Median Days Research Articles

End-of-life (EOL) outcomes and healthcare utilization for patients with hepatocellular carcinoma (HCC) who received immune checkpoint inhibition (ICI).

560 Background: ICI is standard of care treatment for advanced HCC. EOL outcomes for patients with HCC who receive ICI prior to death are unknown. We examine relationships between EOL outcomes, healthcare utilization, and receipt of ICI for patients with advanced HCC referred to our tertiary center. Methods: Patients with advanced HCC evaluated at our center on or after January 1, 2020 and who died by March 29, 2024 were included. Patients were identified using diagnostic codes for liver cancer and HCC, and subsequently verified by manual review of the electronic health record. Demographic data, Child-Pugh (CP) status, and treatment history were collected. Primary EOL outcomes include: documentation of advance directives and goals of care (GOC) conversations, location of death, palliative care referral, hospice referral, days in hospice, and code status. Secondary healthcare utilization outcomes include: systemic therapy receipt, emergency department (ED) visits, hospitalization, and intensive care unit (ICU) admissions within 14, 30, and 90 days of death. Outcomes were stratified by ICI or non-ICI as last therapy received and p-values were derived using Pearson’s chi-square test for equality of proportions. Results: Of 221 evaluated patients, 71 died and met criteria for analysis. Baseline characteristics include mean age 64.1 years, 70.8% male, 71.8% received systemic treatment (median 1 line, range [1-7]), 54.1% CPA, 37.5% CPB, and 8.3% CPC at the time of last treatment. No statistically significant differences in primary EOL outcomes were detected when stratified by receipt of ICI or non-ICI as last therapy. Median days enrolled in hospice were not statistically significant between groups (24.5 days [non-ICI] vs 10 days [ICI]; p = 0.39). A higher proportion of patients who received ICI as last therapy had increased healthcare utilization across all outcomes (see Table). Conclusions: Patients with advanced HCC receiving ICI as their last treatment before death compared to those receiving non-ICI had similar EOL outcomes but higher healthcare utilization. This may be due to increased real-world use of ICI in CPB patients. Further investigation into risk stratification to predict high healthcare utilizers could guide decision-making and conversations around ongoing use of ICI, particularly near the EOL. Healthcare utilization outcomes stratified by receipt of ICI. Outcome Before Death n = 71 90 days 30 days 14 days Therapy within Total: Last therapy ICI 33/71 (46.5%)69.7% 18/71 (25.4%)66.7% 6/71 (8.5%)33.3% ED visit Total: Last therapy ICI 29/71 (40.8%)58.6% 27/71 (38.0%)55.6% 22/71 (30.1%)59.1% Hospitalization Total: Last therapy ICI 32/71 (45.1%)59.4% 30/71 (42.3%)56.6% 29/71 (40.8%)58.6% ICU admission Total: Last therapy ICI 6/71 (8.5%)66.7% 6/71 (8.5%)66.7% 6/71 (8.5%)66.7%

Association between magnetic resonance imaging use and recovery time following concussion: a CARE consortium study

ABSTRACT Researchers may implement magnetic resonance imaging (MRI) to evaluate neurophysiological metrics (e.g. connectivity) in athletes with sports-related concussion (SRC). MRI usage has been purported to exacerbate symptoms that mimic SRC symptomatology, possibly influencing recovery. The present study examined MRI use on SRC recovery outcomes in collegiate athletes. Ninety student-athletes (45 with MRI acutely post-SRC, 45 non-MRI) from four collegiate sites were analysed. Multivariable Cox proportional hazard regressions were used to measure the SRC recovery risk [return-to-play (RTP) initiation (RTP-I) and unrestricted RTP] with hazard ratios (HR) and 95% confidence intervals (95% CI). No hazard differences for median days to RTP-I [MRI: 10, interquartile range (IQR) = 7–15; non-MRI: 7 (IQR = 4–9)] were observed (HR = 0.75; 95% CI: 0.28–1.21). No hazard differences for median days to RTP [(MRI: 17 (IQR = 11–60); non-MRI: 12 (IQR = 8–24)] were observed (HR = 0.77; 95% CI: 0.29–1.26). MRI use post-SRC does not affect recovery; researchers/clinicians can employ such a procedure without affecting athlete recovery.

