Long-term Patients Research Articles

Clinical characteristics and long-term outcomes of Venoarterial extracorporeal membrane oxygenation in children with congenital heart disease.

To analyze the clinical outcomes of extracorporeal membrane oxygenation (ECMO) support in children with congenital heart disease (CHD) after surgery and explore the risk factors associated with mortality during long-term follow-up for 3-5 years. We conducted a retrospective observational study at Shanghai Children Medical Center (SCMC) from 2017 to 2021 and reviewed the clinical results and laboratory findings of 188 CHD patients who received ECMO support during this period. The 5-year overall survival rate was 56.38% (106/188) among CHD patients who received ECMO support. Kaplan-Meier curve showed residual anatomical malformation (RAM) (p < 0.0001), gastrointestinal bleeding (p = 0.019), single ventricular (SV) (p = 0.028), and pre-ECMO lactate level >10 mmol/L (p < 0.0001) were significantly associated with higher mortality in follow-up. Cox analysis identified RAM (p = 0.039) and pre-ECMO lactate level >10 mmol/L (p < 0.001) as independent risk factors for overall survival. Conversely, a minimum platelet count ≥50 × 109/L (p < 0.001) was found to be a protective factor. Moreover, a competing risk model showed that a CPR time ≥60 min (p < 0.001) was identified as a risk factor for death in patients who failed to be discharged from the hospital. Our study showed characteristics of long-term follow-up patients and revealed several risk factors associated with mortality in children with CHD who received ECMO support. These findings can provide valuable insights for clinical decision-making and contribute to improving patient outcomes.

Association of phenylalanine and tyrosine metabolism with mortality and response to nutritional support among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT

BackgroundElevated phenylalanine serum level is a surrogate marker of whole-body proteolysis and has been associated with increased mortality in critically ill patients. Tyrosine is a metabolite of phenylalanine and serves as a precursor of thyroid hormones and catecholamines with important functions in the oxidative stress response among others. Herein, we examined the prognostic significance of phenylalanine, tyrosine, as well as its metabolites nitrotyrosine, L-3,4-dihydroxyphenylalanine (DOPA), and dopamine regarding clinical outcomes and response to nutritional therapy in patients at nutritional risk.MethodsThis is 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 investigating individualized nutritional support compared to standard care in patients at risk of malnutrition. The primary outcome was 30-day all-cause mortality.ResultsWe analyzed data of 238 patients and found a significant association between low plasma levels of phenylalanine [adjusted HR 2.27 (95% CI 1.29 to 3.00)] and tyrosine [adjusted HR 1.91 (95% CI 1.11 to 3.28)] with increased 30-day mortality. This association persisted over a longer period, extending to 5 years. Additionally, trends indicated elevated mortality rates among patients with low nitrotyrosine and high DOPA and dopamine levels. Patients with high tyrosine levels showed a more pronounced response to nutritional support compared to patients with low tyrosine levels (HR 0.45 versus 1.46, p for interaction = 0.02).ConclusionIn medical inpatients at nutritional risk, low phenylalanine and tyrosine levels were associated with increased short-and long-term mortality and patients with high tyrosine levels showed a more pronounced response to nutritional support. Further research is warranted to gain a deeper understanding of phenylalanine and tyrosine pathways, their association with clinical outcomes in patients at nutritional risk, as well as their response to nutritional therapy.Clinical trial registrationwww.clinicaltrials.gov, identifier NCT02517476.

Abstract 4140100: Outcomes of Percutaneous Coronary Intervention of the Left Main Coronary Artery Bifurcation: Insights from PROGRESS-BIFURCATION registry

