Lower Body Research Articles

P0541 Placebo rates in randomised clinical trials of Ulcerative Colitis: An individual patient data meta-analysis

Abstract Background Information on placebo rates is important for designing clinical trials. We aimed to assess placebo rates and associated factors using individual patient data from multiple randomised clinical trials in ulcerative colitis. Methods We conducted a meta-analysis of individual participant-level data from nine randomised trials using Vivli and Yale University Open Data Access data-sharing platforms. Phase 2 and 3 placebo-controlled randomised clinical trials of advanced biologic therapies in adults with moderate-to-severe active ulcerative colitis published since 2010 were included. Pooled placebo rates and 95% CIs were estimated using one-stage and two-stage meta-analytical approach. Significant patient-level factors (P<0.05) associated with placebo rates were identified using regression analyses. The pre-specified primary outcomes were placebo clinical response and remission. Results Outcome data were available for 1,703 patients from nine studies (three induction-only, one maintenance-only, and five including both phases). For induction trials, overall placebo response and remission rates were 33% (95% CI 29-38%) and 9% (95% CI 7-11%), respectively (Figure). Overall placebo response and remission rates in maintenance trials were 28% (95% CI 17%-41%) and 14% (95% CI 9-20%), respectively (Figure). A lower body mass index reduced odds of placebo response and remission, while higher baseline albumin levels and left-sided UC (compared to extensive) increased the odds of these outcomes. A one-point increase in the Mayo Clinic Score and adapted Mayo Clinic Score was associated with a 26% and 27% reduction in the odds of clinical remission. For induction trials, prior exposure to biologics or tumour necrosis factor antagonist therapy was associated with lower odds of both response and remission. Multi-centre trials have lower placebo effect than single-centre trials. Conclusion These results will enable future trials that include placebo to incorporate design elements that enable reduction of placebo rates as well as a precise benchmark for expected rates in clinical trials that do not include placebo.

P0312 Sarcopenia as a feature of musculoskeletal manifestations of paediatric Crohn’s disease

Abstract Background Musculoskeletal (MSK) manifestations are the most common extraintestinal manifestation (EIM) of Crohn’s disease (CD). Features include arthralgias, axial/peripheral arthritis, enthesitis, tenosynovitis and dactylitis. CD is associated with impaired nutritional status which can lead to unintentional loss of skeletal muscle mass, known as sarcopenia. Few studies report on sarcopenia in paediatric CD, but it is estimated to affect up to one-third of patients and may be associated with more treatment refractory disease and poorer quality of life.1 This study aims to investigate the prevalence of sarcopenia in paediatric CD, in paediatric CD with MSK EIM and to assess the impact of sarcopenia on CD related clinical outcomes. Methods In this single centre, retrospective cohort study, data were collected from 139 newly diagnosed (< 1 year) paediatric CD patients who had undergone magnetic resonance enterography (MRE) at the Children’s Hospital, London Health Sciences Center (Ontario, Canada) over four years (2019 – 2023). Bowel disease activity was assessed by weighted paediatric Crohn’s disease activity index (wPCDAI) scores. Sarcopenia was assessed, by an MSK-trained radiologist, by measuring total psoas muscle area (tPMA) from MRE images and comparing to age and sex matched reference values.2 Sarcopenia was defined as a tPMA z-score less than – 2.0. Univariate descriptive statistics were used. Results 139 patients with CD were included (mean age 13.1 ± 3.1 years, 59% male). Sarcopenia was found in 22 patients (15.8%). Children with sarcopenia had lower body surface area (BSA) (p=0.020), higher wPCDAI scores (p=0.033), higher ESR (p=0.035), lower hemoglobin (Hb) (p<0.001) and a higher number of hospital admissions (p=0.041) compared to children without sarcopenia. Of these, 52 children (37.4%) had MSK EIM. Among the 52 patients with CD-MSK EIM, 7 had sarcopenia (13.5%) [Table 1]. No statistically significant difference was found in the prevalence of sarcopenia in patients with CD-MSK EIM compared to CD-alone (17.2%) (p=0.555). Only 15.8% (22/139) of the total cohort and 40% (21/52) of the MSK-EIM group had seen a rheumatologist. Conclusion Initial findings demonstrate that 15.8% of paediatric patients with CD have sarcopenia. Of those with CD-MSK EIM, 13.5% have sarcopenia. At baseline, patients with CD related sarcopenia did demonstrate higher bowel disease activity, increased admissions to hospital and more systemic inflammation (higher ESR, lower Hb). Limitations of this study include the lack of systematic rheumatology assessment of CD patients for MSK EIM, resulting in potential under-reporting of MSK-EIM. Further analyses are planned to evaluate the impact of sarcopenia on bowel disease outcomes over time in both groups.

