Community-acquired pneumonia (CAP) is a leading cause of hospitalization and often results in impaired health-related quality of life (HRQoL). The prognostic value of HRQoL at admission and its recovery trajectory after CAP remain unclear. We investigated associations between HRQoL at admission and adverse outcomes, including ICU admission, rehospitalization, and mortality, and described changes in HRQoL 180 days post-discharge. In this prospective cohort study, 552 patients hospitalized with CAP completed the EQ-5D-5L questionnaire at admission; 262 patients were reassessed 180 days post-discharge. Patients were categorized into tertiles based on the EQ-5D utility index and dimension-specific scores. Associations between HRQoL and outcomes were analyzed using logistic and Cox regression models. The mean EQ-5D utility index at admission was 0.609 ± 0.266. Severe impairments were most common in usual activities (42%) and mobility (30%) dimensions. Lower HRQoL at admission (lowest vs. highest tertile) was associated with an increased risk of rehospitalization at 30 days (aHR 1.92, 95% CI: 1.18-3.13), 90 days (aHR 2.01, 95% CI: 1.33-3.03), and 180 days (aHR 1.82, 95% CI: 1.27-2.59) and an increased risk of mortality at 90 days (aHR 1.91, 95% CI 1.01-3.63) and 180 days (aHR 1.84, 95% CI 1.05-3.20). Severe impairment in the mobility dimension was associated with increased risks of ICU admission, rehospitalization within 30, 90, and 180 days, and mortality within 90 and 180 days, while severe impairment in the self-care dimension was associated with increased risks of rehospitalization within 30, 90, and 180 days and mortality within 180 days. Among survivors who completed the follow-up, HRQoL improved modestly over 180 days (+ 0.109 ± 0.247). Low HRQoL at admission, particularly impairments in the mobility and self-care dimensions, was associated with adverse outcomes in patients with CAP. HRQoL is an independent prognostic marker that may support clinical risk stratification in patients with CAP. The observed improvement in HRQoL over time should be interpreted cautiously as it reflects survivors who completed follow-up.Trial registration: ClinicalTrials.gov (NCT03795662).

BACKGROUND:Malnutrition, inflammation, limited exercise, and low muscle mass increase the risk of cystic fibrosis (CF) bone disease (CFBD). Additionally, dysfunction of the CF transmembrane conductance regulator (CFTR) directly affects bone-forming cells. Elexacaftor/Tezacaftor/Ivacaftor (ETI) could influence these aspects. We examined the impact of ETI on bone health in Danish people with CF. METHODS:This nationwide cohort study evaluated changes in bone status in adults with CF after ETI treatment. Dual energy X-ray absorptiometry (DXA) was used to assess bone mineral density Z-scores in lumbar spine, femoral neck, and total hip. To assess calcium metabolism, plasma levels of vitamin D, calcium, and parathyroid hormone (PTH) were evaluated. Data were collected from 2 years pre- to 3.5 years post-ETI initiation, comparing pre-ETI levels with 1-, 2- and 3-year post-ETI measurements. Data were analyzed using linear mixed effects regression models and subgroup interaction analyses. RESULTS:197 Danish adults with CF were included in the study, contributing 435 DXA scans. Mean change from pre-ETI period (95%CI) in femoral neck and total hip Z-scores showed a decrease by year 3 of -0.16 (-0.31; -0.01; p=0.04) and -0.15 (-0.30; <0.01; p=0.05), respectively, while lumbar spine showed a slight increase of 0.13 (-0.05, 0.31; p=0.15). Vitamin D levels initially decreased but subsequently increased by 8.9 nmol/L (4.5-13.3; p<0.01) by year 3 as compared to pre-ETI levels. Calcium and PTH levels remained stable. CONCLUSION:After 3 years of ETI treatment in Danish adults with CF, no clinically significant changes in bone health or calcium metabolism were observed.

