ABSTRACT
Metastatic non-small cell lung cancer (NSCLC) poses a significant clinical challenge, prompting a focused investigation into the role of KRAS mutations in prognosis and treatment response. Targeted therapies offer promising avenues for intervention, motivating a comprehensive analysis of existing evidence. Conducted in June 2023, our review delved into MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Scopus, and the Cochrane Register of Controlled Trials. Rigorous inclusion and exclusion criteria guided the selection of 12 articles, comprising two randomized controlled trials (RCTs) and 10 observational studies. Multiple investigators independently executed data extraction, evaluating prognostic factors (overall and progression-free survival) and predictive outcomes (treatment and objective response). The Newcastle-Ottawa Scale (NOS) and modified Jadad scores were used for study quality assessment of observational studies and RCTs, respectively. From an initial pool of 120 articles, the 12 selected studies, spanning 2013 to 2022, encompassed 2,845 metastatic NSCLC patients. KRAS mutations, particularly the G12C variant, emerged as a pivotal factor influencing treatment response. Notably, KRAS wild type patients displayed enhanced responses to platinum-based chemotherapy, while those with KRAS mutations exhibited favourable outcomes with immune checkpoint inhibitors (ICIs). The role of KRAS mutations as prognostic indicators in metastatic NSCLC is underscored by this systematic review, with implications for both survival and treatment response. The discernment between KRAS wild type and mutant patients offers insights into tailored therapeutic strategies, with platinum-based chemotherapy and immune checkpoint inhibitors emerging as context-dependent options. Nevertheless, more research is required to solidify the predictive role of KRAS and explore the efficacy of KRAS inhibitors and other targeted therapies, paving the way for refined and personalized interventions in the management of metastatic NSCLC.
ABSTRACT
This umbrella meta-analysis aims to investigate two surgical treatments for abdominal aortic aneurysm (AAA): endovascular aneurysm repair (EVAR) and open surgery repair (OSR). Our study aims to elucidate the 30-day mortality rate, reintervention rates, and aneurysm-related mortality in EVAR versus OSR for AAA. We conducted a comprehensive assessment of meta-analyses (n = 34 articles) comparing EVAR and OSR for AAA. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and considered statistical significance at P ≤ 0.05. For the 30-day mortality rate, a pooled odds ratio (pOR) of 0.59 (95% confidence interval [CI] 0.45-0.77, P = 0.0001, and I2 = 98%) indicates that EVAR was associated with a lower risk of mortality compared to OSR. For reintervention rates, a pOR of 1.33 (95% CI = 0.98-1.82, P = 0.11, and I2 = 90%). In aneurysm-related mortality, a pOR of 0.78 (95% CI = 0.63-0.97, P = 0.03, and I2 = 43%). In postoperative rupture of aneurysm, a pOR of 3.28 (95% CI = 2.16-4.98, P < 0.00001, and I2 = 50%). Furthermore, when analyzing systemic complications, only for visceral ischemia, significant results showed lower odds for EVAR, with a pOR of 0.57 (95% CI = 0.40-0.80, P = 0.001, and I2 = 0%) was found. EVAR is better in terms of short-term mortality rate and aneurysm-related mortality. Furthermore, EVAR is still a safer procedure in elective settings, as the studies we included recruited patients for this setting. However, given the high reintervention rates and recent developments in surgical techniques and materials, more recent data and extensive research are needed.
ABSTRACT
Chronic kidney disease (CKD) is a progressive disease and has multiple clinical manifestations; when CKD reaches the end stage, at least one cutaneous manifestation appears due to some increased toxin levels or a constant proinflammatory state. Nonspecific manifestations include pruritus, xerosis, pigmentation disorders, acquired ichthyosis, purpuric spots, and nail disorders. Some specific manifestations are bullous dermatoses, acquired perforating dermatoses (APD), eruptive xanthoma, access site infections, calcifying disorders, and nephrogenic systemic fibrosis (NSF). All these cutaneous changes negatively impact patients; early recognition and diagnosis of these dermatoses will make a difference in their quality of treatment. Exploring a patient's skin is fundamental to suspect some diseases and increased toxin levels; pruritus occurs when uremic toxins are raised, and nail disorders are associated with hypoalbuminemia. This review provides the clinician with information on the clinical manifestations that occur in CKD, including epidemiology, pathophysiology, clinical manifestations, diagnosis, histopathology, treatment, and life impact of the dermatoses in CKD.
ABSTRACT
Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with an increased risk of stroke due to disrupted heart function and potential clot formation. This review examines current management strategies for stroke prevention in AF, focusing on the efficacy, safety, and long-term outcomes of anticoagulation therapies. Anticoagulants, including novel oral anticoagulants (NOACs) and vitamin K antagonists, play a crucial role in reducing stroke risk by preventing clot formation in the heart. Recent studies highlight NOACs as superior alternatives to traditional therapies, offering improved safety profiles and enhanced patient adherence. Despite the risk of bleeding complications, judicious use of anticoagulants significantly improves clinical outcomes in AF patients. The review synthesizes evidence from clinical trials and meta-analyses to underscore the pivotal role of NOACs in transforming stroke prevention strategies in AF. Moreover, it discusses emerging interventions such as left atrial appendage occlusion and emphasizes the importance of personalized, patient-centered care in optimizing treatment decisions for AF patients at risk of stroke.
