Evaluation of health care utilisation and mortality in medical hospitalisations with multimorbidity and kidney disease, according to frailty: a nationwide cohort study.

INTRODUCTION: The impact of impaired kidney function on healthcare use among medical hospitalisations with multimorbidity and frailty is incompletely understood. In this study, we assessed the prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD) among multimorbid medical hospitalisations in Switzerland and explored the associations of kidney disease with in-hospital outcomes across different frailty strata. METHODS: This observational study analysed nationwide hospitalisation records from 1 January 2012 to 31 December 2020. We included adults (age ≥18 years) with underlying multimorbidity hospitalised in a medical ward. The study population consisted of hospitalisations with AKI, CKD or no kidney disease (reference group), and was stratified by three frailty levels (non-frail, pre-frail, frail). Main outcomes were in-hospital mortality, intensive care unit (ICU) treatment, length of stay (LOS) and all-cause 30-day readmission. We estimated multivariable adjusted odds ratios (OR) and changes in percentage of log-transformed continuous outcomes with 95% confidence intervals (CI). RESULTS: Among 2,651,501 medical hospitalisations with multimorbidity, 198,870 had a diagnosis of AKI (7.5%), 452,990 a diagnosis of CKD (17.1%) and 1,999,641 (75.4%) no kidney disease. For the reference group, the risk of in-hospital mortality was 4.4%, for the AKI group 14.4% (adjusted odds ratio [aOR] 2.56 [95% CI 2.52-2.61]) and for the CKD group 5.9% (aOR 0.98 [95% CI 0.96-0.99]), while prevalence of ICU treatment was, respectively, 10.5%, 21.8% (aOR 2.39 [95% CI 2.36-2.43]) and 9.3% (aOR 1.01 [95% CI 1.00-1.02]). Median LOS was 5 days (interquartile range [IQR] 2.0-9.0) in hospitalisations without kidney disease, 9 days (IQR 5.0-15.0) (adjusted change [%] 67.13% [95% CI 66.18-68.08%]) in those with AKI and 7 days (IQR 4.0-12.0) (adjusted change [%] 18.94% [95% CI 18.52-19.36%]) in those with CKD. The prevalence of 30-day readmission was, respectively, 13.3%, 13.7% (aOR 1.21 [95% CI 1.19-1.23]) and 14.8% (aOR 1.26 [95% CI 1.25-1.28]). In general, the frequency of adverse outcomes increased with the severity of frailty. CONCLUSION: In medical hospitalisations with multimorbidity, the presence of AKI or CKD was associated with substantial additional hospitalisations and healthcare utilisation across all frailty strata. This information is of major importance for cost estimates and should stimulate discussion on reimbursement.

Longterm-outcomes in patients with Cushing's disease vs. non-functioning pituitary adenoma after pituitary surgery: An active-comparator cohort study.

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 non-functioning 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 (i.e., myocardial infarction, unstable angina, heart failure, cardiac arrest, 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. CD presence was associated with a higher incidence rate of the primary endpoint (40.6 vs. 15.7 events per 1,000 person-years, HR 2.75; 95% CI, 1.54 to 4.90). CD patients also showed increased hospitalization rates for psychiatric disorders (HR 3.27; 95% CI, 1.59 to 6.71) and a trend for sepsis (HR 3.15; 95% CI, 0.95 to 10.40). CONCLUSIONS: Even after pituitary surgery, CD patients faced a higher hazard of complications, especially psychiatric hospitalizations and sepsis.

Trends in antidiabetes medication use among hospitalised patients with type 2 diabetes: a retrospective single-centre cohort study.