Improved Image Quality Through Deep Learning Acceleration of Gradient-Echo Acquisitions in Uterine MRI: First Application with the Female Pelvis.

The aim of this study was to compare the image quality of a deep learning (DL)-accelerated volumetric interpolated breath-hold examination (VIBE) sequence with a standard (ST) VIBE sequence in assessing the uterus. Between April and December 2023, a total of 61 female patients (aged 41 ± 14 years) who were referred for anmagnetic resonance imaging (MRI) of the pelvis were included in this prospective study, after providing informed consent. All examinations were performed with a 1.5T MRI scanner. The DL VIBE and ST VIBE were acquired before (noncontrast [NC]) and after (contrast-enhanced [CE]) contrast administration in the sagittal orientation. Three readers independently evaluated the following aspects of the images' quality using 4-point Likert scales (1 = nondiagnostic; 4 = excellent): global image quality, anatomy delineation, and lesion detection/demarcation. Motion artifacts and noise were also assessed (1 = no artifacts; 4 = severe artifacts). In addition, all three readers selected their preferred sequence and the sequence in which they had the highest diagnostic confidence. After exclusions, the data for 54 patients were analyzed. The DL VIBE was preferred by all three readers in almost all cases (NC: 99%; CE: 96%) and rated highest for diagnostic confidence (NC: 98%; CE: 90%). The image quality of the DL VIBE was rated statistically significantly better than that of the ST VIBE, with simultaneously reduced noise and motion artifacts (p < 0.01). The image quality of the DL VIBE was predominantly rated with a score of 4 (NC: 54%; CE: 78%), while the image quality of the ST VIBE was mostly rated with a score of 3 (NC: 53%; CE: 80%). The anatomy of the female pelvis was significantly better delineated by the DL VIBE (p < 0.01; log[OR] = 5.3; 95% CI: 3.7-6.8), and lesions were more clearly demarcated (p < 0.01; log[OR] = 6.7; 95% CI: 4.5-8.8). The DL VIBE sequence showed a significant overall improvement in all image quality characteristics for all readers and was preferred in most cases. The clinical implementation of DL VIBE in MRI of the female pelvis could improve the diagnostic value of the examination.

Association of Community Characteristics as Measured by Social Deprivation Index Score with Prenatal Care and Obstetrical Outcomes.

We aimed to determine the relationships between socioeconomic disadvantage, as measured by the Social Deprivation Index (SDI), and prenatal care (PNC) utilization, obstetrical outcomes, and neonatal complications. All spontaneously conceived singleton deliveries of nulliparous gravida with residence zip code available (n = 4,786) were identified in a population-based database. Deliveries were assigned SDI scores based on preconception zip code. SDI scores (1-100) are a composite measure of seven community demographic characteristics of poverty, education, transportation, employment, and household composition. SDI scores were categorized into quartiles and grouped for analysis (Q1 [n = 1,342], Q2 + 3 [n = 1,752], and Q4 [n = 1,692]) with higher scores indicative of greater disadvantage. Statistical analysis was performed using a generalized linear mixed method. Among our cohort, gravida in the lowest (least-deprived) SDI quartile (Q1) were older, had lower prepregnancy body mass indices, and were more likely to receive PNC from a physician specializing in Obstetrics and Gynecology. Gravida residing in the highest (most-deprived) SDI quartile (Q4) attended fewer prenatal visits (mean [standard deviation] 11.17 [2.9]) than those living in Q1 (12.04 [2.3], p < 0.0001). Gravida in Q4 were less likely to receive sufficient PNC compared with those in Q1 (52 vs. 64.2%, p < 0.0001) and were more likely to fail to achieve appropriate gestational weight gain (GWG) (19.6 in Q4 vs. 15.9% in Q1, p < 0.01). No significant differences in composite maternal (CMM) or neonatal morbidity (CNM) were associated with SDI quartile. Outer quartile social deprivation was associated with higher proportions of primigravida not meeting recommendations for GWG and attending fewer prenatal visits, but it did not affect CMM or CNM. Improving care access and providing nutritional support to all gravida are likely important steps toward health equity. · Neighborhood social deprivation was not associated with composite maternal or neonatal morbidity.. · Community-level deprivation was associated with decreased PNC utilization.. · It is important to understand the underlying disparities that lend to suboptimal patterns of PNC.. · Doing so may inform programs that promote favorable birth outcomes in at-risk communities..