DOP057 Early serum and faecal cytokines predict clinical outcomes in Acute Severe Ulcerative Colitis: results from PREDICT-UC

Abstract Background Acute severe ulcerative colitis (ASUC) is a medical emergency with variable outcomes. We aimed to evaluate whether early serum and faecal cytokine levels predict treatment response. Methods Serum and stool were collected from patients with ASUC. Steroid-refractory patients received infliximab (IFX, monoclonal antibody to tumour necrosis factor [TNF]) as part of PREDICT-UC (NCT02770040), a multi-centre randomised controlled trial that evaluated escalated infliximab (IFX) dosing.1 Specimens were collected at screening, and if steroid-refractory at days 1 and 3 post-IFX. Response to first IFX dose was assessed by day 7. Interleukin (IL)-6 and TNF levels were quantified using ELISA after clinical study conclusion. Results Within the cohort of 190 patients, 54 were steroid-responsive and 136 steroid-refractory and received IFX. Of the steroid-refractory patients, 85 (62.5%) were IFX responders and 51 (37.5%) were IFX non-responders. 17/136 (12.5%) patients underwent colectomy by 3 months. Steroid response At screening, serum IL-6 was higher in steroid non-responders compared to responders (10.5 pg/mL vs 3.5 pg/mL, P<0.001), whereas faecal IL-6 was similar in both groups (154.7 pg/mL vs 138 pg/mL, P=0.09). Faecal TNF at screening was higher in non-responders compared to responders (48.6 pg/mL vs 14.6 pg/mL, P=0.032). IFX response Serum IL-6 at was higher in IFX non-responders compared to responders at all timepoints (P<0.005); however, this finding was not observed with faecal IL-6. Whilst faecal TNF at screening, days 0 and 1 did not differ between IFX responders and non-responders, median day 3 faecal TNF was suppressed below detection limits (<1.56 pg/mL) in IFX responders compared to 4.4 pg/mL in non-responders (P=0.006, AUC=0.65). Colectomy by month 3 Higher serum IL-6 at screening (P=0.009, AUC=0.71) and day 1 (P=0.002, AUC=0.75) were associated with month 3 colectomy. Similarly, day 3 faecal IL-6 was higher in patients who required colectomy versus those who did not (159.0 pg/mL vs 110.7 pg/mL, P=0.02, AUC 0.69). Median faecal TNF at day 3 post-IFX was 6.3 pg/mL in patients who required colectomy but dropped below detection limit in those who avoided colectomy (P=0.004). Day 3 faecal TNF predicted colectomy (AUC=0.72) with a threshold of ≥7.07 pg/mL on Youden’s index having 50% sensitivity, 89.8% specificity, 43.8% PPV and 91.9% NPV. Conclusion Early serum and faecal cytokines predict outcomes in ASUC. Faecal TNF persistence 3 days after IFX is associated with non-response and colectomy, and might help identify patients who benefit from early IFX re-dosing. IL-6 elevation in non-responders suggests activation of an alternate immune pathway that may benefit from non-TNF-targeted therapy.

Analysis of Clinical Outcomes Following Implementation of a Rapid Antiretroviral Therapy Initiation Protocol at aLocal HIV Clinic.

Rapid antiretroviral therapy (ART) refers to initiating HIV treatment within seven days of diagnosis. Multidisciplinary teams that implement rapid ART protocols can be effective in addressing the holistic needs of HIV patients. The purpose of this study was to evaluate a multidisciplinary team's implementation of a rapid ART protocol through a retrospective pre and post study design among 627 patients referred to a local HIV clinic between January 2017 and December 2022. We observed a 46% difference in the median number of days from diagnosis to first visit (p < 0.001) between pre implementation ("pre") [median days = 13] and post implementation groups ("post") [median days = 7] and a 17% difference in median days from first visit to viral suppression (p < 0.05) between pre (median days = 63) and post groups (median days = 52). An adjusted Cox proportional hazards model showed a higher probability of having a first visit with a medical provider following diagnosis sooner in the post group compared to the pre group (hazard ratio [HR]: 1.53, p < 0.001). The post group also had a higher probability of achieving viral suppression sooner compared to the pre group (HR: 1.55, p < 0.01) where 98% achieved viral suppression in the post group within 12-months compared to 90% in the pre group. These results show that after the introduction of a rapid ART protocol implemented by a multidisciplinary team, there were significantly shorter days to first visit and greater viral suppression outcomes among the post group compared to the pre group.

Thromboembolic prophylaxis in bariatric and metabolic surgery: state-of-the-art according to the results of a nationwide registry study.