OBJECTIVES: Novel antidiabetes medications with proven cardiovascular or renal benefit, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), have been introduced to the market. This study explored the 4-year trends of antidiabetes medication use among medical hospitalisations with type 2 diabetes (T2D). DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital in Switzerland. PARTICIPANTS: 4695 adult hospitalisations with T2D and prevalent or incident use of one of the following antidiabetes medications (metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), sulfonylureas, GLP-1 RA, SGLT-2i, short-acting insulin or long-acting insulin), identified using electronic health record data. Quarterly trends in use of antidiabetes medications were plotted overall and stratified by cardiovascular disease (CVD) and chronic kidney disease (CKD). RESULTS: We observed a stable trend in the proportion of hospitalisations with T2D who received any antidiabetes medication (from 77.6% during 2019 to 78% in 2022; p for trend=0.97). In prevalent users, the largest increase in use was found for SGLT-2i (from 7.4% in 2019 to 21.8% in 2022; p for trend <0.01), the strongest decrease was observed for sulfonylureas (from 11.4% in 2019 to 7.2% in 2022; p for trend <0.01). Among incident users, SGLT-2i were the most frequently newly prescribed antidiabetes medication with an increase from 26% in 2019 to 56.1% in 2022 (p for trend <0.01). Between hospital admission and discharge, SGLT-2i also accounted for the largest increase in prescriptions (+5.1%; p<0.01). CONCLUSIONS: These real-world data from 2019 to 2022 demonstrate a significant shift in antidiabetes medications within the in-hospital setting, with decreased use of sulfonylureas and increased prescriptions of SGLT-2i, especially in hospitalisations with CVD or CKD. This trend aligns with international guidelines and indicates swift adaptation by healthcare providers, signalling a move towards more effective diabetes management.

Corrigendum to "Classifying Hypotonic Hyponatremia by Projected Treatment Effects - A Quantitative 3-Dimensional Framework" [Kidney International Reports Volume 8, Issue 12, December 2023, Pages 2720-2732].

[This corrects the article DOI: 10.1016/j.ekir.2023.09.002.].

Cardiovascular risk in patients with acromegaly vs. non-functioning pituitary adenoma following pituitary surgery: an active-comparator cohort study.

PURPOSE: Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients with acromegaly and non-functioning pituitary adenoma (NFPA) following pituitary surgery. METHODS: This was a nationwide cohort study using data from hospitalized patients with acromegaly or NFPA undergoing pituitary surgery in Switzerland between January 2012 and December 2021. Using 1:3 propensity score matching, eligible acromegaly patients were paired with NFPA patients who underwent pituitary surgery, respectively. The primary outcome comprised a composite of cardiovascular events (myocardial infarction, cardiac arrest, ischemic stroke, hospitalization for heart failure, unstable angina pectoris, cardiac arrhythmias, intracranial hemorrhage, hospitalization for hypertensive crisis) and all-cause mortality. Secondary outcomes included individual components of the primary outcome, surgical re-operation, and various hospital-associated outcomes. RESULTS: Among 231 propensity score-matched patients with acromegaly and 491 with NFPA, the incidence rate of the primary outcome was 8.18 versus 12.73 per 1,000 person-years (hazard ratio [HR], 0.64; [95% confidence interval [CI], 0.31-1.32]). Mortality rates were numerically lower in acromegaly patients (2.43 vs. 7.05 deaths per 1,000 person-years; HR, 0.34; [95% CI, 0.10-1.17]). Individual components of the primary outcome and in-hospital outcomes showed no significant differences between the groups. CONCLUSION: This cohort study did not find an increased risk of cardiovascular outcomes and mortality in patients with acromegaly undergoing pituitary surgery compared to surgically treated NFPA patients. These findings suggest that there is no legacy effect regarding higher cardio-metabolic risk in individuals with acromegaly once they receive surgical treatment.

Association of tryptophan pathway metabolites with mortality and effectiveness of nutritional support among patients at nutritional risk: secondary analysis of a randomized clinical trial.

Tryptophan is an essential amino acid and is the precursor of many important metabolites and neurotransmitters. In malnutrition, the availability of tryptophan is reduced, potentially putting patients at increased risks. Herein, we investigated the prognostic implications of the tryptophan metabolism in 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 trial comparing individualized nutritional support to usual care in patients at risk for malnutrition. Among 238 patients with available measurements, low plasma levels of metabolites were independently associated with 30-day mortality with adjusted hazard ratios (HR) of 1.77 [95% CI 1.05-2.99, p 0.034] for tryptophan, 3.49 [95% CI 1.81-6.74, p < 0.001] for kynurenine and 2.51 [95% CI 1.37-4.63, p 0.003] for serotonin. Nutritional support had more beneficial effects on mortality in patients with high tryptophan compared to patients with low tryptophan levels (adjusted HR 0.61 [95% CI 0.29-1.29] vs. HR 1.72 [95% CI 0.79-3.70], p for interaction 0.047). These results suggest that sufficient circulating levels of tryptophan might be a metabolic prerequisite for the beneficial effect of nutritional interventions in this highly vulnerable patient population.

