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Objective There is increasing evidence that multisystem morbidity in patients with Cushing's disease (CD) is only partially reversible following treatment. We investigated complications from multiple organs in hospitalized patients with CD compared to patients with nonfunctioning pituitary adenoma (NFPA) after pituitary surgery. Design Population-based retrospective cohort study using data from the Swiss Federal Statistical Office between January 2012 and December 2021. Methods Through 1:5 propensity score matching, we compared hospitalized patients undergoing pituitary surgery for CD or NFPA, addressing demographic differences. The primary composite endpoint included all-cause mortality, major adverse cardiac events (ie, myocardial infarction, unstable angina, heart failure, cardiac arrest, and ischemic stroke), hospitalization for psychiatric disorders, sepsis, severe thromboembolic events, and fractures in need of hospitalization. Secondary endpoints comprised individual components of the primary endpoint and surgical reintervention due to disease persistence or recurrence. Results After matching, 116 patients with CD (mean age 45.4 years [SD, 14.4], 75.0% female) and 396 with NFPA (47.3 years [14.3], 69.7% female) were included and followed for a median time of 50.0 months (IQR 23.5, 82.0) after pituitary surgery. Cushing's disease presence was associated with a higher incidence rate of the primary endpoint (40.6 vs 15.7 events per 1000 person-years, hazard ratio [HR] 2.75; 95% CI, 1.54-4.90). Cushing's disease patients also showed increased hospitalization rates for psychiatric disorders (HR 3.27; 95% CI, 1.59-6.71) and a trend for sepsis (HR 3.15; 95% CI,.95-10.40). Conclusions Even after pituitary surgery, CD patients faced a higher hazard of complications, especially psychiatric hospitalizations and sepsis. [ABSTRACT FROM AUTHOR]

Background: Serum albumin concentrations are frequently used to monitor nutritional therapy in the hospital setting but supporting studies are largely lacking. Within this secondary analysis of a randomized nutritional trial (EFFORT), we assessed whether nutritional support affects short-term changes in serum albumin concentrations and whether an increase in albumin concentration has prognostic implications regarding clinical outcome and response to treatment. Methods: We analyzed patients with available serum albumin concentrations at baseline and day 7 included in EFFORT, a Swiss-wide multicenter randomized clinical trial that compared individualized nutritional therapy with usual hospital food (control group). Results: Albumin concentrations increased in 320 of 763 (41.9%) included patients (mean age 73.3 years (SD ± 12.9), 53.6% males) with no difference between patients receiving nutritional support and controls. Compared with patients that showed a decrease in albumin concentrations over 7 days, those with an increase had a lower 180-day mortality [74/320 (23.1%) vs. 158/443 (35.7%); adjusted odds ratio 0.63, 95% CI 0.44 to 0.90; p = 0.012] and a shorter length of hospital stay [11.2 ± 7.3 vs. 8.8 ± 5.6 days, adjusted difference −2.2 days (95%CI −3.1 to −1.2)]. Patients with and without a decrease over 7 days had a similar response to nutritional support. Conclusion: Results from this secondary analysis indicate that nutritional support did not increase short-term concentrations of albumin over 7 days, and changes in albumin did not correlate with response to nutritional interventions. However, an increase in albumin concentrations possibly mirroring resolution of inflammation was associated with better clinical outcomes. Repeated in-hospital albumin measurements in the short-term is, thus, not indicated for monitoring of patients receiving nutritional support but provides prognostic information. Trail Registration: ClinicalTrials.gov Identifier: NCT02517476. [ABSTRACT FROM AUTHOR]

Context: During illness, deiodination of thyroxine (T4) to triiodothyronine (T3) is downregulated. This is called "low T3 syndrome", an adaptive metabolic mechanism to reduce energy expenditure and prevent catabolism. Objective: We aimed to investigate the prognostic role of low T3 syndrome in patients at nutritional risk regarding mortality, clinical outcomes, and response to nutritional support. Methods: This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled, Swiss, multicenter trial comparing effects of individualized nutritional support with usual care in adult medical inpatients at nutritional risk. The primary endpoint was all-cause mortality over 30, 180 days, and 5 years. Results: We had complete data including fT3 concentration of 801/2028 (39.5%) patients from the initial trial. Of these 492 (61.4%) had low T3 syndrome (fT3<3.2 pmol/L). Low T3 syndrome was associated with higher mortality over 30 days (adjusted hazard ratio 1.97, 95% CI 1.17-3.31, P = .011) and other adverse clinical outcomes. Nutritional support only lowered mortality in the group of patients with low T3 syndrome but not in those without low T3 syndrome (adjusted odds ratio of nutritional support of 0.82 [95% CI 0.47-1.41] vs 1.47 [95% CI 0.55-3.94]). This finding, however, was not significant in interaction analysis (P for interaction= .401). Conclusion: Our secondary analysis of a randomized trial suggests that medical inpatients at nutritional risk with low T3 syndrome have a substantial increase in mortality and may show a more pronounced beneficial response to nutritional support interventions. [ABSTRACT FROM AUTHOR]