The present study employed a large scaled multicenter nationwide study data analysis to elucidate the impact of thromboembolism prophylaxis (TEP) in the context of bariatric and metabolic surgery and to investigate the peri- and postoperative complications associated with TEP. A total of 63,909 patients who underwent primary bariatric surgery between 2005 and 2020 were included in the analysis. The data were collected prospectively and multicentrically in the German Bariatric Surgery Registry (GBSR) and subsequently analyzed retrospectively. A p value of ≤ 0.05 was deemed to correspond to a significant result. 96.65% of patients were prophylactically anticoagulated postoperatively. 99.3% of the anticoagulated patients received low molecular weight heparin on a median of 7days. With regard to postoperative complications, a significantly higher incidence of transfusion (p < 0.001) or postoperative bleeding requiring surgery (p = 0.002) was observed in the group of patients who underwent TEP. At 0.67% and 0.87% respectively, these were nevertheless rare complications. The incidence of deep vein thrombosis (DVT) (TEP n = 46, no TEP n = 1; p = 0.642) and pulmonary artery embolism (PAE) was 0.1% each (TEP n = 57, no TEP n = 2; p = 0.985). The surgical technique was associated with a minimal risk of consequences for DVT. Here was the occurrence of DVT following surgical procedures in patients with TEP 0.1% for gastric banding (GB) and sleeve gastrectomy (SG), and less than 0.1% for Roux-Y gastric bypass (RYGB). The mortality rate was between patients with TEP and patients without TEP not significantly different (n [TEP] = 102; 0.17%, n [no TEP] = 6; 0.28%) (p = 0.198). The study's findings validate the efficacy of TEP in bariatric surgery. However, to prevent adverse TEP consequences, like hemorrhage, the dosage and timing of prophylactic medication must be appropriately modified.However, it is evident that randomized controlled trials are necessary to establish uniform, high-quality recommendations on TEP.

Low-risk febrile neutropenia: does combined chemotherapy/immune checkpoint inhibitor necessitate a change in approach?

Management of patients with low-risk febrile neutropenia in an outpatient setting guided by the MASCC score is proven to be safe and effective. Most patients on ambulatory low-risk febrile neutropenia pathways are undergoing treatment for breast cancer. Recent data has shown benefit of the addition of immune checkpoint inhibitor therapy to cytotoxic chemotherapy in the neoadjuvant setting for patients with early triple-negative breast cancer. We examined whether the addition of ICI therapy altered the clinical severity of febrile neutropenia in this cohort and the ability to manage these patients in an ambulatory setting. An observational analysis was performed at a specialist oncology hospital in the North West of England. We compared patients with triple negative breast cancer presenting with febrile neutropenia following treatment with PC-EC/pembrolizumab to those treated with PC-EC in the neoadjuvant setting. In the study periods, 152 patients received PC-EC and 151 PC-EC/Pembro. Twenty-five patients presented with FN in the PC-EC/Pembro group compared to 16 in those receiving PC-EC (16% vs 11%, p > 0.05). Patients with febrile neutropenia treated with PC-EC/Pembro had more severe clinical presentations as assessed by the MASCC score (18 vs 24; p = 0.01), had worse physiological parameters (NEWS2 at presentation 3 vs 2; p = 0.023) and had a longer length of hospital stay (median 5days vs 0days; p = 0.044). There were no deaths at 30 or 90days in either cohort. Triple-negative breast cancer patients receiving neoadjuvant pembrolizumab in addition to PC-EC appear to have more severe presentations with febrile neutropenia. This may necessitate greater caution in pathways for ambulatory management for this cohort.

Factors Associated with the Timing of Initial Visit to Healthcare Providers for Injured Workers with Low Back Pain Claims: A Multijurisdiction Retrospective Cohort.

Evidence shows that patient outcomes following musculoskeletal injury have been associated with the timing of care. Despite the increasing number of injured workers presenting with low back pain (LBP) in primary care, little is known about the factors that are associated with the timing of initial healthcare provider visits. This study investigated factors that are associated with the timing of initial workers' compensation (WC)-funded care provider visits for LBP claims. We used a retrospective cohort design. A standardised multi-jurisdiction database of LBP claims with injury dates from July 2011 to June 2015 was analysed. Determinants of the time to initial general practitioner (GPs) and or musculoskeletal (MSK) therapists were investigated using an accelerated failure time model, with a time ratio (TR) > 1 indicating a longer time to initial healthcare provider visit. 9088 LBP claims were included. The median time to first healthcare provider visit was 3days (interquartile range (IQR) 1-9). Compared to General practitioners (GPs) (median 3days, IQR 1-8), the timing of initial consultation was longer if the first healthcare providers were MSK therapists (median 5days, IQR 2-14) (p < 0.001). Female workers had a shorter time to first healthcare provider visit [TR = 0.87; 95% CI (0.78, 0.97)] compared to males. It took twice as long to see MSK therapists first as it did to see GPs for injured workers [TR = 2.12; 95% CI (1.88, 2.40)]. Professional workers and those from remote areas also experienced delayed initial healthcare provider visits. The time to initial healthcare provider visit for compensable LBP varied significantly by certain occupational and contextual factors. Further research is needed to investigate the impact of the timing of initial visits to healthcare providers on claim outcomes.

