Meta-analysis of Targeted Therapies in EGFR-mutated Non-Small Cell Lung Cancer: Efficacy and Safety of Osimertinib, Erlotinib, and Gefitinib as First-line Treatment.

BACKGROUND: Some of the non-small cell lung cancer (NSCLC) cases enhance somatic mutations of the epidermal growth factor receptor (EGFR) gene within the tyrosine kinase inhibitor (TKI) domain. In such cases, first-line treatments are EGFR-TKIs, including osimertinib, erlotinib, or gefitinib. Therefore, this meta-analysis aims to assess the safety and efficacy of first-line targeted therapies for EGFR-mutated advanced NSCLC patients, focusing on osimertinib, erlotinib, and gefitinib. METHODS: A systematic electronic search was conducted on 3 electronic databases-Scopus, PubMed, and Web of Science-from inception to May 2024 to locate relevant trials reporting the safety and efficacy of osimertinib, erlotinib, or gefitinib in treating EGFR-mutated advanced NSCLC. No language or data restriction was applied to the search strategy. The assessed effects were objective response rate (ORR) and disease control rate (DCR). RoB 2 tool was utilized to determine the risk of bias while R programming language performed all the statistical synthesis. RESULTS: Out of 15,275 search results, only 19 trials were eligible for this meta-analysis. All the 3 EGFR-TKIs depicted effectiveness and safety among NSCLC patients, but osimertinib improved the ORR by 72% (95% CI: 65%, 78%) as compared with erlotinib (69% [95% CI: 58%, 79%]) and gefitinib (64% [95% CI: 64%, 78%]). Overall, the 3 EGFR-TKIs were effective by improving ORR 68% (95% CI: 63%, 73%). Similarly, osimertinib demonstrated highly effective impacts in disease control among NSCLC patients by 94% (95% CI: 91%, 97%) compared with gefitinib (68% [95% CI: 41%, 89%]). Overall, the 2 EGFR-TKIs were effective in disease control among NSCLC patients (82% [95% CI: 67%, 93%]). CONCLUSIONS: The pooled analyses have shown that erlotinib, gefitinib, and osimertinib are safe and effective first-line treatment options for patients with EGFR-mutated advanced NSCLC. The meta-analysis outcomes have demonstrated that osimertinib, erlotinib, or gefitinib positively impact overall response rate and disease control.

Rituximab as a Therapeutic Strategy in Hemophagocytic Lymphohistiocytosis: Efficacy, Outcomes, and Survival-Insights From a Systematic Review.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system activation and is often triggered by infections such as Epstein-Barr virus (EBV). Rituximab, an anti-CD20 monoclonal antibody, has been suggested as a treatment, particularly for EBV-associated HLH. METHODS: A systematic review was conducted using PRISMA guidelines, with a literature search spanning PubMed, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria focused on studies that assessed rituximab's efficacy in treating HLH. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. RESULTS: Of 783 identified records, 24 studies were included in the final analysis. Rituximab was typically administered at 375 mg/m2, with varying doses and treatment frequency. Clinical response, often seen within 1 month, was assessed by improvements in clinical symptoms and laboratory findings. Survival rates posttreatment displayed a wide range, with instances of complete remission and disease-free periods, as well as reports of relapse and mortality. CONCLUSION: Rituximab demonstrates the potential for significant clinical benefit in treating HLH, particularly when associated with EBV, showing promise in reducing disease activity and contributing to remission. These findings encourage further research and clinical trials to refine the therapeutic protocols and better understand the long-term effects of rituximab in HLH management.