Background: There is limited data on the long-term outcomes of percutaneous coronary intervention (PCI) in patients with left main coronary artery (LM) bifurcation lesions. Methods: This retrospective, observational, cohort study was performed across 6 centers in the United States, Russia, and Turkey between 2013-2024, as part of the Prospective Global Registry of Percutaneous Coronary Intervention in Bifurcation Lesions (PROGRESS-BIFURCATION, NCT05100992). We examined procedural characteristics and follow-up outcomes of patients with versus without LM bifurcation lesions undergoing PCI. Multivariable adjusted hazard ratios (aHR) with 95% CI were calculated using Cox regression. Results: Of 1,089 patients who underwent bifurcation PCI, 289 (26.5%) underwent LM PCI. Patients in the LM group were older (70.1±11.9 vs 65.4±11.5 years; p&lt;0.001) and had more comorbidities, such as diabetes, heart failure, prior PCI, and prior coronary artery bypass graft surgery. Two-stent techniques were more commonly used in LM patients vs. non-LM patients (39.3% vs 26.5%, p&lt;0.001), with similar technical success (94.8% vs 95.9%, p=0.41) and procedural success (93.1% vs 93.1%; p=0.99). The incidence of in-hospital major adverse cardiovascular events (MACE) was higher in LM patients (7.9% vs 4.5%, p=0.04). During long-term follow-up LM PCI patients had higher mortality (aHR 3.17; 95% CI 1.22-8.18; p&lt;0.001), without significant differences in MACE (aHR 1.81; 95% CI 0.93-3.52; p=0.08), myocardial infarction (aHR 0.50; 95% CI 0.07-3.52; p=0.50), and target-vessel PCI revascularization (aHR 2.56; 95% CI 0.75-8.78; p=0.14). Conclusion: Follow-up mortality in patients undergoing bifurcation PCI, classified according to whether they underwent left main or non-left main PCI.

Pharmacologic or genetic interference with atrogene signaling protects against glucocorticoid-induced musculoskeletal and cardiac disease.

Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of vitamin D receptor (VDR) signaling with the VDR ligands calcitriol or eldecalcitol prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of the 3 tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ΔRING mice afforded temporary or sustained protection from GC excess in bone or skeletal and heart muscle. We concluded that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the 3 tissues.

Successful kidney transplantation improves atrophic bladder capacity and function within 3 months in long-term dialysis patients.

Successful kidney transplantation improves atrophic bladder capacity and function within 3 months in long-term dialysis patients.

High-dose denosumab (Xgeva®) Associated Medication-Related Osteonecrosis of the Jaws (MRONJ): incidence and clinical characteristics in a retrospective analysis of 1278 patients.

High-dose denosumab (Xgeva®) is increasingly used for treating bone metastasis and various malignant diseases but carries the risk of medication-related osteonecrosis of the jaw (MRONJ). This study aimed to evaluate the incidence, risk factors, and clinical outcomes of MRONJ in patients treated with high-dose denosumab. A retrospective review was performed on 1278 patients who received high-dose denosumab at Severance Hospital, Seoul, South Korea, from September 2014 to February 2023. Data on the incidence of MRONJ, patient demographics, primary diseases, and treatment outcomes were analyzed. Among the 1278 patients (average age 64.72years; 728 males and 550 females) treated, 34 developed MRONJ, with a 2.66% incidence rate. The average age of those with MRONJ was 68.32years, and they received more Xgeva® injections on average (13.62) compared to the overall cohort. Factors such as age and the frequency of injections were significantly associated with the risk of MRONJ. Notably, the incidence of MRONJ did not significantly differ between those who underwent oral surgery and those with spontaneous MRONJ, especially if oral surgery occurred within 1month of injection. Surgical interventions have shown higher recovery rates in advanced MRONJ stages. This study confirmed a significant MRONJ incidence of 2.66% among high-dose denosumab recipients, highlighting the importance of careful patient selection, monitoring, and education, particularly in older and long-term treatment patients, to mitigate the risk of MRONJ.

Frequencies or Absolute Numbers? Cluster Analysis of Frequencies and Absolute Numbers of B-Cell Subsets in Dialysis Patients Who Are Candidates for Kidney Transplantation Reveals Different Profiles.

Background: Detailed characterization of B cells in dialysis patients who are candidates for kidney transplant is still lacking, with little information on how dialysis duration and modality impact B cell subsets. Methods: Cluster analysis of flow cytometry determined the frequencies and absolute numbers of B-cell subsets and divided the cohort of 78 candidates into two distinct clusters, one with shorter and one with longer dialysis duration. Results: The immune profiles of the clusters differed depending on whether frequencies or absolute counts were considered. In long-term dialysis patients, the frequency of total memory, double negative and marginal zone B cells increased, while the frequency of naive and regulatory B cells decreased. This pattern was reversed in short-term dialysis patients, with a decrease in memory and an increase in naive and regulatory populations. The B subset number decreased significantly in long-term dialysis patients, while it increased significantly in short-term dialysis patients. The dialysis modality affected the frequency-based subset immune profiles. Conclusions: It is important to determine whether the evaluation is based on frequencies or absolute numbers. The different distribution of B cell subsets in the clusters, in terms of frequencies and absolute numbers, was influenced by dialysis duration. Modality and age only influenced the frequencies.

