Notes

Association Between Probably Inappropriate Medicines and 30-Day Post-Hospital Eliminate Results within People Veterans.
The COVID-19 pandemic underscores the need for nephrologists to be competent in serious illness communication skills that include virtual and remote modalities, to be aware of prognostic tools, and to be willing to engage with interdisciplinary teams of palliative care subspecialists, intensivists, and ethicists to facilitate goal-concordant care during crisis settings.
Several nontraditional risk factors have been the focus of research in an attempt to understand the disproportionately high cardiovascular morbidity and mortality in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) populations. One such category of risk factors is cardiovascular autonomic dysfunction. Its true prevalence in the CKD/ESKD population is unknown but existing evidence suggests it is common. Due to lack of standardized diagnostic and treatment options, this condition remains undiagnosed and untreated in many patients. Nintedanib In this review, we discuss current evidence pointing toward the role of autonomic nervous system (ANS) dysfunction in CKD, building off of crucial historical evidence and thereby highlighting the areas in need for future research interest.

There are several key mediators and pathways leading to cardiovascular autonomic dysfunction in CKD and ESKD. We review studies exploring the mechanisms involved and discuss the current measurement tools and indices to evaluate the ANS and their pitfalls. There is a strong line of evidence establishing the temporal sequence of worsening autonomic function and kidney function and vice versa. Evidence linking ANS dysfunction and arrhythmia, sudden cardiac death, intradialytic hypotension, heart failure and hypertension are discussed.

There is a need for early recognition and referral of CKD and ESKD patients suspected of cardiovascular ANS dysfunction to prevent the downstream effects described in this review.There are many unknowns in this area and a clear need for further research.
There is a need for early recognition and referral of CKD and ESKD patients suspected of cardiovascular ANS dysfunction to prevent the downstream effects described in this review.There are many unknowns in this area and a clear need for further research.
BRAF/MEK inhibitor has changed the treatment landscape in patients with advanced and metastatic melanoma with prolonged overall survival and progression-free survival. Since three treatment combinations exist with similar efficacy therapy decisions are often made based on the side effect profile. Additionally, on-target side effects or class effects have to be properly managed to ensure treatment adherence.

Sequential treatment with BRAF/MEK inhibition and immunotherapy might increase toxicity with a sepsis-like syndrome and triple therapy with concomitant BRAF/MEK inhibition and anti-PD1/PD-L1 antibody therapy induces severe side effects in the vast majority of patients.

Toxicity of combination therapy with BRAF/MEK inhibitors is generally manageable, reversible and infrequently associated with treatment discontinuation. In case of persisting off-target effects the change to another combination therapy can resolve side effects.
Toxicity of combination therapy with BRAF/MEK inhibitors is generally manageable, reversible and infrequently associated with treatment discontinuation. In case of persisting off-target effects the change to another combination therapy can resolve side effects.
An early understanding of the role of the Ras/Raf/MEK/ERK signalling pathway in regulating cell proliferation has set the stage for the development of several potent and selective MEK inhibitors (MEKi). MEKi represent promising therapies for RAS-driven neoplasias and RASopathies associated with increased Ras/MAPK activity.

Neurofibromatosis 1 (NF1) is a prototypic RASopathy in which early-phase clinical trials with MEKi have been successful in the treatment of plexiform neurofibromas (pNF) and low-grade gliomas (LGGs). The phase 2 trial (SPRINT) of selumetinib in pNF resulted in at least 20% reduction in the size of pNF from baseline in 71% of patients and was associated with clinically meaningful improvements. On the basis of this trial, selumetinib (Koselugo) received FDA approval for children 2 years of age and older with inoperable, symptomatic pNF. The phase 2 trial of selumetinib in LGG resulted in 40% partial response and 96% of patients had 2 years of progression-free survival.

Given the potential of MEK inhibition as an effective and overall well tolerated medical treatment, the use of targeted agents in the NF1 population is likely to increase considerably. Future work on non-NF1 RASopathies should focus on developing preclinical models and defining endpoints for measurement of efficacy in order to conduct clinical trials.
Given the potential of MEK inhibition as an effective and overall well tolerated medical treatment, the use of targeted agents in the NF1 population is likely to increase considerably. Future work on non-NF1 RASopathies should focus on developing preclinical models and defining endpoints for measurement of efficacy in order to conduct clinical trials.
The COVID-19 pandemic resulted in a statewide stay-at-home (SAH) order in California beginning March 19, 2020, forcing large-scale behavioral changes and taking an emotional and economic toll. The effects of SAH orders on the trauma population remain unknown. We hypothesized an increase in rates of penetrating trauma, gunshot wounds, suicide attempts, and domestic violence in the Southern California trauma population after the SAH order.

A multicenter retrospective analysis of all trauma patients presenting to 11 American College of Surgeons levels I and II trauma centers spanning seven counties in California was performed. Demographic data, injury characteristics, clinical data, and outcomes were collected. Patients were divided into three groups based on injury date before SAH from January 1, 2020, to March 18, 2020 (PRE), after SAH from March 19, 2020, to June 30, 2020 (POST), and a historical control from March 19, 2019, to June 30, 2019 (CONTROL). POST was compared with both PRE and CONTROL in two separate analyses.
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