Peroperative administration of tranexamic acid in Roux-en-Y and one-anastomosis gastric bypass to reduce haemorrhage in patients with morbid obesity: protocol for randomised controlled trial (PATRY trial).

INTRODUCTION: By implementation of Enhanced Recovery After Bariatric Surgery protocols and day-care surgery, early discharge poses a challenge if excessive bleeding occurs after bariatric surgery. Tranexamic acid (TXA) has demonstrated efficacy in other surgical fields and in bariatric pilot studies. This trial aims to assess the efficacy of peroperative administration of TXA in reducing haemorrhage in patients undergoing gastric bypass surgery. METHOD AND ANALYSIS: This is a multicentre, phase III, double-blind randomised controlled trial in six high-volume bariatric centres in the Netherlands. A total of 1524 eligible patients, aged 18 years or older, undergoing primary gastric bypass surgery (either Roux-en-Y gastric bypass or one-anastomosis gastric bypass) will be randomised between TXA and placebo (1:1, variable block, stratified for centre, day-care/overnight stay and type of surgery) after obtaining informed consent (2.5% less haemorrhage, power 80%, 2-sided-α 0.05 and 10% dropout). Exclusion criteria are pregnancy, amedical history of acute bleeding (without cause), venous thrombotic events (VTEs), epilepsy, anticoagulant use and iatrogenic bleeding during surgery (aside from staple line). The primary outcome is postoperative haemorrhage requiring intervention within 30 days postoperatively. Secondary outcome measures are staple line reinforcement, blood loss, duration of surgery, postoperative haemoglobin, vital parameters, minor and major complications, side effects of TXA (nausea, hypotension and VTE), length of hospital stay and directly made costs. ETHICS AND DISSEMINATION: Written informed consent will be obtained from all participants. The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 7 February 2023 (registration number: R22.102). Results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT05464394.

Why Veterans Choose VA Versus non-VA Emergency Care: A Qualitative Study.

INTRODUCTION: In ensuring the timely delivery of emergency care to Veterans, Veterans Affairs (VA) offers both emergency care services in its own facilities and, increasingly, purchases care for Veterans in non-VA (community) emergency department (ED) settings. Although in recent years emergency care coverage has become the single largest contributor to VA community care spending, no study to date has examined Veteran decision-making as it relates to ED setting choice. The purpose of this study is to identify and describe reasons why Veterans choose VA versus non-VA emergency care settings. MATERIALS AND METHODS: Veterans Health Administration data were used to identify geographically diverse Veterans who recently used emergency care. We conducted semi-structured telephone interviews from December 2018 through March 2020 with 50 Veterans to understand the factors Veterans consider when deciding where to obtain ED care. Interviews were audio-recorded and transcribed verbatim. We conducted a directed content analysis of interview transcripts and developed a matrix to summarize and categorize each Veteran's decision-making process to compare participants and to identify common patterns. RESULTS: When choosing between VA and non-VA-EDs, Veterans described 3 distinct patterns of decision-making: (1) choosing the closest ED (often community) for acute conditions; (2) traveling farther for VA care due to preference and financial coverage; and (3) selecting VA when both types of ED care were equidistant. Perceptions of community resources, condition-specific needs, financial considerations, and personal preferences dominated the decision-making. For example, most Veterans (74%) rated their acuity as high, and self-perceived severity/urgency of their condition was the most cited factor influencing where Veterans decided to go for ED care. CONCLUSIONS: Our qualitative results help provide insight into how and why Veterans choose to seek emergency care. As the number of Veterans treated in non-VA EDs continues to rise, VA and non-VA ED providers as well as policy makers may benefit from understanding the challenges Veterans face when making this decision.

Within-individual reproducibility of a dual sample oral cholate challenge test (DuO) and simplified versions of the HepQuant SHUNT test.

