagnosis of high grade angiosarcoma was rendered, and the patient underwent chemotherapy. The overall survival of the patient was 8 months to date. Results (if a Case Study enter NA) NA Conclusion Prompt diagnosis of pericardial angiosarcoma is crucial, as nonspecific symptoms may lead to misdiagnosis, such as in this case where the patient was initially diagnosed with pericarditis. Video-assisted thoracic surgery and histologic analysis are necessary to reach a correct diagnosis, which ensures appropriate treatment, as a delayed diagnosis can worsen the prognosis and even lead to death.

Introduction: Heparin-induced thrombocytopenia (HIT) is a serious complication associated with heparin therapy, characterized by an immune reaction involving antibodies against heparin-platelet factor 4 (PF4). This immune complex formation triggers platelet activation, blood clotting, and reduced platelet counts. Several factors, including previous heparin exposure, duration of exposure, and certain comorbidities, have been examined as potential risk factors for HIT development. In this study, our objective was to determine the incidence of HIT and identify predictive factors associated with its occurrence. Methods: We conducted an analysis using the National Inpatient Sample (NIS) data from 2020 to investigate the incidence of HIT during that year and its correlation with specific comorbidities. Patient identification was based on the International Classification of Diseases (ICD-10) code D75.82. The incidence and associated comorbidities were evaluated using multivariate logistic analysis with Stata 17. Results: Among the 32,355,827 adult patients admitted throughout the United States in 2020, a total of 11,380 cases of HIT were identified. The incidence of HIT was significantly higher in male patients, obese individuals, those with acute kidney injury (AKI), chronic kidney disease (CKD), type II diabetes mellitus (DMII), heart failure (HF), primary hypercoagulable states, and autoimmune diseases such as systemic lupus erythematosus (SLE). The highest risk of developing HIT was observed in patients with thrombophilia (OR 4.17, 95% CI 3.66-4.75, P = .000), AKI (OR 3.53, 95% CI 3.19-3.91, P = .000), and HF (OR 2.10, 95% CI 1.90-2.33, P = .000). Among autoimmune diseases studied, only SLE was associated with an increased odds ratio for developing HIT (OR 1.60, 95% CI 1.06-2.41, P = .026). Conclusion: The incidence of HIT varies and is influenced by the presence of specific comorbidities. Further studies are recommended to investigate additional factors that may increase the likelihood of HIT development. This information could aid in validating and implementing standard precautionary measures in patients at higher risk of developing HIT.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy manifesting as hemolytic anemia, thrombocytopenia, fever, neurological symptoms, and renal failure triggered by the immune response leading to reduced levels of ADAMTS-13. We conducted a retrospective study on a national scale utilizing the National Inpatient Sample (NIS) database for year 2020 assessing the influence of COVID-19-induced thrombotic thrombocytopenic purpura (TTP) on morbidity and mortality. Our research focused on adults aged 18 and above who had contracted COVID-19, with the aim of investigating the effects of TTP on mortality rates, cardiovascular complications, and healthcare expenditures within our patient population. Results: Our study included 1,050,045 adult patients admitted with COVID-19. Of these, only 435 (0.0004%) patients developed TTP during the index hospitalization. Patients with TTP were relatively younger than those without (61.09 vs. 64.74, p = 0.03) (Table 1). Compared to patients without TTP, patients with TTP were more likely to have congestive heart failure (CHF) (26.44% vs. 16.81%, p = 0.03), ESRD (6.90% vs. 3.68%, p = 0.04), and were more often admitted to teaching hospitals (86.21% vs. 68.95%, p = 0.02) in the Midwest (51.27% vs. 23.28%, p = 0.01) and West (20.69% vs. 17.19%, p = 0.01) regions. Using multivariate regression analysis to adjust for confounders, including the severity of COVID infection (ARF, sepsis, and organ failure), we found that COVID patients with TTP had significantly higher mortality than patients without TTP (adjusted odds ratio (AOR) 3.39, 95% CI 1.85-6.22, p < 0.01) (Table 2). Additionally, COVID patients with TTP had higher odds of LE DVT/PE (AOR 3.89, 95% CI 1.52-9.93, p < 0.01), AKI (AOR 3.67, 95% CI 1.71-7.87, p < 0.01), AKI requiring dialysis (AOR 10.68, 95% CI 4.86-23.44, p < 0.01), GIB (AOR 3.66, 95% CI 1.70-7.87, p < 0.01), requiring blood transfusion (AOR 6.65, 95% CI 3.19-13.85, p < 0.01), and ICU admission (AOR 3.81, 95% CI 2.15-6.71, p < 0.01). In terms of resource utilization, patients with TTP had a longer adjusted LOS (9.45 days, 95% CI 6.49-12.42, p < 0.01) and higher adjusted total hospitalization charges ($179,916,95% CI −86,141-273,691, p < 0.01). Conclusion: COVID-19 has been associated with TMAs, including TTP. The underlying pathophysiology includes cytokine-mediated endothelial damage and increased levels of pro-coagulant factors, such as factor VIII, vWF, and fibrinogen. Our study found that COVID-19 with concomitant TTP had a threefold higher mortality rate compared to those without TTP. Additionally, patients with TTP had a three to fourfold increased risk of LE DVT/PE, AKI, GIB, and admission to the ICU compared to patients without TTP. The presence of TTP in COVID-19 patients was also associated with longer hospital stays and higher hospitalization charges. To summarize, our study revealed that the presence of TTP in patients with COVID-19 is linked to higher mortality and an increased occurrence of complications including DVT, PE, AKI and GIB. These complications are likely the result of thrombotic events associated with TTP. Further large scale studies are warranted.

