Baseline Parameters Research Articles

The microbiome is dispensable for normal respiratory function and chemoreflexes in mice

Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O2,79% N2) conditions and during challenges in hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic (10% O2, 90% N2) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, Breathe Easy, to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF versus SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.

Wide Variation in Shape of Hypoplastic Left Ventricles Undergoing Recruitment and Biventricular Repair: A Statistical Shape Modeling Study.

Patients with hypoplastic left ventricles (LV) who undergo volume-loading procedures (recruitment, biventricular (BIV) repair) are at risk for adverse outcomes including heart failure and death. We investigated pre-BIV LV shape as a predictor of outcome after BIV repair in patients with hypoplastic LVs. Baseline and post-recruitment cardiac MRI and CT data were analyzed in patients with hypoplastic LV (< 50 ml/m2). Statistical shape modeling (SSM) was utilized to generate a model of the shape and variability of LVs. Traditional measures of LV sphericity and eccentricity were also measured. Major adverse cardiac events (MACE) included heart failure, transplant, and death. Of 95 patients with baseline mean LV volume 29 ± 13ml/m2, 45 (47%) had a right dominant atrioventricular canal defect, 31 (34%) had a variant of hypoplastic left heart syndrome, and 18 (19%) had endocardial fibroelastosis (EFE). A wide variation in LV shape was found by SSM, and shape modes were associated with RV and LV size, and diagnosis. BIV repair was achieved in 74 (78%) patients; and 13 (18%) of BIV patients had MACE. Predictors of MACE following BIV repair included EFE, higher RV mass index, and higher RV end-diastolic volume index. No baseline or post-recruitment LV shape parameter was associated with outcome after BIV repair. The shape model of hypoplastic LVs demonstrated a wide array of LV shapes. LVs gained sphericity and size and lost eccentricity with recruitment. Though the ventricles changed shape with recruitment, no specific LV shape characteristic at the baseline or post-recruitment stage was predictive of decision to proceed with BIV repair nor outcome. Higher RV mass and volume may represent new biomarkers that predict outcome following BIV repair in patients with hypoplastic LV. Further investigation could determine the reproducibility of these findings.

Waiting for in-Lab Polysomnography May Unnecessarily Prolong Treatment Start in Patients with Moderate or Severe OSA at Home Sleep Apnea Testing.

The gold standard in obstructive sleep apnea (OSA) diagnostics is nocturnal full-night polysomnography (PSG). Due to high costs and high time effort portable respiratory polygraphy (PG or home sleep apnea testing-HSAT) has been developed. In contrast to PG the PSG gains relevant further information concerning sleep stages, arousals and leg movements. However, the role of PG in the diagnostic of OSA remains largely undefined. The aim of this study was to investigate the difference of PG- and PSG- related metrics in OSA, to understand if there is a difference in PG and PSG-based treatment decision and show up the time between performed PG and PSG. 99 consecutive patients with existing outpatient performed PG and followed PSG in our tertiary care otorhinolaryngology department between February 2020 and December 2023 were retrospectively assessed. All patients were treatment-naive at the time of consultation. The time between performed outpatient PG and PSG was calculated. Furthermore, clinical baseline parameter and PG as well as PSG data were evaluated. All data were then blinded presented with relevant comorbid diseases to two experts in sleep medicine in our tertiary care centre to decide whether PAP therapy was indicated or not. Mean AHI was significantly higher in PSG (32.32 ± 22.78/h) compared to PG (22.60 ± 15.12/h) (p<0.001). Mean duration between performed PG and PSG was 194.99 ± 131.96 days (range between 37 and 842 days). Only in two patients PAP-therapy was indicated with PG results but not with PSG results. Only in one case PAP-therapy was not indicated with PG results but with PSG results. These data suggest initiating OSA therapy based on PG results for patients with at least moderate OSA on PG, followed by a confirming PSG and a control PSG under treatment to avoid unnecessary prolongation of treatment start.