Multiple introductions of NRCS-A Staphylococcus capitis to the neonatal intensive care unit drive neonatal bloodstream infections: a case-control and environmental genomic survey.

Background. The Staphylococcus capitis NRCS-A strain has emerged as a global cause of late-onset sepsis associated with outbreaks in neonatal intensive care units (NICUs) whose transmission is incompletely understood.Methods. Demographic and clinical data for 45 neonates with S. capitis and 90 with other coagulase-negative staphylococci (CoNS) isolated from sterile sites were reviewed, and clinical significance was determined. S. capitis isolated from 27 neonates at 2 hospitals between 2017 and 2022 underwent long-read (ONT) (n=27) and short-read (Illumina) sequencing (n=18). These sequences were compared with S. capitis sequenced from blood culture isolates from other adult and paediatric patients in the same hospitals (n=6), S. capitis isolated from surface swabs (found in 5/150 samples), rectal swabs (in 2/69 samples) in NICU patients and NICU environmental samples (in 5/114 samples). Reads from all samples were mapped to a hybrid assembly of a local sterile site strain, forming a complete UK NRCS-A reference genome, for outbreak analysis and comparison with 826 other S. capitis from the UK and Germany.Results. S. capitis bacteraemia was associated with increased length of NICU stay at sampling (median day 22 vs day 12 for other CoNS isolated; P=0.05). A phylogeny of sequenced S. capitis revealed a cluster comprised of 25/27 neonatal sterile site isolates and 3/5 superficial, 2/2 rectal and 1/5 environmental isolates. No isolates from other wards belonged to this cluster. Phylogenetic comparison with published sequences confirmed that the cluster was NRCS-A outbreak strain but found a relatively high genomic diversity (mean pairwise distance of 84.9 SNPs) and an estimated NRCS-A S. capitis molecular clock of 5.1 SNPs/genome/year (95% credibility interval 4.3-5.9). The presence of S. capitis in superficial cultures did not correlate with neonatal bacteraemia, but both neonates with rectal NRCS-A S. capitis carriage identified also experienced S. capitis bacteraemia.Conclusions. S. capitis bacteraemia occurred in patients with longer NICU admission than other CoNS. Genomic analysis confirms clinically significant infections with the NRCS-A S. capitis strain, distinct from non-NICU clinical samples. Multiple introductions of S. capitis, rather than prolonged environmental persistence, were seen over 5 years of infections.

Characteristics and outcomes of children ≤ 10 kg receiving continuous kidney replacement therapy: a WE-ROCK study.

Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10kg. Intensive care unit (ICU) mortality in children ≤ 10kg reported by the prospective pediatric CRRT (ppCRRT, 2001-2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry. The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0-25years receiving CKRT (2015-2021) for AKI or FO. This analysis included patients ≤ 10kg at hospital admission. ICU mortality and major adverse kidney events at 90days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90days, respectively. A total of 210 patients were included (median age 0.53years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3days (IQR 1, 9) after ICU admission and lasted a median 6days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68-4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31-3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13-0.65). We report on a contemporary cohort of children ≤ 10kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90days highlights the importance of close follow-up.

Association between cerebrospinal fluid levels of neuro-specific enolase after hypothermia alone and in combination with neurodevelopmental outcomes at age six years.