Elderly patients with decompensated heart failure: prospective analysis from the LECRA-HF registry

Abstract Background/Introduction Heart failure (HF) presents as a clinical syndrome associated with an adverse prognosis, increased mortality risk, and recurrent hospitalizations for HF (HHF). In Poland, there has been a persistent increase in the overall prevalence and hospitalizations of HF among patients. Each subsequent HHF is associated with progressively worsening prognosis. In Europe, HF is most prevalent in elderly individuals, rendering this patient group particularly susceptible to HF exacerbations. Purpose The aim of this study was to conduct a comprehensive analysis of the oldest patients (≥80 years) hospitalized due to HF decompensation, compared to the rest of the evaluated cohort, including overall mortality after median 46 months of observation. Methods The prospective registry of patients with HF decompensation (LECRA-HF) is an ongoing registry conducted at a tertiary cardiology center specializing in HF treatment. Patients enrolled in the registry (n=1394) were evaluated for the presence of cardiovascular risk factors, HF phenotype, laboratory, and echocardiographic findings, as well as overall mortality. Due to the frequent occurrence of HF in elderly patients, we arbitrarily chose to compare two cohorts of patients: those above (n=306) vs. below 80 years of age (n=1088). Results Median age of elderly patients was 84 [82-86] years, of which only 7.8% were &amp;gt;90 years of age. HFrEF was the most common HF phenotype, which, occurred less frequently in the elderly (54.4 vs 74.4%, P&amp;lt;0.001). In turn, HFpEF was more prevalent in elderly group (39.2 vs 17.7%, P&amp;lt;0.001). Elderly patients were more often female (45.1 vs 30.2%, P&amp;lt;0.001) and had more comorbidities: arterial hypertension (85.6 vs 78.6%, P=0.007), atrial fibrillation (61.1 vs 45.7%, P&amp;lt;0.001), renal failure (49.7 vs 28.5%, P&amp;lt;0.001) as well as peripheral arterial disease (17 vs 9.8%, P=0.005). Those patients had more frequently implanted cardiac pacemakers (28.6 vs 12.6%, P&amp;lt;0.001), but less often implantable cardioverter-defibrillators (7.9 vs 14.3%, P=0.003). During HHF they were less often qualified to elective coronary angiography (24.2 vs 31.5%, P=0.039). At discharge mineralocorticoid receptor antagonist were less often prescribed in that group (42.4 vs 50.3%, P=0.010). During long-term observation patients ≥80 years had a higher all-cause mortality (81 vs 67.4%, P&amp;lt;0.001, Panel A). Moreover, it was also higher elderly with NT-proBNP&amp;gt;4497 pg/mL (P&amp;lt;0.001) and LVEF&amp;lt;41% (P=0.014) (Panel B). Conclusion(s) Patients aged ≥80 years were characterized by a higher burden of comorbidities. They were more often qualified to cardiac pacemakers, but less often to implantable cardioverter-defibrillators and invasive coronary procedures. The most common HF phenotype was HFrEF, however with a significant increase in HFpEF. They exhibited significantly higher overall mortality compared to those &amp;lt;80 years old, which was associated with both LVEF and NT-proBNP levels.

Correlation between postdialysis blood pressure assessed at different time points and home blood pressure monitoring

