KRAS as a Prognostic and Predictive Marker in Metastatic Non-Small Cell Lung Carcinoma: A Systematic Review.

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.

Dermatological Manifestations in Patients With Chronic Kidney Disease: A Review.

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.

ViSHWaS: Violence Study of Healthcare Workers and Systems-a global survey.

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.

Upadacitinib in Crohn's Disease: A Comprehensive Systematic Review of Efficacy and Safety.

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.

Efficacy and safety of biological agents in the older rheumatoid arthritis patients compared to Young: A systematic review and meta-analysis.

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; p < 0.001) and higher steroid use (73.2 vs. 64.7%, p < 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.

The effect of rapamycin on DNA synthesis in multiple tissues from late gestation fetal and postnatal rats.

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.