Purpose
Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI) for kidney health is ...lacking. To summarise and evaluate the available evidence for a relation between HPI and kidney diseases, an umbrella review of systematic reviews (SR) was conducted.
Methods
PubMed, Embase and Cochrane Database of SRs published until 12/2022 were searched for the respective SRs with and without meta-analyses (MA) of randomised controlled trials or cohort studies. For assessments of methodological quality and of outcome-specific certainty of evidence, a modified version of AMSTAR 2 and the NutriGrade scoring tool were used, respectively. The overall certainty of evidence was assessed according to predefined criteria.
Results
Six SRs with MA and three SRs without MA on various kidney-related outcomes were identified. Outcomes were chronic kidney disease, kidney stones and kidney function-related parameters: albuminuria, glomerular filtration rate, serum urea, urinary pH and urinary calcium excretion. Overall certainty of evidence was graded as ‘possible’ for stone risk not to be associated with HPI and albuminuria not to be elevated through HPI (above recommendations (> 0.8 g/kg body weight/day)) and graded as ‘probable’ or ‘possible’ for most other kidney function-related parameters to be physiologically increased with HPI.
Conclusion
Changes of the assessed outcomes may have reflected mostly physiological (regulatory), but not pathometabolic responses to higher protein loads. For none of the outcomes, evidence was found that HPI does specifically trigger kidney stones or diseases. However, for potential recommendations long-term data, also over decades, are required.
This umbrella review aimed at assessing whether a protein intake exceeding the current recommendation for younger (0.8 g/kg body weight BW/day) and older (1.0 g/kg BW/day) adults affects bone mineral ...density and fracture risk. Moreover, the effect of animal or plant protein was evaluated. A systematic literature search was conducted in PubMed, Embase, and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with or without meta-analysis of prospective studies published between 11/2008 and 08/2021. Methodological quality, outcome-specific certainty of evidence, and overall certainty of evidence of the retrieved SRs were assessed using established tools and predefined criteria. Eleven SRs of randomized controlled trials (RCTs) and/or cohort studies were included. In SRs of cohort studies and RCTs, protein intake/kg BW/day ranged between 0.21–0.95 g (low intake) and > 1.24 g (high intake), respectively, and between 0.67–1.1 g (control groups) and 1.01–1.69 g (intervention groups), respectively. The vast majority of outcome-specific certainty of evidence was rated “low” or “very low.” The overall certainty of evidence for an association (cohort studies) or effect (RCTs) of total, animal or plant protein intake on each of the investigated outcomes was rated “insufficient,” with the exception of possible evidence for a reduced hip fracture risk by high vs. low protein intake. Since protein intakes in low/control and high/intervention groups were very heterogeneous and with low certainty of evidence, it remains unclear whether a dose above the current recommendation or type of protein intake (animal or plant protein) affects bone health overall. However, there is possible evidence for reduced hip fracture risk with high versus low protein intake.
IntroductionImprecise nutritional recommendations due to a lack of diagnostic test accuracy are a frequent problem for individuals with adverse reactions to foods but no precise diagnosis. ...Consequently, patients follow very broad and strict elimination diets to avoid uncontrolled symptoms such as diarrhoea and abdominal pain. Dietary limitations and the uncertainty of developing gastrointestinal symptoms after the inadvertent ingestion of food have been demonstrated to reduce the quality of life (QoL) of affected individuals and subsequently might increase the risk of malnutrition and intestinal dysbiosis. This trial aims to investigate the effects of a tailored diet based on the confocal laser endoscopy (CLE) examination result to limit the side effects of unspecific and broad elimination diets and to increase the patient’s QoL.Methods and analysisThe study is designed as a prospective, double-blind, monocentric, randomised and controlled trial conducted at the University Hospital of Schleswig-Holstein, Campus Lübeck, Germany. One hundred seventy-two patients with non-IgE-related food allergies and positive CLE results will be randomised to either a tailored diet or a standard fivefold elimination diet. The primary endpoints are the difference between the end and the start of the intervention in health-related QoL and the sum score of the severity of symptoms after 12 weeks. Key secondary endpoints are changes in the severity of symptoms, further QoL measurements, self-assessed state of health and number of days with a pathologically altered stool. Microbiome diversity and metabolome of stool, urine and blood will also be investigated. Safety endpoints are body composition, body mass index and adverse events.Ethics and disseminationThe study protocol was accepted by the ethical committee of the University of Lübeck (AZ: 22-111) on 4 May2022. Results of the study will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberGerman Clinical Trials Register (DRKS00029323).
