Association between prediabetes and breast cancer: a comprehensive meta-analysis.

BACKGROUND: Breast cancer accounts for up to 30% of cancer cases in women in the US. Diabetes mellitus has been recognized as a risk factor for breast cancer. Some studies have suggested that prediabetes may also be associated with breast cancer whereas other studies have shown no or an inverse association; thus, we conducted a meta-analysis to assess the risk of breast cancer in prediabetes. METHODS: We searched PubMed/Medline, EMBASE, Google Scholar, and Scopus to identify studies that reported breast cancer risks in patients having prediabetes compared to normoglycemic patients. Binary random-effects model was used to calculate a pooled odds ratio (OR) with 95% confidence intervals. I2 statistics were used to assess heterogeneity. Leave-one-out sensitivity analysis and subgroup analyses were performed. RESULTS: We analyzed 7 studies with 24,586 prediabetic and 224,314 normoglycemic individuals (783 and 5739 breast cancer cases, respectively). Unadjusted odds ratio (OR) for breast cancer was 1.45 (95% CI = 1.14, 1.83); adjusted OR was 1.19 (95% CI = 1.07, 1.34) in prediabetes. Subgroup analysis revealed a higher breast cancer risk in individuals aged less than 60 years (OR = 1.86, 95% CI = 1.39, 2.49) than in those aged 60 years or more (OR = 1.07, 95% CI = 0.97, 1.18). Subgroup analysis by median follow-up length indicated a higher risk of breast cancer for follow-ups of less than or equal to 2 years (OR = 2.34, 95% CI = 1.85, 2.95) than in those of over 10 years (OR = 1.1, 95% CI = 0.99, 1.23) and 6 to 10 years (OR = 1.03, 95% CI = 0.88, 1.21). CONCLUSIONS: In conclusion, individuals with prediabetes have higher risk of developing breast cancer than those with normoglycemia, especially younger prediabetes patients. These individuals may benefit from early identification, monitoring, and interventions to reverse prediabetes.

Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.

The dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway can lead to uncontrolled cellular growth and tumorigenesis. Targeting PI3K and its downstream substrates has been shown to be effective in preclinical studies and phase III trials with the approval of several PI3K pathway inhibitors by the Food and Drug Administration (FDA) over the past decade. However, the limited clinical efficacy of these inhibitors, intolerable toxicities, and acquired resistances limit the clinical application of PI3K inhibitors. This review discusses the PI3K signaling pathway, alterations in the PI3K pathway causing carcinogenesis, current and novel PI3K pathway inhibitors, adverse effects, resistance mechanisms, challenging issues, and future directions of PI3K pathway inhibitors.

NTRK Therapy among Different Types of Cancers, Review and Future Perspectives.

Neurotrophic tyrosine receptor kinase (NTRK) has been a remarkable therapeutic target for treating different malignancies, playing an essential role in oncogenic signaling pathways. Groundbreaking trials like NAVIGATE led to the approval of NTRK inhibitors by the Food and Drug Administration (FDA) to treat different malignancies, significantly impacting current oncology treatment. Accurate detection of NTRK gene fusion becomes very important for possible targeted therapy. Various methods to detect NTRK gene fusion have been applied widely based on sensitivity, specificity, and accessibility. The utility of different tests in clinical practice is discussed in this study by providing insights into their effectiveness in targeting patients who may benefit from therapy. Widespread use of NTRK inhibitors in different malignancies could remain limited due to resistance mechanisms that cause challenges to medication efficacy in addition to common side effects of the medications. This review provides a succinct overview of the application of NTRK inhibitors in various types of cancer by emphasizing the critical clinical significance of NTRK fusion gene detection. The discussion also provides a solid foundation for understanding the current challenges and potential changes for improving the efficacy of NTRK inhibitor therapy to treat different malignancies.

A Case Report: Monoclonal Gammopathy of Undetermined Significance Presenting With Renal Amyloidosis and Reactive Thrombocytosis.

Monoclonal gammopathy of undetermined significance (MGUS) is a pre-neoplastic condition involving plasma cells or lymphoplasmacytic proliferation-clinical presentations ranging from asymptomatic to symptoms of systematic organ involvement. It is commonly associated with light chain amyloidosis and usually strengthens during diagnosis. It is usually associated with thrombocytopenia in addition to anemia. This case report focuses on a 63-year-old Hispanic female who initially presented without any symptoms but with severe thrombocytosis. The finding of renal amyloidosis boosts the final diagnosis of MGUS. Rarely a patient is initially presented with severe thrombocytosis despite thrombocytopenia, which is commonly associated with plasma cell disorders. The case emphasizes the need for considering plasma cell disorders in patients with abnormal hematologic manifestations. It highlights the importance of timely identification and intervention to prevent irreversible organ damage by providing a detailed analysis of the clinical presentation and diagnostic evaluation.