Current noninvasive liver tests measure fibrosis, inflammation, or steatosis and do not measure function. The HepQuant platform of noninvasive tests uniquely assesses both liver function and physiology through the hepatic uptake of stable isotopes of cholate. However, the prototypical HepQuant SHUNT test (SHUNT V1.0) is cumbersome to administer, requiring intravenous and oral administration of cholate and six peripheral venous blood samples over 90 min. To alleviate the burden of test administration, we explored whether an oral only (DuO) version, and other simplified versions, of the test could provide reproducible measurements of liver function. DuO requires only oral dosing and two blood samples over 60 min. The simplified SHUNT test versions were SHUNT V1.1 (oral and IV dosing but four blood samples) and SHUNT V2.0 (oral and IV dosing but only two blood samples over 60 min). In this paper, we describe the reproducibility of DuO and the simplified SHUNT tests relative to that of SHUNT V1.0; equivalency is described in a separate paper. Data from two studies comprising 236 SHUNT tests in 94 subjects were analyzed retrospectively by each method. All simplified methods were highly reproducible across test parameters with intraclass correlation coefficients >0.93 for test parameters Disease Severity Index (DSI) and Hepatic Reserve. DuO and SHUNT V2.0 improved reproducibility in measuring portal-systemic shunting (SHUNT%). These simplified tests, particularly DuO and SHUNT V2.0, are easier to administer and less invasive, thus, having the potential to be more widely accepted by care providers administering the test and by patients receiving the test.

Genetic and pharmacological reduction of CDK14 mitigates synucleinopathy.

Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons (DaNs) and the abnormal accumulation of α-Synuclein (α-Syn) protein. Currently, no treatment can slow nor halt the progression of PD. Multiplications and mutations of the α-Syn gene (SNCA) cause PD-associated syndromes and animal models that overexpress α-Syn replicate several features of PD. Decreasing total α-Syn levels, therefore, is an attractive approach to slow down neurodegeneration in patients with synucleinopathy. We previously performed a genetic screen for modifiers of α-Syn levels and identified CDK14, a kinase of largely unknown function as a regulator of α-Syn. To test the potential therapeutic effects of CDK14 reduction in PD, we ablated Cdk14 in the α-Syn preformed fibrils (PFF)-induced PD mouse model. We found that loss of Cdk14 mitigates the grip strength deficit of PFF-treated mice and ameliorates PFF-induced cortical α-Syn pathology, indicated by reduced numbers of pS129 α-Syn-containing cells. In primary neurons, we found that Cdk14 depletion protects against the propagation of toxic α-Syn species. We further validated these findings on pS129 α-Syn levels in PD patient neurons. Finally, we leveraged the recent discovery of a covalent inhibitor of CDK14 to determine whether this target is pharmacologically tractable in vitro and in vivo. We found that CDK14 inhibition decreases total and pathologically aggregated α-Syn in human neurons, in PFF-challenged rat neurons and in the brains of α-Syn-humanized mice. In summary, we suggest that CDK14 represents a novel therapeutic target for PD-associated synucleinopathy.

Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child-Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine.

HepQuant tests quantify liver function from clearance of deuterium- and 13C-labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child-Pugh classification to categorize the degree of hepatic dysfunction. We compared HepQuant tests with Child-Pugh classification in predicting the pharmacokinetics of ampreloxetine. Twenty-one subjects with hepatic impairment (8 Child-Pugh A, 7 Child-Pugh B, and 6 Child-Pugh C), and 10 age- and sex-matched controls were studied. The pharmacokinetics of ampreloxetine were measured after oral administration of a single dose of 10 mg. Disease severity index (DSI), portal-systemic shunting (SHUNT%), hepatic reserve, and hepatic filtration rates (HFRs) were measured from serum samples obtained after intravenous administration of [24-13C]-cholate and oral administration of [2,2,4,4-2H]cholate. Ampreloxetine plasma exposure (AUC0-inf) was similar to controls in Child-Pugh A, increased 1.7-fold in subjects with Child-Pugh B, and 2.5-fold in subjects with Child-Pugh C and correlated with both Child-Pugh score and HepQuant parameters. The variability observed in ampreloxetine exposure (AUC0-inf) in subjects with moderate (Child-Pugh B) and severe hepatic impairment (Child-Pugh C) was explained by HepQuant parameters. Multivariable regression models demonstrated that DSI, SHUNT%, and Hepatic Reserve from SHUNT and DuO were superior predictors of ampreloxetine exposure (AUC0-inf) compared to Child-Pugh score. HepQuant DSI, SHUNT%, and hepatic reserve were more useful predictors of drug exposure than Child-Pugh class for ampreloxetine and thus may better optimize dose recommendations in patients with liver disease. The simple-to-administer, oral-only DuO version of the HepQuant test could enhance clinical utility.