Abstract Background Hemodialysis patients undergo blood pressure (BP) measurements during the predialysis, intradialytic and postdialysis (POSBP) periods at the dialysis sessions. However, there is no consensus regarding the time point when POSBP measurement should be performed. Purpose This study investigated the relationship of POSBP measurements performed at different time points with home blood pressure monitoring (HBPM). Methods This prospective study included 98 long-term dialysis patients (67% men; age=59.4 ±17.7 years; 79% using antihypertensive medications). During one week, POSBP measurements were obtained in sitting patients by trained health staff using oscillometric BP monitors lodged in the dialysis machines at all dialysis sessions in three different periods: 1) immediately after the dialysis period ended (POSBP1); 2) after returning the patient's blood (POSBP2) and 3) after hemostasis of the fistula or catheter sealing (POSBP3). In the same week, HBPM was performed using validated devices and was calculated as the mean of BP measurements obtained on six consecutive days, comprising three readings in the morning and in the evening after at least 3 min of rest, before antihypertensive medications were taken, with the patients seated. Abnormal BP was defined as HBPM≥135/85 mmHg. Based on the optimal cut-point values derived from ROC curves analysis, we built cutoffs for POSBP1 (143/79 mmHg), POSBP2 (153/78 mmHg) and POSBP3 (151/80 mmHg) corresponding to HBPM values of 135/85 mmHg. Results The values of POSBP1, POSBP2, POSBP3 and HBPM were 138±21/72±13, 143±24/73±13, 142±22/72±13 and 128±19/76±13 mmHg, respectively. Systolic HBPM showed greater correlation with systolic POSBP3 (r=0.71), followed by POSBP1 (r=0.68), POSBP2 (r=0.67), while diastolic HBPM showed greater correlation with diastolic POSBP2 and POSBP3 (both r=0.56), followed by POSBP1 (r=0.49) (all p&amp;lt;0.05). The POSBP3 cutoff showed the highest association (odds ratio [95% CI]= 8.06 [3.21, 20.27]), accuracy (area under the curve [95% CI]= 0.74 [0.65, 0.83]) and concordance (kappa coefficient=0.47) to identify elevated BP at HBPM in comparison with the POSBP1 and POSBP2 cutoffs (Figure). Conclusion(s) POSBP3 exhibited the strongest correlation with HBPM and had the highest accuracy to detect elevated HBPM in dialysis patients and may be a potentially preferable POSBP measurement in clinical practice.

Evaluation of asthma control after reinforcement of proper inhaler techniques in a tertiary care center in northern India.

Asthma is an obstructive lung disease with high prevalence. Symptom control in asthma remains poor despite significant advancements in treatment guidelines and inhalational devices. This is often attributed to inadequate patient adherence to the inhaler technique and insufficient education on its long-term use. Through this study, we aimed to assess the impact of reinforcement of proper inhaler technique on asthma symptom control and quality of life. A prospective cohort of 400 asthma patients using dry powder inhalers and metered dose inhalers was recruited in the outpatient clinic of our hospital. At the time of recruitment, the correctness of inhaler technique usage was assessed, and the pre-test Inhaler Technique Score (ITS) was recorded for each patient. Then, a ten-step inhalation technique was taught through demonstration, and the post-test ITS score was recorded again. This was done for each patient at monthly intervals for 3 months. Along with it, two tailored questionnaires, the Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ), were administered at each visit to assess disease control and quality of life. Significant enhancements in inhalation technique were noted from the first to the third visit using the ten-step inhalation usage scores, which improved from 6.91 to 9.87 (out of 10) (p<0.001), paralleled by ACT score increases from 17.06 to 19.37 (out of 25) (p<0.001) from visits one to two, and from 19.37 to 20.52 (out of 25) (p<0.001) from visits two to three, signifying improvement in symptom control. Quality of life similarly improved from 4.45 to 5.12 to 5.45 (out of 7) (p<0.001) across the three visits as assessed by AQLQ. In conclusion, promoting proper inhaler technique through structured education programs is crucial for optimizing long-term asthma management and enhancing patients' quality of life.

Persistent dysfunctions of brain metabolic connectivity in long-covid with cognitive symptoms.