SLE and multiple myeloma: an underlooked link? A review of case reports from the last decade.

Systemic lupus erythematosus (SLE) affects multiple organ systems, and there has recently been increasing evidence that suggests a considerable rise in cancer risk. Despite growing evidence, the relationship between SLE and multiple myeloma (MM) remains underlooked. This review synthesizes findings from case reports published between 2012 and 2023 to explore this relationship. We conducted a comprehensive search using PubMed, Embase, and Google Scholar with the keywords 'SLE' and 'multiple myeloma' and described the clinical profile of MM in patients with SLE. Seven case reports were reviewed. Five case reports included female participants, two had a simultaneous diagnosis of SLE and MM, and in others, MM followed SLE varying from 7 months to 30 years. Two cases reported an improvement in MM. Four cases reported death due to complications, which included shock, myocardial infarction, and pneumonia. Lupus nephritis was seen to complicate MM and SLE complex in 2 cases. Larger, well-developed studies focusing on clinical presentation, diagnostic strategy, treatment, and outcomes are needed to better understand the association between SLE and MM. Healthcare workers should be aware of the increased risk of malignancy in SLE and customize screening accordingly.

A Case Report of Aggressive Post-Infectious Hemophagocytic Lymphohistiocytosis in an Immunocompetent Adult.

Hemophagocytic lymphohistiocytosis (HLH) is an acute inflammatory syndrome triggered by immune events such as infections, inflammation, autoimmune diseases, and malignancies. Initial presentations can range from vague symptoms to infectious features such as fever. Given its aggressive nature, timely diagnosis and immediate treatment are crucial to achieving optimal patient outcomes. Recently, the HLH score (HScore) criteria have been applied as diagnostic criteria, offering a broader scope compared to the previous HLH-2004 score, which was primarily based on pediatric populations. The standard treatment for decades has involved the combination of etoposide and high-dose steroids, and it is recommended to initiate treatment as soon as possible, even in the absence of a bone marrow test or when there is suspicion of the diagnosis. In this case presentation, we aim to underscore the significance of maintaining a high level of suspicion for HLH and the importance of promptly initiating treatment.

Diversity and Disparities in Lung Cancer Outcomes Among Minorities.

ABSTRACT: Because of diversities and disparities, lung cancer incidence and mortality rates among minorities are disproportionate compared with non-Hispanic White (NHW) populations. This review focuses on the disparities in lung cancer screening, diagnosis, treatment, and outcomes that minorities, mainly Hispanic and Black, experience compared with NHW populations. Despite efforts such as improving the eligibility criteria for screening to improve lung cancer survival rates, disparities persist, particularly among minority populations. However, the "Hispanic Paradox" describes the lower incidence and better survival rates observed in Hispanics compared with other ethnic groups best explained by possible contributions such as genetics and other factors such as dietary habits. Disparities in screening, particularly among underrepresented populations, are frequently explained by cultural, socioeconomic, and health care access barriers. There are also disparities in receiving appropriate treatment, such as surgical treatment, with fewer Hispanics and Blacks undergoing surgery than NHW individuals, resulting in lower overall survival rates. In addition, the prevalence of biomarker testing varies by racial and ethnic groups, influencing personalized treatment plans and outcomes. Finally, because of genetic and social determinants of health, the clinical outcomes of targeted therapy and immunotherapy may differ among minority populations. Identifying and addressing social determinants of health in real time are a "must" to have a significant impact in reducing lung cancer disparities. A comprehensive and multifaceted strategy is required to rectify disparities in cancer treatment. This strategy includes increasing levels of awareness and education, reducing financial and access barriers, and promoting increased diversity in clinical trial recruitment. By effectively addressing these complex challenges, the objective of providing equitable cancer care to all patients, regardless of race or ethnicity, can be achieved. To identify and address disparities, heightened awareness and education are essential. Access to health care is ensured by reducing financial and access barriers. Finally, increased diversity in clinical trial recruitment advances the generalizability of findings and promotes equitable representation of all racial and ethnic groups, resulting in improved outcomes for all patients.

The Outcomes of Acute Coronary Syndrome in Patients Suffering From Schizophrenia: A Systematic Review.