Persistently different patterns of patient’s global assessment of health in rheumatoid arthritis are associated with pain and impaired function more than with inflammation: an inception cohort study over 15 years

ObjectiveTo assess patient’s self-reported global assessment of health (PGA) in relation to inflammation, pain and disability in patients with rheumatoid arthritis (RA).MethodsData were obtained from the Better Anti-Rheumatic PharmacOTherapy early...

Predicting lower body joint moments and electromyography signals using ground reaction forces during walking and running: An artificial neural network approach.

This study leverages Artificial Neural Networks (ANNs) to predict lower limb joint moments and electromyography (EMG) signals from Ground Reaction Forces (GRF), providing a novel perspective on human gait analysis. This approach aims to enhance the accessibility and affordability of biomechanical assessments using GRF data, thus eliminating the need for costly motion capture systems. Can ANNs use GRF data to accurately predict joint moments in the lower limbs and EMG signals? We employed ANNs to analyze GRF data and to use them to predict joint moments (363-trials; 4-datasets) and EMG signals (63-trials; 2-datasets). We selected the EMG timeseries of 6 muscles (Biceps Femoris, Gluteus Maximus, Rectus Femoris, Medial Gastrocnemius, Soleus, and Tibialis Anterior) and joint moment timeseries in the lower limbs (ankle, knee, and hip). The ANN models demonstrated high predictive accuracy for joint moments (R-value: 0.97, p < 0.0001) and EMG signals (R-value: 0.95, p < 0.0001) across various gait activities, including walking and running. This underscores the potential of using GRF data to understand complex biomechanical interactions, offering significant insights into human locomotion. The significance of this research extends broadly, touching upon the development of portable devices, assistive technologies, and personalized rehabilitation programs. Our findings have the potential to broaden the accessibility of advanced biomechanical analysis with implications spanning disciplines such as sports science, rehabilitation, and the advancement of innovative assistive devices and exoskeletons.

A Qualitative Longitudinal Exploration of Interactions Between Female Athletes and Sport Medicine Staff During Injury Rehabilitation.

Sport injury is a prevalent setback experienced by athletes, wherein they are required to spend time in rehabilitation and interact with sport medicine staff. Sport medicine staff are a frequent line of contact line of contact for athletes at this time and represent an important part of their support network. There is little exploration surrounding the interactions that female athletes have with sport medicine staff during injury rehabilitation and how these interactions may impact the rehabilitation process. The purpose of this research is to explore the experiences of injured female athletes and their interactions with sport medicine staff during injury rehabilitation. Qualitative study using semistructured qualitative interviews and audio diaries. Interpretive descriptive methodology. A total of 11 injured female varsity athletes who had sustained a musculoskeletal injury within 2 to 4 weeks of being recruited participated. A total of 6 upper body injuries and 5 lower body injuries are represented. Athletes completed 2 semistructured interviews and weekly audio diary entries across 6 weeks. Data were analyzed using reflexive thematic analysis. Results demonstrated that female athletes felt supported by sport medicine staff when provided with clear information about rehabilitation, when they perceived sport medicine staff as competent, and when sport medicine staff made a personal connection. An overarching theme of mattering was identified as underpinning the athletes' experiences of feeling supported by sport medicine staff during rehabilitation. When sport medicine staff made female athletes feel that they mattered, they were perceived as more supportive during rehabilitation. Sport medicine staff can help athletes to feel that they matter by engaging in supportive behaviors during the rehabilitation process.