Our study examines brain metabolic connectivity in SARS-CoV-2 survivors during the acute-subacute and chronic phases, aiming to elucidate the mechanisms underlying the persistence of neurological symptoms in long-COVID patients. We perfomed a cross-sectional study including 44 patients (pts) with neurological symptoms who underwent FDG-PET scans, and classified to timing infection as follows: acute (7 pts), subacute (17 pts), long-term (20 pts) phases. Interregional correlation analysis (IRCA) and ROI-based IRCA were applied on FDG-PET data to extract metabolic connectivity in resting state networks (ADMN, PDMN, EXN, ATTN, LIN, ASN) of neuro-COVID pts in acute/subacute and long-term groups compared with healthy controls (HCs). Univariate approach was used to investigate metabolic alterations from the acute to sub-acute and long-term phase. The acute/subacute phase was characterized by hyperconnectivity in EXN and ATTN networks; the same networks showed hypoconnectivity in the chronic phase. EXN and ATTN hypoconnectivity was consistent with clinical findings in long-COVID patients, e.g. altered performances in neuropsychological tests of executive and attention domains. The ASN and LIN presented hyperconnectivity in acute/subacute phase and normalized in long-term phase. The ADMN and PDMN presented a preseverved connectivity. Univariate analysis showed hypometabolism in fronto-insular cortex in acute phase, which reduced in sub-acute phase and disappeared in long-term phase. A compensatory EXN and ATTN hyperconnectivity was found in the acute/subacute phase and hypoconnectivity in long-term. Hypoconnectivity and absence of hypometabolism suggest that connectivity derangement in frontal networks could be related to protraction of neurological symptoms in long-term COVID patients.

Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery.

Secondary lymphedema (LE) following breast cancer-related surgery is a life-long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery-induced LE in short- and long-term LE patients and compared the transcriptomic landscape of LE adipose tissue to the obesity-induced adipose tissue. Adipose tissue biopsies were obtained from breast cancer-operated females with LE from the affected and non-affected arms (n = 20 patients). To decipher the molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses. Differential gene expression data from a cohort of lean and obese patients without LE was used for comparisons. Integrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis, and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue; whereas, epidermal differentiation, cell-cell junction organization, water homeostasis, and neurogenesis were downregulated in the LE arm. Surprisingly, only a few genes were found to be the same in the LE-induced and the obesity-induced adipose tissue expansion, indicating a different type of adipose tissue development in these two conditions. In metabolomics analysis, we found reduced levels of a branched-chain amino acid valine in the LE arm and downregulation of the mRNA levels of its transporter SLC6A15. Lipidomics analyses did not show any significant differences between the LE and non-LE arms, suggesting that other factors affect the lipid composition of the adipose tissue more than the LE in these patients. Our results provide a detailed molecular characterization of adipose tissue in secondary LE after breast cancer-related surgery. We also show distinct differences in transcriptomic signatures between LE-induced adipose tissue and obesity-induced adipose tissue, but only minor differences in metabolome and lipidome between the LE and the non-LE arm.

Tracheotomy : Indication and implementation

Tracheotomy has long been performed outside of intensive care medicine. In modern medicine, it has afirm place in the management of critically ill and emergency care patients as well as in cancer surgery of the head and neck, the care of long-term ventilated patients, patients with swallowing disorders, and neurological diseases. The indication, technique, and timing of tracheotomy are very different for the various diseases. This article provides an overview of the different indications, surgical techniques, and timing of tracheotomy in modern intensive care medicine.

Association Between Rapid Opioid Reduction or Discontinuation and Self-Harm, Suicide Attempt, and Suicide Death Among High-Dose Long-Term Opioid Therapy Patients in North Carolina, 2006-2018.

We examined the association between rapid opioid reduction or discontinuation and self-harm, suicide attempt, and suicide death among high-dose long-term opioid therapy (HD-LTOT) patient and examined effect measure modification by individual and neighborhood-level characteristics. Using private insurance data from North Carolina, this retrospective cohort study covered January 2006 to September 2018, with up to four years of follow-up. Participants included patients aged 18-64 years who were prescribed HD-LTOT. Time-varying exposure was ever exposed to rapid opioid reduction or discontinuation vs never exposed. The outcomes were self-harm or suicide attempt, suicide death, and the combined outcome. We estimated cumulative incidence and used Fine-Gray models to estimate sub-distribution hazard ratios (HRs). There were 21,450 HD-LTOT patients. In year 1, rapid opioid reduction or discontinuation was not associated with the combined outcome, HR: 1.09 (95% CI: 0.61-1.96). However, in years 2-4, rapid opioid reduction or discontinuation was associated with higher hazard of the combined outcome, HR: 2.77 (95% CI: 1.45-5.27). This association was stronger among patients with mental health conditions and those residing in underserved neighborhoods. These findings underscore the importance of provider training in adhering to guideline-concordant gradual tapering, offering mental health support, and ensuring patient safety throughout the tapering process.