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A balanced diet has the goal of providing adequate amounts of different nutrients to promote and maintain physical and psychological health. Our aim was to study the association between different sociodemographic, socioeconomic and lifestyle factors and low energy or protein intake among the Swiss population. This is a cross-sectional cohort study based on the national nutritional survey "MenuCH", which is the first representative, detailed assessment of dietary habits in the adult Swiss population conducted in 2014/2015. We compared the mean protein and caloric intake based on two 24 h recall nutritional assessments with current recommendations based on resting metabolic rate calculation and DACH guidelines. A total of 1919 participants with a median age of 46 years and 53% females were included. Overall, 10.9% and 20.2% of participants had an energy and protein intake, respectively, below the dietary reference values. However, a high income (>9000 CHF per month) reduced the risk of low energy intake (OR 0.49 [0.26–0.94], p = 0.032), obesity (OR 6.55 [3.77–11.38], p < 0.01), and living in a household with children (OR 2.1 [1.15–3.85], p = 0.016) was associated with higher risk. Regarding low protein intake, the most important risk factors were an age group of 65–75 years (OR 2.94 [1.57–5.52], p = 0.001) and female gender (OR 1.73 [1.15–2.6], p = 0.008). Regular meat consumption reduced the risk of low protein intake (OR of 0.23 (0.1–0.53), p = 0.001). Within this survey, several socio-economic and lifestyle factors were associated with low energy and protein intake in the healthy Swiss population. A bunderstanding of these factors may help to reduce the risk of malnutrition. [ABSTRACT FROM AUTHOR]

Background: Because of the shorter half‐life as compared with albumin, serum prealbumin concentrations have been proposed to be useful nutrition biomarkers for the assessment of patients at nutrition risk. In a post hoc analysis of patients at nutrition risk from a randomized controlled nutrition trial, we tested the hypothesis that (1) prealbumin is associated with higher all‐cause 180‐day mortality rates and that (2) individualized nutrition support compared with usual‐care nutrition more effectively improves survival at 30 days in patients with low prealbumin levels compared with patients with normal prealbumin levels. Methods: We performed a prespecified cohort study in patients included in the pragmatic, Swiss, multicenter randomized controlled EFFORT trial comparing the effects of individualized nutrition support with usual care. We studied low prealbumin concentrations (<0.17 g/L) in a subgroup of 517 patients from one participating center. Results: A total of 306 (59.2%) patients (mean age 71.9 years, 53.6% men) had low admission prealbumin levels (<0.17 g/L). There was a significant association between low prealbumin levels and mortality at 180 days (115/306 [37.6%] vs 47/211 [22.3%], fully adjusted hazard ratio [HR]=1.59, 95% CI 1.11–2.28; P = 0.011). Prealbumin levels significantly improved the prognostic value of the Nutritional Risk Screening total score regarding mortality prediction at short‐ and long‐term. The difference in mortality between patients receiving individualized nutrition support and usual‐care nutrition was similar for patients with low prealbumin levels compared with patients with normal prealbumin levels (HR=0.90 [95% CI=0.51–1.59] vs HR=0.88 [95% CI=0.35–2.23]) with no evidence for interaction (P = 0.823). Conclusion: Among medical inpatients at nutrition risk, low admission prealbumin levels correlated with different nutrition markers and higher mortality risk, but patients with low or high prealbumin levels had a similar benefit from nutrition support. Further studies should identify nutrition markers that help further personalize nutrition interventions. [ABSTRACT FROM AUTHOR]

