Biological and therapeutic implications of RKIP in Gastrointestinal Stromal Tumor (GIST): an integrated transcriptomic and proteomic analysis.

BACKGROUND: Gastrointestinal stromal tumors (GIST) represent a significant clinical challenge due to their metastatic potential and limited treatment options. Raf kinase inhibitor protein (RKIP), a suppressor of the MAPK signaling pathway, is downregulated in various cancers and acts as a metastasis suppressor. Our previous studies demonstrated low RKIP expression in GIST and its association with poor outcomes. This study aimed to expand on the previous findings and investigate the biological and therapeutic implications of RKIP loss on GIST. METHODS: To validate the RKIP prognostic significance, its expression was evaluated by immunohistochemistry in 142 bona fide GIST cases. The functional role of RKIP was evaluated in vitro, using the GIST-T1 cell line, which was knocked out for RKIP. The biological and therapeutic implications of RKIP were evaluated by invasion, migration, apoptosis, and 2D / 3D viability assays. Additionally, the transcriptome and proteome of RKIP knockout cells were determined by NanoString and mass spectrometry, respectively. RESULTS: Immunohistochemical analysis revealed the absence of RKIP in 25.3% of GIST cases, correlating with a tendency toward poor prognosis. Functional assays demonstrated that RKIP knockout increased GIST cells' invasion and migration potential by nearly 60%. Moreover, we found that RKIP knockout cells exhibited reduced responsiveness to Imatinib treatment and higher cellular viability in 2D and 3D in vitro models, as assessed by apoptosis-related protein expression. Through comprehensive genetic and proteomic profiling of RKIP knockout cells, we identified several putative RKIP-regulated proteins in GIST, such as COL3A1. CONCLUSIONS: Using a multidimensional integrative analysis, we identified, for the first time in GIST, molecules and pathways modulated by RKIP that may potentially drive metastasis and, consequently, poor prognosis in this disease.

Impact of a training strategy on improving compliance of hand hygiene and gloving during the placement of a short peripheral venous catheter: the multicentre study CleanHand4.

BACKGROUND: Patients who have short peripheral venous catheters (PVC) face an elevated risk of developing bloodstream infections. Preventing catheter-related infections relies on implementing multiple measures, including practicing proper hand hygiene (HH) during catheter placement. METHODS: We conducted a four-part study: (1) an evaluation of HH practices through direct observation of PVC placements, coupled with the study of the microbial flora of the HCWs fingers just before the placement; (2) the development of an educational tool based on the collected observational and microbiological data; (3) the training to the HCWs observed during the first part, using this tool; and (4) the subsequent observation of the trained HCWs to measure the impact of the training on practice improvement. RESULTS: Compliant HH was observed in 23.5% of the 647 HCWs observed during PVC placement before training. The microbiological study revealed fewer pathogens on the fingertips of the HCWs practicing compliant HH compared other HCWs (2.6 vs 11,7%; p = 0.003). The comparison of practices before and after training, assessed among 180 HCWs, showed an increase in the proportion of HCWs performing compliant HH (25.0 vs 63.2%; p < 0.001). CONCLUSIONS: Training HCWs using our educational tool, which combines reminders of best practices and risk factors associated with PVC-related infections, engaging HCWs (presentation of practice evaluation), identifying professionals deviating from best practices (simulation videos), and objectively assessing fingertip contamination (microbiological study), significantly improved compliance with HH gestures and glove usage. We encourage infection control teams to utilize this tool to raise awareness among HCWs responsible for PVC placement about the risk of infection associated inadequate hand hygiene.

Prioritization of ICU beds with renal replacement therapy support by court order and mortality in a Brazilian metropolitan area.

The shortage of intensive care unit (ICU) resources, including equipment and supplies for renal replacement therapy (RRT), is a critical problem in several countries. This study aimed to assess hospital mortality and associated factors in patients treated in public hospitals of the Federal District, Brazil, who requested admission to ICU with renal replacement therapy support (ICU-RRT) in court. Retrospective cohort study that included 883 adult patients treated in public hospitals of the Federal District who requested ICU-RRT admission in court from January 2017 to December 2018. ICU-RRT was denied to 407 patients, which increased mortality (OR 3.33, 95% CI 2.39-4.56, p ≪ 0.01), especially in patients with priority level I/II (OR 1.02, 95% CI 1.01-1.04, p ≪ 0.01). Of the requests made in court, 450 were filed by patients with priority levels III/IV, and 44.7% of these were admitted to ICU-RRT. In admitted patients, priority level III priority level I/II was associated with a low mortality (OR 0.47, 95% CI 0.32-0.69, p < 0.01), and not. The admission of patients classified as priority levels III/IV to ICU-RRT considerably jeopardized the admission of patients with priority levels I/II to these settings. The results found open new avenues for organizing public policies and improving ICU-RRT triage.

Intensive Care Unit prioritization: The impact of ICU bed availability on mortality in critically ill patients who requested ICU admission in court in a Brazilian cohort.

PURPOSE: To assess hospital mortality in patients who requested ICU admission in court due to the scarcity of ICU beds in the Brazilian public health system and the consequences of these judicial litigations. MATERIAL AND METHODS: Retrospective cohort study that included adult patients from the public health system of the Federal District, Brazil, who claimed ICU admission in court from January 2017 to December 2019. RESULTS: Of the 1752 patients, 1031 were admitted to ICU (58.8%). Hospital mortality was 61.1% (1071/1752). Of the requests, 768 (43.8%) were made by patients with priority levels III or IV, resulting in the ICU admission of 33.9% of these patients. Denial of ICU admission (p < 0.001) increased mortality. ICU admission reduced hospital mortality in patients classified as priority level I (p < 0.001), priority level II (p < 0.001), and priority level III (p < 0.001), but not as priority level IV (p = 0.619). CONCLUSION: A large proportion of patients was denied ICU admission and it was associated with an increased mortality. A considerable portion of the ICU-admitted patients were classified as priority level III and IV, impairing the ICU admission of patients with priority level I which are the ones with the greatest benefit from it.

Paraneoplastic pemphigus associated with chronic lymphocytic leukemia: a case report.

BACKGROUND: Paraneoplastic pemphigus is a rare multiorgan disease of autoimmune causes, usually triggered by neoplasias, mainly of lymphoproliferative origin, such as leukemia and lymphoma. This disorder is categorized by the presence of autoantibodies that react against proteins, such as desmoplakins, desmogleins, desmocollins, and others that exist in cellular junctions. Paraneoplastic pemphigus can manifest clinically in a variety of ways, ranging from mucositis to lesions involving the skin and pulmonary changes. The diagnosis depends on the correlation between the clinical and histopathologic evaluations. Currently, the treatment of this disease is still very difficult and ineffective. The prognosis is poor, and the mortality rate is very high. CASE PRESENTATION: We report a case of a Caucasian patient who had chronic lymphocytic leukemia and developed paraneoplastic pemphigus with severe impairment of skin and mucosa. The initial diagnostic hypothesis was Stevens-Johnson syndrome. The histopathological examination of the skin biopsy was compatible with paraneoplastic pemphigus, and the definitive diagnosis was made on the basis of clinical-pathological correlation. CONCLUSIONS: With the presence of multiorgan lesions in patients with lymphoproliferative neoplasia, paraneoplastic pemphigus should always be considered among the possible diagnostic hypotheses, because diagnosis and early treatment may allow a better prognosis for the patient.