Mutations in homologous recombination (HR) genes predispose to cancer but also sensitize to chemotherapeutics. Although therapy can initially be effective, cancers frequently cease responding, leading to recurrence and poor prognosis. Here we identify a germline mutation in RAD51C, a critical HR factor and known tumor suppressor, in an ovarian cancer patient with exceptionally long, progression-free survival. The RAD51C-T132P mutation is in a highly conserved residue within the nucleotide-binding site and interferes with single-strand DNA binding of the RAD51 paralog complex RAD51B-RAD51C-RAD51D-XRCC2 and association with another RAD51 paralog XRCC3. These biochemical defects lead to highly defective HR and drug sensitivity in tumor cells, ascribing RAD51C-T132P as a deleterious mutation that was likely causal for tumor formation. Conversely, its position within a critical site suggests that it is refractory to secondary mutations that would restore RAD51C gene function and lead to therapy resistance. A need for a greater understanding of the relationship between mutation position and reversion potential of HR genes is underscored, as it may help predict the effectiveness of therapies in patients with HR-deficient cancers.During Switzerland's first wave of COVID-19, clinical pharmacy activities during medical rounds in Geneva University Hospitals were replaced by targeted remote interventions. We describe using the electronic PharmaCheck system to screen high-risk situations of adverse drug events (ADEs), particularly targeting prescriptions of lopinavir/ritonavir (LPVr) and hydroxychloroquine (HCQ) in the presence of contraindications or prescriptions outside institutional guidelines. Of 416 patients receiving LPVr and/or HCQ, 182 alerts were triggered for 164 (39.4%) patients. The main associated risk factors of ADEs were drug-drug interactions, QTc interval prolongation, electrolyte disorder and inadequate LPVr dosage. Therapeutic optimisation recommended by a pharmacist or proposals for additional monitoring were accepted in 80% (n=36) of cases. Combined with pharmacist contextualisation to the clinical context, PharmaCheck made it possible to successfully adapt clinical pharmacist activities by switching from a global to a targeted analysis mode in an emergency context.Hepatotoxicity secondary to exposure of volatile anaesthetics is an exceptional finding, but its clinical interest depends on their frequent use, unpredictable appearance and potential severity. Halothane is the volatile anaesthetic most frequently involved in the development of liver dysfunction, especially after re-exposure. Sevoflurane has rarely been related to this life-threatening complication. We present the case of a 1-year-old girl who had undergone previous surgery for closure of a patent ductus arteriosus, and who developed severe acute hepatitis and died after undergoing surgical repair of an aortic isthmus narrowing by means of general anaesthesia with sevoflurane. https://www.selleckchem.com/products/dir-cy7-dic18.html Other possible causes of liver failure were excluded. This adverse event was classified as serious and was included in the national and European pharmacovigilance network, with the aim of preventing dangerous effects on patient health in clinical practice, by contributing to the enrichment of the literature.
To ensure patient safety and the preparedness of medication processes during hospital relocations and evacuations by using Failure Modes, Effects, and Criticality Analysis (FMECA).
The relocation of six regional hospitals to a single building, resulting in 400 beds being moved, could be compared with an emergency evacuation. An FMECA was performed on the hospital group's internal medicine and intensive care units (IMU and ICU), examining how medication processes would be affected by a hospital relocation or evacuation.
We identified 59 hospital relocation and 68 evacuation failure modes. Failure modes were ranked based on their criticality index (CI; range 1-810). The higher the CI, the greater the patient-related risk. Average initial IMU and ICU hospital relocation CI scores were 160 (range 105-294) and 201 (range 125-343), respectively, subsequently reduced to 32 (-80%) and 49 (-76%) after mitigation measures. Average initial IMU and ICU evacuation CI scores were 319 (range 245-504) and 592 (range 441-810), respectively, subsequently reduced to 194 (-39%) and 282 (-52%). Most mitigation measures (17/22), such as for example checklists, could be implemented in both situations. Due to their unpredictable nature, five measures were specific to evacuation situations.
This study highlights the value of using an FMECA on medication processes to anticipate potential negative impacts on patient safety during hospital relocations or evacuations. Preparation for a hospital relocation can provide useful knowledge and an opportunity to test mitigation measures that might prove useful in evacuations.
This study highlights the value of using an FMECA on medication processes to anticipate potential negative impacts on patient safety during hospital relocations or evacuations. Preparation for a hospital relocation can provide useful knowledge and an opportunity to test mitigation measures that might prove useful in evacuations.
Trigger finger is one of the complications affecting the upper extremity in patients with diabetes. Diabetes is also a well-known risk factor that predisposes individuals to cardiovascular diseases (CVDs). This retrospective cohort study aimed to establish the association between trigger finger and the patients with incident CVD with type 2 diabetes.
Trigger finger was diagnosed by palpating a thickened tendon during flexion or on the manifestation of a locking phenomenon during extension or flexion of either finger. The relationship between trigger finger and other clinical parameters or complications of diabetes was examined by a comparative analysis. Cox regression analysis was used to evaluate the association between trigger finger and incidence of CVD. We calculated the propensity scores using sex, body mass index, age, smoking status, duration of diabetes, estimated glomerular filtration rate, hypertension, dyslipidemia, and hemoglobin A1c as the number of patients with incident CVD during the follow-up period was low.