Hematopoietic stem cell transplant (HSCT) is an expensive and complex treatment regimen that can be curative in many diseases of the bone marrow, including malignant and non-malignant conditions. The introduction of the Affordable Care Act increased access to potential candidates and removed or reduced many barriers previously identified in the literature, however, racial disparities continue to persist. As HSCT expands its utilization and indications, there is a continued need to understand the multifactorial
There are two major groups of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLCs can be further separated into three different categories: lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Pulmonary adenocarcinomas represent nearly half of all lung cancer cases and are known to be caused by smoking, certain occupational exposures, and specific genetic mutations. Scientists have noticed that most NSCLCs are driven by defects in the following genes: EGFR, BRAF, ALK, MET, and HER. Abnormalities in the STK11/LKB1 gene have also been shown to induce lung adenocarcinoma. LKB1-deficient cancer cells contain an overactive AMPK "energy sensor," which inhibits cellular death and promotes glucose, lipid, and protein synthesis via the mTOR protein complex. Studies have also discovered that the loss of STK11/LKB1 favors oncogenesis by creating an immunosuppressive environment for tumors to grow and accelerate events such as angiogenesis, epithelial-mesenchymal transition (EMT), and cell polarity destabilization. STK11/LKB1-mutant lung cancers are currently treated with radiotherapy with or without chemotherapy. Recent clinical trials studying the effects of glutaminase inhibitors, mTOR inhibitors, and anti-PD-L1 therapy in lung cancer patients have yielded promising results. This narrative review provides an overview of the STK11/LKB1 gene and its role in cancer development. Additionally, a summary of the LKB1/APMK/mTOR is provided.
Triple-negative breast cancers (TNBCs) are aggressive tumors that are more common in young women, African American populations, and those with hereditary mutations. These tumors are notable for their high recurrence rate and predilection for chemoresistance. The goal of this narrative review is to describe the current treatment options for patients diagnosed with TNBC and to review the studies that have put forward these recommendations. We searched PubMed and Cochrane databases for free full-text, English-language studies published within the last several years pertaining to the search items "triple negative breast cancer" and "treatment". We included clinical trials and retrospective reviews that had clear designs and assessed their findings against a gold standard or placebo and included evidence of overall response and/or survival outcomes.Patients with early-stage (I-III) TNBC still benefit from treatment with chemotherapeutic regimens involving anthracyclines, taxanes, and antimetabolites. Platinum-based therapies have been shown to improve the overall pathologic complete response (pCR), but there is conflicting evidence with regard to their contribution to disease-free survival (DFS) and overall survival (OS), even with the addition of a poly (ADP-ribose) polymerase (PARP) inhibitor. Patients with residual disease after neoadjuvant chemotherapy and surgical intervention have shown a significant improvement in OS when treated with adjuvant capecitabine. The high mutation burden in metastatic TNBC (mTNBC) allows for targeted therapies and immune checkpoint inhibitors. mTNBCs that express programmed death ligand-1 (PD-L1) receptors may achieve improved response and survival if their regimen includes a monoclonal antibody. Antibody-drug conjugates (ADCs) can deliver high doses of chemotherapy and significantly impact survival in mTNBC regardless of the level of biomarkers expressed by the tumor cells. PARP inhibitors significantly improve survival in newly diagnosed, treatment-naive mTNBC, but have shown mixed results in patients with a history of previous therapy. PARP inhibitors may also target patients with somatic breast cancer (BRCA) and partner and localizer of BRCA-2 (PALB2) mutations, which would allow for more options in this subset of patients. While other rare targets have shown mixed results, the future of treatment may lie in antiandrogen therapy or the development of cancer vaccinations that may increase the immunogenicity of the tumor environment.The management of TNBC includes treatment with multimodal chemotherapy, immune checkpoint inhibitors, and ADCs. The optimal approach depends on a multitude of factors, which include the stage of the tumor, its unique mutational burden, comorbid conditions, and the functional status of the patient. Physicians should be familiar with the advantages and disadvantages of each therapy in order to appropriately counsel and guide their patients.
BACKGROUND Coronavirus disease 2019 (COVID-19) has left a significant impact on the world's health, economic and political systems; as of November 20, 2020, more than 57 million people have been infected worldwide, with over 1.3 million deaths. While the global spotlight is currently focused on combating this pandemic through means ranging from finding a treatment among existing therapeutic agents to inventing a vaccine that can aid in halting the further loss of life. AIM To collect all systematic reviews and meta-analyses published related to COVID-19 to better identify available evidence, highlight gaps in knowledge, and elucidate further meta-analyses and umbrella reviews that are yet to be performed. METHODS We explored studies based on systematic reviews and meta-analyses with the key-terms, including severe acute respiratory syndrome (SARS), SARS virus, coronavirus disease, COVID-19, and SARS coronavirus-2. The included studies were extracted from Embase, Medline, and Cochrane databases. The publication timeframe of included studies ranged between January 01, 2020, to October 30, 2020. Studies that were published in languages other than English were not considered for this systematic review. The finalized full-text articles are freely accessible in the public domain. RESULTS Searching Embase, Medline, and Cochrane databases resulted in 1906, 669, and 19 results, respectively, that comprised 2594 studies. 515 duplicates were subsequently removed, leaving 2079 studies. The inclusion criteria were systematic reviews or meta-analyses. 860 results were excluded for being a review article, scope review, rapid review, panel review, or guideline that produced a total of 1219 studies. After screening articles were categorized, the included articles were put into main groups of clinical presentation, epidemiology, screening and diagnosis, severity assessment, special populations, and treatment. Subsequently, there was a second subclassification into the following groups: gastrointestinal, cardiovascular, neurological, stroke, thrombosis, anosmia and dysgeusia, ocular manifestations, nephrology, cutaneous manifestations, D-dimer, lymphocyte, anticoagulation, antivirals, convalescent plasma, immunosuppressants, corticosteroids, hydroxychloroquine, renin-angiotensin-aldosterone system, technology, diabetes mellitus, obesity, pregnancy, children, mental health , smoking, cancer, and transplant. CONCLUSION Among the included articles, it is clear that further research is needed regarding treatment options and vaccines. With more studies, data will be less heterogeneous, and statistical analysis can be better applied to provide more robust clinical evidence. This study was not designed to give recommendations regarding the management of COVID-19.