Relationship between malaria vector survival, infectivity and insecticide treated net use in western Kenya.

Background: Much effort and resources have been invested to control malaria transmission in Sub-Saharan Africa, but it remains a major public health problem. For the disease to be transmitted from one person to another, the female Anopheles vector must survive 10-14 days following an infective bite for the Plasmodiumgametocytes to develop into infectious sporozoites which can be transmitted to the next person during a bloodmeal. The goal of this investigation was to assess factors associated with wild-caught Anopheles survival and infection following host-seeking and indoor resting. Methods: The study was conducted in a longitudinal cohort of 75 households in 5 villages including a total of 755 household members in Bungoma County, Kenya. Monthly adult mosquito collection was conducted by attenuated aspiration in all the enrolled households, and the mosquitoes were reared in the insectary for 7 days. The daily mortality rate was determined through day 7, and all the mosquitoes were morphologically identified. Female Anopheline mosquitoes were dissected, and species-level members of the Anopheles gambiae complex were resolved by molecular methods. The abdomen for all samples were processed for P. falciparum detection by PCR. Results: Within a period of 25 months, the total number of culex and Anopheles mosquitoes collected indoors were 12,843 and 712 respectively. Anopheles gambiaeand Anopheles funestus were the major vectors though their population varied between different villages. 61.2% (n=436/712) of the Anopheles species survived up to day 7 with the lowest mortality rate recorded on day 5 of captivity. The survival rate also varied between the different Anophelesspecies. 683 of 712 mosquito abdomens were tested for P. falciparumdetection and 7.8% (53/683) tested positive for P. falciparum with An. funestus having a higher (10%) prevalence than An. gambaie s.s.(6.0%, p=0.095, Pearson Chi square test). The proportion of household members sleeping under a bednet the night before mosquito collection varied across time and village. An. funestus survival times were refractory to household ITN coverage and An. gambaie s.s. survival was reduced only under very high (>95%) ITN coverage. Conclusion: Despite ITN coverage, mosquitoes still acquired bloodmeals and P. falciparum infections. Survival differed across species and was inversely correlated with high ITN exposure in the household, but not oocyst development.

Diagnostic survey of analytical methods used to determine bone mineralization in pigs.

Pigs from 64 commercial sites across 14 production systems in the Midwest United States were evaluated for baseline biological measurements used to determine bone mineralization. There were three pigs selected from each commercial site representing: 1) a clinically normal pig (healthy), 2) a pig with evidence of clinical lameness (lame), and 3) a pig from a hospital pen that was assumed to have recent low feed intake (unhealthy). Pigs ranged in age from nursery to market weight, with the three pigs sampled from each site representing the same age or phase of production. Blood, urine, metacarpal, fibula, 2nd rib, and 10th rib were collected and analyzed. Each bone was measured for density and ash (defatted and non-defatted technique). A bone × pig type interaction (P < 0.001) was observed for defatted and non-defatted bone ash and density. For defatted bone ash, there were no differences among pig types for the fibulas, 2nd rib, and 10th rib (P > 0.10), but metacarpals from healthy pigs had greater (P < 0.05) percentage bone ash compared to unhealthy pigs, with the lame pigs intermediate. For non-defatted bone ash, there were no differences among pig types for metacarpals and fibulas (P > 0.10), but unhealthy pigs had greater (P < 0.05) non-defatted percentage bone ash for 2nd and 10th ribs compared to healthy pigs, with lame pigs intermediate. Healthy and lame pigs had greater (P < 0.05) bone density than unhealthy pigs for metacarpals and fibulas, with no difference observed for ribs (P > 0.10). Healthy pigs had greater (P < 0.05) serum Ca and 25(OH)D3 compared to unhealthy pigs, with lame pigs intermediate. Healthy pigs had greater (P < 0.05) serum P compared to unhealthy and lame pigs, with no differences between the unhealthy and lame pigs. Unhealthy pigs excreted significantly more (P < 0.05) P and creatinine in the urine compared to healthy pigs with lame pigs intermediate. In summary, there are differences in serum Ca, P, and vitamin D among healthy, lame, and unhealthy pigs. Differences in bone mineralization among pig types varied depending on the analytical procedure and bone, with a considerable range in values within pig type across the 14 production systems sampled.