Hypoxic-ischemic encephalopathy (HIE) is still associated with death and sequelae including cerebral palsy and intellectual disability despite induced hypothermia. Biomarkers, as early predictive indicators of adverse outcomes, are lacking. To investigate whether post-rewarming cerebrospinal fluid (CSF)-neuro-specific enolase (NSE) levels after hypothermia are associated with neurodevelopmental outcomes at age six years, alone or when combined with amplitude-integrated electroencephalography (aEEG) and brain magnetic resonance imaging (MRI), as neuroimaging and neurophysiological indicators, respectively. We retrospectively enrolled 157 patients with HIE from 2011 to 2018 with available post-rewarming CSF-NSE levels and developmental tests at age six years. Of these, 148 met the inclusion criteria, and 87 were evaluated in the final analysis. Multivariate receiver operating characteristic analysis determined the predictive ability of post-rewarming CSF-NSE levels for adverse outcomes including death and cerebral palsy, intellectual disability, and borderline disability at age 6years either singly or in combination with aEEG and MRI findings, using logistic regression analysis. The cut-off value for CSF-NSE at a median 5days after birth was 233ng/dL (area under the curve 0.97, 95% confidence intervals of 0.93-1.00, sensitivity 1, specificity 0.94) for death. Regarding cerebral palsy and intellectual disability, the combination of abnormal aEEG at 72h, moderate-severe MRI injury findings, and with or without CSF-NSE (cut-off value: 55ng/mL), odds ratio (95% confidence intervals) improving from 8.6 (2.7-27.8) to 12.4 (3.5-43.9) (p<0.01). In patients with HIE, post-rewarming CSF-NSE levels were associated not only with death independently but with cerebral palsy and intellectual disability in combination with EEG and MRI findings.

Intravenous Steroids Do Not Improve Short-Term Outcomes of Patients With Crohn's Disease Presenting With an Acute Small Bowel Obstruction.

Intravenous (IV) steroids are commonly used to treat acute flares of Crohn's disease (CD). However, it is unclear if they are beneficial in the setting of uncomplicated small bowel obstruction (SBO). We sought to examine if IV steroid administration improved short-term outcomes in patients with CD hospitalized for acute, uncomplicated SBO across three New York City hospital systems. This retrospective study included patients ≥ 18 years old admitted between January 1, 2011, and December 31, 2019, with Crohn's disease and an admission diagnosis of uncomplicated acute SBO, defined as cases without adhesions, fistula, phlegmon, and sepsis. Primary endpoints (length of stay and frequency of surgery) were compared between patients who received IV steroids upon admission and those who did not. Our analysis included 674 unique patients. Ninety-two (14%) received IV steroids, and 582 (86%) did not. IV steroid use did not result in shorter hospital stays (median days [IQR]: 3.0 (2.0-5.5) days vs 3.0 (2.0-6.0) days in the no-steroid group, P = .65) or reduce the need for surgery (4 patients (4.4%) vs 28 patients (4.8%) in the no-steroid group, P = .85). Sex, age, disease duration, concomitant biologic therapy, and NG tube placement did not independently contribute to either outcome. These findings suggest that IV steroid administration for uncomplicated SBO in CD patients does not decrease hospital length of stay or need for surgery. Further research may help identify specific obstruction patterns or other therapies associated with different outcomes.

Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients.

The angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are central human molecules in the SARS-CoV-2 virus-host interaction. Evidence indicates that ACE1 may influence ACE2 expression. This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA expression levels, along with the ACE1 Alu 287 bp polymorphism (rs4646994), contribute to the severity and mortality of COVID-19. Swabs were collected in two Brazilian cities in 2020: Belo Horizonte (n=134) and Rio de Janeiro (n=41). A swab of mild patients in Rio de Janeiro who were not hospitalized (n=172) was also collected. All analyzed biological material was obtained from residual diagnostic samples in 2020, prior to the emergence of SARS-CoV-2 variants of concern. ACE1, ACE2, TMPRSS2, and B2M (reference gene) expression levels were evaluated in 40 cycles of quantitative PCR. ACE1 Alu 287 bp polymorphism was genotyped using the FastStart Universal SYBR Green Master kit. The median age differed between clinical sites (p=0.016), but no difference in median days of hospitalization was observed (p=0.329). Age was associated with severity (p=0.014) and mortality (p=0.014) in the Belo Horizonte cohort. No alteration in ACE1, ACE2 and TMPRSS2 expression was associated with severity or mortality. ACE1 polymorphism rs4646994 did not influence the likelihood of either outcome. A meta-analysis including available data from the literature showed significant effects: the D-allele conferred risk (OR = 1.39; 95% CI [1.12-1.72]).

Multilevel intervention for follow-up of abnormal FIT in the safety-net: IMProving Adherence to Colonoscopy through Teams and Technology (IMPACTT).