Background Existing comorbidity indices were not developed for adolescent and young adults (AYA) 15–39 years of age. The aim of this study was to assess impact of comorbidities on healthcare service needs and health status among AYA cancer survivors using the newly developed AYA HOPE comorbidity index in comparison with the existing indices. Methods Data on comorbid conditions were obtained from medical records and service needs and health status were from a survey of AYA cancer survivors. Prevalence of comorbidities based on the AYA HOPE index. Charlson and NCI indices) were compared. Multivariable logistic regression was employed. Results Of the 485 patients, 14.6% had ≥2 comorbidities based on the AYA HOPE Index. Prevalence of mental illness and obesity/overweight, which were not included in existing indices, were 8.2% and 5.8%, respectively. Prevalence of cardiovascular, endocrine, gastrointestinal and neurologic conditions were higher with the AYA HOPE Index than the other two indices. Forty percent of AYA patients reported service needs, particularly for mental health services (25.2%) and support groups (17.7%). Having ≥2 comorbidities on the AYA index was associated with higher mental health service needs (OR: 2.05; 95% CI 1.10–3.82) adjusting for demographic and clinical factors. Comorbidities were associated with fair/poor self-reported health status. Conclusion The AYA HOPE Index is a more comprehensive comorbidity index for AYA cancer patients than existing indices and the number of comorbidities is associated with service needs and health status. Impact The AYA HOPE index could identify patients’ additional service needs early in therapy.
Cardiac rehabilitation programs support the health, wellness, and recovery of patients with cardiovascular conditions. This systematic review attempts to expand these findings while analyzing the latest randomized controlled trials (RCTs) focusing on the long-term advantages of home/center-based cardiac rehabilitation interventions. This study also comparatively analyzes the benefits of opting for home-based cardiac rehabilitation instead of center-based measures to improve the long-term clinical outcomes of cardiac patients. We extracted and analyzed 10 studies (based on 1,549 cardiac patients) concerning the therapeutic efficacy of center/home-based cardiac rehabilitation interventions. The included studies complied with the year range of 2000-2021. The risk of bias assessment was undertaken using the Cochrane Risk-of-Bias tool to evaluate random sequence generation, allocation concealment, blinding of subjects, outcome data completeness, and selective reporting patterns concerning the included RCTs. The findings of our systematic review confirmed the capacity of a home-based cardiac rehabilitation program to effectively improve left ventricular ejection fraction, health-related quality of life, physical fitness, recovery rate, self-efficacy, sedentary lifestyle, physical activity, satisfaction level, functional capacity, social support, and hemodynamic parameters of patients with cardiovascular diseases. Home-based cardiac rehabilitation had the potential to minimize the levels of triglycerides, anxiety, depression, waist circumference, and body mass index/weight of cardiac patients. The results of our systematic review affirmed the long-term therapeutic efficacy of a home-based cardiac rehabilitation program compared to a center-based cardiac rehabilitation program for adult cardiac patients.
Objective: The purpose of this review article is to describe the pathogenesis of pancreatic cancer and to better understand the role of abnormal stem cells in the development of pancreatic cancer.Background: Pancreatic cancer is a highly fatal disease that is caused by the uncontrolled proliferation of pancreatic exocrine or neuroendocrine glands. It is believed that pancreatic cancers arise from a small population of abnormal cancer stem cells (CSCs) that promote tumorigenesis, tumor metastasis and therapeutic resistance. The molecular markers CD133, CXCR4, DCLK1, c-MET, ABCG2 and Lgr5 are routinely used to detected and observe the behaviours of pancreatic cancer stem cells (PCSCs).Methods: A comprehensive search was performed on PubMed, Google Scholar, Scopus, Clinicaltrials.gov and Web of Science using related keywords. Articles focusing on PCSCs and pancreatic cancer pathogenesis, biochemistry and clinical trials were selected.Conclusions: Although very little is known about the exact cause of pancreatic cancer, PCSCs seem to play an important role in carcinogenesis. Mutated biochemical cascades include Sonic Hedgehog, K-RAS-JNK, DLL4/Notch and Nodal/Activin. Several clinical trials are trying to determine if the transplantation of hematopoietic stem cell or peripheral stem cells could be useful for the treatment of such an aggressive tumor.
Primary neuroendocrine tumors (NETs) are rare types of malignancies that can have a variety of presentations due to the ubiquitous distribution of neuroendocrine cells within the body. While mediastinal masses are not uncommon, NETs arising from the anterior mediastinum are rare and often originate from the thymus gland. A subset of NETs, atypical carcinoids, are more commonly seen in the lungs or gastrointestinal organs and often present with endocrine syndromes, chiefly Cushing's syndrome. The behavior of atypical carcinoid tumors within the mediastinum is often aggressive and clinical presentations vary widely. In this report, we describe a case of an atypical carcinoid tumor within the anterior mediastinum in an otherwise healthy young male with signs and symptoms of Cushing's syndrome.
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