Acute coronary syndrome (ACS) is a principal cause of mortality and morbidity worldwide. Recent studies have suggested poorer outcomes in ACS patients who have a concurrent diagnosis of schizophrenia as compared with those without. However, the degree of interplay between schizophrenia and ACS remains poorly understood. For this reason, we conducted a systematic review on ACS outcomes in patients with schizophrenia by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We collected relevant data from PubMed, Cochrane Library, PubMed central, Jisc Library Hub Discover, and the National Library of Medicine (NLM) and performed a thorough quality appraisal. Fourteen shortlisted, relevant studies were meticulously reviewed. Mortality and major adverse cardiac events (MACE), bleeding, and stroke were more prevalent in patients with a schizophrenia diagnosis compared to those without. Additionally, schizophrenia patients received suboptimal care and follow-up when compared to patients without a psychiatric diagnosis. Clinicians need to be aware that patients with schizophrenia have worse outcomes following ACS which may relate to biological, health care, or patient-related factors.

Relationship and Effects of Vitamin D on Metabolic Syndrome: A Systematic Review.

Metabolic syndrome (MetS) is a persistent public health problem in the United States (U.S.) due to its increasing prevalence and its positive correlation with type-2 diabetes (T2DM) and cardiovascular disease (CVD). According to National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) criteria, MetS has six main components, which are obesity, dyslipidemia, raised blood pressure (BP), insulin resistance (IR) or glucose intolerance, pro-inflammatory state, and prothrombotic state. Vitamin D (Vit D) regulates the absorption of calcium and phosphorus and thus, is universally accepted as an essential vitamin for bone strength as well as a facilitator of immune system function. Vit D was also shown to reduce the risks of CVD, multiple sclerosis, and developing seasonal flu. We conducted a systematic review to identify the general association between Vit D level and MetS, to highlight specific associations between Vit D level and individual components of MetS, and finally, to explore the effects of Vit D supplementation on each component of MetS. In this paper, we reviewed 14 recent studies investigating the relationships between Vit D, MetS, and components of MetS. From the review of seven studies, we confirmed a significant association between Vit D and MetS as a whole. Four out of the five observational studies we reviewed support that Vit D level is significantly associated with the following components of MetS: obesity and BMI, dyslipidemia, BP, and insulin and glucose metabolism. We did not discover any significant relationship between Vit D level and other MetS components. The review of seven additional randomized clinical trials (RCT)-based studies suggest that Vit D supplementation has significant effects on BP, abdominal obesity, and insulin and glucose metabolism.

Do SGLT2 Inhibitors Improve Cardio-Renal Outcomes in Patients With Type II Diabetes Mellitus: A Systematic Review.

Diabetes mellitus (DM) is associated with dreadful changes in the cardiovascular and renal systems, causing increased morbidity and mortality. Sodium-glucose cotransport-2 (SGLT2) inhibitors belong to the oral hypoglycemic group of drugs believed to reduce these events by various mechanisms in DM. We performed a systematic review to determine the effectiveness of SGLT2 inhibitors in reducing cardiovascular and renal complications and address safety concerns in participants with type 2 diabetes mellitus (T2DM). We explored PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane library, and ResearchGate for randomized controlled trials and observational studies done on the advantages of SGLT2 inhibitors in the prevention or reduction of worsening cardiovascular and renal changes in T2DM. Studies were screened for the quality assessment using the Cochrane risk-of-bias assessment tool and Newcastle-Ottawa scale. We screened 5615 articles, out of which 22 articles with 7,02,977 diabetes mellitus patients treated with SGLT2 inhibitors were used for the systematic review after meticulously filtering articles based on inclusion and exclusion criteria. The trials included one of the following drugs - empagliflozin, dapagliflozin, canagliflozin, and luseogliflozin. SGLT2 inhibitors significantly reduced the risk of heart failure (HF), frequency of hospitalizations due to HF, all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction. Renal outcomes showed a significant lowering of risk of acute kidney failure, progression of chronic kidney disease, renal mortality, and improvement in urinary albumin creatinine ratio. We noticed an initial worsening of the estimated glomerular filtration rate followed by stabilizing and reaching the baseline on long-term treatment, especially in end-stage renal failure patients. The review showed that SGLT2 inhibitors have adverse reactions similar to that of a placebo, with a slight increase in treatable genital mycotic and urinary tract infections but no evidence of diabetic ketoacidosis, fractures, and amputations. According to the available data, SGLT2 inhibitors can significantly prevent or reduce cardiovascular diseases and kidney abnormalities in patients with type 2 diabetes mellitus with tolerable safety outcomes.