Women with pathogenic BRCA germline mutations have an increased risk for breast and ovarian cancer that seems to be modified by life-style factors. Though, randomized trials investigating the impact ...of lifestyle interventions on cancer prevention and prognosis in BRCA carriers are still missing.
We implemented a multicenter, prospective randomized controlled trial in BRCA1/2 patients, comparing a lifestyle intervention group (IG) with a control group (CG) with the primary aim to prove feasibility. Intervention comprised a structured, individualized endurance training alongside nutrition education based on the Mediterranean diet (MD) for 3 months, plus monthly group training and regular telephone contact during the subsequent 9 months. The CG attended one session on healthy nutrition and the benefits of physical activity. Primary endpoints were feasibility, acceptance and satisfaction over 12 months. Furthermore, effects on physical fitness, diet profile, body mass index (BMI), quality of life and perceived stress were investigated.
Sixty-eight participants (mean age 41, mean BMI 23.2 kg/m
) were enrolled, of whom 55 (81%, 26 IG, 29 CG) completed 12 months. 73% (n = 26) participated in at least 70% of all intervention sessions. Predictors for drop-outs (19%; n = 13) or non-adherence (27%; n = 7) were not found. 73% rated the program highly and 80% would participate again. Severe adverse events did not occur. Positive effects in the IG compared to the CG were observed for secondary endpoints: BMI, MD eating pattern and stress levels.
This lifestyle intervention was feasible, safe and well accepted. Positive results on eating habits, physical fitness and stress levels warrant a larger randomized trial.
The study has been retrospectively registered at ClinicalTrials.gov (reference: NCT02087592 ) on March 12, 2014. The first patient was included on February 24, 2014.
Hearing loss is among the leading causes of disability in persons 65 years and older worldwide and is known to have an impact on quality of life as well as social, cognitive, and physical ...functioning. Our objective was to assess statewide prevalence of self-reported hearing ability in Arizona adults and its association with general health, cognitive decline, diabetes and poor psychosocial health.
A self-report question on hearing was added to the 2015 Behavioral Risk Factor Surveillance System (BRFSS), a telephone-based survey among community-dwelling adults aged > 18 years (n = 6462). Logistic and linear regression were used to estimate the associations between self-reported hearing loss and health outcomes.
Approximately 1 in 4 adults reported trouble hearing (23.2, 95% confidence interval: 21.8, 24.5%), with responses ranging from "a little trouble hearing" to being "deaf." Adults reporting any trouble hearing were at nearly four times higher odds of reporting increased confusion and memory loss (OR 3.92, 95% CI: 2.94, 5.24) and decreased odds of reporting good general health (OR = 0.50, 95% CI: 0.40, 0.64) as compared to participants reporting no hearing difficulty. Those reporting any trouble hearing also reported an average 2.5 more days of poor psychosocial health per month (β = 2.52, 95% CI: 1.64, 3.41). After adjusting for sex, age, questionnaire language, race/ethnicity, and income category the association between diabetes and hearing loss was no longer significant.
Self-reported hearing difficulty was associated with report of increased confusion and memory loss and poorer general and psychosocial health among Arizona adults. These findings support the feasibility and utility of assessing self-reported hearing ability on the BRFSS. Results highlight the need for greater inclusion of the full range of hearing disability in the planning process for public health surveillance, programs, and services at state and local levels.
Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, ...we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.