Introduction Glomerular filtration rate (GFR) is invasive to measure. Therefore, in clinical care, estimated GFR is derived from serum levels of endogenous filtration markers such as creatinine and cystatin C. Multiple studies from high income countries showed differences between estimated glomerular filtration rate based on cystatin C (eGFRcys) and creatinine (eGFRcr). This study aimed to assess the agreement between eGFRcys and eGFRcr in Ethiopian children and identify factors influencing higher eGFRcys and eGFRcr. Method We studied 350 Ethiopian children who were part of the iABC birth cohort study. At the recent follow-up (average age 10 years), serum cystatin C and creatinine were measured. Formulas by Berg (2015) and Hoste (2014) were used to estimate eGFRcys and eGFRcr, respectively, and Bland–Altman plots assessed their agreement. The difference in eGFR (eGFRdiff) was calculated and categorized as less than -15 mL/min/1.73 m2 (higher eGFRcr), between -15 and <15 mL/min/1.73 m2 (concordant), and greater than or equal to 15 mL/min/1.73 m2 (higher eGFRcys). Multinomial logistic regression was used to identify factors associated with higher eGFRcr and higher eGFRcys. Result Estimated glomerular filtration rate (eGFR) showed significant variation based on the estimation formula used. When using formulas by Berg (2015) and Hoste (2014), the median (IQR) eGFRcys and eGFRcr were 99.4 (90.0; 114.1), and 123.2 (110.3; 143.8) mL/min/1.73 m2, respectively. Overall, we observed a poor agreement between eGFRcys and eGFRcr, with only 94 (27.6%) children having concordant results compared to 220 (64.7%) with higher eGFRcr and 26 (7.6%) with higher eGFRcys. If the eGFRcys results are considered reliable, 27.5% of the children had eGFR below 90 mL/min/1.73 m2. Conclusion There was very marked variation in the distributions of estimated eGFRs depending on which formulas for children were used. Agreement between eGFR estimated using cystatin C and creatinine was poor among Ethiopian children. Relative to eGFRcys, kidney function may be overestimated by creatinine-based equation as up to 30ml/min in Ethiopia. Ideally, a validation study with GFR measured by gold standard methods (Inlulin clearance) among children is required. However, because of its invasive nature and financial concerns, Iohexol clearance studies are recommended. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial N/A. ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for the study was granted by Jimma University Ethical Review Board of the College of Public Health and Medical Sciences (reference IHRPHD/333/18) and by the ethics committee of the London School of Hygiene and Tropical Medicine (reference 15976). Parents/guardians signed consent after getting detailed information regarding the study was provided. Any abnormal findings detected during clinical and laboratory evaluations were communicated to families of children and they were linked to Jimma University Medical Center for further evaluation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data supporting the findings of this study cannot be made publicly available because the ethical approvals obtained from the Institutional Review Boards of Jimma University and the London School of Hygiene & Tropical Medicine did not include provisions for public data sharing. However, the data may be made available upon reasonable request to the corresponding author.

OBJECTIVES:To examine the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on markers of intestinal inflammation and enterocyte mass among stunted children. Furthermore, to explore whether gut status modifies effects of LNS on growth and micronutrient status. METHODS:In a 2 × 2 factorial trial 12-59 months-old Ugandan children with stunting were randomized to four LNS formulations (100 g/day for 12 weeks) containing MP or soy protein and WP or maltodextrin, or to no supplementation. Linear mixed-effects models were used to explore faecal myeloperoxidase (f-MPO) and plasma citrulline (p-cit) as outcomes and modifiers of the intervention effects (ISRCTN13093195). RESULTS:Of 750 children, mean ± SD age was 32.0 ± 11.7 months and height-for-age Z-score was -3.02 ± 0.74. Neither MP nor WP had effects on p-cit or f-MPO. f-MPO decreased over time among controls (ratio of change 0.54, 95% confidence interval [CI]: 0.35, 0.84), but not among those given LNS (0.99, 95% CI: 0.79, 1.23) (p = 0.016). In contrast, LNS had no effect on p-cit (p = 0.27). The effect of LNS on cobalamin (B12) status was reduced in children with p-cit <20 µmol/L; whereby there was 20% (95% CI: 2, 35) lower increase in plasma cobalamin and 59% (95% CI: 13, 125) smaller decrease in plasma methylmalonic acid. p-cit or f-MPO did not modify the effects of LNS on growth or other micronutrient markers. CONCLUSION:LNS had no effect on enterocyte mass and possibly increased intestinal inflammation. The effect of LNS on cobalamin status was reduced in those with low enterocyte mass.