Prognostic implications of the arginine metabolism in patients at nutritional risk: A secondary analysis of the randomized EFFORT trial.

BACKGROUND: Arginine, a conditionally essential amino acid, is key component in metabolic pathways including immune regulation and protein synthesis. Depletion of arginine contributes to worse outcomes in severely ill and surgical patient populations. We assessed prognostic implications of arginine levels and its metabolites and ratios in polymorbid medical inpatients at nutritional risk regarding clinical outcomes and treatment response. METHODS: 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), we investigated the association of arginine, its metabolites and ratios (i.e., ADMA and SDMA, ratios of arginine/ADMA, arginine/ornithine, and global arginine bioavailability ratio) measured on hospital admission with short-term and long-term mortality by means of regression analysis. RESULTS: Among the 231 patients with available measurements, low arginine levels ≤90.05 µmol/l (n = 86; 37 %) were associated with higher all-cause mortality at 30 days (primary endpoint, adjusted HR 3.27, 95 % CI 1.86 to 5.75, p < 0.001) and at 5 years (adjusted HR 1.50, 95 % CI 1.07 to 2.12, p = 0.020). Arginine metabolites and ratios were also associated with adverse outcome, but had lower prognostic value. There was, however, no evidence that treatment response was influenced by admission arginine levels. CONCLUSION: This secondary analysis focusing on medical inpatients at nutritional risk confirms a strong association of low plasma arginine levels and worse clinical courses. The potential effects of arginine-enriched nutritional supplements should be investigated in this population of patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov as NCT02517476 (registered 7 August 2015).

Rate of cardiovascular events up to 8 years after uncomplicated myocarditis: a nationwide cohort study.

AIMS: While prognosis of acute myocarditis with uncomplicated presentation is perceived as benign, data on long-term outcomes are scarce. We evaluated rates of myocarditis-associated cardiovascular events after a first-time hospitalization with uncomplicated acute myocarditis in patients without known heart disease. METHODS AND RESULTS: In this retrospective nationwide population-based cohort study from 2013 to 2020, hospitalized patients with uncomplicated acute myocarditis but without known heart disease were 1:1 propensity score-matched with surgical controls hospitalized for laparoscopic appendectomy. As assessed in time-to-event analyses, the primary outcome was a composite of rehospitalization for myocarditis, pericardial disease, heart failure and its complications, arrhythmias, implantation of cardiac devices, and heart transplant. After matching, we identified 1439 patients with uncomplicated acute myocarditis (median age of 35 years, 74.0% male) and 1439 surgical controls (median age of 36 years, 74.4% male). Over a median follow-up of 39 months, compared with surgical controls, the hazard ratio for the primary composite outcome was 42.3 [95% confidence interval (CI) 17.4-102.8], corresponding to an incidence rate of 43.7 vs. 0.9 per 1000 patient-years (py) and an incidence rate difference of 42.7 (95% CI 36.7-48.8) per 1000 py. CONCLUSION: Patients hospitalized with uncomplicated acute myocarditis and no known prior heart disease were associated with substantial risk for cardiovascular events over a follow-up of up to 8 years. This calls for a more efficient therapeutic management of this population of patients.

Adaptation of nutritional risk screening tools may better predict response to nutritional treatment: a secondary analysis of the randomized controlled trial Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT).