Comparative Efficacy of Carbamazepine Therapy With and Without Transcutaneous Electrical Nerve Stimulation Therapy in Trigeminal Neuralgia Patients: A Randomised Controlled Trial Protocol

Introduction: Trigeminal Neuralgia (TN) is one of the most painful diseases. Typically, medication therapy starts at an initial titrated dose of 100 mg every other day of Carbamazepine (CBZ) 200-1200 mg/day. There is less evidence to support secondline treatments such as clonazepam, valproic acid, baclofen, gabapentin, lamotrigine, and baclofen. Transcutaneous Electrical Nerve Stimulation (TENS) is a widespread technique used for managing neuropathic pain. TENS therapy, which involves the transmission of an electric current across the intact skin surface to activate deeper nerves in an attempt to relieve pain, is a recent and promising alternative for the treatment of both acute and chronic pain. Need of the Study: Few research has been done on TENS therapy for pain management in TN. These studies have poor study designs, no control groups, and unclear information regarding the type of concurrent pharmacological therapy. TENS in combination with CBZ may reduce the dose of CBZ therapy, therefore, there is a need to conduct the study on “Comparative efficacy of CBZ therapy with and without TENS therapy for the management of TN”. Aim: To evaluate and compare the efficacy of CBZ therapy with and without TENS therapy for the management of TN. Materials and Methods: A Randomised Controlled Trial (RCT) will be conducted in the Outpatient Department (OPD) of Oral Medicine and Radiology at Sharad Pawar Dental College and Hospital, Wardha, Maharashatra, India between July 2024 and May 2026. Once diagnosed and enrolled, 38 individuals between the ages of 20 years and 80 years will receive a primary diagnosis of TN will be included and they will receive further treatment, based on International Headache Soceity (IHS) diagnostic criteria (IHS, 2018). Then these patients will randomly be allocated to one of the following groups, 19 subjects in each group, respectively: Group 1 (CBZ therapy): The baseline parameters of patients will be evaluated who will be treated with CBZ Initially at 100 mg TDS per day (300 mg), the patient will receive an additional titrated dose 100 mg of CBZ every 48 hours until they reach the maximum tolerated dose or total relief and Group 2 (CBZ with TENS therapy): CBZ initially, at 100 mg TDS per day (300 mg), the patient will receive an additional titrated dose 100 mg of CBZ every 48 hours until they reach the maximum tolerated dose or total relief. The pulse duration of TENS therapy will be 125 µS. The TENS will be applied during the first twenty minutes at a low frequency (2 to 10 Hz) and the last twenty minutes at a high frequency (50 to 100 Hz), with no break in between, for a total of 40 minutes per session. The outcome of Group 2 will be more efficacious in reduction of Visual Analogue Scale (VAS) score as compare to Group 1. The statistical analysis will be performed using Chi-square test at 5% level of significance (p&lt;=0.05).

Diagnostic efficacy of combined high- and low-frequency ultrasound in post-hematopoietic stem cell transplantation ureteral obstruction in leukemia patients.

The objective of this study was to evaluate the diagnostic efficacy of high- and low-frequency ultrasound (H&LFUS) in the imaging of post-hematopoietic stem cell transplantation (post-HSCT) ureteral obstruction in leukemia patients. A total of 103 patients who received HSCT for leukemia were included in this retrospective study. Patients underwent examinations using high-frequency ultrasound (HFUS), low-frequency ultrasound (LFUS), and the combined use of H&LFUS approach. Baseline data, clinical laboratory parameters, and clinical parameters were compared among the groups. Ultrasound findings and diagnostic sensitivity, specificity and accuracy were also analyzed to assess the diagnostic value of the imaging modalities. The investigation demonstrated no statistically significant distinctions in demographic, baseline, and clinical parameters among the HFUS group, LFUS group, and H&LFUS group. Nonetheless, notable differences emerged in the detection rates of specific ultrasound abnormalities, encompassing ureteral dilatation, wall thickening, urine flow obstruction, hydronephrosis, bladder wall thickening, andrenal masses. Regarding diagnostic performance metrics, H&LFUS approach exhibited superior efficacy across sensitivity, specificity, and overall accuracy, registering rates of 91.43%, 88.57%, and 90%, respectively, surpassing those of the individual HFUS and LFUS methodologies. The amalgamation of H&LFUS techniques manifests as a formidable diagnostic modality, characterized by heightened sensitivity, specificity, and diagnostic accuracy.