Children with stunting are at risk of infections. We assessed the effect of lipid-based nutrient supplement (LNS) on morbidity in children with stunting. This was a secondary analysis of a randomized, 2×2 factorial trial among 12–59 months-old, stunted children in Uganda. Children were randomized to LNS containing milk or soy protein and whey permeate or maltodextrin, or no supplementation, for 12 weeks. The outcomes were caregiver-reported morbidity after 2, 4, 8 and 12 weeks, serum C-reactive protein (S-CRP), α1-acid glycoprotein (S-AGP), and phase-angle (PhA) by bioimpedance. Of 750 children, mean (SD) age was 32.0 (11.7) months, 55% (n = 412) were male. LNS increased diarrhoea prevalence (18.1% vs 7.3%, P = 0.001) during the first two weeks, but not thereafter. There was no effect of LNS on cough or fever. LNS resulted in greater decline in S-AGP (−0.10 g/L, 95% CI: −0.17, −0.03, P = 0.003) but not S-CRP (25%, 95% CI: −11, 74, P = 0.193), and greater increase in PhA (0.10 degrees, 95% CI: 0.01, 0.18, P = 0.030), explained by greater fat-free mass. Milk compared to soy protein in LNS resulted in higher PhA (0.10 degrees, 95% CI: 0.02, 0.17, P = 0.013), not explained by fat-free mass. LNS supplementation in children with stunting had no effect on morbidity but resulted in a small reduction in sub-acute systemic inflammation. The possible effect of LNS supplementation on inflammation in stunted children requires further evaluation. ( www.isrctn.com : ISRCTN13093195).

This study aimed to identify linear growth trajectories from 0 to 5 years and assess their associations with cognitive function and school achievement in Ethiopian children aged 10 years. Latent class trajectory modelling was used to identify distinct height-for-age (HAZ) trajectories. Cognitive function was assessed using the Peabody Picture Vocabulary Test, while school achievement was measured by math, English and science (MES) combined scores and grade-for-age. Associations were assessed using multiple linear or logistic regressions. We identified four distinct HAZ trajectories. Decreasing trajectory (n 145, 31·9 %) started high at birth but dropped sharply. The increasing-decreasing trajectory (n 196, 43·2 %) increased up to 3 months, followed by a decrease. The stable low (n 74, 16·3 %) had low HAZ at birth, followed by a slight decrease. The rising trajectory (n 39, 8·6 %) started low but then increased to HAZ above, yet close to zero. At 10 years, children in the rising trajectory had 4·54 (95 % CI: -0·45, 9·55, P = 0·075) higher MES combined score and 2·4 times (95 % CI: 1·12, 5·15, P = 0·025) higher odds of being in the appropriate grade-for-age compared to those in the increasing-decreasing trajectory. The association between stable low and decreasing trajectory with appropriate grade-for-age had odds ratio close to null. In conclusion, we found that three of the four linear growth trajectory classes showed a declining pattern. Data suggest that greater linear growth in early childhood may be associated with higher school achievement and better cognitive function.