CT-derived measures of muscle mass may help to identify patients with sarcopenia. We investigated the prognostic significance of CT-derived sarcopenia and muscle attenuation with nutritional markers, clinical outcomes and response to nutritional support in medical in-patients at nutritional risk. Within this secondary analysis of the randomized-controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) comparing individualized nutritional support with usual care nutrition in medical inpatients, we investigated associations of CT-based sarcopenia and muscle attenuation at the level L3 with different nutritional and clinical outcomes, and the response to the nutritional intervention. The primary composite endpoint was adverse clinical outcome within 30 days of hospital admission. We included 573 of 2028 EFFORT patients with available CT scans, of which 68.4% met the CT-based definition of sarcopenia and 72.9% had low muscle attenuation. In multivariate analysis, low skeletal muscle index was associated with higher nutritional risk (coefficient per NRS class −0.94 (95%CI −1.87 to −0.01) p = 0.049) and higher risk for adverse clinical outcomes (adjusted odds ratio 1.59 (95% CI 1.06 to 2.38), p = 0.024). Low muscle attenuation was also associated with adverse clinical outcome (adjusted odds ratio 1.67 (95%CI 1.08 to 2.58), p = 0.02). Nutritional support tended to be more effective in reducing mortality in non-sarcopenic patients compared to patients with CT-based sarcopenia (p for interaction 0.058). Within a population of medical patients at nutritional risk, CT-based sarcopenia and muscle attenuation were associated with several nutritional parameters and predicted adverse clinical outcomes. Information from CT scans, thus may help to better characterize these patients, and may be helpful in guiding therapeutic interventions. [ABSTRACT FROM AUTHOR]

In patients with malnutrition there is an increased long-term risk for mortality beyond the preciding hospital stay. We investigated the effects of postdischarge nutritional support in the outpatient setting on all-cause mortality in the populaton of malnourished medical patients in a systematic review of randomized controlled trials. We searched MEDLINE and EMBASE, from inception to December 21, 2022. Randomized-controlled trials investigating nutritional support in medical patients following hospital discharge vs. control group (usual care, placebo and no nutritional support) were included. Data were independently extracted by two authors and were pooled using random effects model. Our primary outcome was all cause-mortality up to 12-months (end of intervention) of hospital discharge. We included 14 randomized-controlled trials with a total of 2438 participants and mostly moderate trial quality. Compared to the control group, patients receiving outpatient nutritional support had lower mortality (13 trials, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.48 to 0.84, p = 0.001, I2 = 1%). Nutritional support was also associated with a significant increase in the mean daily intake of energy (568 kcal, 95% CI 24 to 1,113, p = 0.04), proteins (24 g, 95% CI 7 to 41), p = 0.005) and body weight (1.1 kg, 95% CI 0.6 to 1.7), p < 0.001). No differences were found on hospital readmissions and handgrip strength. This meta-analysis of randomized-controlled trials with mostly moderate trial quality suggests that nutritional support in the outpatient setting significantly increases nutritional intake as well as body weight, and importantly improves survival. Further large-scale and high-quality intervention trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Cancer-related malnutrition is a prevalent condition associated with a loss of muscle mass and impaired functional status, leading to immunodeficiency, impaired quality of life and adverse clinical outcomes. Handgrip strength (HGS) is a practical measure to assess muscle strength in individual patients during clinical practice. However, HGS reference values refer to populations of healthy people, and population-specific values, such as those in the population of cancer patients, still need to be defined. Methods: Within a secondary analysis of a previous randomized controlled nutritional trial focusing on hospitalized cancer patients at risk for malnutrition, we investigated sex-specific HGS values stratified by age and tumor entity. Additionally, we examined the association between HGS and 180-day all-cause mortality. Results: We included data from 628 cancer patients, which were collected from eight hospitals in Switzerland. Depending on the age of patients, HGS varied among female patients from 7 kg to 26 kg and among male patients from 20.5 kg to 44 kg. An incremental decrease in handgrip strength by 10 kg resulted in a 50% increase in 180-day all-cause mortality (odds ratio 1.52 (95%CI 1.19 to 1.94), p = 0.001). Conclusion: Our data provide evidence of the prognostic implications of HGS measurement in cancer patients and validate the prognostic value of handgrip strength in regard to long-term mortality. In addition, our results provide expected HGS values in the population of hospitalized malnourished cancer patients, which may allow better interpretation of values in individual patients. [ABSTRACT FROM AUTHOR]