There is little literature or data comparing bone diagnostic results for healthy, lame, and unhealthy pigs. Typically, diagnosticians assessing clinical lameness cases in pigs will measure bone mineralization along with histopathological evaluation to diagnose and assess the severity of metabolic bone disease. Bone ash is the primary method to determine bone mineralization, with the removal of the lipid in the bone (defatting) before the bone is ashed, compared to not removing the lipid before the ashing (non-defatted). Defatting the bone reduces the amount of variation across the bones compared to non-defatting. In this diagnostic survey, there was no difference among the healthy, lame, or unhealthy pigs when comparing defatted bone ash, however, unhealthy pigs had an increased bone ash percentage compared to the healthy and lame pigs when the bones were assessed using the non-defatted procedure. There was variation across production systems and pig types for serum vitamin D. When comparing the pig types, healthy pigs had increased serum Ca, P, and vitamin D [25(OH)D3] compared to the unhealthy pigs, with the lame pigs intermediate.

Green Light from Red-Emitting Nanocrystals: Broadband, Low-Threshold Lasing from Colloidal Quantum Shells in Optical Nanocavities.

Spherical semiconductor nanoplatelets, known as quantum shells (QSs), have captured significant interest for their strong suppression of Auger recombination, which leads to long multiexciton lifetimes and wide optical gain bandwidth. Yet, the realization of benefits associated with the multiexciton lasing regime using a suitably designed photonic cavity remains elusive. Here, we demonstrate broadly tunable lasing from close-packed films of CdS/CdSe/CdS QSs deposited over nanopillar arrays on Si substrates. Wide spectral tuning of the stimulated emission in QSs with a fixed bandgap value was achieved by engaging single exciton (λX ∼ 634 nm), biexciton (λBX ∼ 627 nm), and multiple exciton (λMX ∼ 615-565 nm) transitions. The ensemble-averaged gain threshold of ∼ 2.6 electron-hole pairs per QS particle and the low photonic cavity fluence threshold of ∼4 µJ/cm2 were attributed to Auger suppression. The tuning of the lasing emission closely aligns with our model predictions achieved by varying the array period while preserving mode confinement and quality (Q) factors. These results mark a notable step toward the development of colloidal nanocrystal lasers.

Neuropathological Assessment as an Endpoint in Clinical Trial Design.

Different neurodegenerative conditions can have complex, overlapping clinical presentations that make accurate diagnosis during life very challenging. For this reason, confirmation of the clinical diagnosis still requires postmortem verification. This is particularly relevant for clinical trials of novel therapeutics where it is important to ascertain what disease- and/or pathology-modifying effects the therapeutics have had. Furthermore, it is important to confirm that patients in the trial had the correct clinical diagnosis as this will have a major bearing on the interpretation of trial results. Here we present a simple protocol for pathological assessment of neurodegenerative changes.

A topographical atlas of α-synuclein dosage and cell type-specific expression in adult mouse brain and peripheral organs.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and presents pathologically with Lewy pathology and dopaminergic neurodegeneration. Lewy pathology contains aggregated α-synuclein (αSyn), a protein encoded by the SNCA gene which is also mutated or duplicated in a subset of familial PD cases. Due to its predominant presynaptic localization, immunostaining for the protein results in a diffuse reactivity pattern, providing little insight into the types of cells expressing αSyn. As a result, insight into αSyn expression-driven cellular vulnerability has been difficult to ascertain. Using a combination of knock-in mice that target αSyn to the nucleus (SncaNLS) and in situ hybridization of Snca in wild-type mice, we systematically mapped the topography and cell types expressing αSyn in the mouse brain, spinal cord, retina, and gut. We find a high degree of correlation between αSyn protein and RNA levels and further identify cell types with low and high αSyn content. We also find high αSyn expression in neurons, particularly those involved in PD, and to a lower extent in non-neuronal cell types, notably those of oligodendrocyte lineage, which are relevant to multiple system atrophy pathogenesis. Surprisingly, we also found that αSyn is relatively absent from select neuron types, e.g., ChAT-positive motor neurons, whereas enteric neurons universally express some degree of αSyn. Together, this integrated atlas provides insight into the cellular topography of αSyn, and provides a quantitative map to test hypotheses about the role of αSyn in network vulnerability, and thus serves investigations into PD pathogenesis and other α-synucleinopathies.

