Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID-19 patients: A meta-analysis.

INTRODUCTION: Anakinra is being empirically considered for the treatment of COVID-19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c-reactive protein (CRP) concentrations, serum ferritin, and serum d-dimer levels. METHODS: Adhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS-CoV-2, inflammatory, CRP, D-dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review Manger 5.4 (Cochrane). RESULTS: In total, 2032 patients were included (881 in the anakinra and 1151 in the control/standard care group); 69.1% of them were males. Overall, the mean difference from admission until last follow-up in CRP values was -9.66, where notable reductions were seen in the anakinra group (SMD = -0.46, p < 0.00001, N = 655). Serum ferritin mean values were reduced by 1467.16 in the anakinra group (SMD = -0.31, p = 0.004, N = 537). D-dimer mean values were largely reduced by 4.04 in the anakinra group (SMD = -0.38, p = 0.0004, N = 375). CONCLUSION: This study finds that anakinra is potentially a strong candidate as an anti-inflammatory agent to reduce mortality in COVID-19 patients, specifically in patients with elevated inflammatory biomarkers.

Adult-onset hypophosphatasia diagnosed following bilateral atypical femoral fractures in a 55-year-old woman.

We report the case of a 55-year-old woman who presented to the emergency department having woken from sleep with right sided thigh swelling. Pelvic radiographs revealed bilateral atypical subtrochanteric femoral fractures (ASFFs). In the two years leading up to this admission, the patient had experienced gradually increasing pain and weakness in her legs which had resulted in a decrease in her mobility from fully mobile to bed-bound. During this time a neurologist had organised a magnetic-resonance imaging (MRI) scan of the brain and spine which was normal. There was no history of bisphosphonate (BP) use. Historical and admission blood tests revealed a persistently low serum alkaline phosphatase (ALP), with all other results within normal limits. The patient was treated with intramedullary nailing of both femurs and histological analysis of bone reamings were characteristic of hypophosphatasia (HPP). The patient was independently mobilising with a walking frame on discharge. Subsequent genetic testing revealed bi-allelic pathogenic variants in the TNSALP gene: c.526G>A, p.(Ala176Thr) and c.1171C>T, p.(Arg391Cys). HPP is an inborn error in metabolism caused by mutation in the gene coding for tissue non-specific alkaline phosphatase (TNSALP), resulting in a decrease in serum ALP concentrations. The age at which it presents which can vary from childhood to middle age, with symptoms ranging from perinatal death to late-onset osteomalacia. In those patients who survive to adulthood, there is a predisposition to fractures, including ASFFs. Treatment with asfotase alfa (a bone-targeted, recombinant human TNSALP) has been approved for perinatal, infantile and paediatric-onset hypophosphatasia. This case emphasises the importance of viewing persistent low ALP as a 'red flag' in patients presenting with musculoskeletal symptoms. Timely diagnosis and treatment of HPP can reduce the risk of serious complications, such as those experienced by this patient.

Unraveling the Paradox: Can Anticoagulation Improve Outcomes in Patients With Heart Failure and Increased Bleeding Risk?

Heart failure (HF) patients frequently present with comorbidities such as atrial fibrillation (AF) or other cardiovascular conditions, elevating their risk of thromboembolic events. Consequently, anticoagulation therapy is often considered for thromboprophylaxis, although its initiation in HF patients is complicated by concomitant bleeding risk factors. This review explores the paradoxical relationship between HF, increased bleeding risk, and the potential benefits of anticoagulation. Through an examination of existing evidence from clinical trials, observational studies, and meta-analyses, we aim to elucidate the role of anticoagulation in HF patients with increased bleeding risk. Despite guidelines recommending anticoagulation for certain HF patients with AF or other thromboembolic risk factors, uncertainty persists regarding the optimal management strategy for those at heightened risk of bleeding. The review discusses the pathophysiological mechanisms linking HF and thrombosis, challenges in bleeding risk assessment, and strategies to minimize bleeding risk while optimizing thromboprophylaxis. Shared decision-making between clinicians and patients is emphasized as essential for individualized treatment plans that balance the potential benefits of anticoagulation against the risk of bleeding complications. Furthermore, it examines emerging anticoagulant agents and their potential role in HF management, highlighting the need for further research to delineate optimal management strategies and inform evidence-based practice. In conclusion, while anticoagulation holds promise for improving outcomes in HF patients, careful consideration of patient-specific factors and ongoing research efforts are essential to optimize therapeutic strategies in this population.

Navigating the Crossroads: Understanding the Link Between Chronic Kidney Disease and Cardiovascular Health.

Chronic Kidney Disease (CKD) has emerged as a global healthcare challenge affecting a significant portion of the world's population. This comprehensive narrative review delves into the intricate relationship between CKD and cardiovascular disease (CVD). CKD is characterized by kidney damage persisting for at least three months, often with or without a decline in glomerular filtration rate (GFR). It is closely linked with CVD, as individuals with CKD face a high risk of cardiovascular events, making cardiovascular-associated mortality a significant concern in advanced CKD stages. The review emphasizes the importance of precise risk assessment using biomarkers, advanced imaging, and tailored medication strategies to mitigate cardiovascular risks in CKD patients. Lifestyle modifications, early intervention, and patient-centered care are crucial in managing both conditions. Challenges in awareness and recognition of CKD and the need for comprehensive interdisciplinary care are highlighted. Recent advances in research offer promising therapies, such as SGLT2 inhibitors, MRAs, GLP-1R agonists, and selective endothelin receptor antagonists. Stem cell-based therapies, gene editing, and regenerative approaches are under investigation. Patient-physician "risk discussions" and tailored risk assessments are essential for improving patient outcomes. In conclusion, the review underscores the complexity of the interconnected CKD and cardiovascular health domains. Ongoing research, innovative therapies, and personalized healthcare will be instrumental in addressing the challenges, reducing the disease burden, and enhancing well-being for individuals facing CKD and cardiovascular issues. Recognizing the intricate connections between these conditions is imperative for healthcare providers, policymakers, and researchers as they seek to improve the quality of care and outcomes for affected individuals.

Reactive lymphoid hyperplasia of the liver and pancreas. A report of two cases and a comprehensive review of the literature.

BACKGROUND: Reactive lymphoid hyperplasia (RLH) is a rare non-neoplastic extranodal pathology with exceedingly rare occurrence in the liver and pancreas. We present two cases of hepatic RLH, one which had coinciding pancreatic involvement. To the best of our knowledge, concomitant hepatic and pancreatic RLH has not been previously reported. We also present a comprehensive review of the literature on hepatic and pancreatic RLH. METHODS: An extensive literature search for all published reports on hepatic or pancreatic RLH was conducted. Data on clinical, radiographic and histopathological features were extracted in addition to therapeutic options and outcomes. RESULTS: Forty-two hepatic and three pancreatic cases of RLH were described in the literature. The mean age of hepatic cases was 58 years, with a male-to-female ratio of above 1:7. Almost 25% of cases were associated with internal malignancy. Four hepatic cases were managed through active observation. The remainder (84%) underwent surgical resection. Due to their small number, no meaningful analysis could be made on the pancreatic cases. No recurrences were identified in any of the reported cases. CONCLUSION: RLH should be considered in the diagnosis of hepatic nodules where biopsies fail to demonstrate malignant cells. Confirmed RLH lesions should be managed by active observation. Investigation and treatment of any potential source of lymphoid reactivity should be undertaken. More reports on pancreatic RLH need to be studied prior to drawing any useful recommendations on its management.