Native learning ability and not age determines the effects of brain stimulation

Healthy aging often entails a decline in cognitive and motor functions, affecting independence and quality of life in older adults. Brain stimulation shows potential to enhance these functions, but studies show variable effects. Previous studies have tried to identify responders and non-responders through correlations between behavioral change and baseline parameters, but results lack generalization to independent cohorts. We propose a method to predict an individual’s likelihood of benefiting from stimulation, based on baseline performance of a sequential motor task. Our results show that individuals with less efficient learning mechanisms benefit from stimulation, while those with optimal learning strategies experience none or even detrimental effects. This differential effect, first identified in a public dataset and replicated here in an independent cohort, was linked to one’s ability to integrate task-relevant information and not age. This study constitutes a further step towards personalized clinical-translational interventions based on brain stimulation.

Short-Term Weight Loss Outcomes of 104 Mini-Gastric Bypass or One-Anastomosis Gastric Bypass Operations: Retrospective study.

This study aimed to examine the short-term effects of mini-gastric bypass (MGB) or one-anastomosis gastric bypass (OAGB) procedures on weight loss in individuals with obesity. This retrospective study was conducted in Medicano Hospital, Erbil, Iraq, from January 2019 to May 2020. Preoperative body mass index (BMI), age, height and preoperative weight were recorded as baseline measures. Weight-related changes were evaluated during a follow-up phase of 48 weeks. A total of 104 patients with obesity underwent MGB or OAGB surgery. The mean baseline parameters of the subjects before surgery included 1.64 m for height, 122.9 kg for weight and 45.6 kg/m2 for BMI. During the 48-week follow-up period, there was a substantial reduction in mean weight, which dropped from 122.9 kg at baseline to 75.5 kg at week 48. The weight change (in percentage) gradually increased from -11.8% at week 12 to -37.9% at week 48, without statistically significant association with demographic factors or chronic diseases. From week 12 to week 48, the percentage of excess weight loss (%EWL) increased substantially from 26.8% to 86.1%. The results of the subgroup analysis indicated that the %EWL was considerably higher among those aged 30 or older at week 36 and singles at week 48. This study's results illustrate the efficacy of MGB or OAGB procedures in significantly reducing weight in the short term. The %EWL increased with the follow-up time and was significantly associated with age and marital status.

Physiological response to exercise in the heat: Implications for risk mitigation and adaptation

ABSTRACT Purpose Recentfield studies of physical exertion in challenging environmentalconditions have reported dissociation between elevation in body coretemperature (Tc)and successful task completion. This prompted us to further examinephysiological mechanisms that might underlie variability in theresponse to exertional heat exposure. We hypothesized that, inresponse to exercise in the heat, systematic differences in centraland peripheral physiological variables would be apparent betweenparticipants who successfully completed the task, versus those whobecame hyperthermic or symptomatic. Methods 38healthy participants attempted a 120-min walk (5 km/h, 2%grade) in aclimate-controlled chamber (40⸰C,50%RH). At rest and at regular intervals during the walk, measures ofphysiological heat strain were assessed. Twenty-seven participantswere Completers, seven were stopped because their Tcexceeded 39⸰C(Hyperthermics), and four became Symptomatic (e.g. lightheaded,headache, dizzy)and did not complete the walk. Results Visceraladipose tissue was higher in those who became Hyperthermic, comparedto the Completers (437 ± 183vs 245 ± 268 g; p = 0.034),despite similar height and body mass. Hyperthermics also had higherheart rate (p = 0.009),and lower end-diastolic volume (p = 0.031),and stroke volume (p = 0.031)during the early stages of walking, compared to the Completers. Noneof theSymptomatics reached a Tc >39⸰C(symptoms occurred at 38.1 ± 0.4⸰C),and none of the Hyperthermics reported symptoms. Conclusions Duringexertional heat exposure, adiposity and exaggerated early-stagehemodynamic responses were related to Tcelevation, but hyperthermia was not related to the development ofsymptoms, and baseline parameters relating to body composition andfitness were not related to symptom development.

Dynamic Simulation and Analysis of Three Phase Induction Motor for Faults Detection using Matlab/Simulink

