Explore the vast range of titles available.

Weight loss appears as a strong predictor of survival of patients with amyotrophic lateral sclerosis, yet no data are currently available to describe the life course history of pre-diagnostic body mass index (BMI) in these patients. 393 ALS cases (mean age: 65.8 years, 57.3% men) and 791 controls matched by age and sex from a population-based case-control study of the ALS Registry Swabia were analyzed. Differences of BMI change in cases and controls over time were modeled using a multilevel additive model. In addition, survival in ALS cases by BMI change was modeled using an accelerated failure time model adjusted for prognostic factors. In ALS cases, BMI was consistently higher than in controls in the 20-70 years before the interview. Conditional logistic regression revealed an odds ratio of 1.05 (95% confidence interval (CI) 1.00-1.11, p = 0.041) per 1 kg/m² higher BMI 35-45 years before interview. However, a sharp decrease was evident in the BMI of ALS cases about 10 years before disease onset. Moreover, weight loss was strongly associated with shorter survival in ALS patients. Illustrating this, patients with stable weight showed a median survival time of 22.1 (95%-CI 19.2-25.0) months, as compared to 13.4 (95%-CI 10.5-16.3) months for patients with weight loss of 2.5 kg/m² over the last 3 months before the interview. Thus, alterations in body weight are present in ALS patients already decades before clinical manifestation of ALS, while weight loss precedes motor symptoms of several years and is associated with poor prognosis.

Background: Obesity and its health consequences will dominate health care systems in many countries during the next decades. However, the body mass index (BMI) optimum in relation to all-cause mortality is still a matter of debate.Material and Methods: Data of the Vorarlberg Health Monitoring & Prevention Program (VHM&PP, 1985–2005) and data provided by the Main Association of Austrian Social Security Institutions (MAASSI, 2005–2015) were analyzed. Information was available on age, sex, smoking status, measured height and weight, and mortality. Generalized additive models were used to model mortality as a function of BMI, calendar time, age, and follow-up.Results: In MAASSI (N = 282,216, 46.0% men), men and women were on average 2.7 years older than in VHM&PP (N = 185,361, 46.1% men). Average BMI was slightly higher in men (26.1 vs 25.7 kg/m2) but not in women (24.6 vs 24.7 kg/m2). We found an interactive effect of age and follow-up on the BMI optimum. Over age 35 years in men and 55 years in women, the BMI optimum decreased with length of follow-up. While keeping covariates fixed, BMI optimum increased slightly between 1985 and 2015 in men and women, 24.9 (95% CI, 23.9–25.9) to 26.4 (95% CI, 25.3–27.3), and 22.4 (95% CI, 21.7–23.1) to 23.3 (95% CI, 22.6–24.5) kg/m2, respectively.Conclusion: Age and length of follow-up have a pronounced effect on the BMI associated with the lowest all-cause mortality. After controlling for age and length of follow-up, the BMI optimum increased slightly over 30 years in this large study sample.

Klemm et al. (mBio 9:e00105-18, 2018, https://doi.org/10.1128/mBio.00105-18 ) present comprehensive antibiotic sensitivity patterns and genomic sequence data on Salmonella enterica serovar Typhi blood culture isolates from typhoid fever cases during an epidemic in Pakistan. Microbiologic and genomic data pinpoint the identities and locations of the antimicrobial resistance genes and the outbreak strain’s lineage. They propose that Salmonella enterica serovar Typhi be added to the list of bacterial pathogens of public health importance that have become extensively drug resistant (XDR). This paper portends possible dire scenarios for typhoid fever control if XDR strains disseminate globally. Since the outbreak strain is of the H58 haplotype, known for its ability to spread worldwide and displace endemic S . Typhi, this concern is well-founded. The report of Klemm et al. forewarns the global community to address control of typhoid fever more aggressively through prevention, should therapeutic options disappear. This Commentary frames the Klemm et al. findings within a historic perspective.