The burden of type 2 diabetes is rapidly increasing in low- and middle-income countries (LMICs), but determinants are not well-characterized. Household air pollution (HAP) from indoor biofuel use for cooking has been associated with non-communicable diseases and could be contributing to the increasing burden of diabetes in LMICs, though data are limited. We assessed the association between indoor biofuel use for cooking and glucose metabolism in HIV-infected and HIV-uninfected Tanzanian adults. This cross-sectional analysis included Tanzanian adults with and without HIV, from whom we collected sociodemographic and non-communicable disease risk factor data. The main predictor variable was indoor biofuel use for cooking, established using self-reported cooking location (indoor or outdoor) and fuel type (electricity/gas or biomass fuel), and categorized as minimal or no exposure, moderate exposure, and high exposure. Blood glucose and insulin were measured during oral glucose tolerance tests, allowing computation of outcome variables including markers of β-cell dysfunction (homeostatic model assessment-β, insulinogenic index, oral disposition index), insulin resistance (HOMA-IR and Matsuda index), and pre-diabetes and diabetes status. Logistic regression was used to assess associations, adjusting for age, sex, physical activity, smoking, socioeconomic status, HIV status, and body mass index. Among 1,871 participants (mean age 40.6 ± 11.9 years; 59.8% female), those with moderate and high exposure to HAP had approximately two-fold higher odds of a lower insulinogenic index (adjusted odds ratio [aOR] = 2.13, 95% CI: 1.27–3.57 and aOR = 2.31, 95% CI: 1.39–3.83, respectively) compared to those with minimal or no exposure. HAP was not associated with other markers of β-cell function, insulin resistance, pre-diabetes, or diabetes. In conclusion, HAP is associated with increased risk of β-cell dysfunction among individuals using biofuel for indoor cooking. Longitudinal studies using objective HAP measurements are needed to confirm these findings.

BACKGROUND:Elexacaftor/Tezacaftor/Ivacaftor (ETI) has raised concerns about liver-related side effects. This study evaluated changes in liver function tests (LFTs) and the prevalence of hepatotoxicity over two years of ETI treatment in a nationwide cohort of Danish people with cystic fibrosis (pwCF) METHODS: Changes in LFTs were assessed in pwCF aged ≥12 years, including those with pre-existing hepatic impairment, using data from the Danish CF Registry (2016-2025). Statistical analyses included piecewise linear mixed models for long-term changes and descriptive analysis of abnormal LFTs to assess hepatotoxicity. RESULTS:A total of 331 pwCF were included. Compared to pre-ETI levels, alanine aminotransferase (ALT) levels were significantly elevated at six months post-ETI but stabilized and approached pre-ETI levels by 24 months. Alkaline phosphatase (ALP) levels were lower at all timepoints, with a statistically significant decrease at 24 months. Gamma-glutamyl transferase (GGT) levels were consistently lower post-ETI. The prevalence of abnormal ALT, ALP, and GGT was initially higher post-ETI, peaking at one month, then steadily declining to pre-treatment values within two years. Three individuals (0.9 %) had signs of severe hepatotoxicity with ALT >5x upper limit of normal (ULN) and bilirubin >2xULN post-ETI. Among those with pre-existing hepatic impairment and those with unexpected liver complications post-ETI 5/7 and 5/8, respectively, reached the full ETI dose. CONCLUSION:ALT levels almost normalized, while GGT and ALP levels declined within two years of ETI treatment. Reassuringly, severe hepatotoxicity was rare, suggesting that close monitoring may suffice for managing mild to moderate hepatotoxicity in pwCF.

INTRODUCTION:Elexacaftor/tezacaftor/ivacaftor (ETI) is a breakthrough therapy for cystic fibrosis (CF). We aimed to assess ETI's real-world impact on peripheral airway disease assessed as ventilation distribution inhomogeneity using nitrogen multiple breath washout (N2MBW) in children aged 6-17 years. Additionally, we compared the two outcomes, lung clearance index (LCI), and ventilation distribution efficiency (VDE), as VDE is considered to adjust for a theoretical overestimation of lung disease when using LCI. METHODS:This nationwide study included data from N2MBW performed during routine clinical care. Linear mixed effect regression was used to assess changes in LCI and VDE after 12 months of ETI treatment. Subgroup analyses included baseline age (6-11 vs. 12-1 years) and disease severity (normal-moderate vs. severe-very severe). RESULTS:We included 131 children (78% homozygous for F508del mutation, mean [SD] age 11.5 [3.4]), and 339 N2MBW tests. The median (range) number of tests per child was 3 (1-10). The estimated mean (95% CI) 12-months post-ETI improvement in LCI and VDE were 1.7 units (-2.1; -1.2, p < 0.001) and 2.1%-point (1.6; 2.6, p < 0.001), respectively. Similar LCI and VDE improvements were observed across age groups. Using VDE, fewer children were categorized with very severe lung disease, and the ETI-effect did not differ between the severity groups, unlike LCI. CONCLUSION:Our research demonstrates that ETI treatment significantly improves lung function, as measured by N2MBW, in Danish children and adolescents with CF. VDE improvements were consistent across age and disease severity groups. In contrast, LCI revealed larger effect estimates for those with severe to very-severe lung impairment.