Optimization Strategies in CAR T-cell Therapy: A Comprehensive Evaluation of Cytopenia, HLH/MAS, and Other Adverse Events.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for various hematological malignancies. Still, its remarkable efficacy is accompanied by unique adverse events that must be carefully managed. This comprehensive literature review evaluates the safety profile of CAR T-cell therapy, focusing on cytopenia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), and other potential complications. Cytopenia, characterized by reduced blood cell counts, affects a significant proportion of patients, with rates of anemia, neutropenia, and thrombocytopenia reaching up to 60%, 70%, and 80%, respectively. Risk factors include high tumor burden, prior chemotherapy, and bone marrow involvement. Cytokine release syndrome (CRS) occurs in 13% to 77% of patients and is linked to the cytokine storm induced by CAR T cells, target antigen expression, and preexisting immune dysregulation. Other notable adverse events discussed are cytokine release syndrome, neurotoxicity, and infections. Understanding the mechanisms, risk factors, and management strategies for these adverse events is crucial for optimizing patient outcomes and unlocking the full potential of this revolutionary therapy. The review highlights the need for continued research, interdisciplinary collaboration, and evidence-based approaches to enhance the safety and efficacy of CAR T-cell therapy.

Schwann Cell Hamartoma Presenting as a Colonic Polyp: A Rare Case Report With a Literature Review.

Mucosal Schwann cell hamartomas (MSCHs) are non-common noncancerous growths derived from Schwann cells in the peripheral nervous system, often found unexpectedly during routine colonoscopy examinations. These growths primarily occur in the colon, although they can also appear in the esophagus and are not linked to familial cancer syndromes. Diagnosis relies on specific histological characteristics and staining patterns. It is essential to distinguish MSCHs accurately since their appearance can closely resemble that of malignant tumors. Characteristically, these hamartomas test positive for S-100 protein but do not exhibit markers typical of other gastrointestinal growths, such as gastrointestinal stromal tumors (negative for KIT), leiomyomas (negative for smooth muscle actin), neurofibromas (negative for CD34), and perineuromas (negative for epithelial membrane antigen or claudin-1). This report discusses the case of a 48-year-old woman who was diagnosed with MSCH during a screening colonoscopy.

Crushing Muscles: A Case Study on Rhabdomyolysis, Renal Failure, and Compartment Syndrome Triggered by Pre-Workout Supplement Abuse.

The use of steroids and protein-based dietary supplements for muscle enhancement is prevalent in contemporary society. While these products promise increased muscle mass and strength, they carry significant risks, including severe medical complications. The consumption of these supplements has been linked to adverse symptoms, including dehydration, gastrointestinal distress, dizziness, and alterations in heart rate and blood pressure, primarily due to ingredients like creatine, arginine, and caffeine. Following the proper dosage, ensuring adequate hydration, and consulting a healthcare provider to verify if the supplement's components could affect any pre-existing conditions is recommended. Indiscriminate use of these products, including taurine, can lead to serious side effects. We present a 36-year-old patient with severe rhabdomyolysis, life-threatening acid-base imbalance, renal and liver injury, and peripheral neuropathy associated with the use of performance-enhanced unregulated supplements and exercise. This case highlights the importance of recognizing and managing complications related to exercise-aid supplements, emphasizing early identification and management. Increasing social awareness and research on those products is highly needed to avoid supplement-associated complications and potential long-term disabilities.

Safety, Efficacy, and Predictive Factors of Venetoclax-Based Regimens in Elderly Acute Myeloid Leukemia Patients: A Meta-Analysis.

Venetoclax synergizes with low-intensity regimens such as hypomethylating agents (HMAs) and low-dose cytarabine (LDAC). However, less is known about the clinical activity of venetoclax combined with HMAs or LDAC. Therefore, the current study focused on assessing the clinical efficacy, safety, and predictive factors for response to these venetoclax-based regimens in elderly patients with acute myeloid leukemia (AML). A comprehensive search for literature related to our study objective was performed on PubMed, Embase, Web of Science, and Google Scholar databases. The statistical analyses were performed using Review Manager or the Comprehensive Meta-Analysis software. In addition, methodological quality evaluation of nonrandomized studies was conducted using the Newcastle Ottawa Scale, while bias assessment of randomized studies was performed with Cochrane's risk of bias tool. Twelve studies, including 1432 elderly AML patients treated with venetoclax-based regimens, were identified for review and analysis. The pooled analysis showed that the rate of complete response with or without incomplete blood count recovery (CR/CRi) and overall response rate (ORR) among patients treated with venetoclax and HMAs was 59% and 64%, respectively. On the other hand, an CR/CRi of 50% was observed in patients treated with venetoclax and LDAC. Furthermore, venetoclax combined with HMAs demonstrated a significant survival benefit over HMAs alone and intensive chemotherapy (HR: 0.57; 95% CI: 0.47-0.68; P < .00001). The most common grade ≥ 3 hematologic disorder, nonhematological event, and infection in AML patients treated with venetoclax and HMAs were febrile neutropenia (39%), hypokalemia (12%), and pneumonia (19%), respectively. Conversely, thrombocytopenia, hypokalemia, and pneumonia were more common in patients treated with venetoclax and LDAC (41%, 15%, and 12%, respectively). Venetoclax combined with HMAs or LDAC has good clinical activity and a manageable safety profile in elderly patients with AML.