Fecal immunochemical testing (FIT) is a widely used first step for colorectal cancer (CRC) screening. Abnormal FIT results require a colonoscopy for screening completion and CRC diagnosis, but the rate of timely colonoscopy is low, especially among patients in safety-net settings. Multi-level factors at the clinic- and patient-levels influence colonoscopy completion after an abnormal FIT. Our study aims to implement a multi-level approach consisting of a clinic- and patient-level intervention to improve the completion of diagnostic colonoscopy after an abnormal FIT. We will test a multilevel intervention with one safety-net system across 12 primary care clinics - a clinic-level intervention using a stepped wedge design and a patient-level intervention with patient-level randomization. At the clinic level, we will implement a "best practices bundle" to improve workflow for primary care providers and staff using a stepped-wedge design. At the patient level, we will randomize 2000 patients to receive text messages and call reminders or usual care. For the main analysis, we will use a mixed effects logistic model to assess the impact of the clinic intervention on the primary outcome (completion of colonoscopy within 180 days after abnormal FIT). Secondary outcomes include median days to colonoscopy completion, rate of referral to colonoscopy at 42 days, rate of scheduled colonoscopy at 56 days, and bowel preparation quality at colonoscopy. This study will assess the extent to which a multi-level intervention can improve timely colonoscopy completion in a diverse patient population cared for in a safety-net setting. NCT, NCT06191185. Registered 20 December 2023, https://clinicaltrials.gov/study/NCT06191185.

Efficacy of oral modafinil on accelerating consciousness recovery in adult patients with moderate to severe acute traumatic brain injury admitted to intensive care unit: a randomized double-blind clinical trial.

Traumatic Brain Injury (TBI) is a leading cause of hospitalization and disability in young and middle-aged adults. This study aims to survey the efficacy of oral modafinil, a low-side-effect central nervous system stimulant, in the enhancement of consciousness recovery in moderate to severe TBI patients in the ICUs of a referral trauma center. All ICU patients meeting inclusion criteria between April 2021 and April 2023 were screened. Eligible patients had a motor Glasgow Coma Score(GCS) of 4 or 5 and did not receive continuous intravenous sedatives within 24 h before screening. They were randomly assigned to receive 200mg of enteral modafinil or placebo daily for 7 days. Motor GCS and total GCS scores, ICU/hospital stay duration, mechanical ventilation requirement, tracheal tube removal time, and tracheostomy needs were recorded. Among the included 85 eligible patients, there was no significant difference between the modafinil and placebo groups in the median days between the intervention and the time of a 2-unit increase in total GCS (P = 0.25) or a 1-unit increase in motor GCS (P-value = 0.31). The group assignment also had no impact on the mean GCS (P-value = 0.533) and mean motor GCS (P-value = 0.167) over time. The only significant difference was in the proportion of patients with an increase in total GCS by 2 units, which was 54% for the modafinil vs. 32% for the placebo group (P-value = 0.04), and an increase in motor GCS by 1 unit, with 56% in the modafinil vs. 34% in the placebo group (P-value = 0.04). The administration of modafinil appears to be safe and beneficial for patients with severe TBI during their stay in the ICU.

Characterising the metabolic functionality of the preterm neonatal gut microbiome prior to the onset of necrotising enterocolitis: a pilot study

Abstract Background Necrotising enterocolitis (NEC) is a devastating bowel disease that primarily occurs in infants born prematurely and is associated with abnormal gut microbiome development. While gut microbiome compositions associated with NEC have been well studied, there is a lack of experimental work investigating microbiota functions and their associations with disease onset. The aim of this pilot study was to characterise the metabolic functionality of the preterm gut microbiome prior to the onset of NEC compared with healthy controls. Results Eight NEC infants were selected of median gestation 26.5 weeks and median day of life (DOL) of NEC onset 20, with one sample used per infant, collected within one to eight days (median four) before NEC onset. Each NEC case was matched to a control infant based on gestation and sample DOL, the main driver of microbiome composition in this population, giving a total cohort of 16 infants for this study. Dietary exposures were well matched. The microbiota of NEC and control infants showed similar wide-ranging metabolic functionalities. All 94 carbon sources were utilised to varying extents but NEC and control samples clustered separately by supervised ordination based on carbon source utilisation profiles. For a subset of eight samples (four NEC, four control) for which pre-existing metagenome data was available, microbiome composition was found to correlate significantly with metabolic activity measured on Biolog plates (p = 0.035). Comparisons across all 16 samples showed the NEC microbiota to have greater utilisation of carbon sources that are the products of proteolytic fermentation, specifically amino acids. In pairwise comparisons, L-methionine was highly utilised in NEC samples, but poorly utilised in controls (p = 0.043). Carbon sources identified as discriminatory for NEC also showed a greater enrichment for established markers of inflammatory disease, such as inflammatory bowel disease, irritable bowel syndrome and diverticular disease. Conclusions Before NEC onset, the preterm gut microbiota showed greater metabolic utilisation of amino acids, potentially indicating a shift from predominantly saccharolytic to proteolytic fermentation. Products of amino acid breakdown could therefore act as biomarkers for NEC development. A larger study is warranted, ideally with infants from multiple sites.