Circulating mucosal-associated invariant T cell alterations in adults with recent-onset and long-term oral lichen planus

BackgroundMucosal-associated invariant T (MAIT) cells play key roles in many inflammatory diseases. However, their effects on the long-term course of oral lichen planus (OLP) and recent-onset OLP remain unclear. In this study, we aimed to investigate the function of MAIT cells in the different processes of OLP and to explore the immunological background of this disease.MethodsThe frequency, phenotype, cytokine secretion, and clinical relevance of MAIT cells were investigated. MAIT cells were collected from the peripheral blood of 14 adults with recent-onset OLP (7–120 days after disease onset) and 16 adults with long-term course OLP (>2 years after diagnosis) using flow cytometry and compared with 15 healthy blood donors. Statistical analyses were performed using the GraphPad Prism software.ResultsMAIT cells from adults with recent-onset OLP exhibited an activated phenotype, as indicated by an increased frequency of CD69+ (p < 0.05) and CD38+MAIT cells (p < 0.01) and elevated production of the proinflammatory cytokine IL-17 A (p < 0.01), compared with healthy adult donors. In adults with long-term OLP, MAIT cells exhibited an activated and exhausted phenotype, characterized by high expression of CD69 (p < 0.01) and PD-1 (p < 0.001) and increased production of granzyme B released (p < 0.01). Compared with recent-onset OLP patients, long-term OLP patients showed a decreased production of CD8+, and CD4−CD8− cells, but an increase in PD-1+ production (p < 0.05).ConclusionsCirculating MAIT cells exhibited activation in OLP patients across varying disease durations. Given that PD-1 expression is elevated in adults with long-term OLP, it is reasonable to infer that circulating MAIT cells in long-term OLP may exhibit a more exhausted state than those in recent-onset OLP.

6861 Pre- And Peri-Operative Predictors Of Glycemic Outcomes From Total Pancreatectomy And Islet Auto-Transplantation

Abstract Disclosure: E.N. Haddad: None. M. Lansang: None. H. Xiao: None. R. Walsh: None. R. Simon: None. B.A. Hatipoglu: None. K. Zhou: None. Background: There is a lack of information regarding the immediate post-operative period as a predictor of early and long-term insulin independence after total pancreatectomy and islet auto-transplantation (TPIAT). This study examined the baseline and peri-operative variables that are associated with one-year and longer-term insulin independence following TPIAT. Methods: This was a retrospective study of 46 TPIAT patients in a single hospital system between 2010 and 2022. Perioperative variables were compared between short- (one year) and long-term (last follow up outside of year one) insulin-independent versus dependent patients. Multivariable models were used to adjust for clinically important variables. Results: The median age of the cohort at time of TPIAT was 38.5 years (IQR 30, 49). Patients were predominantly white (91%) and 50% were female. Nine (20%) and seven (15%) patients achieved short- and long-term insulin independence, respectively. The patients were followed for a median of 2.8 years (IQR 1.0, 4.7). There were no significant differences in patient demographics (age, sex, ethnicity), duration of pancreatitis, HbA1c, or mixed meal testing results (area under c-peptide curve from 0 to 4 hours) between those achieving insulin independence and those who did not. Short term insulin-independence was associated with higher median transplanted islet equivalents (IEQ)/kg (6,981 vs 4,493, p=0.02), lower units of basal insulin on discharge (7 vs 12, p=0.009), and lower rates of discharge from the hospital with an insulin regimen (67% vs 100%, p=0.006). Short-term insulin independence was also associated with decreased median insulin use in the immediate 24-hour post-operative period (14.3 vs 45.3 units, p=0.03), though this was not statistically significant when adjusting for patient weight (0.23 vs 0.56 units/kg, p=0.13). The odds of having short term insulin independence increased by 80% for every 1,000 increase in IEQ/kg (OR 1.80, CI 1.18 to 3.12, p=0.005) and decreased by 32% for every additional basal unit of insulin on discharge (OR 0.68, CI 0.42 to 0.91, p=0.003). This was no longer statistically significant after adjusting for sex, age, mixed meal testing area under c-peptide curve at 4 hours, and HbA1c. Long-term insulin independence was also associated with transplanted IEQ/kg and basal insulin units at discharge in univariable analysis. None of the patients on insulin or any other antihyperglycemic medication prior to surgery achieved short- or long-term insulin independence. Conclusion: Short- and long-term insulin independence after TPIAT is associated with a higher transplanted IEQ/kg and fewer units of basal insulin at discharge. Immediate post-operative variables can be used to inform the discussions clinicians have with their patients regarding glycemic prognosis following TPIAT. Presentation: 6/2/2024

Weightlessness damaged the ultrastructure of knee cartilage and quadriceps muscle, aggravated the degeneration of cartilage.