The Global Leadership Initiative on Malnutrition (GLIM) recently suggested specific criteria to standardize the diagnosis of malnutrition. There is need for validation of these criteria regarding response to nutrition treatment. Our aim was to validate modified GLIM (mGLIM) criteria among medical inpatients at risk of disease related malnutrition for prediction of outcome and response to nutritional therapy. This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicenter randomized controlled trial conducted between April 2014 and February 2018. Adult medical inpatients at nutritional risk (Nutrition Risk Score 2002 ≥ 3 points) were randomly assigned to receive nutritional therapy according to an algorithm based on individualized nutritional requirements (intervention group) or standard hospital food (control group). We included all participants with available information regarding mGLIM criteria. The primary outcome was adverse clinical outcome, which was a composite of 30-day all-cause mortality, ICU-admission, rehospitalization rate, major complications and decline in functional status. Of 1917 eligible participants at nutritional risk, 1181 (61.6%) met the diagnosis of malnutrition based on mGLIM criteria. The incidence of adverse clinical outcome was significantly higher in mGLIM-positive participants compared with mGLIM-negative participants [330/1181 (27.9%) versus 140/736 (19.0%); multivariable adjusted odds ratio [OR] 1.53; 95% CI 1.22–1.93; p < 0.001]. Regarding the effect of nutritional therapy, the reduction in adverse clinical outcomes was higher in mGLIM-positive participants [180/581 (31.0%) vs. 150/600 (25.0%), OR 0.69; 95% CI 0.53–0.9, p = 0.007], compared with mGLIM-negative participants [75/379 (19.8%) versus 65/357 (18.2%), OR 0.95; 95% CI 0.65–1.40, p = 0.797], a finding that was, however, not significant in interaction analysis (p for interaction = 0.217). Data from this secondary analysis of a multicenter randomized trial involving medical inpatients at nutritional risk validate the strong prognostic value of mGLIM criteria regarding adverse clinical outcomes and other long-term outcomes. However, further research is needed to improve the ability of GLIM criteria to predict therapeutic response to nutritional interventions. ClinicalTrials.gov Identifier: NCT02517476. [ABSTRACT FROM AUTHOR]

Unlike classical voltage-gated sodium (NaV) channels, NaX has been characterized as a voltage-insensitive, tetrodotoxin-resistant, sodium (Na+)-activated channel involved in regulating Na+ homeostasis. However, NaX remains refractory to functional characterization in traditional heterologous systems. Here, to gain insight into its atypical physiology, we determine structures of the human NaX channel in complex with the auxiliary β3-subunit. NaX reveals structural alterations within the selectivity filter, voltage sensor-like domains, and pore module. We do not identify an extracellular Na+-sensor or any evidence for a Na+-based activation mechanism in NaX. Instead, the S6-gate remains closed, membrane lipids fill the central cavity, and the domain III-IV linker restricts S6-dilation. We use protein engineering to identify three pore-wetting mutations targeting the hydrophobic S6-gate that unlock a robust voltage-insensitive leak conductance. This constitutively active NaX-QTT channel construct is non-selective among monovalent cations, inhibited by extracellular calcium, and sensitive to classical NaV channel blockers, including tetrodotoxin. Our findings highlight a functional diversity across the NaV channel scaffold, reshape our understanding of NaX physiology, and provide a template to demystify recalcitrant ion channels. NaX is an atypical member of the voltage-gated sodium channel family that may contribute to Na+ homeostasis. Here, the authors describe the structural and functional attributes of the human NaX channel to reveal new insights into its physiology. [ABSTRACT FROM AUTHOR]

Although automated patch clamp (APC) devices have been around for many years and have become an integral part of many aspects of drug discovery, high throughput instruments with gigaohm seal data quality are relatively new. Experiments where a large number of compounds are screened against ion channels are ideally suited to high throughput APC, particularly when the amount of compound available is low. Here we evaluate different APC approaches using a variety of ion channels and screening settings. We have performed a screen of 1920 compounds on GluN1/GluN2A NMDA receptors for negative allosteric modulation using both the SyncroPatch 384 and FLIPR. Additionally, we tested the effect of 36 arthropod venoms on NaV1.9 using a single 384-well plate on the SyncroPatch 384. As an example for mutant screening, a range of acid-sensing ion channel variants were tested and the success rate increased through fluorescence-activated cell sorting (FACS) prior to APC experiments. Gigaohm seal data quality makes the 384-format accessible to recording of primary and stem cell-derived cells on the SyncroPatch 384. We show recordings in voltage and current clamp modes of stemcell-derived cardiomyocytes. In addition, the option of intracellular solution exchange enabled investigations into the effects of intracellular Ca2+ and cAMP on TRPC5 and HCN2 currents, respectively. Together, these data highlight the broad applicability and versatility of APC platforms and also outlines some limitations of the approach. [ABSTRACT FROM AUTHOR]