Sarcopenia is poorly documented in geriatric rehabilitation inpatients: REStORing health of acutely unwell adulTs (RESORT)

Introduction: Sarcopenia is highly prevalent in older inpatients. However, it is unclear if sarcopenia is documented routinely in geriatric rehabilitation. This study aimed to investigate the documentation of sarcopenia in medical records among geriatric rehabilitation patients. Methods: Geriatric rehabilitation inpatients in a statewide hospital in Victoria, Australia were included. Patient characteristics, muscle measurements, and medical records at admission and discharge were collected. Sarcopenia was defined using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Patient characteristics were compared between the groups with documented and non-documented sarcopenia using the Wilcoxon rank-sum or chi-square test. Results: Of 1,890 geriatric rehabilitation inpatients (aged 83.4 [IQR 77.6-88.4] years, 56.3% female), muscle measurements were available in 1,334 patients at admission. The prevalence of sarcopenia was 20.8% (n=278). Sarcopenia was documented in 68 out of 1890 patients; 23 of them did not have muscle mass or muscle strength measured. Forty-five out of 1334 patients with muscle measurements available were documented with sarcopenia either at discharge from acute admissions (n=9), on rehabilitation admission (n=25), orand at discharge from rehabilitation (n=26). Of these 45 patients, eight patients had sarcopenia following the EWGSOP2 criteria. Compared with patients without sarcopenia documented, patients documented with sarcopenia had lower body mass index (BMI) and sarcopenia screening (SARC-F) scores, higher Clinical Frailty Scale (CFS) scores and were likely to come from nursing homes. Conclusions: Documentation of sarcopenia was lower than the prevalence of sarcopenia in geriatric rehabilitation inpatients. Sarcopenia was incorrectly documented as data on muscle measurement were missing to define sarcopenia. Practitioners likely used clinical impressions to document sarcopenia, rather than the formal diagnostic criteria.

In vivo Differential Effects of Extractable and Non-Extractable Phenolic Compounds from Grape Pomace on the Regulation of Obesity and Associated Metabolic Alterations.

Grape pomace (GP) is a by-product rich in phytochemicals, including extractable polyphenols (EPPs) and non-extractable polyphenols (NEPPs), which have distinct metabolic fates that may affect their biological activities. The benefits of GP have been reported in relation to obesity and its comorbidities, particularly when administered preventively focusing on EPPs. Therefore, the aim of this study was to investigate the effects of EPPs and NEPPs from GP as a treatment for obesity and its associated metabolic alterations. A previous comprehensive characterization of the selected GP revealed the most relevant individual compounds in the EPPs fraction (malvidin hexoside, (-)-epicatechin, quercetin, and procyanidin dimer B2 isomer II), as well as in the NEPPs fraction (hydroxybenzoic acid isomers I-II). The experiment was performed in obese rats with insulin resistance, treated for 8 weeks with EPPs or NEPPs grape pomace fractions (100mg/kg). After the intervention, the HFFD + EPP group showed a significantly lower weight gain (9.6%) and body mass index (9.7%) compared to the HFFD group. While liver triglyceride levels were only significantly reduced in the HFFD + NEPP group (47%) compared to the HFFD group. Neither treatment resulted in a reduction of insulin resistance. Therefore, the supplementation with grape pomace phenolic fractions to an animal model of obesity exerted differential beneficial effects on body weight and liver lipid accumulation, overall contributing to an amelioration of some the metabolic alterations present in obesity, although not to aspects such as glycemic homeostasis.

Associations Between Sugar-Sweetened Beverage Taxes and Weight Outcomes Among US Adolescents.

Given the recent implementation and preemption of sugar-sweetened beverage taxes across the United States, we aimed to evaluate the associations between sugar-sweetened beverage (SSB) taxes and adolescent weight-related outcomes using data on 364,540 adolescents drawn from 1999 to 2021 district Youth Risk Behavior Surveys. We used difference-in-differences models to assess the associations and the potential mediating roles of SSBs, milk, and 100% fruit juice consumption. We found that a one cent per ounce increase in SSB taxes was associated with a 0.26 lower body mass index (P <.01), and a 2.19 (P <.01) and 1.68 (P <.01) percentage point decrease in the probability of being affected by overweight and obesity, respectively. SSB consumption had a mediating role, as tax increases were associated with a 2.45 (P <.01) percentage point decrease in adolescents' probability of drinking any SSB. Milk and 100% fruit juices likely also played a role, as we found changes in their consumption in response to tax increases.

Genotype-Phenotype Correlation in Progressive External Ophthalmoplegia: Insights From a Retrospective Analysis.