Efficacy and Safety of Abemaciclib in Combination With Endocrine Therapy for HR+/HER2- Advanced or Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Breast cancer, particularly the hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) subtype, remains a major global health concern. Abemaciclib, a CDK4/6 inhibitor, has shown promising results in treating advanced cases. This study comprehensively assesses the efficacy and safety of abemaciclib in combination with endocrine therapy for HR+/HER2- advanced or metastatic breast cancer. METHODS: Following PRISMA guidelines, a systematic review and meta-analysis was conducted. A thorough literature search was conducted on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov til December 2023. Inclusion criteria encompassed randomized controlled trials and retrospective cohort studies reporting on abemaciclib in approved doses, either as monotherapy or in combination. Outcome assessments included progression-free survival (PFS), overall response rate (ORR), side effects/adverse effects (SE/AE), and overall survival (OS). Quality assessment utilized Cochrane's revised risk of bias tool and Newcastle-Ottawa scale. RESULTS: Pooled results of 22 studies involving 14,010 patients revealed that abemaciclib significantly improved PFS (hazard ratio=0.53; 95% CI: 0.48-0.59; P=0.00; I2=0%), ORR (risk ratio=2.31; 95% CI: 1.93-2.75; P=0.00; I2=0%), and OS (risk ratio=0.76 (95% CI: 0.65-0.87; P=0.001; I2=0%). However, abemaciclib increased the risk of adverse events in the fulvestrant and nonsteroidal aromatase inhibitor (NSAI) combinations, respectively. CONCLUSIONS: Abemaciclib, particularly in combination with fulvestrant, emerges as an effective therapeutic option for HR+/HER2- advanced or metastatic breast cancer, improving PFS and OS. The higher toxicity profile warrants cautious use, especially in treatment-naive patients.

Navigating uncharted waters: assessing the impact of the COVID-19 pandemic on hematopoietic stem cell transplantation: challenges and innovations.

The COVID-19 pandemic has significantly impacted hematopoietic stem cell transplantation (HSCT), necessitating adaptations across pre-transplant, transplantation, and post-transplant phases. HSCT recipients with compromised immune systems face heightened risks of severe COVID-19 outcomes, including increased mortality. The pandemic prompted significant changes in treatment strategies, with many patients experiencing delays or deferrals in autologous stem cell transplantation (ASCT), alongside adjustments to chemotherapy regimens to prevent disease recurrence. Clinical practices have evolved to address pandemic-related challenges, including a decrease in allo-HSCT procedures, a shift towards using domestic donors and peripheral blood stem cells over bone marrow grafts, and integration of telemedicine to reduce patient burden. These adaptations aim to balance COVID-19 exposure risks with the need for lifesaving HSCT. Innovations in response to the pandemic include stringent infection control measures, modified conditioning regimens, and revised post-transplant care protocols to mitigate infection risks. The importance of optimizing antiviral treatments, exploring new immunomodulatory interventions, and researching broadly neutralizing antibodies for HSCT recipients has been underscored. Despite the difficulties, the pandemic has catalyzed significant learning and innovation in HSCT practices, emphasizing the need for ongoing adaptation and research to protect this vulnerable patient population.

Capivasertib in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative advanced breast cancer.