Incorporation of noncanonical amino acids (ncAAs) can endow proteins with novel functionalities, such as crosslinking or fluorescence. In ion channels, the function of these variants can be studied with great precision using standard electrophysiology, but this approach is typically labor intensive and low throughput. Here, we establish a high-throughput protocol to conduct functional and pharmacological investigations of ncAA-containing human acid-sensing ion channel 1a (hASIC1a) variants in transiently transfected mammalian cells. We introduce 3 different photocrosslinking ncAAs into 103 positions and assess the function of the resulting 309 variants with automated patch clamp (APC). We demonstrate that the approach is efficient and versatile, as it is amenable to assessing even complex pharmacological modulation by peptides. The data show that the acidic pocket is a major determinant for current decay, and live-cell crosslinking provides insight into the hASIC1a–psalmotoxin 1 (PcTx1) interaction. Further, we provide evidence that the protocol can be applied to other ion channels, such as P2X2 and GluA2 receptors. We therefore anticipate the approach to enable future APC-based studies of ncAA-containing ion channels in mammalian cells. This study describes a method to rapidly screen hundreds of ion channel variants containing non-canonical amino acids. A proof-of-principle introducing photocrosslinking non-canonical amino acids into the human ion channel hASIC1a shows how this approach can provide insights into function and pharmacology. [ABSTRACT FROM AUTHOR]

Background Disease-related malnutrition is associated with loss of muscle mass and impaired functional status. Handgrip strength (HGS) has been proposed as an easy-to-use tool to assess muscle strength in clinical practice. Objectives We investigated the prognostic implications of HGS in patients at nutritional risk with regard to clinical outcomes and response to nutritional support. Methods This was a secondary analysis of the randomized controlled, multicenter, Effect of Early Nutritional Support on Frailty, Functional Outcome, and Recovery of Malnourished Medical Inpatients Trial, which compared the effects of individualized nutritional support with usual hospital food in medical inpatients at nutritional risk. Our primary endpoint was 30-d all-cause mortality. The association between sex-specific HGS and clinical outcomes was investigated using multivariable regression analyses, adjusted for randomization, age, weight, height, nutritional risk, admission diagnosis, comorbidities, interaction terms, and study center. We used interaction terms to investigate possible effect modification regarding the nutritional support intervention. Results Mean ± SD HGS in the 1809 patients with available handgrip measurement was 17.0 ± 7.1 kg for females and 28.9 ± 11.3 kg for males. Each decrease of 10 kg in HGS was associated with increased risk of 30-d mortality (female: adjusted OR: 2.11; 95% CI: 1.23, 3.62, P  = 0.007; male: adjusted OR: 1.44; 95% CI: 1.07, 1.93, P  = 0.015) and 180-d mortality (female: adjusted OR: 1.45; 95% CI: 1.0, 2.10, P  = 0.048; male: adjusted OR: 1.55; 95% CI: 1.28, 1.89, P  < 0.001). Individualized nutritional support was most effective in reducing mortality in patients with low HGS (adjusted OR: 0.29; 95% CI: 0.10, 0.82 in patients in the ≤10th percentile compared with OR: 0.98; 95% CI: 0.66, 1.48 in patients in the >10th percentile; P for interaction = 0.026). Conclusions In medical inpatients at nutritional risk, HGS provided significant prognostic information about expected mortality and complication risks and helps to identify which patients benefit most from nutritional support. HGS may thus improve individualization of nutritional therapy. This trial was registered at clinicaltrials.gov as NCT02517476. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) are at substantial risk of malnutrition, which negatively affects clinical outcomes. We investigated the association of kidney function assessed at hospital admission and effectiveness of nutritional support in hospitalized medical patients at risk of malnutrition. This is a secondary analysis of an investigator-initiated, randomized-controlled, Swiss multicenter trial (EFFORT) that compared individualised nutritional support with usual hospital food on clinical outcomes. We compared effects of nutritional support on mortality in subgroups of patients stratified according to kidney function at the time of hospital admission (estimated glomerular filtration rates [eGFR] <15, 15–29, 30–59, 60–89 and ≥ 90 ml/min/1.73 m2). We included 1943 of 2028 patients (96%) from the original trial with known admission creatinine levels. Admission eGFR was a strong predictor for the beneficial effects of nutritional support in regard to lowering of 30-day mortality. Patients with an eGFR <15, 15–29 and 30–59 had the strongest mortality benefit (odds ratios [95%CI] of 0.24 [0.05 to 1.25], 0.37 [0.14 to 0.95] and 0.39 [0.21 to 0.75], respectively), while patients with less severe impairment in kidney function had a less pronounced mortality benefits (p for interaction 0.001). A similar stepwise association of kidney function and response to nutritional support was found also for other secondary outcomes. In medical inpatients at nutritional risk, admission kidney function was a strong predictor for the response to nutritional therapy. Initial kidney function may help to individualize nutritional support in the future by identification of patients with most clinical benefit. Registered under ClinicalTrials.gov Identifier no. NCT02517476. [ABSTRACT FROM AUTHOR]

