Obesity is associated with adverse outcomes in primary immune thrombocytopenia - a retrospective single-center study.

The pathophysiology of immune thrombocytopenia (ITP) involves immune-mediated platelet destruction. The presence of adipose tissue in obese individuals creates an inflammatory environment that could potentially impact the clinical course and outcomes of ITP. However the relationship between obesity and ITP outcomes has not been well described. We evaluated ITP outcomes in 275 patients diagnosed with primary ITP from 2012 to 2022. Patients were categorized into four groups based on their body mass index (BMI) at diagnosis. Female gender was associated with a lower platelet count at the time of diagnosis at any BMI. Patients with high BMI had lower platelet counts at diagnosis and at platelet nadir (p < 0.001), an increased likelihood of requiring therapy (p < 0.001) and requiring multiple lines of therapy (p = 0.032). Non-obese patients who required corticosteroid treatment experienced a longer remission duration compared to obese patients (p = 0.009) and were less likely to be steroid-dependent (p = 0.048). Our findings suggest that obesity may be a significant risk factor for developing ITP and for ITP prognosis. Future studies are needed to evaluate the role of weight loss intervention in improving ITP outcomes.

Rasburicase-induced hemolytic anemia and methemoglobinemia: a systematic review of current reports.

Since the FDA's approval of rasburicase use for treatment of tumor lysis syndrome (TLS), multiple cases of rasburicase-induced methemoglobinemia and hemolytic anemia have been reported among patients with G6PD deficiency. This study aims to provide a systematic review of cases reporting such adverse reactions to rasburicase. A literature review of published cases in PubMed, Embase, Cochrane, and Web of Science was conducted. Descriptive studies reporting cases of rasburicase-induced methemoglobinemia and/or hemolytic anemia in English were analyzed and summarized in this study. Forty-three cases, including a case from our institution, were included in this study. Most cases (60.5%) received rasburicase for TLS treatment. Almost all patients (93.8%) were tested for G6PD after rasburicase administration. The median time to symptom onset was 24 h. The median methemoglobin level was 10%, peaking after a median of 24 h. The median hemoglobin nadir was 6.1 g/dL, and most patients (n = 32) required blood transfusion. Out of 39 cases with reported outcomes, 35 patients (89.7%) recovered, while four patients (three females and one male) died. The median time to recovery was 4.5 days while the median time to death was 8 days. Screening for G6PD deficiency among high-risk patients is important but not practical in acutely severe settings. When prior screening for G6PD deficiency is not feasible, close monitoring for methemoglobinemia and hemolytic anemia is recommended. Exchange transfusion is increasingly reported as a potentially successful therapeutic modality. Ascorbic acid may provide limited benefits. Methylene blue should be avoided as it may exacerbate hemolysis among these patients.

Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. METHODS: A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. RESULTS: Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. CONCLUSIONS: Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.

Current Communication Practices Between Internal Medicine Subspecialty Fellowship Applicants and Program Directors: A National Survey.

Purpose: As fellowship applications increasingly transition to virtual interviews, the role of social media in this process remains uncertain. This study explores internal medicine subspecialty program directors' (PDs) perspectives on current communication practices, including the use of social media and email, between applicants and programs. Method: A national survey was conducted among U.S. internal medicine subspecialty fellowship PDs from November to December 2023. The survey collected demographic information about PDs, program-level information, and their views on using social media platforms (Twitter/X and Instagram) and email for program promotion and application review. Results: Out of 297 PDs who responded (18.5% response rate), 52% were male, 69% identified as White/Caucasian, majority from age group 46-50 years. The subspecialties with the highest representation were infectious disease (15%), pulmonology and critical care (14%), and cardiology (12%). Among respondents, 41% used Twitter/X and 24% used Instagram for program promotion. A smaller fraction reviewed applicants through these platforms for interview invitations (14% via Twitter/X and 7% via Instagram). PDs reported receiving an average of 35 letters of intent emails and calling 36% of applicants for interviews. Conclusions: This study is the first to assess the value PDs place on social media and email in the fellowship application review process across various internal medicine subspecialties. While social media is a valuable tool for program promotion and engagement, traditional email outreach remains crucial in the interview selection process.

Secondary haemophagocytic lymphohistiocytosis in a patient with new-onset systemic lupus erythematosus: the challenges of timely diagnosis and successful treatment.

Haemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disease driven by abnormal macrophage activation and regulatory cell dysfunction. HLH can be primary due to genetic mutations or secondary due to infection, malignancy or autoimmune conditions. We describe a woman in her early 30s who developed HLH while being treated for newly diagnosed systemic lupus erythematosus (SLE) complicated by lupus nephritis as well as concomitant cytomegalovirus (CMV) reactivation from a dormant infection. The trigger for this secondary form of HLH may have been either aggressive SLE and/or CMV reactivation. Despite prompt treatment with immunosuppressive therapies for SLE consisting of high-dose corticosteroids, mycophenolate mofetil, tacrolimus, etoposide for HLH and ganciclovir for CMV infection, the patient developed multiorgan failure and passed away. We demonstrate the difficulty in identifying a specific cause for secondary HLH when multiple conditions are present (SLE and CMV) and the fact that, despite aggressive treatment for both conditions, the mortality for HLH remains high.

The role of immune checkpoint inhibitors for patients with advanced stage microsatellite stable colorectal cancer and high tumor mutation burden: quantity or quality?

INTRODUCTION: The US Food and Drug Administration (FDA) approved pembrolizumab for patients with unresectable or metastatic solid tumors with tumor mutational burden (TMB) of ≥ 10 mutations/megabase. However, the clinical implications of this universal cutoff of TMB ≥ 10 for patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC) remain debatable. AREAS COVERED: In this review, we discuss the tissue agnostic approval of pembrolizumab, its efficacy, and clinical relevance in the management of patients with MSS CRC patients with high TMB (defined as TMB ≥ 10). We also elaborate on molecular subgroups of MSS CRC that influence the immune checkpoint inhibitor (ICI) response for patients with MSS CRC, including pathogenic POLE and POLD1 mutations associated with ultramutated tumors. EXPERT OPINION: Patients with microsatellite stable CRC with TMB ≥ 10 without POLE and POLD1 mutations may not significantly benefit from immune checkpoint inhibitors therapy. Predetermined cutoff TMB ≥ 10 mutation per MB does not seem to define a universal cutoff for the benefit of disease-agnostic ICI therapy, particularly for patients with MSS CRC. Patients with POLE/POLD1 mutations with MSS CRC represent a unique biological subgroup of MSS CRC with favorable responses to ICI therapy.

Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm.

Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers. Recently, several clinical trials have utilized ICIs as potential neoadjuvant therapies for MSI-H gastrointestinal cancers and demonstrated deep clinical and pathological responses, creating opportunities for organ preservation. However, there are potential challenges to the neoadjuvant use of ICIs for certain disease types due to the clinical risk of overtreatment for a disease that can be cured through a surgery-only approach. In this review article, we discuss neoadjuvant management approaches with ICI therapy for patients with MSI-H gastrointestinal cancers, including those with oligometastatic disease. We also elaborate on potential challenges and opportunities for the neoadjuvant utilization of ICIs and provide further insight into the changing treatment paradigm of MMR-D/MSI-H gastrointestinal cancers.

Role of innate immunological/inflammatory pathways in myelodysplastic syndromes and AML: a narrative review.

Dysregulation of the innate immune system and inflammatory-related pathways has been implicated in hematopoietic defects in the bone marrow microenvironment and associated with aging, clonal hematopoiesis, myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). As the innate immune system and its pathway regulators have been implicated in the pathogenesis of MDS/AML, novel approaches targeting these pathways have shown promising results. Variability in expression of Toll like receptors (TLRs), abnormal levels of MyD88 and subsequent activation of NF-κß, dysregulated IL1-receptor associated kinases (IRAK), alterations in TGF-ß and SMAD signaling, high levels of S100A8/A9 have all been implicated in pathogenesis of MDS/AML. In this review we not only discuss the interplay of various innate immune pathways in MDS pathogenesis but also focus on potential therapeutic targets from recent clinical trials including the use of monoclonal antibodies and small molecule inhibitors against these pathways.

Mortality of COVID-19 in patients with hematological malignancies versus solid tumors: a systematic literature review and meta-analysis.