BACKGROUND & AIMS:Weight gain after elexacaftor/tezacaftor/ivacaftor (ETI) initiation among people with cystic fibrosis (CF) has been widely reported. How these weight changes compare with pre-existing trends, how they compare with linear growth, if they persist over time, and how they affect body composition have yet to be investigated. We assessed changes in body mass, linear growth, and body composition after ETI initiation. METHODS:Anthropometric data from people with CF in the Danish CF Registry were collected from 5 years pre-ETI initiation to 2 years post. Linear mixed-effects models with linear splines were used to assess changes in body mass index (BMI) in adults, and in BMI-for-age z-score (BMZ) and height-for-age z-score (HAZ) in children. Fat and fat-free mass from dual-energy X-ray absorptiometry (DXA) were compared using paired t-tests in adults. RESULTS:We included 392 people with CF. Among 154 children, BMZ was stable 5 years pre-ETI. Mean (95%CI) BMZ increased from -0.22 (-0.37, -0.07) at ETI initiation to 0.24 (0.05, 0.43) 2 years later. BMZ increased at a continuously higher rate post-ETI initiation compared to pre-ETI. HAZ increased by 0.05 (0.01, 0.09) per year pre-ETI, then remained stable post-ETI initiation, with no change from ETI initiation (0.12 (-0.03, 0.26)) to 2 years post-ETI. Among 238 adults, BMI increased by 0.05 (0.004, 0.10) kg/m2 per year pre-ETI. BMI increased from 22.55 (22.08, 23.02) kg/m2 at ETI initiation to 23.75 (23.25, 24.25) kg/m2 after 2 years, but the annual rate of change returned to pre-ETI trends after 9 months. In a subset of 115 adults with available DXA data, mean fat mass index increased by 0.68 kg/m2 (0.01, 1.35) 1 year post-ETI initiation, with no significant gain of fat-free mass index. CONCLUSIONS:Children with CF continued to increase their BMZ 2 years post-ETI initiation, while HAZ remined stable. The rate of change in BMI returned to pre-ETI trends among adults with CF. Adult BMI gains were primarily driven by an increase of fat mass.

BACKGROUND:Vitamin B12 deficiency is related to impaired neurodevelopment and anemia and is a global health concern in children with severe acute malnutrition (SAM). OBJECTIVES:We investigated vitamin B12 status in children with SAM and among non-malnourished comparisons and assessed the validity of the plasma vitamin B12 assay. METHODS:This study was part of a pilot study of a nutritional intervention. We measured plasma concentrations of vitamin B12, methylmalonic acid (MMA), total haptocorrin (HC), and total transcobalamin (TC) in children with SAM before and after 8 wk of nutritional treatment and at a single timepoint in non-malnourished children. RESULTS:We included 82 children with SAM and 82 children without acute malnutrition. Plasma vitamin B12 was higher in children with SAM at enrollment than in controls (median 647 compared with 411 pmol/L) and declined after treatment (median 469 pmol/L). Baseline plasma vitamin B12 was particularly high in children with edematous SAM compared to those without edema (P = 0.050). In contrast, plasma MMA was higher in those with SAM, reflecting lower vitamin B12 function (median 220 compared with 170 nmol/L), and declined after treatment (median 190 nmol). HC was positively correlated with vitamin B12 concentration (P < 0.001) and was also higher in children with SAM than in comparison children (median 959 compared with 789 pmol/L), decreasing after treatment (median 815 pmol/L). TC was higher in children with SAM than comparisons but did not decrease after treatment. Overall, 23% of children with SAM had MMA concentrations suggesting vitamin B12 deficiency compared to 4.5% of non-malnourished children. CONCLUSIONS:In contrast to our initial expectations, we found that plasma vitamin B12 was higher in children with SAM, especially those with edema. However, analysis of MMA revealed lower vitamin B12 function in malnourished children and improvement after treatment, warranting caution in the interpretation of plasma vitamin B12 in SAM. Elevated HC in SAM may explain high vitamin B12 concentration, but the cause of elevated HC needs further investigation.