BACKGROUND: Nutritional screening tools have proven valuable for predicting clinical outcomes but have failed to determine which patients would be most likely to benefit from nourishment interventions. The Nutritional Risk Screening 2002 (NRS) and the Mini Nutritional Assessment (MNA) are 2 of these tools, which are based on both nutritional parameters and parameters reflecting disease severity. OBJECTIVES: We hypothesized that the adaptation of nutritional risk scores, by removing parameters reflecting disease severity, would improve their predictive value regarding response to a nutritional intervention while providing similar prognostic information regarding mortality at short and long terms. METHODS: We reanalyzed data of 2028 patients included in the Swiss-wide multicenter, randomized controlled trial EFFORT (Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial) comparing individualized nutritional support with usual care nutrition in medical inpatients. The primary endpoint was 30-d all-cause mortality. RESULTS: Although stratifying patients by high compared with low NRS score showed no difference in response to nutritional support, patients with high adapted NRS showed substantial benefit, whereas patients with low adapted NRS showed no survival benefit [adjusted hazard ratio: 0.55 [95% confidence interval (CI): 0.37, 0.80]] compared with 1.17 (95% CI: 0.70, 1.93), a finding that was significant in an interaction analysis [coefficient: 0.48 (95% CI: 0.25, 0.94), P = 0.031]. A similar effect regarding treatment response was found when stratifying patients on the basis of MNA compared with the adapted MNA. Regarding the prognostic performance, both original scores were slightly superior in predicting mortality than the adapted scores. CONCLUSIONS: Adapting the NRS and MNA by including nutritional parameters only improves their ability to predict response to a nutrition intervention, but slightly reduces their overall prognostic performance. Scores dependent on disease severity may best be considered prognostic scores, whereas nutritional risk scores not including parameters reflecting disease severity may indeed improve a more personalized treatment approach for nourishment interventions. The trial was registered at clinicaltrials.gov as NCT02517476.

Red blood cell distribution width (RDW) - A new nutritional biomarker to assess nutritional risk and response to nutritional therapy?

BACKGROUND & AIMS: Red cell distribution width (RDW) has been proposed as a surrogate marker for acute and chronic diseases and may be influenced by nutritional deficits. We assessed the prognostic value of RDW regarding clinical outcomes and nutritional treatment response among medical inpatients at nutritional risk. METHODS: This is a secondary analysis of EFFORT, a randomized, controlled, prospective, multicenter trial investigating the effects of nutritional support in patients at nutritional risk in eight Swiss hospitals. We examined the association between RDW and mortality in regression analysis. RESULTS: Among 1,244 included patients (median age 75 years, 46.6 % female), high RDW (≥15 %) levels were found in 38 % of patients (n = 473) with a significant association of higher malnutrition risk [OR 1.48 (95%CI 1.1 to 1.98); p = 0.009]. Patients with high RDW had a more than doubling in short-term (30 days) mortality risk [adjusted HR 2.12 (95%CI 1.44 to 3.12); p < 0.001] and a signficant increase in long-term (5 years) mortality risk [adjusted HR 1.73 (95%CI 1.49 to 2.01); p < 0.001]. Among patients with high RDW, nutritional support reduced morality within 30 days [adjusted OR 0.56 (95%CI 0.33 to 0.96); p = 0.035], while the effect of the nutritional intervention in patients with low RDW was markedly smaller. CONCLUSIONS: Among medical patients at nutritional risk, RDW correlated with several nutritional parameters and was a strong prognostic marker for adverse clinical outcomes at short- and long-term, respectively. Patients with high baseline RDW levels also showed a strong benefit from the nutritional intervention. Further research is needed to understand whether monitoring of RDW over time severs as a nutritional biomarker to assess effectiveness of nutritional treatment in the long run. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Association of Glutamine and Glutamate Metabolism with Mortality among Patients at Nutritional Risk-A Secondary Analysis of the Randomized Clinical Trial EFFORT.

Glutamine and its metabolite glutamate serve as the main energy substrates for immune cells, and their plasma levels drop during severe illness. Therefore, glutamine supplementation in the critical care setting has been advocated. However, little is known about glutamine metabolism in severely but not critically ill medical patients. We investigated the prognostic impact of glutamine metabolism in 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 trial comparing individualized nutritional support to usual care in patients at nutritional risk. Among 234 patients with available measurements, low plasma levels of glutamate were independently associated with 30-day mortality (adjusted HR 2.35 [95% CI 1.18-4.67, p = 0.015]). The impact on mortality remained consistent long-term for up to 5 years. No significant association was found for circulating glutamine levels and short- or long-term mortality. There was no association of glutamate nor glutamine with malnutrition parameters or with the effectiveness of nutritional support. This secondary analysis found glutamate to be independently prognostic among medical inpatients at nutritional risk but poorly associated with the effectiveness of nutritional support. In contrast to ICU studies, we found no association between glutamine and clinical outcome.