Background: RSV is a prevalent cause of acute lower respiratory infections, primarily in young children, but can also lead to severe pneumonia in adults, especially the elderly and immunocompromised. Hematological malignancies, a group of neoplastic disorders affecting blood, bone marrow, and lymph nodes, can render patients more susceptible to infections and complications. The aim of this study is to evaluate the impact of hematological malignancies on inpatient mortality, hospital length of stay, and hospitalization costs and charges in adult patients during RSV-related hospitalizations, using retrospective data from the National Inpatient Sample (NIS) 2020. Methods: In this retrospective cohort study, we used NIS data for 2020. International Classification of Diseases, Tenth Revision, with Clinical Modification (ICD-10-CM) codes were utilized to query the NIS database and identify adults (Age ≥18 years) hospitalized with RSV pneumonia. Our population of interest was subsequently divided into two groups based on the presence or absence of unremitted hematological malignancies. Inpatient mortality served as the primary outcome, with secondary outcomes being hospital length of stay, hospitalization charges, and costs. A multivariate logistic regression analysis was conducted using STATA MP 16.1, incorporating various hospital and patient-level factors. The Charlson comorbidity index was utilized to account for the burden of comorbidities in the analysis. Results: The total population of adult patients admitted in 2020 with RSV pneumonia was 13,900. From this, 980 individuals (7.1%) were diagnosed with a hematological malignancy, of which 43% were female. Conversely, 93% of individuals did not have a hematological malignancy, and, females accounted for 59% of this group. Patients with a hematological malignancy had a mean age of 66, while those without had a mean age of 69. In comparison to those without hematological malignancy, patients with this malignancy demonstrated a higher all-cause inpatient mortality rate for PSV pneumonia (12.24% versus 5.23%). When hospital and patient-level factors were taken into consideration, it was noted that RSV pneumonia patients with hematologic malignancy had a higher odds of all-cause inpatient mortality, with an adjusted odds ratio (aOR) of 1.99 (95% Confidence Interval (CI) 1.21- 3.28). Moreover, these patients had a longer hospital stay (12.2 days) compared to those without hematological malignancy (7.5 days), which reflects an adjusted mean difference of 3.8 days (95% CI 1.7-1.9). Overall, patients with hematological malignancies incurred higher mean hospitalization charges and costs, with an adjusted mean difference of USD 29,044 (95% CI 11,928 - 36,008) and USD 105,210 (95% CI 30,947 - 133,730), respectively. Clinical Implications: This study highlights the increased risk of inpatient mortality and resource utilization in RSV-related hospitalizations for patients with hematological malignancies. These findings emphasize the need for timely detection, prophylaxis, preference for antiviral treatment, and the inclusion of the RSV pneumonia vaccine in the prevention strategy. The results also inform healthcare administrators and policymakers about the importance of effective infection control measures, resource allocation, and public health initiatives to protect this vulnerable population.