Evaluation and Treatment of Sacroiliac Joint Pain in Patients with History of Vertebral Compression Fractures: A Retrospective Case Series.

BACKGROUND: Vertebral compression fractures (VCFs) can affect the entire spinopelvic complex and cause unpredictable patterns of back pain due to their effects on spinal tensegrity and biomechanical compensation. They can lead to significant morbidity and mortality in the aging population and are difficult to diagnose. We aimed to establish a relationship between VCFs and sacroiliac (SI) joint pain. OBJECTIVES: Demonstration of SI joint (SIJ) pain relief at up to 6 months after kyphoplasty (KP) in patients with VCFs and diagnosed SI dysfunction. STUDY DESIGN: Retrospective study. SETTING: All patients were from a private chronic pain and orthopedics practice in the northeastern United States. METHODS: Fifty-one patients with VCFs diagnosed through imaging and SIJ dysfunction diagnosed through 2 diagnostic SIJ blocks who had failed conservative management were considered for KP. Numeric Rating Scale (NRS 11) scores were recorded at the baseline, after each SIJ block, and at 4 weeks and then 6 months after KP. RESULTS: Forty-nine patients underwent KP. At 4 weeks after the procedure, there was an 84% average reduction in NRS scores from the baseline (P < 0.01). At 6 months after the procedure, there was an 80% reduction in NRS scores from the baseline (P < 0.01). LIMITATIONS: Larger sample sizes and a randomized control trial would be important steps in furthering the relationship between VCFs and SIJ. CONCLUSION: VCFs can cause a referred pain pattern to the SIJ that is best treated by KP for long-term management.

Bacterial isolates from positive paired venous catheter and peripheral blood cultures taken during parenteral nutrition were the same species but different strains: A case report.

OBJECTIVE: The same microbial species isolated from blood simultaneously drawn from a central venous catheter hub and a peripheral vein (paired blood cultures) during parenteral nutrition may be assumed to represent the same strain. This case report provides an example of this assumption being incorrect along with a comparator example of it being correct. This has implications for interpretation of differential time to positivity and differential quantitative blood cultures during investigation of suspected intraluminal intravascular catheter or cannula bloodstream infection. CASE DESCRIPTION: Two patients ages ≥18 y prescribed parenteral nutrition each had positive paired blood cultures that had been taken for suspected catheter bloodstream infection because of temperature spikes ≥38°C. The paired Staphylococcus epidermidis isolates from the first patient and the paired Enterococcus faecium isolates from the second patient were each tested beyond routine clinical care to establish if they could be different strains. The central and peripheral isolates of Staphylococcus epidermidis from the first patient were different strains based on hospital-reported antibiograms, genomic DNA profiles, thermograms, and weaker growth and different sizes of colonies of the central strain compared with the peripheral strain. There were no such differences for the isolates of Enterococcus faecium from the second patient. RESULTS: The central and peripheral isolates of Staphylococcus epidermidis from the first patient were different strains based on hospital-reported antibiograms, genomic DNA profiles, thermograms, and weaker growth and different sizes of colonies of the central strain compared with the peripheral strain. There were no such differences for the isolates of Enterococcus faecium from the second patient. CONCLUSION: This case report indicates consideration should be given to reporting whether bacteria have been identified at either species or strain level if differential time to positivity or differential quantitative blood cultures are used to define catheter or cannula bloodstream infection.

The flashbulb-like nature of memory for the first COVID-19 case and the impact of the emergency. A cross-national survey.

Flashbulb memories (FBMs) refer to vivid and long-lasting autobiographical memories for the circumstances in which people learned of a shocking and consequential public event. A cross-national study across eleven countries aimed to investigate FBM formation following the first COVID-19 case news in each country and test the effect of pandemic-related variables on FBM. Participants had detailed memories of the date and others present when they heard the news, and had partially detailed memories of the place, activity, and news source. China had the highest FBM specificity. All countries considered the COVID-19 emergency as highly significant at both the individual and global level. The Classification and Regression Tree Analysis revealed that FBM specificity might be influenced by participants' age, subjective severity (assessment of COVID-19 impact in each country and relative to others), residing in an area with stringent COVID-19 protection measures, and expecting the pandemic effects. Hierarchical regression models demonstrated that age and subjective severity negatively predicted FBM specificity, whereas sex, pandemic impact expectedness, and rehearsal showed positive associations in the total sample. Subjective severity negatively affected FBM specificity in Turkey, whereas pandemic impact expectedness positively influenced FBM specificity in China and negatively in Denmark.