Treatment of glucocorticoid- induced hyperglycemia in hospitalized patients - a systematic review and meta- analysis.

PURPOSE: Glucocorticoid (GC)-induced hyperglycemia is a frequent issue, however there are no specific guidelines for this diabetes subtype. Although treat-to-target insulin is recommended in general to correct hyperglycemia, it remains unclear which treatment strategy has a positive effect on outcomes. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess whether treating GC-induced hyperglycemia improves clinical outcomes. METHODS: MEDLINE and EMBASE were systematically searched for RCTs on adults reporting treatment and outcomes of GC-induced hyperglycemia since the beginning of the data bases until October 21, 2023. Glucose-lowering strategies as compared to usual care were investigated. RESULTS: We found 17 RCTs with 808 patients and included seven trials in the quantitative analysis. Patients with an intensive glucose-lowering strategy had lower standardized mean glucose levels of - 0.29 mmol/l (95%CI -0.64 to -0.05) compared to usual care group patients. There was no increase in hypoglycemic events in the intensively treated groups (RR 0.91, 95%CI 0.70-1.17). Overall, we did not have enough trials reporting clinical outcomes for a quantitative analysis with only one trial reporting mortality. CONCLUSION: In GC-induced hyperglycemia, tight glucose control has a moderate effect on mean glucose levels with no apparent harmful effect regarding hypoglycemia. There is insufficient data whether insulin treatment improves clinical outcomes, and data on non-insulin based treatment regimens are currently too sparse to draw any conclusions. SYSTEMATIC REVIEW REGISTRATION: Registered as CRD42020147409 at PROSPERO ( https://www.crd.york.ac.uk/prospero/ ) on April 28, 2020.

Adjunct prednisone in community-acquired pneumonia: 180-day outcome of a multicentre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia). METHODS: This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence. RESULTS: From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension. CONCLUSIONS: In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP. TRIAL REGISTRATION: This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.

Hospital Outcomes in Medical Patients With Alcohol-Related and Non-Alcohol-Related Wernicke Encephalopathy.

OBJECTIVE: To conduct a nationwide retrospective cohort study to assess trends and hospitalization-associated outcomes in patients with Wernicke encephalopathy. PATIENTS AND METHODS: In this nationwide retrospective cohort study, we used in-hospital claims data of patients hospitalized with Wernicke encephalopathy in Switzerland from January 1, 2012, to December 31, 2020. We estimated incidence rates per 100,000 person-years among the overall Swiss population stratified by alcohol and non-alcohol-induced Wernicke encephalopathy. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included progression to Korsakoff syndrome and 1-year hospital readmission. We estimated odds ratios (ORs) for binary outcomes. RESULTS: It was found that 4098 of 4393 hospitalizations (93.3%) for Wernicke encephalopathy during the 8-year study were alcohol-related. Incidence rates for hospitalizations were 14-fold higher in alcohol-related compared with non-alcohol-related Wernicke encephalopathy (5.43 vs 0.39 per 100,000 person-years). The risk for in-hospital mortality was significantly lower in patients with alcohol-related vs non-alcohol-related Wernicke encephalopathy (3.2% vs 8.5%; adjusted OR, 0.38; 95% CI, 0.23 to 0.62). Patients with alcohol-related Wernicke encephalopathy had higher risk for development of Korsakoff syndrome (16.9% vs 1.7%; adjusted OR, 10.64; 95% CI, 4.37 to 25.92) and 1-year hospital readmission (31.6% vs 18.7%; adjusted OR, 1.4; 95% CI, 1.04 to 1.88). CONCLUSION: In this Swiss nationwide cohort study, Wernicke encephalopathy was a rare but serious cause for hospitalization and mainly alcohol-related. Patients with alcohol-related Wernicke encephalopathy had lower risks of in-hospital mortality but were more likely to develop Korsakoff syndrome and be readmitted to the hospital.

Classifying Hypotonic Hyponatremia by Projected Treatment Effects - A Quantitative 3-Dimensional Framework.