Millions of children under 5 years in low- and middle-income countries fail to attain their development potential with accruing short- and long-term consequences. Low length/height for age (stunting) is known to be a key factor, but there is little data on how child characteristics are linked with developmental changes among children with stunting. We assessed the socioeconomic, household, anthropometric, and clinical predictors of change in early child development (ECD) among 1-5-year-old children with stunting. This was a prospective cohort study nested in a randomized trial testing effects of lipid-based nutrient supplementation among children with stunting in Uganda. Development was assessed using the Malawi Development Assessment Tool (MDAT). Multiple linear regression analysis was used to assess for predictors of change. We included 750 children with mean ±SD age of 30.2 ±11.7 months 45% of whom were female. After 12 weeks, total MDAT z-score increased by 0.40 (95%CI: 0.32; 0.48). Moderate vs severe stunting, higher fat-free mass, negative malaria test and no inflammation (serum α-1-acid glycoprotein <1 g/l) at baseline predicted greater increase in ECD scores. Older age and fat mass gain predicted a lesser increase in ECD. Our findings reinforce the link between stunting and development with more severely stunted children having a lesser increase in ECD scores over time. Younger age, freedom from malaria and inflammation, and higher fat-free mass at baseline, as well as less gain of fat mass during follow-up predicted a higher increase in developmental scores in this study. Thus, supporting fat-free mass accretion, focusing on younger children, and infection prevention may improve development among children with stunting.

BACKGROUND:Micronutrient deficiencies and anemia are widespread among children with stunting. OBJECTIVES:We assessed the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on micronutrient status and hemoglobin (Hb) among children with stunting. METHODS:This was a secondary analysis of a randomized controlled trial. Children aged 12-59 mo with stunting were randomly assigned to LNS (100 g/d) with milk or soy protein and WP or maltodextrin for 12 wk, or no supplement. Hb, serum ferritin (S-FE), serum soluble transferrin receptor (S-TfR), plasma cobalamin (P-Cob), plasma methylmalonic acid (P-MMA), plasma folate (P-Fol), and serum retinol-binding protein (S-RBP) were measured at inclusion and at 12 wk. Data were analyzed using linear and logistic mixed-effects models. RESULTS:Among 750 children, with mean age ± SD of 32 ± 11.7 mo, 45% (n = 338) were female and 98% (n = 736) completed follow-up. LNS, compared with no supplementation, resulted in 43% [95% confidence interval (CI): 28, 60] greater increase in S-FE corrected for inflammation (S-FEci), 2.4 (95% CI: 1.2, 3.5) mg/L greater decline in S-TfR, 138 (95% CI: 111, 164) pmol/L greater increase in P-Cob, 33% (95% CI: 27, 39) reduction in P-MMA, and 8.5 (95% CI: 6.6, 10.3) nmol/L greater increase in P-Fol. There was no effect of LNS on S-RBP. Lactation modified the effect of LNS on markers of cobalamin status, reflecting improved status among nonbreastfed and no effects among breastfed children. LNS increased Hb by 3.8 (95% CI: 1.7, 6.0) g/L and reduced the odds of anemia by 55% (odds ratio: 0.45, 95% CI: 0.29, 0.70). MP compared with soy protein increased S-FEci by 14% (95% CI: 3, 26). CONCLUSIONS:LNS supplementation increases Hb and improves iron, cobalamin, and folate status, but not vitamin A status among children with stunting. LNS should be considered for children with stunting. This trial was registered at ISRCTN as 13093195.