Long-term exposure to weightlessness can result in bone and muscle degradation, significantly impacting musculoskeletal function. Recent studies have also indicated damage to articular cartilage due to weightlessness. This study aims to observe the effects of simulated weightlessness on the cartilage microstructure of the quadriceps muscle and the muscular knee joint in rats. A total of 30 rats were used in this study, of which 20 rats were subjected to simulated weightlessness by tail suspension, which may be suitable for clinical long-term bedridden patients. At 14 and 28 days, the microscopic morphology of knee cartilage and quadriceps femoris muscle was observed by transmission electron microscopy, and the collagen and water content of cartilage was evaluated by magnetic resonance imaging. The mitochondrial activity of knee muscle and the levels of inflammatory factors in synovial fluid were detected by enzyme-linked immunosorbent assay (ELISA). Biomechanical and histological evaluation of cartilage was performed. On day 14, T2 mapping revealed no significant loading effect. However, transmission electron microscopy revealed altered mitochondrial inner membrane structure in cartilage, with vacuolization, disrupted endoplasmic reticulum, alongside mitochondrial ultrastructural damage in muscle. ELISA results showed that a large number of mitochondria in muscle were inactivated, and the levels of inflammatory factors in synovial fluid were increased. The staining results showed slight fracture of the cartilage surface and the type II collagen-positive cells were reduced. Nanoindentation showed that the cartilage microsurface was uneven, and the elastic modulus and hardness were decreased. On day 28, T2 mapping analysis indicated increased cartilage T2 values. Transmission electron microscopy showed alterations in the structure of the mitochondrial inner membrane in cartilage, severe vacuolization, disrupted endoplasmic reticulum, and substantial mitochondrial damage in muscle tissue. Muscle mitochondrial activity was markedly decreased, inflammatory factors levels were elevated, and the cartilage surface exhibited severe damage. The type II collagen positive cells were further reduced, the micro-surface of cartilage was uneven, and the elastic modulus and hardness were significantly decreased. The weightless environment resulted in the damage of endoplasmic reticulum and mitochondria of cartilage, mitochondrial damage of quadriceps muscle, inactivation of muscle mitochondria (P=0.01), increased intra-articular inflammation (P=0.01), decreased elastic modulus and hardness (P=0.03), and damaged cartilage surface, which aggravated cartilage degeneration.

Seroprevalence of SARS-CoV-2 in pediatric hematology-oncology patients.

The COVID-19 pandemic disproportionately affected persons with underlying medical conditions. SARS-CoV-2 infection susceptibility and vaccine effectiveness in pediatric hematology-oncology patients were unknown. From February to July 2022, anti-spike and anti-nucleocapsid Ig were assayed in 354 pediatric hematology-oncology subjects, including 53 oncology patients receiving chemotherapy (cancer), 150 patients with sickle cell disease (SCD), and 151 benign consult and long-term follow-up patients (controls). Participants completed a questionnaire. Frequencies of COVID-19 infection, defined by positive PCR/antigen test or anti-nucleocapsid Ig, were 62% in cancer, 71% in SCD, 52% in controls, with SCD statistically different than controls (p=.001). Infection was associated with COVID-19 exposure, Hispanic/Latino or Black/African American ethnicity, multi-family dwelling, sports participation; COVID-19 booster decreased association with infection. In COVID-19-positive cancer patients, 58% had positive anti-nucleocapsid and 76% had positive anti-spike (≥10U/mL), compared to essentially 100% seroconversion in SCD and controls (p<.0001, p=.01, respectively). Infection led to high anti-spike (≥2500U/mL) in 12% cancer, 14% SCD, and 15% controls (p=.93). Vaccination resulted in anti-spike positivity in 90% cancer, 100% SCD, and 100% controls (p=.06), and in high anti-spike in 20% cancer, 47% SCD, and 41% controls (p=.36). Of boosted subjects, one of two cancer, 6/6 SCD, and 19/19 controls exhibited high anti-spike. Cancer patients demonstrated similar SARS-CoV-2 infection frequency as controls, but diminished antibody response to infection and vaccination. SCD patients exhibited seroconversion indistinguishable from controls. Vaccination was associated with higher frequency of high anti-spike than infection; vaccination plus booster was most effective in eliciting high anti-spike antibody detectable beyond 90days.