Introduction: The diagnostic algorithms currently used for hypotonic hyponatremia focus primarily on impaired urinary dilution and often neglect the influence of free water intake and solute excretion. We hypothesized that, in each case of hypotonic hyponatremia different pathophysiological mechanisms play a role simultaneously. Methods: Using clinical data of the previous observational Co-Med study, we defined each case of hypotonic hyponatremia concurrently in 3 dimensions as follows: (i) high net free water intake (HNFWI), (ii) impaired dilution of the urine (IDU), and (iii) low nonelectrolyte solute excretion (LNESE). For each dimension, a "standard delta sodium" (sdna) was calculated reflecting the expected difference to the serum sodium concentration, that would result from changing a dimension to a specific and equivalent target level. Results: Results from 279 patients were used for this analysis. With target levels of free water intake and urine osmolality at the fifth percentile, and nonelectrolyte solute excretion at the 95th percentile, median (interquartile range) sdna values were 7.1 (4.8-10.2) for HNFWI, 11.8 (7.0-18.6) for IDU and 2.6 (1.6-4.2) mmol/l per 24 hours for LNESE. Sdna results in individual patients were highest with IDU in 68.5%, HNFWI in 30.8% and 0.7% with LNESE. At an sdna-level of at least 4mmol/l per 24 hours, the prevalence of HNFWI was 78.9%, IDU 87.1%, and LNESE 26.5%. 77.5% of patients had 2 or all 3 mechanisms present. Hyponatremia was mostly multifactorial in subgroups according to classic categories of hyponatremia and typical comorbidities as well. Conclusion: Hypotonic hyponatremia can be quantitatively defined by 3 dimensions. Most cases should be considered multifactorial.

Barakat syndrome diagnosed decades after initial presentation.

Summary: Barakat syndrome, also called HDR syndrome, is a rare genetic disorder encompassing hypoparathyroidism (H), sensorineural deafness (D) and renal disease (R). A 64-year-old woman was referred to our endocrinology clinic for a switch in treatment (from dihydrotachysterol to calcitriol). She had progressive sensorineural deafness since the age of 18 and idiopathic hypoparathyroidism diagnosed at age of 36. Her medical history included osteoporosis with hip/spine fractures, nephrolithiasis and a family history of hearing loss, osteoporosis and kidney disease. The patient's clinical presentation indicated Barakat syndrome. Genetic analysis found a GATA3:c.916C>T nonsense variant. Further tests such as audiometry, labs and renal imaging supported the diagnosis. Due to rarity and manifold symptoms, diagnosis can be challenging. Optional GATA3 testing was suggested in 2018, except in cases of isolated sensorineural deafness or renal disease with pertinent family history. In isolated 'H' cases without 'D' and 'R', GATA3 studies are not required, as no haploinsufficiency cases were reported. Given the rise in genetic disorders, physicians should consistently consider rare genetic disorders in patients with suggestive symptoms, even decades after onset. Although diagnosis might not always impact management directly, it aids patients in accepting their condition and has broader family implications. Learning points: There is currently an important increase in genetic and clinical characterization of new orphan diseases and their causative agents. Unbiased re-evaluation for possible genetic disorders is necessary at every consultation. It is essential to recognize the differential diagnosis of idiopathic hypoparathyroidism. The patient's clinical presentation and family history can be important to establish the correct diagnosis. Physicians should not hesitate to search a patient's signs and symptoms online.

Association of admission cortisol levels with outcomes and treatment response in patients at nutritional risk : A secondary analysis of a randomized clinical trial.