Early childhood growth is associated with cognitive function. However, the independent associations of fat mass (FM) and fat-free mass (FFM) with cognitive function are not well understood. We investigated associations of FM and FFM at birth and 0-5 years accretion with cognitive function at 10 years. Healthy-term newborns were enrolled in this cohort. FM and FFM were measured at birth, 1·5, 2·5, 3·5, 4·5 and 6 months and 4 and 5 years. Cognitive function was assessed using the Peabody Picture Vocabulary Test (PPVT) at 10 years. FM and FFM accretions were computed using statistically independent conditional accretion from 0 to 3 months, 3 to 6 months, 6 months to 4 years and 4 to 5 years. Multiple linear regression was used to assess associations. At the 10-year follow-up, we assessed 318 children with a mean (sd) age of 9·8 (1·0) years. A 1 sd higher birth FFM was associated with a 0·14 sd (95 % CI 0·01, 0·28) higher PPVT at 10 years. FFM accretion from 0 to 3 and 3 to 6 months was associated with PPVT at 10 years: β = 0·5 sd (95 % CI 0·08, 0·93) and β = -0·48 sd (95 % CI -0·90, -0·07, respectively. FFM accretion after 6 months showed no association with PPVT. Neither FM at birth nor 0-5 years accretion showed an association with PPVT. Overall, birth FFM, but not FM, was associated with cognitive function at 10 years, while the association of FFM accretion and cognitive function varied across distinct developmental stages in infancy. The mechanisms underlying this varying association between body composition and cognitive function need further investigation.

Background The extent of cardiac involvement in cystic fibrosis (CF) remains to be determined. The remarkable therapeutic advancements with new highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. We aimed to explore the prevalence of cardiac alterations in people with CF (pwCF) compared to matched controls and investigate potential cardiovascular risk factors. Methods In this cross-sectional study, 104 pwCF underwent clinical and echocardiographic assessment. All participants were matched 1:1 with controls from the general population. Results Of 104 pwCF, 44 % were female, mean age was 34 years, and 93 % received CFTR modulator treatment. The prevalence of abnormal cardiac function in pwCF was 44 %, more than double the prevalence in controls. PwCF were found to have smaller left ventricular (LV) dimensions, worse LV diastolic function, and reduced right ventricle (RV) as well as LV systolic function. After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained poorer in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p = 0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p = 0.008, respectively). Conclusions Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were associated with abnormal cardiac function in pwCF.

The increased burden of non-communicable diseases (NCDs) is fueled by lifestyle factors including diet. This cross-sectional study explored among Tanzanian adults whether unhealthy dietary patterns are associated with intestinal and systemic inflammation which could increase the risk of NCDs. The study included 574 participants, with both diet and inflammatory markers data. Dietary patterns were derived using principal component analysis and reduced rank regression, revealing three main patterns: vegetable-rich, vegetable-poor, and carbohydrate-dense diets. Fecal myeloperoxidase (MPO) and neopterin (NEO) were markers of intestinal inflammation whereas plasma lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP) were assessed as markers of systemic inflammation. Ordinal logistic regression was used to assess associations between terciles of dietary patterns and quintiles of the inflammatory markers adjusting for potential confounders. High adherence to a vegetable-poor dietary pattern was associated with elevated MPO (adjusted OR, 1.7 95% CI 1.1, 2.8). NEO tended to be higher in people with high adherence to both vegetable-poor pattern (adjusted OR, 2.6 95% CI 1.0, 6.4) and vegetable-rich pattern (adjusted OR, 2.7, 95% CI 1.1, 6.5). No associations were found between dietary patterns and systemic inflammation markers (LBP and CRP). We found links between dietary vegetable intake and intestinal inflammation but not systemic inflammation. However, the cross-sectional nature of the study limits establishing causality and the sample size for some variables may have been inadequate, emphasizing the need for further studies to understand how dietary habits influence inflammation in this population.