PURPOSE: This review discusses the role and efficacy of Capivasertib in managing Hormone Receptor-Positive (HR+) breast cancer. SUMMARY: Breast cancer is the most prevalent type of cancer among women worldwide. This article is an in-depth analysis of advanced therapeutic options involving Capivasertib in treating HR+ Breast Cancer. It focuses on the mode of action, efficacy, clinical trials, and comparison with fulvestrant alone. This review also highlights the therapy's precision in targeting specific cancer cells. Its mechanism of action involves preventing cancer cells from growing and having a cytotoxic effect on them. It improves progression-free survival while maintaining the quality of life. The side effects can be easily managed by dose reduction or discontinuation of the drug. This article sheds light on the ongoing trials and FDA recognition. CONCLUSION: In conclusion, Capivasertib-fulvestrant therapy shows potential as an innovative therapeutic option for HR+ breast cancer but warrants additional research, especially in randomized control trials (RCT). It resulted in longer progression-free survival compared to fulvestrant alone. Its side effect profile is minimal.

Efficacy of Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Comprehensive Systematic Review and Meta-analysis.

OBJECTIVES: Breast cancer is the most diagnosed cancer in women, with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) being the predominant subtype. Sacituzumab govitecan (SG), a novel antibody-drug conjugate, has emerged as a promising treatment for metastatic HR+/HER2- breast cancer. This systematic review and meta-analysis aimed to evaluate its efficacy and safety. METHODS: Adhering to "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines, a comprehensive search was conducted in PubMed, Scopus, and Cochrane databases up to December 2023. We included clinical trials and observational studies evaluating SG in patients with HR+/HER2- advanced breast cancer. The primary outcome was progression-free survival (PFS). In contrast, the secondary outcomes included overall survival, objective response rate, clinical benefit rate, duration of response (DOR), and adverse event profiles. Review Manager (Version 5.4) was used for the statistical analysis. RESULTS: Nine studies met the inclusion criteria for systematic review; 2 were suitable for meta-analysis. The pooled analysis showed a hazard ratio of 0.53 (95% CI: 0.34-0.83; P= 0.005; I2 = 86%) for PFSl and a hazard ratio of 0.63 (95% CI: 0.36-1.11; P= 0.11; I2 = 92%) for overall survival. The pooled analysis of the duration of response showed significant results with a standard mean difference = 0.22 (95% CI: 0.03-0.42; P = 0.02; I2 = 61%). CONCLUSION: SG demonstrates significant benefit in PFS and duration of response in patients of HR+/HER2- advanced breast cancer.

Efficacy and Safety of BRCA-targeted Therapy (Polyadenosine Diphosphate-ribose Polymerase Inhibitors) in Treatment of BRCA-mutated Breast Cancer: A Systematic Review and Meta-analysis.

Breast cancer is the second leading cause of women's cancer deaths after lung cancer. Risk factors such as environment, lifestyle, and genetics contribute to its development, including mutation in the breast cancer (BRCA) gene. Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) target these mutations, benefiting patients with advanced cancers. This review summarizes PARPi' safety and efficacy in the treatment of BRCA-mutated breast cancer. PubMed, The Cochrane Library for Clinical Trials, and Science Direct, were searched for articles from inception to April 2024. Eligible articles were analyzed, and data were extracted for meta-analysis using RevMan 5.4 software with a random-effect model. Out of 430 articles identified from online databases, only 6 randomized control trials including 3610 patients were included in the analysis. PARPi therapy improved progression-free survival (hazard ratio: 0.64; 95% CI: 0.56, 0.73; P< 0.00001) and overall survival (hazard ratio: 0.84; 95% CI: 0.73, 0.98 P = 0.02), according to the analysis. In our safety analysis, the risk of adverse events was not statistically different between PARPi versus chemotherapy (relative risk [RR]: 1.08; 95% CI: 0.44, 2.68; P = 0.86), and combined PARPi and standard chemotherapy (RR: 1.00; 95% CI: 0.93, 1.07; P = 0.80). The only statistically significant difference was observed in anemia, where PARPi increased the risk of developing anemia compared with standard chemotherapy (RR: 6.17; 95% CI: 2.44, 15.58; P = 0.0001). In BRCA-mutated breast cancer, PARPi treatment shows better overall survival and progression-free survival compared with standard chemotherapy or placebo. Furthermore, PARPi, either alone or in combination therapy, does not increase the risk of adverse events in these patients, as per the meta-analysis.