INTRODUCTION: Cortisol is a metabolically active stress hormone that may play a role in the pathogenesis of malnutrition. We studied the association between admission cortisol levels and nutritional parameters, disease severity, and response to nutritional support among medical inpatients at nutritional risk. METHODS: Admission cortisol was measured in a subset of 764 patients participating in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicentre, randomized-controlled trial that compared individualized nutritional support with usual nutritional care. RESULTS: Overall, mean cortisol levels were 570 (± 293) nmol/L and significantly higher in patients with high nutritional risk (NRS ≥ 5) and in patients reporting loss of appetite. Cortisol levels in the highest quartile (> 723 nmol/l) were associated with adverse outcomes including mortality at 30 days and 5 years (adjusted HR 2.31, [95%CI 1.47 to 3.62], p = 0.001 and 1.51, [95%CI 1.23 to 1.87], p < 0.001). Nutritional treatment tended to be more effective regarding mortality reduction in patients with high vs. low cortisol levels (adjusted OR of nutritional support 0.54, [95%CI 0.24 to 1.24] vs. OR 1.11, [95%CI 0.6 to 2.04], p for interaction = 0.134). This effect was most pronounced in the subgroup of patients with severe malnutrition (NRS 2002 ≥ 5, p for interaction = 0.047). CONCLUSION: This secondary analysis of a randomized nutritional trial suggests that cortisol levels are linked to nutritional and clinical outcome among multimorbid medical patients at nutritional risk and may help to improve risk assessment, as well as response to nutritional treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Rate of Cardiovascular Events and Safety Outcomes Seven Years Following Gastric Bypass Versus Sleeve Gastrectomy.

Objective: The study aimed to assess major adverse cardiovascular events (MACEs), complications requiring revision surgery, and bariatric conversion surgery 7 years after gastric bypass (GB) and sleeve gastrectomy (SG) using real-world data. Background: GB and SG both result in weight loss and improved cardiometabolic health. Whether the long-term rate of MACE differs between the 2 bariatric procedures is unclear. Methods: In this population-based retrospective cohort study, we used inhospital National Health Registry data from January 2012 to December 2018. Patients undergoing GB were 1:1 propensity score-matched with patients who had SG. The primary outcome was the incidence of MACE, defined as acute myocardial infarction, ischemic stroke, cardiac arrest, or hospitalization for heart failure. Secondary outcomes encompassed individual MACE components, postoperative complications, and the need for bariatric conversion surgery. Results: Among 5240 propensity score-matched pairs, the incidence rate per 1000 person-years of MACE was 2.8 among patients undergoing GB and 3.2 among those undergoing SG (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.62-1.37). Single components of MACE were not different between both groups. Patients after GB had a higher risk of long-term postoperative complications requiring a revision surgery compared with those after SG (HR, 3.53 [95% CI, 2.78-4.49]). Bariatric conversion surgery was less frequently performed among patients undergoing GB compared with patients undergoing SG (HR, 0.09 [95% CI, 0.06-0.13]). Conclusions: In this study, the performance of GB versus SG was associated with a similar risk of MACE. While postoperative complications were more frequent among patients undergoing GB, patients following SG had a higher probability of bariatric conversion surgery.

Changes in serum albumin concentrations over 7 days in medical inpatients with and without nutritional support. A secondary post-hoc analysis of a randomized clinical trial.

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.

Prediction of In-Hospital Falls Using NRS, PACD Score and FallRS: A Retrospective Cohort Study.

BACKGROUND: Harmful in-hospital falls with subsequent injuries often cause longer stays and subsequently higher costs. Early identification of fall risk may help in establishing preventive strategies. OBJECTIVE: To assess the predictive ability of different clinical scores including the Post-acute care discharge (PACD) score and nutritional risk screening score (NRS), and to develop a new fall risk score (FallRS). METHODS: A retrospective cohort study of medical in-patients of a Swiss tertiary care hospital from January 2016 to March 2022. We tested the ability of the PACD score, NRS and FallRS to predict a fall by using the area under curve (AUC). Adult patients with a length of stay of ≥ 2 days were eligible. RESULTS: We included 19,270 admissions (43% females; median age, 71) of which 528 admissions (2.74%) had at least one fall during the hospital stay. The AUC varied between 0.61 (95% confidence interval (CI), 0.55-0.66) for the NRS and 0.69 (95% CI, 0.64-0.75) for the PACD score. The combined FallRS score had a slightly better AUC of 0.70 (95% CI, 0.65-0.75) but was more laborious to compute than the two other scores. At a cutoff of 13 points, the FallRS had a specificity of 77% and a sensitivity of 49% in predicting falls. CONCLUSIONS: We found that the scores focusing on different aspects of clinical care predicted the risk of falls with fair accuracy. A reliable score with which to predict falls could help in establishing preventive strategies for reducing in-hospital falls. Whether or not the scores presented have better predictive ability than more specific fall scores do will need to be validated in a prospective study.