Progressive external ophthalmoplegia (PEO) is a classic manifestation of mitochondrial disease. However, the link between its genetic characteristics and clinical presentations remains poorly investigated. We analysed the clinical, pathological and genetic characteristics of a large cohort of patients with PEO, based on the type of their mtDNA variations. Eighty-two PEO patients were enrolled and grouped into three categories: mtDNA single large-scale deletions (SLDs), multiple deletions (MulDs) and the m.3243A > G point variant. Patients in the SLD category were further divided into 'common deletion' and 'noncommon deletion' groups based on the presence or absence of a 4977-bp deletion. The mutational load of deleted mtDNA of these patients was comprehensively detected by real-time polymerase chain reaction (RT-PCR). SLD Patients showed the highest proportion of cytochrome C oxidase-negative (COX-n) fibres on muscle biopsy. The mutational load of deleted mtDNA exhibited an inverse relationship with deletion length and a direct relationship with the COX-n fibre ratio. Compared with patients having noncommon deletions, those with common deletions tend to have other muscle involvement, lower body mass index (BMI) scores (17 ± 3 vs. 22 ± 4 kg/m2), higher mutational load in muscle (63% ± 22% vs. 46% ± 24%), more COX-n fibres (26% vs. 9%, interquartile range [IQR]: 15%-32% vs. 6%-26%) and higher growth and differentiation factor 15 (GDF15) levels (2583 vs. 1472, IQR: 1746-4081 vs. 924-2155 pg/mL). MulDs patients displayed milder symptoms, especially compared to patients with m.3243A > G variant, as indicated by their later age of onset (31 vs. 13, IQR: 27-49 vs. 6-29 years), higher BMI scores (24.0 ± 4 vs. 16.5 ± 3.4 kg/m2), lower lactate (1.6 ± 1.1 vs. 6.3 ± 6.0 mmol/L) levels and lower proportion of ragged-blue fibres (RBFs) (3 vs. 16, IQR: 1%-9% vs. 7%-27%). The m.3243A > G variant group exhibits more severe symptoms compared to other subgroups, particularly MulDs patients. In the SLD group, those with common deletions experience more severe clinical and pathological manifestations. These findings enhance our understanding of PEO, facilitating its diagnosis, prognosis and genetic counselling.

Retrospective Study of Chronic Coughing in Dogs in a Referral Centre in the UK: 329 Cases (2012-2021).

Chronic coughing is a common complaint in small animal medicine and it has an extensive differential diagnosis with very different treatment and prognosis. Coughing is considered chronic when it lasts at least 8 weeks. This retrospective study aimed to describe the most common causes of chronic coughing in a population of dogs that presented to a referral hospital in England between January 2012 and December 2021. In addition, we aimed to evaluate if an association with signalment, weight, coughing characteristics, and/or concomitant clinical signs could be identified. A total of 329 dogs met the inclusion criteria. The most frequent diagnoses were airway collapse (102/329, 30.7%), chronic bronchitis (80/329, 24.3%), neoplasia (62/329, 18.8%), and infectious bronchopneumonia (54/329, 16.4%). Other diagnoses were also identified in a lower number of cases. Pomeranian, Chihuahua, and Yorkshire Terrier were over-represented breeds for airway collapse. No predictive factors were identified for chronic bronchitis. Lower body weight (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.90-0.95), non-productive (OR 14.3 CI 3.44-50) paroxysmal coughing (OR 4.9, 95%, CI: 2.2-11.0), and exercise intolerance (OR 3.3, 95%, CI: 1.7-6.3) increased the odds of airway collapse. Older dogs (OR 1.025, 95%, CI: 1.014-1.036), higher body weight (OR 1.048, 95%, CI: 1.018-1.080), lethargy (OR 5.1, 95%, CI: 1.5-17.7), haemoptysis (OR 8.6, 95%, CI: 1.9-38.4), weight loss (OR 4.0, 95%, CI: 1.1-15.3), and inappetence (OR 6.5, 95%, CI: 1.9-22.1) increased the odds of neoplasia. Productive coughing (OR 3.0, 95%, CI: 1.5-6) and nasal discharge (OR 4.1, 95%, CI: 1.4-11.9) were predictive factors of infectious bronchopneumonia. Younger age (OR 0.96, 95%, CI: 1.061-1.150), higher body weight (OR 1.097, 95%, CI: 1.037-1.161), and haemoptysis (OR 11.8, 95%, CI: 1.8-78.5), increased the odds of airway foreign body. Higher body weight (OR 1.105, 95%, CI: 1.061-1.150), older age (OR 1.041, 95%, CI: 1.022-1.061), and regurgitation were predictive factors of laryngeal paralysis. Epiglottic retroversion was associated with younger age (OR 0.969, 95%, CI: 0.943-0.994), dysphagia (OR 42.5, 95%, CI: 4.7-382.7), and regurgitation (OR 11.6, 95%, CI: 1.2-113.1). All the aforementioned findings are valuable for prioritising differential diagnoses and consequently increasing the efficacy of the diagnostic plan and prioritising tests, which becomes even more important in cases where financial constraints are present. Finally, an appropriate selection of diagnostics tools helps optimise veterinary resources.

Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretion in vitro and in vivo of a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001.

The use of incretin analogues has emerged in recent years as an effective approach to achieve both enhanced insulin secretion and weight loss in type 2 diabetes (T2D) patients. Agonists which bind and stimulate multiple receptors have shown particular promise. However, off target effects, including nausea and diarrhoea, remain a complication of using these agents, and modified versions with optimized pharmacological profiles and/or biased signaling at the cognate receptors are increasingly sought. Here, we describe the synthesis and properties of a molecule which binds to both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors (GLP-1R and GIPR) to enhance insulin secretion. HISHS-2001 shows increased affinity at the GLP-1R, as well as a tendency towards reduced internalization and recycling at this receptor versus FDA-approved dual GLP-1R/GIPR agonist tirzepatide. HISHS-2001 also displayed significantly greater bias towards cAMP generation versus β-arrestin 2 recruitment compared to tirzepatide. In contrast, Gαs recruitment was lower versus tirzepatide at the GLP-1R, but higher at the GIPR. Administered to obese hyperglycaemic db/db mice, HISHS-2001 increased circulating insulin whilst lowering body weight and HbA1c with similar efficacy to tirzepatide at substantially lower doses. Thus, HISHS-2001 represents a novel dual receptor agonist with an improved pharmacological profile.

Compressed SENSE acceleration factor influence on magnetic resonance image quality in patients with endometrial cancer.

To investigate the impact of compressed sensing - sensitivity encoding (CS-SENSE) acceleration factor on the diagnostic performance of magnetic resonance imaging (MRI) within standard female pelvis protocol in patients with endometrial cancer. T2-weighted turbo spin echo (TSE) sequence from standard female pelvic MRI protocol was chosen due to its long acquisition time and essential role in the evaluation of morphological characteristics of the female pelvic anatomical structures. Fully sampled reference scans and multiple prospectively 2x to 5x under-sampled CS-SENSE scans were acquired. Retrospectively, under-sampled scans were compared to fully sampled scans and visually assessed for image quality and diagnostic quality by two independent radiologists dedicated to urogenital imaging with different experience levels. Images obtained with CS-SENSE accelerated acquisition were of diagnostically acceptable quality at up to 3x acceleration for T2 TSE in both axial and sagittal planes (with an acquisition time reduction of 64%). Among all evaluated uterine structures, the junctional zone proved to be most sensitive to the influence of the acceleration factor. Statistical analysis showed statistically significant differences between image interpretation qualities between two radiologists of different experience levels (p<0.05). CS-SENSE accelerated T2 TSE sequence of the female pelvis shows image quality similar to that of conventional acquisitions with reduced acquisition time. CS-SENSE can moderately reduce scan time, providing many benefits without losing the image quality.

Safety and performance of a novel synthetic biomimetic scaffold for iliac crest defect reconstruction during surgical treatment of pelvic girdle pain: a first-in-human trial.

Surgical treatment of pelvic girdle pain (PGP) involves arthrodesis of sacroiliac (SI) and pubic symphysis joints. Fusion of pubic symphysis involves the implantation of an autologous iliac crest tricortical graft harvested from the iliac crest. The objective was to assess the safety of a novel synthetic graft substitute (b.Bone) for iliac crest reconstruction and to evaluate the results of PGP surgical treatment. Consecutive participants undergoing pelvic fusion and requiring iliac crest reconstruction were enrolled and followed-up for 12months in a prospective first-in-human clinical investigation. Adverse events were documented, and health-related quality of life was evaluated using EuroQol-5D-5L questionnaire. Iliac crest defect healing was evaluated by the Modified Lane and Sandhu radiological scoring system. In addition, relevant published peer-reviewed scientific articles identified from PubMed. The EQ-5D-5L scores improved steadily reaching the highest point at 365days. By 365days complete healing of the bone defect was observed. The management of PGP remains challenging with mixed results reported in the literature. While there is lack of consensus on how to manage PGP, the present study shows improved outcomes at one year following surgery. The synthetic b.Bone scaffold is a safe option with good healing outcomes for iliac crest defect reconstruction. Although b.Bone synthetic scaffold found to be safe, further studies reporting on surgical treatment of PGP are required to confirm the findings in comparative trials.