The nutritional risk screening (NRS 2002) is a validated screening tool for malnutrition. This study aims to investigate the prognostic value of the NRS 2002 and its individual components regarding long-term mortality and adverse outcomes in a well-characterized cohort of medical inpatients. We performed a 5-year follow-up investigation of patients included in the investigator-initiated, prospective, randomized controlled multicenter EFFORT trial that evaluated the effects of individualized nutritional intervention vs. standard hospital food. We used multivariable cox regression analyses adjusted for randomisation arm, study centre, comorbidities and main admission diagnosis to investigate associations between NRS 2002 total scores at time of hospital admission and several long-term outcomes. We had confirmed mortality data over the mean follow-up time of 3.2 years in 1874 from the initial cohort of 2028 EFFORT patients. Mortality showed a step-wise increase in patients with NRS 3 (289/565 [51.2%]) and NRS 4 (355/717 [49.6%]) to 59.5% (353/593) in patient with NRS≥5 corresponding to an adjusted Hazard Ratio (HR) of 1.28 (95%CI 1.15 to 1.42, p ≤ 0.001) for mortality after one year and 1.13 (95%CI 1.05 to 1.23, p = 0.002) for the overall time period. All individual components of NRS including disease severity, food intake, weight loss and BMI provided prognostic information regarding long-term mortality risk. Nutritional risk mirrored by a NRS 2002 total score is a strong and independent predictor of long-term mortality and morbidity in polymorbid medical inpatients particularly in patients with high nutritional risk with an NRS ≥5 points. [ABSTRACT FROM AUTHOR]

In polymorbid patients with bronchopulmonary infection, malnutrition is an independent risk factor for mortality. There is a lack of interventional data investigating whether providing nutritional support during the hospital stay in patients at risk for malnutrition presenting with lower respiratory tract infection lowers mortality. For this secondary analysis of a randomized clinical trial (EFFORT), we analyzed data of a subgroup of patients with confirmed lower respiratory tract infection from an initial cohort of 2028 patients. Patients at nutritional risk (Nutritional Risk Screening [NRS] score ≥3 points) were randomized to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). The primary endpoint of this analysis was all-cause 30-day mortality. We included 378 of 2028 EFFORT patients (mean age 74.4 years, 24% with COPD) into this analysis. Compared to usual care hospital nutrition, individualized nutritional support to reach caloric and protein goals showed a similar beneficial effect of on the risk of mortality in the subgroup of respiratory tract infection patients as compared to the main EFFORT trial (odds ratio 0.47 [95%CI 0.17 to 1.27, p = 0.136] vs 0.65 [95%CI 0.47 to 0.91, p = 0.011]) with no evidence of a subgroup effect (p for interaction 0.859). Effects were also similar among different subgroups based on etiology and type of respiratory tract infection and for other secondary endpoints. This subgroup analysis from a large nutrition support trial suggests that patients at nutritional risk as assessed by NRS 2002 presenting with bronchopulmonary infection to the hospital likely have a mortality benefit from individualized inhospital nutritional support. The small sample size and limited statistical power calls for larger nutritional studies focusing on this highly vulnerable patient population. Registered under ClinicalTrials.gov Identifier no. NCT02517476. [ABSTRACT FROM AUTHOR]

Among medical inpatients at risk of malnutrition, the use of individualized nutritional support during the hospital stay was found to reduce complications and improve mortality at short-term. We evaluated clinical outcomes at 6-months follow-up. We randomly assigned 2028 patients to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or hospital food as usual (control group) during the hospital stay. The intervention was discontinued at hospital discharge and further nutritional support was based on the discretion of the treating team. We had complete follow-up information of 1995 patients (98%), which were included in the final analysis. The primary endpoint was all-cause mortality at 6-months. Prespecified secondary end points included non-elective hospital readmissions, functional outcome and quality of life. At 6-month, 231 of 994 (23.2%) intervention group patients had died compared to 246 of 999 (24.6%) control group patients, resulting in a hazard ratio for death of 0.90 (95%CI 0.76 to 1.08, p = 0.277). Compared to control patients, intervention group patients had similar rates of hospital readmission (27.3% vs. 27.6%, HR 1.00 (95%CI 0.84 to 1.18), p = 0.974), falls (11.2% vs. 10.9%, HR 0.96 (95%CI 0.72 to 1.27), p = 0.773) and similar quality of life and activities of daily living scores. While individualized nutritional support during the hospital stay significantly reduced short-term mortality, there was no legacy effect on longer term outcomes. Future trials should investigate whether continuation of nutritional support after hospital discharge reduces the high malnutrition-associated mortality rates in this vulnerable patient population. ClinicalTrials.gov number, NCT02517476. [ABSTRACT FROM AUTHOR]