The dynamic simulation of three-phase induction motors under fault conditions is essential for understanding and mitigating the impacts of electrical faults on motor performance. This study aims to simulate and analyze the impact of electrical faults on three-phase induction motors to improve fault detection and isolation strategies. Utilizing MATLAB/Simulink software, the behavior of three-phase induction motors under both symmetrical and unsymmetrical faults is modeled and analyzed. The motor’s baseline parameters, include 3 Amps rated power and speed of 1500 RPM. Symmetrical faults, such as line-to-line-to-line (L-L-L), and unsymmetrical faults, like single-phase to ground faults, were simulated to observe their effects on motor operation. The d-q model was used to simulate motor dynamics, employing a block model approach to resolve reference frame theory issues. Major parameters analyzed include rotor speed, electromagnetic torque, and stator current. Through detailed simulations, key performance indicators such as torque fluctuations, current spikes, and decreases in rotor speed are examined. At 1.5 seconds, when the fault was introduced, the rotor speed, electromagnetic torque, and stator current were all affected. For instance, during a symmetrical fault, the rotor speed dropped from 1500 RPM to 1200 RPM, electromagnetic torque declined to -12 Nm, and the stator current increased to 7 Amps from the rated 3 Amps. Under an unsymmetrical single-phase-to-ground fault at the same instant, rotor speed decreased from 1500 RPM to 1400 RPM, electromagnetic torque declined to -12 Nm with greater distortion, and the stator current in the affected phases rose to 7 Amps from the rated 3 Amps. These results underscore the importance of robust fault detection and isolation mechanisms to enhance motor reliability and longevity. This work significantly contributes to engineering by offering validated simulation models and insights into parameter sensitivity, serving as both an educational resource and a foundation for advanced fault detection system development. The findings are applicable in academic research and industrial contexts, providing guidance for improving motor design and fault management strategies.

Measurable disease as baseline criterion for response assessment in glioblastoma: A comparison of PET -based (PET RANO 1.0) and MRI-based (RANO) assessments.

Recently, criteria based on amino acid positron emission tomography (PET) have been proposed for response assessment in diffuse gliomas (PET RANO 1.0). In this study, we compare the prevalence of measurable disease according to PET RANO 1.0 with magnetic resonance imaging (MRI)-based Response Assessment in Neuro-Oncology (RANO) criteria in glioblastoma. We retrospectively identified patients with newly diagnosed IDH-wild-type glioblastoma who underwent [18F] Fluoroethyltyrosine(FET) PET and MRI after resection or biopsy and before radio-/radiochemotherapy. Two independent investigators analyzed measurable disease according to PET RANO 1.0 or MRI-RANO criteria. Additionally, lesion size, congruency patterns, and uptake intensity on [18F]FET PET images were assessed. We evaluated 125 patients including 49 cases after primary resection and 76 cases after biopsy. Using PET criteria, 113 out of 125 patients (90.4%) had measurable disease, with a median PET-positive volume of 15.34cm3 (8.83-38.03). With MRI, a significantly lower proportion of patients had measurable disease (57/125, 45.6%; P < .001) with a median sum of maximum cross-sectional diameters of 35.65mm (26.18-45.98). None of the 12 patients without measurable disease on PET had measurable disease on MRI. Contrariwise, 56/68 patients (82.4%) without measurable disease on MRI exhibited measurable disease on PET. Clinical performance status correlated significantly with PET-positive volume and MRI-based sum of diameters (P < .0059, P < .0087, respectively). [18F]FET PET identifies a higher number of patients with measurable disease compared to conventional MRI in newly diagnosed glioblastoma. PET-based assessment may serve as a novel baseline parameter for evaluating residual tumor burden and improving patient stratification in glioblastoma studies. Further validation in prospective trials is warranted.

NIMG-48. MEASURABLE DISEASE AS BASELINE CRITERION FOR RESPONSE ASSESSMENT IN GLIOBLASTOMA TRIALS – A COMPARATIVE STUDY OF MRI-BASED (RANO 2.0) VERSUS PET-BASED (PET RANO 1.0) ASSESSMENT

