Long-term Patients Research Articles

Long-term clinical and angiographic outcome of T-and protrusion technique with ultrathin strut drug eluting stents.

Data about coronary bifurcations treated with ultrathin strut drug-eluting stents (DES) using T-and-protrusion (TAP) technique is limited. In this study, a total of 84 consecutive patients, who underwent bifurcation percutaneous coronary intervention (PCI) with TAP technique using Orsiro® DES (Biotronik, Berlin, Germany), were included. All pre- and post-procedural data, as well as 1- and 2-year follow-up angiograms, were analyzed. Primary endpoints were procedural success and target lesion failure (TLF); secondary endpoints were all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) during follow-up. Procedural success was achieved in 100% of cases. TLF rate was higher in patients presented with acute coronary syndrome compared to the ones with chronic coronary syndrome (19% vs. 5% p = 0.09). All-cause mortality was 30% during follow-up, from which 26% was due to non-cardiovascular cause, and the MACCE rate was 46%. Coronary bifurcations treated with ultrathin strut DES showed good short-term results and were associated with acceptable cardiovascular mortality. However, in these long-term patients, the rate of MACCE and non-cardiovascular death were rather high.

Personalized diet order compliance is associated with an improved functional independence measure (FIM) score in elderly patients: An eight-week follow-up study in a convalescent hospital.

It is important to establish the relationship between appropriate nutritional intake and improvements in activities of daily living (ADLs) in elderly hospitalized patients. This prospective observational study aimed to investigate diet order compliance (DOC) during 8 weeks of hospitalization and calculate the odds of improved functional independence measure (FIM) scores for high- and low-DOC groups using covariate-adjusted models in geriatric convalescent hospitals. The study subjects were elderly inpatients (>65 years old) with degenerative disease who consumed prescribed oral meals (Functional Oral Intake Scale (FOIS) = 6/7) and who did not receive physical/occupational therapy. The personalized diet order was prescript, and the DOC was calculated using dietitian-monitored daily intake data. The 73 patients were divided into a low-DOC group (< 84.0%, n = 35) and a high-DOC group (≥ 84.0%, n = 38) on the basis of the median DOC (84.0%, average for 8 weeks). Twenty (52.6%) high-DOC patients and nine (25.7%) low-DOC patients experienced motor-FIM improvements (P = 0.017). After 8 weeks, the change in motor-FIM in the high-DOC group (1.6±0.3) was greater than that in the low-DOC group (0.3±0.1; P = 0.001). According to the baseline and nutrition-intake-adjusted model of multiple logistic regression analysis, in the high-DOC group, the motor-FIM improvement OR was 5.102 (95% CI: 1.100-16.233, P = 0.036), and the total-FIM improvement OR was 5.273 (95% CI: 1.102-25.238, P = 0.037). High compliance with individualized nutritional prescriptions can increase FIM scores in clinical settings. Thus, comprehensive approaches to increase dietary compliance are needed for elderly long-term care patients.

Microbial involvement in myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and disabling disease related to persistent fatigue, exercise intolerance, post-exertional malaise, cognitive dysfunction, and musculoskeletal/joint pain. Gastrointestinal comorbidities, including irritable bowel syndrome, have been reported in affected individuals, indicating a potential role of gut microbiota in disease progression. In this paper, bacterial and metabolomic dysbiosis in subjects with ME/CFS are reviewed, and phenotypic, microbial, and metabolic biomarkers specific to individual cohorts are also identified. Furthermore, microbiome fluctuations or metabolic endotoxemia are proposed as possible disorder biomarkers. Based on the fact that gut microbiota dysbiosis reverts to a state of eubiosis in long-term patients with this condition, it may be hypothesized that disease progression begins with the loss of beneficial gut microorganisms, particularly short-chain fatty acid producers, leading to more widespread gastrointestinal phenotypes that are subsequently reflected in plasma metabolite levels. These alterations, specific of each individual, thereby result in metabolic and phenotypic shifts and in ME/CFS.

Metabolic Dysfunction Associated Fatty Liver Disease in Long-Term Cholecystectomy Patients: A Cross-Sectional Study.

Cholecystectomy, while generally safe with low perioperative morbidity and mortality, has been linked to an increase in metabolic disorders. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a globally prevalent condition that leads to both hepatic and systemic complications. This study aimed to investigate the association between cholecystectomy and MAFLD. This cross-sectional study was designed to evaluate the relationship between cholecystectomy and MAFLD. Metabolic dysfunction-associated fatty liver disease was defined by the presence of hepatic steatosis in combination with any of the following conditions: diabetes mellitus (fasting plasma glucose ≥126 mg/dL), overweight (body mass index (BMI) ≥25 kg/m2), or metabolic dysregulation. A total of 163 participants with BMI ≥25 kg/m2, including consecutive cholecystectomized (N = 83) and non-cholecystectomized (N = 80) subjects, were included. The prevalence of MAFLD was found in 64 out of 83 (77.1%) cholecystectomized patients and in 30 out of 80 (37.5%) non-cholecystectomized subjects (P < .001). When age, gender, BMI, exercise habits, hypertension, diabetes mellitus, and cholecystectomy status were included in regression analyses, we found that only BMI [odds ratio (OR) = 1.155 (95% CI: 1.040-1.283)] and cholecystectomy [OR = 4.540 (95% CI: 2.200-9.370)] were independently associated with MAFLD (both P < .01). ROC analysis identified 10 years as the cut-off, with MAFLD risk being 2.7-7.3 times higher in patients with cholecystectomy for ≤10 and >10 years. In our study, MAFLD was found to be 4.5 times more likely in cholecystectomized patients compared to those without cholecystectomy, with a significant increase in frequency observed after 10 years. These results suggest that cholecystectomized patients should be monitored for MAFLD.

Sociogeographic determinants of rapid opioid reduction or discontinuation among High-Dose Long-Term opioid therapy patients in North Carolina, 2006-2018.

Rapid opioid reduction or discontinuation among high-dose long-term opioid therapy patients (HD-LTOT) is associated with increased risk of heroin use, overdose, opioid use disorder, and mental health crises. We examined the association of residential segregation and healthcare access with rapid opioid reduction or discontinuation among HD-LTOT patients, and examined effect measure modification of individual-level characteristics. Using 2006-2018 North Carolina private insurance claims data, we conducted a retrospective cohort study of 18-64 years old HD-LTOT patients (≥ 90 morphine milligram equivalents for 81/90 consecutive days), with one-year follow-up. The outcome was rapid opioid reduction or discontinuation (versus maintenance, increase, or gradual reduction/discontinuation). Individual-level characteristics included age, sex, and clinical diagnoses (post-traumatic stress disorder (PTSD), depression, anxiety, and substance use disorder). Neighborhood-level characteristics included healthcare access (measured as geographic distance to healthcare facilities) and residential segregation (operationalized using the Index of Concentration at the Extremes). We conducted bivariate linear regression to estimate one-year risk differences (RDs) and 95% confidence intervals (CIs). Of 13,375 HD-LTOT patients, 48.6% experienced rapid opioid reduction or discontinuation during one-year follow-up. Female patients and those diagnosed with PTSD who live in areas of least racial and economic privilege have higher risks of rapid opioid reduction or discontinuation compared to those living in areas with the most racial and economic privilege. Healthcare providers need to address potential biases towards patients living in underserved and marginalized communities and intersectionality with mental health stigma by prioritizing training and education in delivering unbiased care during opioid tapering.

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.

Elevated 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. This 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. We 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). In 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. www.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.