Evidence-based medicine is the art of combining "best external evidence", "clinical judgement" and "patient values" for improved daily clinical decision making and is the ultimate goal in modern medicine. Historically, in the field of medical nutrition, there had been a lack of strong evidence from large and high-quality trials resulting in often weak guideline recommendations and therefore insufficient implementation in clinical practice. Particularly in the field of malnutrition, the medical community has long struggled to find evidence-based approaches for effective management by means of screening, assessment and treatment of patients. With recent trials showing that individual medical nutrition therapy has strong effects on clinical outcomes, we should now aim to practice "evidence-based medical nutrition" (EBMN) by combining clinical judgement (e.g., thorough clinical assessment of the malnourished patient), patient preferences (e.g., integration of perspectives of patients and relatives, consideration of comorbidities to define specific energy/protein goals and appropriate route of medical nutrition therapy) and the most current scientific evidence (e.g., trial-supported use of nutritional interventions for individual patients). Such an approach may certainly be helpful to improve clinical outcomes of the vulnerable population of malnourished medical inpatients. [ABSTRACT FROM AUTHOR]

The Nutritional Risk Screening 2002 (NRS 2002) identifies patients at risk of malnutrition. We studied the prognostic implications of this score with regard to short-term and long-term clinical outcomes in a well-characterised cohort of medical inpatients from a previous trial. This is a secondary analysis of an investigator-initiated, prospective randomised controlled multicenter trial in Switzerland (EFFORT) that compared the effects of an individualised nutritional support intervention with standard of care. We investigated associations between admission NRS and several short-term and long-term outcomes using multivariable regression analyses. Of the 2028 patients, 31% had an NRS of 3, 38% of 4 and 31% of ≥5 points, and 477 (24%) died during the 180 days of follow-up. For each point increase in NRS, we found a stepwise increase in risk of 30-day mortality (adjusted Hazard Ratio (HR) 1.22 (95% CI 1.00 to 1.48), p = 0.048) and 180-day mortality (adjusted HR 1.37 (95% CI 1.22 to 1.55), p < 0.001). NRS was associated with length of hospital stay (adjusted difference of 0.60 days per NRS point increase, 95%CI 0.23 to 0.97, p = 0.002) and functional outcomes at 180 days (adjusted decrease in Barthel index of −4.49 points per NRS point increase, 95%CI -6.54 to −2.45, p < 0.001). In a subgroup analysis, associations of NRS and short-term adverse outcomes were less pronounced in patients receiving nutritional support (intervention group) compared to control group patients (adjusted HR for 30-day mortality 1.12 [95%CI 0.83 to 1.52, p = 0.454] vs. 1.33 [95%CI 1.02 to 1.72, p = 0.032]). The NRS is a strong and independent risk score for malnutrition-associated mortality and adverse outcomes over 180 days. Our data provide strong evidence that the nutritional risk, however, is modifiable and can be reduced by the provision of adequate nutritional support. [ABSTRACT FROM AUTHOR]

Retinoic acid-loading of the major birch pollen allergen Bet v 1 may improve specific allergen immunotherapy: In silico, in vitro and in vivo data in BALB/c mice Even if this was not due to altered endolysosomal stability of Bet v 1a due to RA binding (Figure S3), it seemed so far like RA-loading transforms the hyperallergen Bet v 1a to a hypoallergen with improved tolerogenic capacity of potential implications for allergen immunotherapy. Mice were first made allergic against the major birch pollen allergen Bet v 1a and subsequently treated intranasally with either the I apo i -Bet v 1a, or with the RA-loaded I holo i -Bet v 1a, or as a control with RA alone. [Extracted from the article]

The ventrolateral thalamic nucleus (VL), as part of the 'motor thalamus', is main relay station of cerebellar and pallidal projections. It comprises anterior (VLa) and posterior (VLpd and VLpv) subnuclei. Though the fibre architecture of cerebellar and pallidal projections to of the VL nucleus has already been focus in a numerous amount of in vitro studies mainly in animals, probabilistic tractography now offers the possibility of an in vivo comparison in healthy humans. In this study we performed a (a) qualitative and (b) quantitative examination of VL-cerebellar and VL-pallidal pathways and compared the probability distributions between both projection fields in the VL after an (I) atlas-based and (II) manual-based segmentation procedure. Both procedures led to high congruent results of cerebellar and pallidal connectivity distributions: the maximum of pallidal projections was located in anterior and medial parts of the VL nucleus, whereas cerebellar connectivity was more located in lateral and posterior parts. The median connectivity for cerebellar connections in both approaches (manual and atlas-based segmentation) was VLa > VLpv > VLpd, whereas the pallidal median connectivity was VLa ~ VLpv > VLpd in the atlas-based approach and VLpv > VLa > VLpd in the manual approach. [ABSTRACT FROM AUTHOR]