Obesity is suggested to underlie development of other metabolic aberrations, but longitudinal relationships between metabolic factors at various ages has not been studied in detail. Data from 27,379 men and 32,275 women with in total 122,940 health examinations in the Västerbotten Intervention Project, Sweden and the Vorarlberg Health Monitoring and Prevention Programme, Austria were used to investigate body mass index (BMI), mid-blood pressure, and fasting levels of glucose, triglycerides, and total cholesterol at baseline in relation to 10-year changes of these factors and weight. We included paired examinations performed 10±2 years apart and used them for longitudinal analysis with linear regression of changes between the ages 30 and 40, 40 and 50, or 50 and 60 years. Higher levels of BMI were associated with increases in glucose and mid-blood pressure as well as triglycerides levels, and, to a lesser extent, decreases in cholesterol levels. For instance, per 5 kg/m2 higher BMI at age 40, glucose at age 50 increased by 0.24 mmol/l (95%CI: 0.22-0.26) and mid-blood pressure increased by 1.54 mm Hg (95%CI: 1.35-1.74). The strongest association observed was between BMI at age 30 and mid-blood pressure, which was 2.12 mm Hg (95% CI: 1.79-2.45) increase over ten years per 5 kg/m2 higher BMI level. This association was observed at an age when blood pressure levels on average remained stable. Other associations than those with BMI at baseline were much weaker. However, triglyceride levels were associated with future glucose changes among individuals with elevated BMI, particularly in the two older age groups. BMI was most indicative of long-term changes in metabolic factors, and the strongest impact was observed for increases in blood pressure between 30 and 40 years of age. Our study supports that lifestyle interventions preventing metabolic aberrations should focus on avoiding weight increases.

Osteoarthritis (OA) is associated with adverse cardio-metabolic features. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponins T and I (hs-cTnT and hs-cTnI) are well-characterized cardiac markers and provide prognostic information. The objective was to assess the association of cardiac biomarker concentrations with long-term mortality in subjects with OA. In a cohort of 679 OA subjects, undergoing hip or knee replacement during 1995/1996, cardiac biomarkers were measured and subjects were followed over 20 years. During a median follow-up of 18.4 years, 332 (48.9%) subjects died. Median of hs-cTnT, hs-cTnI, and NT-proBNP at baseline was 3.2 ng/L, 3.9 ng/L, and 96.8 ng/L. The top quartile of NT-proBNP was associated with increased risk of mortality (Hazard Ratio (HR) 1.79, 95% confidence interval (CI) 1.17–2.73) after adjustment for covariates including troponins (hs-cTnT HR 1.30 (95% CI 0.90–1.89), hs-cTnI HR 1.32 (95% CI 0.87–2.00) for top category). When biomarker associations were evaluated as continuous variables, only NT-proBNP (HR per log-unit increment 1.34, 95% CI 1.16–1.54) and hs-cTnI (HR 1.38, 95% CI 1.11–1.72) showed robust results. Elevated cardiac biomarker concentrations predicted an increased risk of long-term mortality and strongest for NT-proBNP and hs-cTnI. These results might help to identify subjects at risk and target preventive efforts early.

To investigate variation of care dependency after hip fracture across German regions based on the assessment by the German statutory long-term care insurance. Patient-level statutory health and long-term care insurance claims data from 2009-2011 and official statistical data from Germany. We performed a retrospective cohort study. Investigated multinomial outcome categories were increase in care dependency (new onset or a higher care dependency than pre-fracture), no change as reference and death as competing risk in the quarterly period following hip fracture (follow-up 3 months). Regional variation was operationalized with the variance of regional-level random intercepts based on generalized linear mixed models. We adjusted for patient and regional characteristics. The study included 122,887 hip fracture patients in 95 German postal code regions. Crude outcomes were 30.87% increase in care dependency and 14.35% death. Results indicated modest variation on regional level. Male sex, increasing age, increasing comorbidity, pertrochanteric and subtrochanteric fracture site compared to femoral neck, time from hospital admission to surgery of 3 or more days, as well as increasing inpatient length of stay, non-participation in rehabilitation and regions with lower hospital density were positively associated with an increase in care dependency. Several characteristics on patient and regional level associated with the outcome were identified. Variation in the increase in care dependency after hip fracture appeared to be attributable primarily to patient characteristics. Variation on regional level was only modest.