Temporal Changes in PROMs Improvement and Recovery Kinetics Following Transforaminal Endoscopic Lumbar Discectomy.

Retrospective cohort study. to analyze trends in PROMs improvement and recovery kinetics following transforaminal endoscopic lumbar discectomy and foraminotomy (TELD). As TELDs become an increasingly common alternative to fusions for lateral disc herniations, it is important to understand patients' postoperative recovery timelines to manage patient expectations. Although studies have shown improvement after TELD compared to preoperative baseline, there is a paucity of information regarding rate of postoperative improvement. Patients who underwent primary one- or two-level TELD for far lateral disc herniations with a minimum of 6-month follow-up were included. Outcomes included: patient reported outcome measures (PROMs), including Oswestry Disability Index (ODI), 12-Item Short Form Survey Physical Component Score (SF-12 PCS), and Visual Analog Scale (VAS) for back and leg; PROMs minimally clinically important difference (MCID); global rating of change (GRC); and return to activities. Timepoints included were preoperative, 2 weeks, 6 weeks, 12 weeks, 6 months. Trends in improvement were plotted on graphs and with P values displayed in tables. 51 patients were included. Mean operative time was 68.4±23.0 minutes and mean length of stay was 9.6±10.5 hours. There were statistically significant improvements in VAS back and leg at 2 weeks and 6 weeks, with a plateau after 6 weeks. ODI and SF-12 PCS did not experience statistically significant improvement until 6 weeks, which was also the point of plateau. VAS leg MCID and GRC peaked at 6 weeks. All patients returned to driving and discontinued opioids, and most patients returned to work. Median days to return to driving, work, and discontinue opioids were 8, 35, and 1, respectively. Patients can expect the majority of postoperative improvement to occur within 6 weeks, after which improvements tend to plateau. Around 75% of patients feel better compared to preoperative at 6 months. TELD may therefore spare some patients of a more invasive fusion initially. 3.

Long-Term Function Recovery Following Upper Versus Lower Lobectomy for Lung Cancer: A Multicenter Longitudinal Cohort Study.

The effects of lobectomy at various lung sites on postoperative function and recovery vary. This study aimed at assessing the long-term impact of upper versus lower lobectomy on patients' postoperative daily function by analyzing patient-reported outcomes. This multicenter prospective cohort study enrolled patients from six hospitals in China. Functional impairments and symptom severity were measured using the MD Anderson Symptom Inventory-Lung Cancer. A mixed-effects linear model was employed to analyze the average trajectories of each functional item and the top five symptoms over the first year following surgerybetween patients undergoing upper and lower lobectomy. The median recovery days for daily function were estimated using the Kaplan-Meier method, with the log-rank test comparing differences between upper and lower lobectomy. Two hundred twenty-six patients met the final analysis criteria, with 137 undergoing upper and 89 undergoing lower lobectomies. Those in the lower lobectomy group reported significantly greater interference with daily activities (estimate = 0.872, SE = 0.306, p = 0.004), mood (estimate = 0.667, SE = 0.297, p = 0.025), and work (estimate = 0.856, SE = 0.358, p = 0.017), indicating a more pronounced impact on postsurgical functional recovery compared to the upper lobectomy group within the first year after surgery. They also experienced longer median recovery times for daily activities (15 vs. 4 days), mood (6 vs. 3.5 days), and walking (7 vs. 4 days) compared to the upper lobectomy group. Within the first year after surgery, lower lobectomy patients experienced greater impairment in daily functions and required longer recovery times compared to upper lobectomy patients. NCT03341377.

Prevalence of hepatitis coinfection and substance use among antiretroviral therapy clinic clients with hazardous alcohol use in Vietnam.