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs. Emerging evidence indicates an elevated risk of cardiovascular complications in people with CF (pwCF), with some studies implicating CF-related cardiomyopathy as an underlying mechanism. Whether screening for cardiac symptoms and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels may aid in identifying cardiac impairment in pwCF remains unknown. Purpose To assess prevalence of dyspnea and chest pain in pwCF and investigate whether symptoms and NT-pro-BNP are predictive of cardiac impairment. Methods We interviewed 104 adult pwCF and 104 age- and sex-matched controls from the general population about symptoms of dyspnea and chest pain. All participants were examined with transthoracic echocardiography and NT-proBNP. Cardiac impairment was defined as left ventricular (LV) ejection fraction (LVEF) <50%, LV global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Results Chest pain was more frequent in pwCF than in controls: (29% vs. 1%, p<0.001), although primarily characterized as atypical and non-exertional chest pain (27%). PwCF also suffered more from dyspnea than controls (89% vs. 18%, p<0.001) (Figure 1) and more pwCF had abnormal cardiac function compared to controls (44% versus 22%, p<0.001). Median NT-proBNP in pwCF was 50.0 pg/ml (40.7; 100.8) and increasing NT-proBNP level was associated with decreasing FEV1 (L) (estimate: -0.008, p<0.001). NT-proBNP level was not associated with neither dyspnea nor chest pain (p=0.60 and p=0.15, respectively). PwCF with dyspnea did not differ from those without on clinical or echocardiographic parameters. However, pwCF with chest pain had lower absolute GLS compared to pwCF without (17.4% vs.18.5%, p=0.026). Neither dyspnea nor chest pain was more frequent in pwCF with cardiac impairment versus normal cardiac function (54% vs. 39%, p=0.17 and 29% vs. 28%, p=0.91, respectively). Decreasing absolute GLS was associated with increased odds of chest pain (OR 1.25, 95% CI 1.02; 1.53, p=0.030) (Figure 2). Neither dyspnea or chest pain alone, nor in combination with NT-proBNP were able to predict abnormal cardiac function. While dyspnea and chest pain combined showed a slight improvement in sensitivity and positive predictive value for diagnosing cardiac impairment, the combination of symptoms and increased NT-proBNP did not enhance diagnostic accuracy. Conclusions In this cross-sectional study, dyspnea and atypical, non-exertional chest pain were common symptoms in adult pwCF. While abnormal cardiac function was prevalent in pwCF, neither symptoms, NT-proBNP nor a combination of these were associated with increased odds of cardiac impairment. Dyspnea and chest pain, though prevalent, are multifactorial in pwCF and do not seem to serve as sensitive markers of cardiac impairment, even when combined with NT-proBNP level.

Background: Improved growth in children with CF may have resulted from advances in treatment for cystic fibrosis (CF) over the past two decades, including the implementation of newborn screening in Denmark in 2016. This observational cohort study focuses on changes in early growth in Danish children with CF born between 2000 and January 2022. Methods: Age, length/height, and weight data of children 0-5 years old were obtained from the Danish CF Cohort. Data were stratified to four birth cohorts born between 2000 and 2022. Weight-for-age (WAZ), lengthfor-age (LAZ), height-for-age (HAZ) and body-mass-index (BMZ) z-scores were computed using WHO growth curves. Cubic spline mixed effects models were used to evaluate growth over 5 years between birth cohorts. Results: We included 255 children in the analyses. Cubic spline mixed effects models show that catch-up growth improved in birth cohorts over time, with the 2016-2022 birth cohort achieving growth reference curve values in WAZ, LAZ/HAZ and BMZ the earliest. The proportion of underweight and stunting observations among children born 2000-2004 decreased by the 2016-2022 birth cohort, while the proportion of overweight, low BMZ and high BMZ observations increased. Conclusion: Advances in care for young children with CF have led to improvements in growth - with the 2016-2022 birth cohort approaching potential for overweight. Nonetheless, low BMZ remains. Immediate, individualized nutrition care throughout early childhood remain crucial in mitigating malnutrition.

BackgroundPast and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population.MethodsThis nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality.ResultsThe Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts.ConclusionsThe disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.