Trajectories of Short-Term Post-Traumatic Stress Disorder Symptoms in Patients with Post-Intensive Care Syndrome: A Longitudinal Observational Study.

Post-traumatic stress disorder (PTSD) is a major psychiatric health issue among intensive care unit (ICU) survivors with post-intensive care syndrome (PICS). Although early PTSD intervention has been demonstrated to decrease the risk of progression from acute to chronic PTSD, information on the progression trajectory of short-term PTSD symptoms and modifiable risk factors in PICS patients is limited. This study aimed to explore the clinical progression trajectories of short-term PTSD symptoms and the associated factors in PICS patients by conducting a prospective longitudinal observational study. This study was conducted at a tertiary hospital in China. The impact of event scale-revised was used to collect data on the PTSD symptoms of patients at 1, 2, 3, and 4 months post-discharge from the ICU. The latent growth mixture model was used to construct trajectory models for PTSD symptoms and multivariate logistic regression was used to determine the factors associated with the trajectories. A total of 130 ICU survivors with PICS completed the 4-month short-term follow-up. Our results showed that PTSD symptoms in PICS patients manifested as three trajectories, namely, moderate chronic (n = 17, 13.1%), recovery (n = 25, 19.2%), and resilience (n = 88, 67.7%). Compared with the resilience trajectory, age and female were identified as risk factors for the moderate chronic trajectory, while prolonged ICU stay was a risk factor for the recovery trajectory. Our study showed that short-term PTSD symptoms in PICS patients manifested as moderate chronic, recovery, and resilience trajectories. Additionally, our results showed that PTSD screening should be conducted for critically ill patients, especially younger, female, or long-term ICU patients, immediately after their discharge from the ICU.

Healthcare professionals' experience with nutritional care beyond formal quality systems - A qualitative study.

Numerous formal strategies, screening tools, and interventions have been used to prevent malnutrition in long-term care patients. Despite these efforts, the proportion of screened patients is low, and a large proportion are malnourished. Previous research has revealed that healthcare professionals use a broad approach in their nutritional care but has also emphasised the need for further investigation into these approaches. To explore how healthcare professionals working in long-term care experience and apply nutritional care. A descriptive, exploratory, qualitative design containing 240 h of participant observation, 12 focus groups and 2 individual interviews. Twelve nursing homes and home care units in three Norwegian municipalities. Participant observation of interactions between healthcare professionals and patients. Forty-three registered nurses participated in focus group or individual interviews. The data were analysed using inductive thematic analysis. The analysis identified three themes: The first theme, limited significance of nutritional screening, showed that healthcare professionals experienced the limited value of nutritional screening, as it often did not capture patients' nutritional challenges. They also perceived nutritional screening as unsuitable for patients at the end of their lives, those with overweight-related complications, or undergoing rehabilitation. In addition, nutritional screening was perceived as something healthcare professionals did for their managers or administrators, not because it was crucial to providing good nutritional care. The second theme, provision of individualised food, captures the healthcare professionals' efforts in adapting and preparing food according to the patient's preferences. Facilitation to enable patients to make individual food choices and the use of food cards or lists were two approaches to individualising nutrition care. The third theme, making meals more than about food, elucidated how healthcare professionals used meals to help patients cope with their situations and experience social belonging. Conversations about or around meals were used to provide patients with a sense of belonging to their past or present situation. The meals were also used as a diversion strategy for patients with unrest, as arenas for daily activity training, and for meaningful social interactions between patients around the tables. Nutritional screening and prevention of malnutrition are only one part of healthcare professionals' nutritional care. Individualised food and meals that create coping, a sense of belonging, and social experiences are equally important parts of their care. Emphasising healthcare professional's person-centred approach to nutritional care would be beneficial, as it could strengthen and further develop long-term nutritional care services.