ABSTRACT
Crohn's disease (CD) presents a formidable challenge as a chronic inflammatory condition. This systematic review aimed to comprehensively assess upadacitinib, a novel Janus kinase (JAK) inhibitor, regarding its efficacy, safety, and mechanistic insights in CD treatment. A thorough search of electronic databases identified studies investigating upadacitinib's impact on CD patients. Study characteristics, efficacy outcomes (clinical remission and endoscopic response), safety profiles, and mechanistic insights were extracted and qualitatively synthesized. Methodological quality was assessed using established tools. The synthesis of three studies consistently demonstrated improvements in clinical remission rates and endoscopic outcomes in upadacitinib-treated patients. Adverse events, such as herpes zoster, intestinal perforation, non-melanoma skin cancer, adjudicated cardiovascular events, and anemia, were reported, necessitating vigilant safety monitoring. Upadacitinib emerges as a promising therapeutic option for CD, supported by its observed clinical benefits and mechanistic implications. However, safety concerns underscore the importance of careful patient selection. These findings contribute to the ongoing discussion surrounding personalized treatment approaches for CD, emphasizing the need for further research to confirm its enduring efficacy and safety.
ABSTRACT
OBJECTIVE: To provide insights into the nature, risk factors, impact and existing measures for reporting and preventing violence in the healthcare system. The under-reporting of violence against healthcare workers (HCWs) globally highlights the need for increased public awareness and education. METHODS: The Violence Study of Healthcare Workers and Systems study used a survey questionnaire created using Research Electronic Data Capture (REDCap) forms and distributed from 6 June to 9 August 2022. Logistic regression analysis evaluated violence predictors, including gender, age, years of experience, institution type, respondent profession and night shift frequency. A χ2 test was performed to determine the association between gender and different violence forms. RESULTS: A total of 5405 responses from 79 countries were analysed. India, the USA and Venezuela were the top three contributors. Female respondents comprised 53%. The majority (45%) fell within the 26-35 age group. Medical students (21%), consultants (20%), residents/fellows (15%) and nurses (10%) constituted highest responders. Nearly 55% HCWs reported firsthand violence experience, and 16% reported violence against their colleagues. Perpetrators were identified as patients or family members in over 50% of cases, while supervisor-incited violence accounted for 16%. Around 80% stated that violence incidence either remained constant or increased during the COVID-19 pandemic. Among HCWs who experienced violence, 55% felt less motivated or more dissatisfied with their jobs afterward, and 25% expressed willingness to quit. Univariate analysis revealed that HCWs aged 26-65 years, nurses, physicians, ancillary staff, those working in public settings, with >1 year of experience, and frequent night shift workers were at significantly higher risk of experiencing violence. These results remained significant in multivariate analysis, except for the 55-65 age group, which lost statistical significance. CONCLUSION: This global cross-sectional study highlights that a majority of HCWs have experienced violence, and the incidence either increased or remained the same during the COVID-19 pandemic. This has resulted in decreased job satisfaction.
Subject(s)
COVID-19 , Physicians , Humans , Female , Adult , Middle Aged , Aged , Cross-Sectional Studies , Pandemics , COVID-19/epidemiology , Health PersonnelABSTRACT
OBJECTIVE: Biologic anti-rheumatic drugs are used with less frequency among older patients compared to young patients. This population is less represented in studies performed to evaluate the efficacy and safety of this drugs. We aimed to assess the efficacy and safety of biological agents between the older RA patients compared to young. METHODS: A comprehensive, systematic search was conducted in major indexing databases using key terms for RA and each biological agent. The review process was completed by 2 investigators. Both randomized controlled trials and observational studies of at least 6-month duration conducted in adult RA patients were included. Outcomes of interest were clinical efficacy and safety. Effect-estimates were pooled using random-effects modeling if 4 or more studies used the same scale and time-frame for measuring outcomes. RESULTS: 24 studies (16 focusing on anti-TNF agents) representing 63,705 patients (24% were older) were included. Older RA patients had worse baseline RA disease activity, longer disease duration at the time of enrollment in the trial (14.4⯱â¯3.6 vs. 10.9⯱â¯3.6 years; pâ¯<â¯0.001) and higher steroid use (73.2 vs. 64.7%, pâ¯<â¯0.001) than younger. 5 out of 6 studies assessing anti-TNF agents showed worse efficacy outcomes in older patients. The pooled OR of infection and ADRs with anti-TNF agents in older compared to young RA patients was OR 1.59 (95% CI: 1.45-1.76) and 1.40 (95% CI: 1.23-1.61) respectively. CONCLUSIONS: Older patients had worse safety and efficacy with biological agents but also had worse baseline disease activity. There was significant heterogeneity in reporting outcomes and very limited studies in biological agents other than anti-TNF drugs.
Subject(s)
Age Factors , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biological Factors/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Aged , Humans , Observational Studies as Topic , Randomized Controlled Trials as Topic , Severity of Illness Index , Treatment OutcomeABSTRACT
Rapamycin is a potent antiproliferative agent that arrests cells in the G1 phase of the cell cycle through a variety of mechanisms involving the inhibition of the mammalian target of rapamycin (mTOR) pathway. The majority of normal cells in culture are sensitive to the cytostatic effects of rapamycin, whereas the growth of many malignant cells and tumors is rapamycin resistant. We had shown previously that hepatic DNA synthesis in the late gestation rat fetus is rapamycin resistant even though signaling through the mTOR/S6 kinase (S6K) pathway is attenuated. On the basis of this finding, we went on to characterize the response to rapamycin in a spectrum of tissues during late gestation and the early postnatal period in the rat. We found that rapamycin had no effect on DNA synthesis in major organs such as heart, intestine, and kidney in the fetal and early postnatal rat despite a marked attenuation in the phosphorylation of ribosomal protein S6. In contrast, the proliferation of mature hepatocytes during liver regeneration was highly sensitive to rapamycin. These data indicate that basal cellular proliferation in a wide variety of tissues is rapamycin resistant and occurs independently of mTOR/S6K signaling. Furthermore, the well-characterized effects of rapamycin in tissue culture systems are not recapitulated in the asynchronous cell proliferation that accompanies normal growth and tissue remodeling.