Abstract Response assessment in glioblastoma relies on measuring contrast enhancement on MRI according to RANO 2.0 criteria, and ‘measurable disease’ often serves as inclusion criterion for clinical trials. Recently, criteria based on amino acid PET have been proposed for response assessment in clinical trials (PET RANO 1.0). Here, we compare ‘measurable disease’ as defined by PET RANO 1.0 with the standard MRI-based RANO 2.0 criteria in glioblastoma patients. In this retrospective single-center study, we identified patients with newly diagnosed IDH-wildtype glioblastoma who underwent [18F]FET PET and MRI after resection or biopsy and before chemoradiotherapy. Two independent investigators analyzed ‘measurable disease’ according to PET RANO 1.0 versus MRI-based RANO 2.0 criteria. Additionally, lesion size and uptake intensity, including maximal and mean target-to-background ratio, were assessed. We evaluated 136 patients with 76 cases after biopsy and 60 after microsurgical resection. Using RANO 2.0, 35/76 patients (46.1%) had measurable disease in the biopsy group, and 25/60 (41.6%) in the resected group (median sum of maximum cross-sectional diameters: 39.7mm and 28.0mm, respectively). Utilizing PET RANO 1.0, a significantly higher proportion (overall 123/136, 90.4%; 66/76 (86.8%) after biopsy; 57/60 (95.0%) after resection) had measurable disease (p&amp;lt;0.001). None of the 10 patients in the biopsy group nor of the 3 patients in the resected group without measurable disease on PET had measurable disease on MRI. Contrariwise, 32/41 patients (73.2%) in the biopsy group and 30/35 (85.7%) in the resected group without measurable disease on MRI exhibited measurable disease on PET. PET RANO 1.0 identifies a significantly higher number of patients with ‘measurable disease’ compared to conventional MRI-based criteria in the perioperative period of glioblastoma. PET-based assessment may thus serve as a novel baseline parameter for evaluating treatment response in glioblastoma trials, that may allow the enrollment of larger patient populations. Further validation in prospective trials is warranted.

Tunnel Technique and Subepithelial Connective Tissue Graft, With or Without Cross-Linked Hyaluronic Acid, in the Treatment of Multiple Gingival Recessions: Prognostic Parameters for Clinical Treatment Outcomes of Randomized Controlled Trial.

Objectives: This study aimed to investigate factors that influence the 12-month outcomes after the treatment of multiple gingival recessions (GRs) with a modified coronally advanced tunnel (MCAT) and a subepithelial connective tissue graft (SCTG), with cross-linked hyaluronic acid (HA, tests) or without (controls). Materials and Methods: Twenty-four patients with 266 GRs were treated. A logistic regression model was set to identify the baseline parameters that could predict the 12-month outcomes. The study protocol was registered at ClinicalTrials.gov (ID No. NCT05045586). Results: The evaluated clinical and esthetic parameters showed marked improvement in both groups without any statistically significant differences between the groups, with the exception of the soft tissue texture (STT). The STT was in favor of the HA group (0.96 versus 0.73, p = 0.0091). The likelihood of an MRC > 85%, of achieving CRC, and of gaining an RES = 10 was the highest for the incisors (reference group) and the lowest for the molars (OR = 0.046, p = 0.005). With each 1 mm increase in the baseline clinical attachment level, the odds of failure (MRC < 85%, not achieving CRC) increased, whereas each 1 mm increase in the baseline keratinized tissue width (KTW) improved the chances of an MRC > 85%, of achieving CRC, and of gaining an RES = 10. The application of HA increased the likelihood of a perfect RES more than twofold (OR = 2.683, p = 0.001). Conclusions: The application of HA improved the 12-month esthetic outcomes after the treatment of GRs with the MCAT technique. The baseline CAL, KTW, and tooth type predicted the 12-month MRC, CRC, and RES. An evaluation of the baseline characteristics of the surgical area might help clinicians develop individualized treatment plans.

A randomised trial of sirolimus- versus paclitaxel-coated balloons for de novo coronary lesions.

Paclitaxel-coated balloons (PCB) are a viable alternative to drug-eluting stents in the treatment of de novo coronary lesions. Whether sirolimus represents an alternative to paclitaxel for drug-coated balloons remains elusive. This randomised, controlled, multicentre, non-inferiority trial investigated a novel sirolimus-coated balloon (SCB) with a crystalline coating versus a PCB in de novo coronary lesions. To compare a novel SCB with a clinically proven PCB, 70 patients with de novo coronary lesions were enrolled at 4 centres in Germany and Switzerland. The primary endpoint was non-inferiority regarding angiographic late lumen loss (LLL) at 6 months, with a predefined margin of δ=0.35 mm. Secondary endpoints included procedural success, major adverse cardiac events, and individual clinical endpoints. Quantitative coronary angiography revealed no differences in baseline parameters. At 6 months, in-segment LLL was 0.04±0.39 mm in the PCB group versus 0.11±0.37 mm in the SCB group (non-significant), respectively. The mean difference between SCB and PCB was 0.07 mm (95% confidence interval: -0.12 to 0.26). Non-inferiority at the predefined margin of 0.35 was shown. Clinical event rates up to 12 months were not different between the groups (3 target lesion revascularisations in the PCB group versus 2 in the SCB group, no myocardial infarctions, no deaths). The novel SCB showed similar angiographic outcomes in the treatment of de novo coronary disease as compared with a clinically proven PCB (ClinicalTrials.gov: NCT03908450).