Safety and Efficacy of Trastuzumab Deruxtecan for Metastatic HER2+ and HER2-low Breast Cancer: An Updated Systematic Review and Meta-Analysis of Clinical Trials.

OBJECTIVES: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data. RESULTS: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis. CONCLUSIONS: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.

Pembrolizumab in combination with trastuzumab for treatment of HER2-positive advanced gastric or gastro-esophageal junction cancer.

Introduction: Gastric cancer remains a challenging malignancy with a high global mortality rate. Recent advances in targeted therapy and immunotherapy have shown promise in improving patient outcomes. This paper reviews the impact of incorporating targeted agents such as trastuzumab and immunotherapeutic agents like pembrolizumab into standard chemotherapy regimens for gastric cancer treatment. Methods: A comprehensive analysis was conducted on pivotal clinical trials, including KEYNOTE-590, KEYNOTE-811, and ToGA, focusing on their methodologies, patient populations, treatment regimens, and outcome measures. The review also explored emerging research avenues in precision medicine, particularly genomic sequencing and biomarker identification. Aim: To assess the efficacy and survival benefits of adding trastuzumab and pembrolizumab to standard chemotherapy in the treatment of gastric cancer and to outline future directions in gastric cancer research. Results: Including trastuzumab and pembrolizumab in treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive and PD-L1-expressing gastric cancers significantly improved progression-free and overall survival rates compared to chemotherapy alone. These findings highlight the potential of personalized therapy in enhancing treatment outcomes. Furthermore, ongoing research into the gastric cancer microenvironment and the role of the microbiome suggests novel targets for future therapeutic interventions. Conclusion: The integration of targeted and immunotherapeutic agents with traditional chemotherapy represents a pivotal shift in gastric cancer treatment, moving towards more personalized and effective regimens.

Uncommon Manifestation: Thrombotic Thrombocytopenic Purpura Presenting Solely as Petechial Rash.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder typically presenting with a classic pentad of symptoms: thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal dysfunction, and fever. This report explores an unusual presentation of TTP in a 47-year-old female with a medical history of hypertension, hyperlipidemia, and chronic TTP, who exhibited only petechial rashes, generalized weakness, and headache. Notably, the petechial rash, a less common manifestation of TTP, became a pivotal clue for the diagnosis, underscoring the necessity for vigilance even when classic symptoms are absent. This case reinforces the imperative of a high suspicion index for TTP, especially in patients with thrombocytopenia and hemolytic anemia, irrespective of other traditional signs. Plasmapheresis remains the treatment cornerstone, removing autoantibodies and replenishing ADAMTS13, as evidenced by the patient's initial response. The administration of rituximab, targeting B cells to mitigate autoantibody production against ADAMTS13, featured prominently in her management, aligning with its recognized role in refractory or relapsing TTP cases. Despite an encouraging response to rituximab, a subsequent decline in platelet count indicated the unpredictable nature of TTP and the necessity for multi-pronged therapeutic strategies. The patient's medical background and persistently low ADAMTS13 levels hinted at a chronic relapsing trajectory associated with increased morbidity and mortality. This necessitates ongoing vigilance and treatment flexibility. Highlighting this atypical TTP presentation, the report calls for immediate, robust intervention, serving as a critical reminder of the heterogeneity of TTP manifestations and the complexities in its management, thereby contributing to broader clinical awareness and improved patient prognoses.

Segmental Shielding: A Rare Case of Acute Respiratory Distress Syndrome with Middle Lobe Sparing.