Cancer patients are more vulnerable to COVID-19 compared to the general population, but it remains unclear which types of cancer have the highest risk of COVID-19-related mortality. This study examines mortality rates for those with hematological malignancies (Hem) versus solid tumors (Tumor). PubMed and Embase were systematically searched for relevant articles using Nested Knowledge software (Nested Knowledge, St Paul, MN). Articles were eligible for inclusion if they reported mortality for Hem or Tumor patients with COVID-19. Articles were excluded if they were not published in English, non-clinical studies, had insufficient population/outcomes reporting, or were irrelevant. Baseline characteristics collected included age, sex, and comorbidities. Primary outcomes were all-cause and COVID-19-related in-hospital mortality. Secondary outcomes included rates of invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission. Effect sizes from each study were computed as logarithmically transformed odds ratios (ORs) with random-effects, Mantel-Haenszel weighting. The between-study variance component of random-effects models was computed using restricted effects maximum likelihood estimation, and 95% confidence intervals (CIs) around pooled effect sizes were calculated using Hartung-Knapp adjustments. In total, 12,057 patients were included in the analysis, with 2,714 (22.5%) patients in the Hem group and 9,343 (77.5%) patients in the Tumor group. The overall unadjusted odds of all-cause mortality were 1.64 times higher in the Hem group compared to the Tumor group (95% CI: 1.30-2.09). This finding was consistent with multivariable models presented in moderate- and high-quality cohort studies, suggestive of a causal effect of cancer type on in-hospital mortality. Additionally, the Hem group had increased odds of COVID-19-related mortality compared to the Tumor group (OR = 1.86 [95% CI: 1.38-2.49]). There was no significant difference in odds of IMV or ICU admission between cancer groups (OR = 1.13 [95% CI: 0.64-2.00] and OR = 1.59 [95% CI: 0.95-2.66], respectively). Cancer is a serious comorbidity associated with severe outcomes in COVID-19 patients, with especially alarming mortality rates in patients with hematological malignancies, which are typically higher compared to patients with solid tumors. A meta-analysis of individual patient data is needed to better assess the impact of specific cancer types on patient outcomes and to identify optimal treatment strategies.

Assessment of the Utilization of Validated Diagnostic Predictive Tools and D-Dimer in the Evaluation of Pulmonary Embolism: A Single-Center Retrospective Cohort Study from a Public Hospital in New York City.

INTRODUCTION: A significant increase in the use of computed tomography with pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism (PE) has been observed in the past twenty years. We aimed to investigate whether the validated diagnostic predictive tools and D-dimers were adequately utilized in a large public hospital in New York City. METHODS: We conducted a retrospective review of patients who underwent CTPA for the specific indication of ruling out PE over a period of one year. Two independent reviewers, blinded to each other and to the CTPA and D-dimer results, estimated the clinical probability (CP) of PE using Well's score, the YEARS algorithm, and the revised Geneva score. Patients were classified based on the presence or absence of PE in the CTPA. RESULTS: A total of 917 patients were included in the analysis (median age: 57 years, female: 59%). The clinical probability of PE was considered low by both independent reviewers in 563 (61.4%), 487 (55%), and 184 (20.1%) patients based on Well's score, the YEARS algorithm, and the revised Geneva score, respectively. D-dimer testing was conducted in less than half of the patients who were deemed to have low CP for PE by both independent reviewers. Using a D-dimer cut-off of <500 ng/mL or the age-adjusted cut-off in patients with a low CP of PE would have missed only a small number of mainly subsegmental PE. All three tools, when combined with D-dimer < 500 ng/mL or 95%. CONCLUSION: All three validated diagnostic predictive tools were found to have significant diagnostic value in ruling out PE when combined with a D-dimer cut-off of <500 ng/mL or the age-adjusted cut-off. Excessive use of CTPA was likely secondary to suboptimal use of diagnostic predictive tools.

Efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19: A systematic review.

Objectives: To systematically review the clinical literature reporting the use of Lopinavir/ritonavir (LPV/r) for the treatment of patients with Cornonavirus disease 19 (COVID-19) to assess the efficacy of LPV/r for the treatment of COVID-19.Methods: The authors systematically searched PubMed and MedRxiv databases for studies describing treatment of COVID-19 patients using LPV/r compared to other therapies. Articles were excluded if they were case reports, opinion editorials, preclinical studies, single-armed studies, not written in English, not relevant to the topic, or published before May 2020. The included outcomes were viral clearance as measured by reverse-transcription polymerase chain reaction (RT-PCR) negativity and/or improvement on chest computed tomography (CT), mortality, and adverse events.Results: Among 858 total studies, 16 studies met the inclusion criteria and were included in the qualitative review. These studies consisted of 3 randomized control trials, 3 open-label trials, and 10 observational studies. Most of these studies did not report positive clinical outcomes with LPV/r treatment.Conclusion: The systematic review revealed insufficient evidence of effectiveness and clinical benefit of LPV/r in the treatment of COVID-19 patients. Specifically, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest CT clearance in patients with COVID-19.

Corticosteroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. METHODS: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. RESULTS: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. CONCLUSION: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.