Real-world outcomes of commercial tisagenlecleucel for children, adolescents, and young adults with acute lymphoblastic leukemia in Japan

Background: Chimeric antigen receptor (CAR) T cells are a major new treatment option for children, adolescents, and young adults (CAYA) patients with relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Therefore, accumulating evidence from real-world experiences of CAR-T outcomes in various regions world-wide is important, particularly when comparing outcomes of patients with differing medical and ethnic backgrounds.Objective: More than 5 years have passed since tisagenlecleucel was approved in Japan. Here, we report a retrospective, multi-institutional investigation examining the association between baseline parameters and clinical outcomes. The aim was to investigate real-world experience, and to better comprehend the efficacy of commercial tisagenlecleucel.Study Design: A nationwide consortium called the Japan CAR-T Consortium conducted a retrospective, multicenter study of CAYA patients who received CAR-T cell treatment with commercial tisagenlecleucel. Forty-two patients with R/R B-ALL whose leukapheresis samples were shipped to Novartis for commercial tisagenlecleucel manufacture were included in the analysis. All infused patients were included in the response, toxicity, and survival analyses.Results: The best overall response rate was 93%. The 1-year overall survival (OS) and event-free survival (EFS) rates after infusion were 82% and 56%, respectively. Twenty-seven (64%) had low disease burden (LB, defined as <5% bone marrow [BM] lymphoblasts) prior to tisagenlecleucel infusion. LB was associated with superior outcomes, with a 1-year EFS rate of 80% compared with 24% in high disease burden (≧5% BM lymphoblasts). Multivariate analysis identified an association between prior hematopoietic stem cell transplantation (HSCT) (n=23, 55%) and superior outcomes, with a 1-year EFS rate of 75% compared with 24% for patients without prior HSCT.Conclusion: This first analysis of CAYA patients with R/R B-ALL undergoing treatment with commercial tisagenlecleucel in Japan reports an efficacy similar to that in clinical trials and other real-world studies and confirms that LB and prior HSCT are associated with superior EFS.

Predictors of liver fibrosis progression in cohort of type 2 diabetes mellitus patients with MASLD

AimTo investigate predictors of liver fibrosis progression in patients with T2DM over a minimum follow-up duration of three years. MethodsTwo hundred and thirty-three patients completed the follow-up period and their clinical, laboratory and liver FibroScan data are reported. Patients were categorized into progressors 42 (18.0 %) and non-progressors 191 (82.0 %) based on liver fibrosis progression. Factors influencing fibrosis progression were identified by comparing these groups. ResultsProgressors showed significantly increased aspartate aminotransferase (AST) (p = 0.010), increased alkaline phosphatase (ALP) (p = 0.001) and decreased platelet count (p = 0.002). Non-progressors exhibited significant decreases in diastolic blood pressure (DBP) (p = 0.050), body mass index (BMI) (p < 0.001), waist circumference (p < 0.001), gamma-glutamyl transferase (GGT) (p < 0.001), albumin (p < 0.001), alanine aminotransferase (ALT) (p = 0.022), glycosylated haemoglobin (HbA1c) (p = 0.002) and fasting blood sugar (FBS) (p = 0.030) with increase in HDL-cholesterol (p < 0.001), creatinine (p < 0.001), bilirubin (p < 0.001), and ALP (p = 0.007). Baseline parameters predictive of liver fibrosis progression included elevated AST and reduced platelet count. Delta changes from baseline to follow-up revealed that increases in ALP, BMI, waist circumference, and reduction in platelet count were correlated with fibrosis progression. Use of GLP-1 receptor agonist was associated with reduced progression. ConclusionIn conclusion, increase in ALP and waist circumference and reduction in platelet count are predictive of liver fibrosis progression in patients with T2DM. GLP-1 receptor agonists use seems to have a promising protective effect against liver fibrosis progression.ClinicalTrials.govID:NCT05697991

Comparative Effectiveness of Abaloparatide and Teriparatide in Women 50 Years of Age and Older: Update of a Real-World Retrospective Analysis