Acute respiratory distress syndrome (ARDS) presents a formidable challenge in critical care, often resulting in high mortality rates, particularly in severe cases or those compounded by preexisting conditions. Despite substantial advancements in critical care, the heterogeneous nature of ARDS necessitates nuanced clinical approaches. ARDS is generally diagnosed through clinical evaluation, radiographic imaging, and laboratory tests, as well as acute onset, bilateral lung infiltrates on imaging, and a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspiratory oxygen concentration (FiO2) ratio of less than 300 mmHg. Management involves measurements to improve oxygenation and provide mechanical ventilation to assist breathing. The typical manifestation of ARDS is diffuse lung involvement, which affects multiple lobes symmetrically. Here, we report an unusual case of ARDS in a 53-year-old female who was brought into the hospital in an unresponsive state, exhibiting hypoxic and hypotension requiring intubation. Subsequent imaging revealed a distinctive pattern: the preservation of the right middle lobe, diverging from the conventional diffuse pulmonary affliction. This case underscores the need for clinical vigilance and adaptability, as such atypical presentations can confound diagnosis and management, posing unique clinical challenges. This case highlights the importance of recognizing ARDS' diverse presentations. Moreover, understanding the mechanisms behind the lobar sparing could provide greater insight into the disease heterogeneity and guide tailored therapeutic approaches. The imperative for further research into these uncommon presentations is clear, as it may be vital to improving outcomes for a broader spectrum of ARDS patients.

Revolutionizing triple-negative metastatic breast cancer treatment: sacituzumab Govitecan's role in advancing chemotherapy.

Purpose: This review aims to discuss the role and efficacy of Sacituzumab Govitecan in the management of breast cancer. Summary: Breast cancer is the most prevalent type of cancer among women worldwide. This comprehensive review delves into the advancements brought about by Sacituzumab Govitecan in the treatment of metastatic triple-negative breast cancer (TNBC). With a focus on its mode of action, efficacious role, clinical trials, and comparative advantages over conventional chemotherapy, the review highlights the therapy's precision in targeting cancer cells through monoclonal antibodies. Sacituzumab Govitecan's ability to deliver a chemotherapeutic payload specifically to cancer cells with the Trop-2 receptor sets it apart from traditional chemotherapy, minimizing collateral damage and reducing severe side effects. The impact of Sacituzumab Govitecan on improving progression-free survival, tumor response rates, and, significantly, the quality of life for patients is discussed. This article also sheds light on ongoing trials, FDA recognition, and the therapy's potential to transform breast cancer treatment. Conclusion: In conclusion, Sacituzumab Govitecan shows potential as an innovative therapeutic option for breast cancer, particularly in metastatic breast cancer and triple-negative breast cancer, but it warrants additional research.

Elacestrant in the treatment landscape of ER-positive, HER2-negative, ESR1-mutated advanced breast cancer: a contemporary narrative review.

Introduction: Estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer with ESR1 mutations presents a significant therapeutic challenge due to its adaptive resistance mechanisms to chemotherapy, especially endocrine treatment. Elacestrant, a novel oral selective estrogen receptor degrader (SERD), has emerged as a promising agent in this treatment-resistant era. Method: A comprehensive search was conducted on pivotal clinical trials, including the RAD1901-005 Trial, EMERALD TRIAL, ELIPSE, and ELEVATE, focusing on their methodologies, patient populations, treatment regimens, and outcomes. Discussion: This narrative review describes the available preclinical and clinical evidence on elacestrant, focusing on its pharmacodynamics, pharmacokinetics, efficacy, and safety within the existing literature. Elacestrant has demonstrated excellent activity against ESR1 mutations associated with resistance to first-line endocrine therapies. Clinical trials have shown improved progression-free survival in patients with advanced ER+/HER2-, ESR1-mutated breast cancer. Safety profiles indicate a tolerable side effect spectrum consistent with other agents. Its oral bioavailability offers a convenient alternative to injectable SERDs, with potential implications for patient adherence and quality of life. The review also discusses the comparative efficacy of elacestrant relative to existing endocrine therapies and its possible use in combination regimens. Conclusion: Ongoing clinical trials assessing elacestrant and other SERDs will yield data that might aid clinicians in determining the optimal selection and order of endocrine treatment drugs for ER+ breast cancer. The integration of targeted and immunotherapeutic agents with traditional chemotherapy represents a pivotal shift in Breast Cancer treatment, moving towards more personalized and effective regimens.

