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Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1st revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the “German Instrument for Methodological Guideline Appraisal” of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

BACKGROUND Antibody-mediated rejection is a leading cause of kidney-transplant failure. The targeting of CD38 to inhibit graft injury caused by alloantibodies and natural killer (NK) cells may be a therapeutic option. METHODS In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with antibody-mediated rejection that had occurred at least 180 days after transplantation to receive nine infusions of the CD38 monoclonal antibody felzartamab (at a dose of 16 mg per kilogram of body weight) or placebo for 6 months, followed by a 6-month observation period. The primary outcome was the safety and side-effect profile of felzartamab. Key secondary outcomes were renal-biopsy results at 24 and 52 weeks, donor-specific antibody levels, peripheral NK-cell counts, and donor-derived cell-free DNA levels. RESULTS A total of 22 patients underwent randomization (11 to receive felzartamab and 11 to receive placebo). The median time from transplantation until trial inclusion was 9 years. Mild or moderate infusion reactions occurred in 8 patients in the felzartamab group. Serious adverse events occurred in 1 patient in the felzartamab group and in 4 patients in the placebo group; graft loss occurred in 1 patient in the placebo group. After week 24, resolution of morphologic antibody-mediated rejection was more frequent with felzartamab (in 9 of 11 patients [82%]) than with placebo (in 2 of 10 patients [20%]), for a difference of 62 percentage points (95% confidence interval [CI], 19 to 100) and a risk ratio of 0.23 (95% confidence interval [CI], 0.06 to 0.83). The median microvascular inflammation score was lower in the felzartamab group than in the placebo group (0 vs. 2.5), for a mean difference of -1.95 (95% CI, -2.97 to -0.92). Also lower was a molecular score reflecting the probability of antibody-mediated rejection (0.17 vs. 0.77) and the level of donorderived cell-free DNA (0.31% vs. 0.82%). At week 52, the recurrence of antibodymediated rejection was reported in 3 of 9 patients who had a response to felzartamab, with an increase in molecular activity and biomarker levels toward baseline levels. CONCLUSIONS Felzartamab had acceptable safety and side-effect profiles in patients with antibodymediated rejection. [ABSTRACT FROM AUTHOR]

Groundwater monitoring to measure a variety of indicator parameters including dissolved gas concentrations, total dissolved gas pressure (TDGP), and redox indicators is commonly used to evaluate the impacts of gas migration (GM) from energy development in shallow aquifer systems. However, these parameters can be challenging to interpret due to complex free‐phase gas source architecture, multicomponent partitioning, and biogeochemical reactions. A series of numerical simulations using a gas flow model and a reactive transport model were conducted to delineate the anticipated evolution of indicator parameters following GM in an aquifer under a variety of physical and biogeochemical conditions. The simulations illustrate how multicomponent mass transfer processes and biogeochemical reactions create unexpected spatial and temporal variations in several analytes. The results indicate that care must be taken when interpreting measured indicator parameters including dissolved hydrocarbon concentrations and TDGP, as the presence of dissolved gases in background groundwater and biogeochemical processes can cause potentially misleading conclusions about the impact of GM. Based on the consideration of multicomponent gas partitioning in this study, it is suggested that dissolved background gases such as N2 and Ar can provide valuable insights on the presence, longevity and fate of free‐phase natural gas in aquifer systems. Overall, these results contribute to developing a better understanding of indicators for GM in groundwater, which will aid the planning of future monitoring networks and subsequent data interpretation. Article impact statement: A modeling study to develop better understanding of groundwater indicators of gas migration from energy development. [ABSTRACT FROM AUTHOR]