BackgroundAbaloparatide and teriparatide are osteoanabolic treatments indicated for postmenopausal women and men with osteoporosis at high risk of fracture. In the Abaloparatide Comparator Trial In Vertebral Endpoints study, bone mineral density improvements were significantly greater with abaloparatide compared to teriparatide at the total hip and femoral neck. We conducted a retrospective claims study to examine the incidences of hip and nonvertebral fractures and cardiovascular events in women aged ≥50 years initiating abaloparatide or teriparatide therapy, expanding on a previous retrospective claims study. MethodsThis retrospective observational study used anonymized claims data from ICON’s Symphony Health, PatientSource for women aged ≥ 50 years with ≥ 1 prescription fill for abaloparatide or teriparatide. The index date was the date of the initial prescription dispensed. Times to first hip fracture, nonvertebral fracture, and serious cardiovascular event were compared between logistic regression-based propensity score–matched cohorts and in predefined subgroups by age, prior antiresorptive use, and prior fracture using Cox proportional hazards models. ResultsPatients (21 676 per cohort) were well matched on 73 baseline parameters. Over 18 months (+ 30 days follow-up), 245 (1.1%) and 296 (1.4%) women in the abaloparatide and teriparatide cohorts, respectively, had a hip fracture (HR [95% CI] 0.83 [0.70, 0.98]; P = .027); 947 (4.4%) and 1078 (5.0%) had a nonvertebral fracture (0.88 [0.80, 0.96]; P = .003). There were no significant treatment-subgroup interactions (P ≥ .2). Cardiovascular events were similar between groups. ConclusionsThere were significantly lower rates of hip and nonvertebral fractures with abaloparatide compared to teriparatide, which were consistent across subgroups. No differences in cardiovascular safety were noted between cohorts.

Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort.

Combined Immuno-chemotherapy consisting of gemcitabine, cisplatin and the programmed death-ligand one inhibitor durvalumab (GCD) is the new standard of care for patients with biliary tract cancers (BTC) based on positive results of the TOPAZ-1 study. We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort. Patients with BTC treated with GCD from 9 German centers were included. Clinicopathological baseline parameters, overall survival (OS), response rate and adverse events (AEs) were retrospectively analyzed. The prognostic impact was determined by Kaplan-Meier analyses and Cox regression models. A total of 165 patients treated with GCD between 2021 and 2024 were included in the study. Median OS and median progression-free survival were 14 months (95% CI 10.3-17.7) and 8months (95% CI 6.8-9.2), respectively. The best overall response rate was 28.5% and disease control rate was 65.5%. While extrahepatic and intrahepatic BTC showed similar outcomes, mOS was significantly shorter in patients with gall bladder cancer (GB-CA) with 9months (95% CI 5.5-12.4; p=0.02). In univariate analyses age ≥70years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥1, status post cholecystectomy, GB-CA and high baseline CRP values were significantly associated with OS. ECOG PS≥1 and GB-CA remained independent prognostic factors for OS in multivariable cox regression analysis. AEs have been reported in 130 patients (78.8%), including 149 grade 3-4 AEs (25.5%). One patient died of severe infectious pneumonia. Immune-related (ir)AEs occurred in 17 patients (10.3%), including 9 grade 3-4 irAEs (2.2%), which led to treatment interruption in 4 patients. Immuno-chemotherapy in patients with BTC was feasible, effective and safe in a real-life scenario. Our results were comparable to the phase 3 clinical trial results (TOPAZ-1). Reduced efficacy was noted in patients with GB-CA and/or a reduced performance status that warrants further investigation.

Effect of home based tele pilates on pelvic girdle pain and lumbo pelvic stability among pregnant women – A randomized controlled trial