The Efficacy of Tafolecimab in Chinese Patients with Hypercholesterolemia: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels. METHODS: A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I2 index. The risk of bias was assessed using Cochrane's RoB 2 tool. This review has been registered with PROSPERO (CRD42023471020). RESULTS: A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = - 63.78, 95% CI - 65.88 to - 61.68, p value < 0.00001, I2 = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, p value < 0.00001, I2 = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, p value < 0.00001, I2 = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB 2 tool. CONCLUSIONS: Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations. REGISTRATION: PROSPERO identifier number CRD42023471020.

Hypercholesterolemia: a literature review on management using tafolecimab: a novel member of PCSK9 monoclonal antibodies.

Background: Cardiovascular diseases (CVD) persist as the leading cause of mortality globally, with atherosclerotic cardiovascular disease (ASCVD), including hypercholesterolaemia, being a significant contributor. Hyperlipidemia management includes various lipid-lowering drugs, including statins, Bempedoic acid, inclisiran, Lomitapide, ANGPTL3 inhibitors, and PCSK9 inhibitors. Statins have traditionally dominated lipid management therapies; however, a subset of patients remains unresponsive or intolerant to this therapy, necessitating novel therapeutic approaches. Tafolecimab, a promising and novel PCSK9 monoclonal antibody, demonstrated significant LDL-C reduction and a favourable safety profile in clinical trials. Objective: This review aimed to discuss the role and efficacy of Tafolecimab in the management of hypercholesterolaemia. Methods: The authors searched online databases, including PubMed, Scopus, and Embase, for articles related to talofecimab. Discussion: The efficacy of Tafolecimab in diverse patient populations, including those with comorbid conditions and various lipid disorders, has been explored. Ongoing trials, such as CREDIT-1, CREDIT-2, and CREDIT-4, have provided valuable insights into Tafolecimab's potential as a lipid-lowering agent. Moreover, the drug's extended dosing interval may enhance patient compliance and reduce treatment costs. It has also been found that Tafolecimab has more affinity for PCSK9 and a longer duration of LDL-C reduction than other monoclonal antibody drugs such as evolocumab. Thus, this review focuses on Tafolecimab, a novel PCSK9 monoclonal antibody, its mechanism of action, clinical trial outcomes, safety profile, and potential role in hypercholesterolaemia management. Despite its assuring potential, the long-term impact of Tafolecimab on cardiovascular outcomes remains to be fully elucidated, necessitating further research. Regulatory authorities like the FDA and EMA should also evaluate Tafolecimab's risks and benefits. Conclusion: In conclusion, Tafolecimab shows potential as an innovative therapeutic option for hypercholesterolaemia, particularly in patients with specific risk factors, but warrants additional research.

Successful Management of Atypical Hemolytic-Uremic Syndrome in Pregnancy Using Eculizumab: A Case Review.

Hemolytic-uremic syndrome (HUS) is a rare thrombotic microangiopathy characterized by the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury. The disease is pathologically marked by fibrinoid necrosis within renal arterioles and glomerular capillaries. HUS can be categorized into typical variants, often linked to Shiga toxin-producing Escherichia coli (STEC) infection, and atypical variants that stem from dysregulation in the alternative complement pathway. Pregnancy is a recognized predisposing condition for HUS due to the potential reduction in complement regulatory proteins and the possibility of heightened maternal immune response. This report illustrates the case of a 36-year-old woman who, at 36 weeks of gestation, faced a breech presentation and was diagnosed with atypical HUS (aHUS) after placental abruption. Following a cesarean section, she developed complications, including a pelvic hematoma and bilateral hydronephrosis. Despite initial suboptimal response to plasmapheresis, the patient exhibited marked clinical improvement with eculizumab treatment, with no evidence of disease relapse.