Display omitted
•Elevated IFN-α plasma levels characteristic for early severe COVID-19 (sCOVID-19)•Differential IFN-α vs. TNF signaling discriminates severe vs. moderate COVID-19•NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in sCOVID-19•Persistent NK cell dysfunction may promote fibrotic lung disease in sCOVID-19
The importance of NK cells in the innate response to viral infection provides rationale for deeper understanding of their role in COVID-19. Here, Krämer et al. utilize longitudinal analysis of NK cells to show early TNF and IFN-α signatures associated with moderate and severe COVID-19, respectively, and NK cell functional impairment in severe disease.
Ancient, SiO2‐rich achondrites have previously been proposed to have formed by disequilibrium partial melting of chondrites. Here, we test the alternative hypothesis that these achondrites formed by ...fractional crystallization of impact melts of Rumuruti (R) chondrites. We identified two new melt clasts in R chondrites, one in Pecora Escarpment (PCA) 91241 and one in LaPaz Icefield (LAP) 031275. We analyzed major, minor, and trace element concentrations, as well as oxygen isotopes, of these two clasts and a third one that had been previously recognized (Bischoff et al. 2011) as an impact melt in Dar al Gani (DaG) 013. The melt clast in PCA 91241 is an R chondrite impact melt closely resembling the one previously recognized in DaG 013. The melt clast in LAP 031275 has an L chondrite provenance. We show that SiO2‐rich melts could form from the mesostases of R chondrite impact melts. However, their CI‐normalized rare earth element patterns are flat, whereas those of ancient SiO2‐rich achondrites (Day et al. 2012; Srinivasan et al. 2018) and those of disequilibrium partial melts of chondrites (Feldstein et al. 2001) have positive Eu anomalies from preferential melting of plagioclase. Thus, we conclude that ancient SiO2‐rich achondrites were probably formed by disequilibrium partial melting (due to an internal heat source on their parent bodies), rather than from impact melts.
Background
Optimal obesity therapy is a matter of debate. Besides weight reduction, other criteria such as safety and nutritional status are of relevance. Therefore, we compared a favored surgical ...intervention with the most effective conservative treatment regarding anthropometry and nutritional status.
Methods
Fifty-four obese patients were included who underwent laparoscopic sleeve gastrectomy (LSG,
n
= 27) or a 52-week multidisciplinary intervention program (MIP,
n
= 27) for weight loss. Body weight, body composition assessed by bioelectrical impedance analysis, and serum protein levels were measured before and within 12 months after intervention.
Results
After 1 year of observation, excess weight loss was more pronounced following LSG (65 %) compared to MIP (38 %,
p
< 0.001). In both groups, body fat was clearly reduced, but a higher reduction occurred in the LSG group. However, protein status deteriorated particularly in the LSG group. Within 1 year, body cell mass declined from 37.1 to 26.9 kg in the LSG group, but only from 35.7 to 32.2 kg in the MIP group. This resulted in an increased mean extracellular mass/body cell mass ratio (1.42 versus 1.00,
p
< 0.001), in a decreased mean phase angle (4.4° versus 6.6°,
p
< 0.001), and in a lower prealbumin level in serum (
p
< 0.02) in the LSG group compared to the MIP group.
Conclusions
LSG, compared to MIP, was more effective regarding excess weight loss and body fat loss within 1 year, however, induced more pronounced muscle mass and protein loss, possibly requiring particular interventions such as exercise or protein supplements.
Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics ...and clinical outcomes over time are limited.
The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period.
TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers.
A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation EuroSCORE: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium-defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased.
The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter FRANCE TAVI; NCT01777828).
The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained ...pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions in most individuals irrespective of age. Using a combination of multiplex IHC, single-cell RNA sequencing, and spatial transcriptomics, we provide the first-ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis.
Precursor lesions to pancreatic cancer are poorly characterized. We analyzed donor pancreata and discovered that precursor lesions are detected at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell-intrinsic factors that restrain or, conversely, promote malignant progression. See related commentary by Hoffman and Dougan, p. 1288. This article is highlighted in the In This Issue feature, p. 1275.
PDF