At present, the dramatic rise in antimicrobial resistance (AMR) among important human bacterial pathogens is reaching a state of global crisis threatening a return to the pre-antibiotic era. AMR, already a significant burden on public health and economies, is anticipated to grow even more severe in the coming decades. Several licensed vaccines, targeting both bacterial (Haemophilus influenzae type b, Streptococcus pneumoniae, Salmonella enterica serovar Typhi) and viral (influenza virus, rotavirus) human pathogens, have already proven their anti-AMR benefits by reducing unwarranted antibiotic consumption and antibiotic-resistant bacterial strains and by promoting herd immunity. A number of new investigational vaccines, with a potential to reduce the spread of multidrug-resistant bacterial pathogens, are also in various stages of clinical development. Nevertheless, vaccines as a tool to combat AMR remain underappreciated and unfortunately underutilized. Global mobilization of public health and industry resources is key to maximizing the use of licensed vaccines, and the development of new prophylactic vaccines could have a profound impact on reducing AMR.

To date, the amount of heterogeneity among studies of the body mass index-mortality association attributable to differences in the age distribution and length of follow-up has not been quantified. Therefore, we wanted to quantify the amount of heterogeneity attributable to age and follow-up in results of studies on the body mass index-mortality relation. We used optima of the body mass index mortality association reported for 30 populations and performed meta-regression to estimate the amount of heterogeneity attributable to sex, ethnicity, mean age at baseline, percentage smokers, and length of follow-up. Ethnicity as single factor accounted for 36% (95% CI, 11–56%) of heterogeneity. Mean age and length of follow-up had an interactive effect and together accounted for 56% (95% CI, 24–74%) of the remaining heterogeneity. Sex did not significantly contribute to the heterogeneity, after controlling for ethnicity, age, and length of follow-up. A considerable amount of heterogeneity in studies of the body mass index-mortality association is attributable to ethnicity, age, and length of follow-up. •The BMI-mortality association varies considerably between study cohorts.•We found ethnicity alone to account for 36% of the heterogeneity.•Age and length of follow-up accounted for 56% of the remaining heterogeneity.

Mammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3–249 months). Positive final margin (tumor transected), age < 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age > 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.

BackgroundPatients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension (PAH/CTEPH) may experience physiological stress at high altitude. We investigated pulmonary haemodynamics and right heart function during incremental (IET) and constant work-rate exercise tests (CWRET) at high (2500 m) vs low altitude (470 m).MethodsIn this randomised crossover trial, patients with stable PAH/CTEPH without resting hypoxaemia performed IET and CWRET at both altitudes. Systolic pulmonary arterial pressure (sPAP) and right ventricular (RV) arterial coupling (tricuspid annular plane systolic excursion/sPAP) were assessed by echocardiography.ResultsAmong 27 patients (44% women, 61±14 years), sPAP was higher at rest at 2500 m vs 470 m (mean difference: 14 mm Hg, 95% CI 7 to 23), but increased linearly during exercise with similar slopes at each altitude (7.9 vs 9.7 mm Hg/min, respectively). RV arterial coupling was lower at high altitude at rest (difference: −0.13 mm/mm Hg, 95% CI −0.26 to −0.04) but decreased comparably during exercise. During CWRET, sPAP rose steeply in the first 3 min, plateauing thereafter, with no altitude-dependent differences in pressure-flow slope. Oxygen delivery was reduced at high altitude.ConclusionDespite higher baseline sPAP and reduced RV coupling at rest, exercise-induced haemodynamic changes were similar at both high and low altitudes, suggesting short-term altitude exposure does not exacerbate cardiopulmonary stress during exercise in stable PAH/CTEPH. The exercise protocol (IET vs CWRET) alters haemodynamic trajectories more than altitude.Trial registration numberNCT05107700.