Advances in noninvasive measurement of liver function and physiology: The HepQuant DuO test.

Current noninvasive liver tests are surrogates for fibrosis and lack ability to directly measure liver function. HepQuant tests measure liver function and physiology through hepatic uptake of stable cholate isotopes. HepQuant SHUNT (V1.0) involves oral and intravenous dosing and six blood samples over 90 min. We developed simplified test versions: SHUNT V2.0 (oral and intravenous dosing, two blood samples over 60 min) and DuO (oral dosing only, two blood samples over 60 min). The aim of this study was to evaluate equivalency of the simplified tests to the original SHUNT test. Data from three studies comprising 930 SHUNT tests were retrospectively analysed by each method. Equivalence was evaluated in terms of proportion of tests in which the difference between methods was less than any clinically meaningful difference and additionally by two one-sided t-test and bioequivalence methods. DuO and SHUNT V2.0 were equivalent to the original SHUNT test for Disease Severity Index, with >99% and >96% of tests falling within equivalence bounds. DuO and SHUNT V2.0 met equivalency criteria by two one-sided t-tests and bioequivalence. DuO and SHUNT V2.0 are easier to administer, are less invasive than the original SHUNT test and have potential to be more accepted by patients and providers.

Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly population. We performed genome-wide DNA methylation mapping of cerebellar tissue from pathologically confirmed DLB cases and controls to study the epigenetic profile of this understudied disease. After quality control filtering, 728,197 CpG-sites in 278 cases and 172 controls were available for the analysis. We undertook an epigenome-wide association study, which found a differential methylation signature in DLB cases. Our analysis identified seven differentially methylated probes and three regions associated with DLB. The most significant CpGs were located in ARSB (cg16086807), LINC00173 (cg18800161), and MGRN1 (cg16250093). Functional enrichment evaluations found widespread epigenetic dysregulation in genes associated with neuron-to-neuron synapse, postsynaptic specialization, postsynaptic density, and CTCF-mediated synaptic plasticity. In conclusion, our study highlights the potential importance of epigenetic alterations in the pathogenesis of DLB and provides insights into the modified genes, regions and pathways that may guide therapeutic developments.

Dynamic Elevation of Aromatic Amino Acids in Hepatitis C Virus-Induced Cirrhosis After a Standard Meal.

INTRODUCTION: Perturbations in aromatic (AAAs) and branched-chain amino acids (BCAAs) are seen in decompensated liver disease. The aim of this study was to evaluate the dynamic, postprandial relationship between hepatitis C virus-induced liver disease and amino acid concentrations in patients with compensated liver disease. METHODS: Patients infected with hepatitis C virus underwent a baseline liver biopsy to determine Ishak Fibrosis Score and evaluate the liver transcriptome. Patients ate a standard meal and underwent peripheral vein sampling at defined intervals. Quantitative analysis of amino acids was performed using liquid chromatography-tandem mass spectrometry. RESULTS: At baseline, there was no difference in AAA and BCAA concentrations between patients with cirrhosis and non-cirrhotic patients. After a standard meal, AAAs, but not BCAAs, were elevated in patients with cirrhosis compared with non-cirrhotic patients at every time point. The HepQuant SHUNT fraction was significantly higher in patients with cirrhosis and positively correlated with AAA concentration at all time points, but not BCAA. Analysis of the hepatic transcriptome demonstrated greater downregulation of the AAA degradation pathways than the BCAA degradation pathways. DISCUSSION: At baseline, cirrhotic patients with compensated liver disease have adequate reserve liver function to metabolize AAAs and BCAAs. When faced with a metabolic stressor, such as a standard meal, patients with cirrhosis are less able to metabolize the increased load of AAAs. This impairment correlates with portosystemic shunting. Further evaluation of AAA levels in compensated liver disease might further the understanding of the liver-muscle axis and the role it may play in the development of sarcopenia in liver disease.

Feasibility of same-day discharge after laparoscopic sleeve gastrectomy in the Netherlands.