The confluence of injection drug use (IDU), alcohol consumption, and viral hepatitis increases morbidity among persons living with HIV (PWH). We present a secondary analysis of a randomized controlled trial of alcohol reduction interventions in Thai Nguyen, Vietnam conducted between 2016-2018. We assessed hepatitis B (HBV) and hepatitis C (HCV) coinfection among PWH reporting hazardous alcohol consumption and examined differences in IDU and alcohol use by coinfection status. Participants were ≥18 years old, living with HIV, and reported hazardous alcohol consumption per the WHO Alcohol Use Disorders Identification Test Consumption (AUDIT-C; score ≥4 for men, score ≥3 for women). At enrollment, participants were tested for hepatitis coinfection with HBV surface antigen tests and rapid serological HCV tests. Demographic information, IDU, and recent alcohol consumption were assessed via behavioral survey and 30-day timeline follow back. Fishers Exact and Kruskal-Wallis tests were used for statistical testing. Hepatitis coinfection was common among the 440 enrolled PWH: HCV: n = 355 (81%); HBV: n = 5 (1%); HBV and HCV: n = 37 (8%). Only 10% (n = 43) of participants had no hepatitis coinfection. Among those who tested positive for HBV, 36% had previously been diagnosed with HBV; among those who tested seropositive for HCV, 18% had previously received an HCV diagnosis. History of IDU was higher among those with hepatitis coinfection (HBV or HCV coinfection: 88%; HBV and HCV coinfections: 97%) than those without hepatitis coinfection (7%; p<0.01). Median days of alcohol consumption in the last 30 days was higher among those with coinfection (HBV or HCV coinfection: 20 (Interquartile Range (IQR): 10-30); HBV and HCV coinfections: 22 (IQR: 13-28) than those without hepatitis coinfection (10; IQR: 6-21; p<0.01). The syndemic conditions of HIV, hepatitis, IDU, and alcohol use are deeply entangled and challenging to parse out. Integrated health services are warranted to reduce the risk of liver-related morbidity.

Characteristics and Risk Factors for Postoperative Bleeding Following Endoscopic Resection of Esophageal Squamous Neoplasms.

Reports on postoperative bleeding after esophageal endoscopic resection are limited. This study aimed to identify the clinical characteristics and risk factors for postoperative bleeding following endoscopic resection of esophageal neoplasms. This single-center, retrospective study included consecutive patients who underwent endoscopic resection for esophageal squamous cell carcinoma or squamous intraepithelial neoplasm between January 2018 and December 2022. We investigated the incidence, timing, severity, and risk factors for postoperative bleeding. Of 1288 patients, 1062 (82%) underwent endoscopic submucosal dissection, and 226 (18%) underwent endoscopic mucosal resection. Postoperative bleeding occurred in seven (0.5%) patients (95% confidence interval [CI] 0.2-1.1%; median postoperative day 8 [range, 4-17 days]). In these seven patients, hemoglobin concentration decreased by a median of 3.0g/dL (range, 1.6-6.8g/dL). Antithrombotic agent use, resection wound circumference, and specimen size were significantly associated with postoperative bleeding (P < 0.001, P = 0.002, and P = 0.024, respectively). Among 43 patients who received direct oral anticoagulants (DOACs), postoperative bleeding occurred in four (9%) patients (95% CI 2.6-22.1%). DOACs were significantly associated with postoperative bleeding even after propensity score matching (4/40 [10%] vs. 0/80 [0%], respectively; P = 0.011). The overall bleeding rate following esophageal endoscopic resection was 0.5%, with a delayed onset, leading to anemia. DOACs emerged as the most significant risk factor for postoperative bleeding.

The burden of adhesive bowel obstruction requiring surgery in children: a single-center retrospective review.

Investigate causes, predictors, and complications of adhesive bowel obstruction (ABO) necessitating surgery in children. Single-center retrospective review of operative cases classified as 'adhesive bowel obstruction ' between May 2014 and December 2023. Parameters assessed included previous surgeries, operative time (indicative of adhesion extent), length of stay and postoperative complications. Results were statistically analyzed afterward. We identified 71 patients with ABO; seven had recurrences. Age (11d-18y, median 5.9 y) and time after surgery (four days-16years, median 6.4months) varied considerably. Preceding appendicitis (16 cases), NEC (seven cases) and gastroschisis (five cases) were most prevalent. Operative time ranged from 43min to 8.4h, was longer after previous surgery during infancy (median 177 vs. 124min), recurrent ABO (median 213 vs. 150min) and significantly shorter after appendicitis (82 vs. 175min). ICU stay (median 2days) and hospital stay (median 11days) reduced with age. 32 patients (41%) suffered complications, doubling mean lengths of stay. Bowel resection and longer surgery were associated with complications, while age and enterostomy creation were not. ABO is an impactful complication with limited predictors. The high incidence of complications adds to the burden for patients, parents, and health systems.