Abstract Background Early diagnosis, prognostication, and treatment initiation are the cornerstones of sepsis management. There remains an immense interest in exploring the diagnostic and prognostic roles of neutrophil-lymphocyte ratio (NLR) in the sepsis population. Methods We performed a retrospective multi-center observational study including patients admitted to different Mayo Clinic sites with a diagnosis of sepsis between October 2018 and August 2022. Patients were excluded if they were aged < 18 years, lacked research authorization, or had missing Neutrophil or Lymphocyte count at admission. Data were collected from an existing sepsis database and Mayo Data Explorer (MDE). Categorical variables were summarized as percentages and continuous variables were summarized as medians. Chi-square test for significance, independent sample t-test, and multivariate Cox Proportional Hazard models were performed on IBM SPSS Statistics v28.0. Results Our study cohort consisted of 13968 patients, of which the majority were males (55.9%), Caucasian (91.6%), and non-Hispanic or Latino (94.3%). The median age of the cohort was 71 (60, 80) years, and the median BMI was 27.7 (23.4, 33.3) kg/m2. Among all sepsis patients, 6.0% had a positive blood culture and the most common organisms were E. coli (26.5%), Klebsiella sp. (15.6%), Streptococcus sp. (12.8%) and Staphylococcus aureus (9.9%). 13131 patients (94.1%) survived the hospital stay and 837 (5.9%) did not. There was no difference in mortality based on blood culture positivity status (6.0% vs 6.6%, p=0.41). However, the median NLR was higher among patients with a positive blood culture (16.4 vs. 12.1, p< 0.001) and among non-survivors (14.3 vs 12.2, p< 0.001). NLR did not significantly vary based on the type of organism growing in the blood culture. A multivariate model revealed NLR as an independent predictor of mortality (HR 1.003, 95% CI: 1.000-1.006, p=0.029) after adjusting for comorbidities, baseline clinical and laboratory variables. (Tables 1 & 2) Conclusion Our retrospective multicentric study showed that the Neutrophil-Lymphocyte ratio at admission was higher among bacteremic sepsis patients and non-survivors. Further prospective studies are needed to explore its diagnostic and prognostic utility. Disclosures All Authors: No reported disclosures

Machine learning algorithms were used to analyze the odds and predictors of complications of thyroid damage after radiation therapy in patients with head and neck cancer. This study used decision tree (DT), random forest (RF), and support vector machine (SVM) algorithms to evaluate predictors for the data of 137 head and neck cancer patients. Candidate factors included gender, age, thyroid volume, minimum dose, average dose, maximum dose, number of treatments, and relative volume of the organ receiving X dose (X: 10, 20, 30, 40, 50, 60 Gy). The algorithm was optimized according to these factors and tenfold cross-validation to analyze the state of thyroid damage and select the predictors of thyroid dysfunction. The importance of the predictors identified by the three machine learning algorithms was ranked: the top five predictors were age, thyroid volume, average dose, V50 and V60. Of these, age and volume were negatively correlated with thyroid damage, indicating that the greater the age and thyroid volume, the lower the risk of thyroid damage; the average dose, V50 and V60 were positively correlated with thyroid damage, indicating that the larger the average dose, V50 and V60, the higher the risk of thyroid damage. The RF algorithm was most accurate in predicting the probability of thyroid damage among the three algorithms optimized using the above factors. The Area under the receiver operating characteristic curve (AUC) was 0.827 and the accuracy (ACC) was 0.824. This study found that five predictors (age, thyroid volume, mean dose, V50 and V60) are important factors affecting the chance that patients with head and neck cancer who received radiation therapy will develop hypothyroidism. Using these factors as the prediction basis of the algorithm and using RF to predict the occurrence of hypothyroidism had the highest ACC, which was 82.4%. This algorithm is quite helpful in predicting the probability of radiotherapy complications. It also provides references for assisting medical decision-making in the future.

The incidence of shoulder arthroplasty has continued to increase over the past decade. In response, commercial payers have implemented strategies to control the medical requirement of these surgeries in attempt to contain the growing costs. For example, most payers require a prolonged trial of conservative management prior to shoulder arthroplasty for patients who may otherwise be surgical candidates. However, little is known regarding the evidence used to support these indications. The purpose of this study was to analyze the references used by commercial payers to substantiate their coverage policies for shoulder arthroplasty. Ten of the leading commercial payers for total shoulder arthroplasty were identified. Publicly available coverage policies were searched on the internet or requested directly from the payer via email or telephone. Cited references were reviewed independently by two authors for type of document, level of evidence, and mention of the efficacy of conservative management. A total of 5 coverage policies were obtained with 118 references. The most common reference type was primary journal article (n=70; 59.3%) followed by review or expert opinion articles (n=35; 29.7%). Most references were of level IV evidence (n=60; 52.2%), with only 6 (5.2%) of level I or II evidence. Only 4 (3.5%) references mentioned the efficacy of conservative management in patients who may be candidates for shoulder arthroplasty. The majority of references used to substantiate the coverage policies for shoulder arthroplasty among major commercial payers within the United States are of low scientific evidence and fail to demonstrate the success of required nonoperative intervention strategies. Our study underscores the need for high-quality, comparative trials that evaluate the outcomes of conservative management vs. shoulder arthroplasty in end-stage glenohumeral osteoarthritis patients in order to determine the most cost-effective treatment algorithm.