Introduction. Pelvic girdle pain is one of the common musculoskeletal problems in pregnancy, resulting from hormonal variations and biomechanical alterations in the muscles that support lumbo-pelvic stability. The Pilates method, which includes mind-body approaches and focuses on core strength, provides relief from pelvic pain. In recent years, tele-rehabilitation has emerged as one of the most popular solutions in clinical practice. Aim. To find out the effect of home-based Tele Pilates on pelvic girdle pain and lumbo-pelvic stability among pregnant women. Materials and methods. A randomized controlled trial was conducted in Sri Ramachandra Hospital, Chennai, from January 2023 to June 2023. Pregnant women with pelvic girdle pain from 20-30 weeks of gestation were screened and randomly divided into a Pilates exercise group (n = 19) and a control group (n = 19). Subjects in the Pilates group followed the exercise thrice a week for eight weeks. Subjects in the control group followed standardized antenatal exercises and education. The outcome measures used were Visual Analogue Scale (VAS) for pain level, Pelvic Girdle Questionnaire (PGQ) for functional disability, and Pressure Biofeedback for lumbo-pelvic stability. Mann-Whitney test, Wilcoxon signed rank test, and ‘t’ test were performed to examine the pain score, Pelvic Girdle Questionnaire, and the lumbo-pelvic stability. Results. Baseline parameters are similar and comparable. (p &lt; 0.05). Between-group analysis revealed that the experimental group showed improvement in the pain and disability with a significant difference (p ≤ 0.001). Both groups showed significant improvement in lumbo-pelvic stability in the within-group analysis (p &lt; 0.001). Conclusion. Home-based tele Pilates (HTPE) can be recommended as an effective and safe method for decreasing pain levels and improving lumbo-pelvic stability among pregnant women with pelvic girdle pain.

Outcomes of Pregnancy in Patients With Chronic Liver Disease.

Background and objectives Chronic liver disease (CLD), due to its increased prevalence, is a global public health concern. With improved care of CLD patients nowadays, more patients with liver cirrhosis or CLD are getting pregnant. Pregnancy in the setting of CLD is associated with significant maternal and fetal complications. The objectives of this study were to determine the outcomes of pregnancy in patients with CLD and to ascertain the association between maternal CLD and pregnancy outcomes. Materials and methods This retrospective study was conducted at the Gastroenterology Department of Hayatabad Medical Complex, Peshawar, after approval from the hospital's ethical committee. A total of 91 pregnant patients with CLD were included. Data of these patients were retrieved from the hospital information management system. Baseline parameters and clinical parameters of the study participants were recorded. Maternal outcomes and fetal outcomes were noted. Data was analyzed using IBMSPSSStatistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States). Inferential statistics, including univariate logistic regression analysis, was used to determine various factors influencing the fetomaternal outcomes. p-value ≤0.05 was considered statistically significant. Results The mean age of patients was 30.85±6.20 years, the mean gestational age was 29.66±4.15 weeks, and the mean CLD duration was 27.65±9.481 months. Viral hepatitis was the most frequent etiology of CLD (62.6%). Fifty-four patients (59.3%) were noted to have used fertility medications. Regarding maternal outcomes, 13 (14.3%) patients had preterm labor, 47 patients (51.6%) had a cesarean section as a mode of delivery, and post-partum hemorrhage (PPH) was observed in 13 (14.3%)patients. In terms of fetal outcomes, low birth weight was observed in 29 (31.9%) babies, intrauterine death (IUD) was noted in 13 (14.3%) babies and 27 babies (29.7%) had low Apgar scores at birth. The CLD duration was significantly associated with the mode of delivery (p<0.001). Similarly, maternal age (p=0.049), body mass index (p=0.017), and decompensated CLD (p=0.030) were associated with a high likelihood of IUD. Maternal age was associated with the likelihood of a low Apgar score (p=0.013). Conclusion Pregnancy in patients with CLD is associated with an increased risk of maternal complications (preterm labor and PPH) and fetal complications (IUD, low birth weight, and low Apgar score). Maternal age, body mass index, and decompensated CLD are associated with an increased likelihood of IUD.

We are all different: Modeling key individual differences in physiological systems

Mathematical models of whole-body dynamics have advanced our understanding of human integrative systems that regulate physiological processes such as metabolism, temperature, and blood pressure. For most of these whole-body models, baseline parameters describe a 35-year-old young adult man who weighs 70 kg. As such, even among adults those models may not accurately represent half of the population (women), the older population, and those who weigh significantly more than 70 kg. Indeed, sex, age, and weight are known modulators of physiological function. To more accurately simulate a person who does not look like that “baseline person,” or to explain the mechanisms that yield the observed sex or age differences, these factors should be incorporated into mathematical models of physiological systems. Another key modulator is the time of day, because most physiological processes are regulated by the circadian clocks. Thus, ideally, mathematical models of integrative physiological systems should be specific to either a man or woman, of a certain age and weight, and a given time of day. We illustrate the importance of capturing these individual differences, using the blood pressure regulatory system as an example, and explain how that such models can be built.