Various nutritional therapies have been proposed in rheumatoid arthritis, particularly diets rich in ω-3 fatty acids, which may lead to eicosanoid reduction. Our aim was to investigate the effect of potentially anti-inflammatory diets (Mediterranean, vegetarian, vegan, ketogenic) on pain. The primary outcome was pain on a 10 cm visual analogue scale. Secondary outcomes were C-reactive protein levels, erythrocyte sedimentation rate, health assessment questionnaire, disease activity score 28, tender/swollen joint counts, weight, and body mass index. We searched MEDLINE (OVID), Embase (Elsevier), and CINAHL for studies published from database inception to 12 November 2021. Two authors independently assessed studies for inclusion, extracted study data, and assessed the risk of bias. We performed a meta-analysis with all eligible randomized controlled trials using RevMan 5. We used mean differences or standardized mean differences and the inverse variance method of pooling using a random-effects model. The search retrieved 564 unique publications, of which we included 12 in the systematic review and 7 in the meta-analysis. All studies had a high risk of bias and the evidence was very low. The main conclusion is that anti-inflammatory diets resulted in significantly lower pain than ordinary diets (−9.22 mm; 95% CI −14.15 to −4.29; p = 0.0002; 7 RCTs, 326 participants). [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend the use of nutritional support during hospital stays for medical patients (patients not critically ill and not undergoing surgical procedures) at risk of malnutrition. However, the supporting evidence for this recommendation is insufficient, and there is growing concern about the possible negative effects of nutritional therapy during acute illness on recovery and clinical outcomes. Our aim was thus to test the hypothesis that protocol-guided individualised nutritional support to reach protein and caloric goals reduces the risk of adverse clinical outcomes in medical inpatients at nutritional risk.Methods: The Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) is a pragmatic, investigator-initiated, open-label, multicentre study. We recruited medical patients at nutritional risk (nutritional risk screening 2002 [NRS 2002] score ≥3 points) and with an expected length of hospital stay of more than 4 days from eight Swiss hospitals. These participants were randomly assigned (1:1) to receive either protocol-guided individualised nutritional support to reach protein and caloric goals (intervention group) or standard hospital food (control group). Randomisation was done with variable block sizes and stratification according to study site and severity of malnutrition using an interactive web-response system. In the intervention group, individualised nutritional support goals were defined by specialist dietitians and nutritional support was initiated no later than 48 h after admission. Patients in the control group received no dietary consultation. The composite primary endpoint was any adverse clinical outcome defined as all-cause mortality, admission to intensive care, non-elective hospital readmission, major complications, and decline in functional status at 30 days, and it was measured in all randomised patients who completed the trial. This trial is registered with ClinicalTrials.gov, number NCT02517476.Findings: 5015 patients were screened, and 2088 were recruited and monitored between April 1, 2014, and Feb 28, 2018. 1050 patients were assigned to the intervention group and 1038 to the control group. 60 patients withdrew consent during the course of the trial (35 in the intervention group and 25 in the control group). During the hospital stay, caloric goals were reached in 800 (79%) and protein goals in 770 (76%) of 1015 patients in the intervention group. By 30 days, 232 (23%) patients in the intervention group experienced an adverse clinical outcome, compared with 272 (27%) of 1013 patients in the control group (adjusted odds ratio [OR] 0·79 [95% CI 0·64-0·97], p=0·023). By day 30, 73 [7%] patients had died in the intervention group compared with 100 [10%] patients in the control group (adjusted OR 0·65 [0·47-0·91], p=0·011). There was no difference in the proportion of patients who experienced side-effects from nutritional support between the intervention and the control group (162 [16%] vs 145 [14%], adjusted OR 1·16 [0·90-1·51], p=0·26).Interpretation: In medical inpatients at nutritional risk, the use of individualised nutritional support during the hospital stay improved important clinical outcomes, including survival, compared with standard hospital food. These findings strongly support the concept of systematically screening medical inpatients on hospital admission regarding nutritional risk, independent of their medical condition, followed by a nutritional assessment and introduction of individualised nutritional support in patients at risk.Funding: The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau, Switzerland. [ABSTRACT FROM AUTHOR]