Little is known about biopsychosocial factors relating to pre-exposure prophylaxis (PrEP) awareness among people with either heterosexual or injection drug use HIV risk behaviors. Participants engaged in vaginal/anal sex with a person of the opposite sex (N = 515) or were people who injected drugs (PWID; N = 451) in the past 12 months from 2018-2019 in Boston, MA. We examined associations between PrEP awareness and: homelessness; perceived HIV-related stigma; country of birth; bacterial STDs, chlamydia, and/or gonorrhea in the past 12 months, lifetime hepatitis C virus (HCV) infection, sexual orientation, and poverty. More PWID (36.8%) were aware of PrEP than people with heterosexual HIV risk (28%; p =.001). Among people with heterosexual risk, homelessness (aOR = 1.99, p =.003), and among PWID: homelessness (aOR = 2.11, p =.032); bacterial STD (aOR = 2.96, p =.012); chlamydia (aOR = 6.14, p =.008); and HCV (aOR = 2.40, p <.001) were associated with increased likelihood of PrEP awareness. In the combined sample: homelessness (aOR = 2.25, p <.001); HCV (aOR = 2.18, p <.001); identifying as homosexual (aOR = 3.71, p =.036); and bisexual (aOR = 1.55, p =.016) were each associated with PrEP awareness. Although having an STD, HCV, identifying as homosexual or bisexual, and experiencing homelessness were associated with increased PrEP awareness, most participants were unaware of PrEP. Efforts to increase PrEP awareness could engage PWID and heterosexual HIV risk behavior. [ABSTRACT FROM AUTHOR]

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized. [ABSTRACT FROM AUTHOR]

Objectives: To compare vascular scanning parameters (vessel diameter, peak systolic velocity, end-diastolic velocity, and resistive index) and scanning time before and after breathing control training program for selected abdominal vessels. Methods: This study was pre and post quasi-experimental. The researchers designed a breathing training program that gives participants instructions through a video describing breathing maneuvers. Data were collected at the ultrasound laboratory/College of Health and Rehabilitation Sciences in Princess Nourah bint Abdul Rahman University, Riyadh, Saudi Arabia from January 2023 to November 2023. About 49 volunteers at the university participated in the study. Scanning was performed two times for the right renal artery, upper abdominal aorta, inferior vena cava, and superior mesenteric artery. Scanning time was measured before and after the program as well. A paired sample t-test was used to compare the parameters means and time before and after the program. Results: The program had a significant effect on the following parameters: right renal artery peak systolic velocity (p=0.042), upper abdominal aortic peak systolic velocity, and resistive index (p=0.014, p=0.014 respectively), superior mesenteric artery and inferior vena cava diameters (p=0.010 and p=0.020). The scanning time was reduced significantly (p<0.001). Conclusion: The breathing training program saves time and improves ultrasound measurement quality. Hospitals and health centers should consider the importance of breathing control training programs before abdominal scanning. [ABSTRACT FROM AUTHOR]

Predation and habitat deterioration are the main reasons for the strong decline of ground‐nesting farmland birds such as the grey partridge Perdix perdix in Europe. Grey partridge nests and incubating females are especially vulnerable to predation. We have previously demonstrated that predator activity is much lower inside flower blocks (agri‐environment schemes sown with a flower seed mix) than at their edges and that predator activity in flower blocks depends on the surrounding landscape. Here, we investigate whether these differences in predator activity translate into differences in grey partridge nest predation and assess predation patterns relative to landscape and nest site characteristics. We recorded the success of 56 nests of radio‐tagged grey partridges between 2009 and 2017 in an agricultural landscape in Central Germany. We used Bayesian logistic regression to analyse the effects of nest site and landscape characteristics on nest predation on a subset of 46 nests (21 nests successful, 25 predated). Distance to the edge of the nesting habitat was the most important predictor, reducing predation probability from 66.8% at the edge to 18.5% at 85.5 m. Predation probability decreased with increasing length of habitat borders, habitat diversity and the area of permanent grasslands and fallows. Predation probability was higher further from settlements and increased with increasing woodland area in the agricultural matrix. When considering linear landscape structures, nest predation patterns matched the patterns of predator activity from our previous studies. Results suggest that the distance to the edge of the nesting habitat is most important and that nest predation may be reduced by providing sufficiently broad nesting habitats. Nest predation may further be minimized by increasing habitat diversity and coverage of extensive vegetation types and by establishing conservation measures for grey partridges further away from woodlands. These measures may also benefit other ground‐nesting farmland birds. [ABSTRACT FROM AUTHOR]