BACKGROUND: There is a trend towards laparoscopic sleeve gastrectomy (SG) with same-day discharge (SDD), as an efficient healthcare pathway to alleviate the burden on clinical capacity. This approach seems to be safe, if patients are carefully selected. In our bariatric center, a protocol for Roux-en-Y gastric bypass with SDD has already been successfully implemented. The aim of this study was to evaluate feasibility of applying the same SDD protocol for SG. METHODS: A single-center prospective feasibility study was conducted at a high-volume bariatric center. Low-risk patients who were scheduled for primary SG were included. Strict criteria were used for approval upon SDD. The primary outcome was the rate of successful SDD without readmission within 48 h. Secondary outcomes included short-term complications, emergency department visits, readmissions, and mortality. RESULTS: Fifty patients were included in the study, of whom 45 were successfully discharged on the same day of the surgery. Nausea and vomiting were the most common reasons for overnight hospitalization (three patients). One patient was readmitted within the first 48 h due to a mild complication related to bleeding, resulting in a success rate of 88% for SDD without readmission within 48 h. No severe complications or mortality were reported in the cohort. CONCLUSION: Our SDD protocol for SG has demonstrated feasibility, with a high success rate of SDD and no severe complications. Strict conditions should be met for the safe implementation of a SDD protocol, including careful patient selection and the establishment of a safety net to detect early complications.

Risk of Malaria Following Untreated Subpatent Plasmodium falciparum Infections: Results Over 4 Years From a Cohort in a High-Transmission Area in Western Kenya.

BACKGROUND: People with suspected malaria may harbor Plasmodium falciparum undetected by rapid diagnostic test (RDT). The impact of these subpatent infections on the risk of developing clinical malaria is not fully understood. METHODS: We analyzed subpatent P. falciparum infections using a longitudinal cohort in a high-transmission site in Kenya. Weighted Kaplan-Meier models estimated the risk difference (RD) for clinical malaria during the 60 days following a symptomatic subpatent infection. Stratum-specific estimates by age and transmission season assessed modification. RESULTS: Over 54 months, we observed 1128 symptomatic RDT-negative suspected malaria episodes, of which 400 (35.5%) harbored subpatent P. falciparum. Overall, the 60-day risk of developing clinical malaria was low following all episodes (8.6% [95% confidence interval, 6.7%-10.4%]). In the low-transmission season, the risk of clinical malaria was slightly higher in those with subpatent infection, whereas the opposite was true in the high-transmission season (low-transmission season RD, 2.3% [95% confidence interval, .4%-4.2%]; high-transmission season RD, -4.8% [-9.5% to -.05%]). CONCLUSIONS: The risk of developing clinical malaria among people with undetected subpatent infections is low. A slightly elevated risk in the low-transmission season may merit alternate management, but RDTs identify clinically relevant infections in the high-transmission season.

Factors associated with decision regret after bariatric surgery.

It is assumed that the individuals who undergo bariatric surgery will experience significant improvements in their health and overall well-being. However, it is yet to be examined whether these individuals may also experience subsequent decision regret. The level of regret regarding the choice to undergo bariatric surgery was assessed 1 year after bariatric surgery using the Decision Regret Scale (DRS). Associations of regret with patient characteristics, complications, weight loss and quality of life (BODY-Q) were investigated using linear regression analyses. In total, 115 patients completed the DRS (92% underwent Roux-en-Y gastric bypass Roux-en-Y gastric bypass and 8% underwent sleeve gastrectomy (SG)). Two out of 115 patients indicated absolute regret about their decision to undergo bariatric surgery because of insufficient weight loss and complications. The median decision regret score was zero (range 0-80). Most patients experienced no decision regret (50.4%), followed by mild regret (34.8%) and moderate to strong regret (14.8%). Higher levels of regret were associated with having osteo-articular disorders, gastro-oesophageal reflux disease or a history of psychiatric disorders at baseline. Patients with mild regret demonstrated significantly more weight loss and better psychological function. Major surgical complications were not associated with increased decision regret. Only two out of 115 patients (1.7%) indicated absolute regret about their decision to undergo bariatric surgery, and 15% reported moderate-to-strong regret according to the results of the DRS. These findings should be considered when providing pre-operative counselling and could assist patients in their decision-making process.