Early-Onset Seizures After Orthotopic Liver Transplantation: A Single-Center Retrospective Study.

After encephalopathy, epileptic seizures (ES) are the second most common neurologic complication after orthotopic liver transplantation (OLT) and may announce a disabling/fatal neurologic disease. In this retrospective study, we collected clinical information from patients who underwent OLT at our institution and analyzed outcomes and potential risk factors for developing ES after OLT. Fourteen of our 376 patients (3.72%) who underwent OLT had ES. After excluding 2 patients with already known epilepsy, among the other 12 patients, 2 were diagnosed with nonanoxic cerebral edema, 2 with anoxic damage, 1 with intracranial hemorrhage, 1 with metabolic derangement, and 4 with neurotoxicity; 2 did not receive a diagnosis of certainty. 9 of 12 patients had structural abnormalities on neuroimaging exams. Patients with ES had lower body mass index, higher rate of pretransplant portal thrombosis, and lower pre-transplant plasma concentration of albumin than patients without ES. Multiple post-transplantation systemic complications, postoperative infections, and graft rejection were correlated with a significantly higher risk of ES. Compared with patients without seizures, patients with ES had longer in-hospital and intensive care unit (ICU) length of stay, higher probability of ICU readmission, in-hospital death, and need for rehabilitation. Just 3 of the 12 patients with ES had a good prognosis, while the other 9 had at least mild neurologic sequelae, 5 of whom died because of the underlying neurologic disease. ES after OLT may announce detrimental neurologic disease. When an underlying neurologic disease is excluded, prognosis in terms of seizure recurrence and long-term antiseizure medication need is warranted.

Growth and development patterns of Noonan syndrome and advances in the treatment of short stature

Patients with Noonan syndrome (NS) are born with normal or slightly lower body length and weight compared to the normal ranges. However, their height gradually falls behind that of the general population, leading to growth retardation and delayed puberty. In China, the incidence of short stature in patients with NS is approximately 65%. Short stature in these patients arises from multiple causes, including feeding difficulties in infancy, comorbidities such as congenital heart disease, genetic heterogeneity, and disorders of the growth hormone/insulin-like growth factor-1 axis. Growth hormone is commonly used to alleviate symptoms of short stature. This article reviews the growth and development patterns at different stages of NS, analyzes the causes of short stature, and summarizes the latest advances in treatment to provide new insights for the diagnosis and management of short stature in patients with NS.

A Guinea Pig Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis: Poor Vitamin C Status May Advance Disease.

Background/Objectives: Children and teenagers display a distinct metabolic dysfunction-associated steatohepatitis (MASH) phenotype, yet studies of childhood MASH are scarce and validated animal models lacking, limiting the development of treatments. Poor vitamin C (VitC) status may affect MASH progression and often co-occurs with high-fat diets and related metabolic imbalances. As a regulator of DNA methylation, poor VitC status may further contribute to MASH by regulating gene expression This study investigated guinea pigs-a species that, like humans, depends on vitC in the diet-as a model of pediatric MASH, examining the effects of poor VitC status on MASH hallmarks and global DNA methylation levels. Methods: Sixty-two juvenile guinea pigs were exposed to a high-fat diet for 16 weeks. Results: Juvenile guinea pigs exhibited hepatic histopathology representative of pediatric MASH, confirmed by portal inflammation and fibrosis. Consistent with pediatric MASH, juvenile guinea pigs displayed increased lobular and portal inflammation (p < 0.05 and p < 0.0001, respectively) but less steatosis (p < 0.001) compared to adults. Compared to the controls, the guinea pigs deprived in VitC showed lower body weight (p < 0.01), higher expression of hepatic inflammatory genes (p < 0.05), and a lower global hydroxymethylcytosine to methylcytosine ratio in the high-fat groups (p < 0.05). Conclusions: Our study validates guinea pigs as a model of pediatric MASH and suggests that VitC contributes to an altered gene expression signature through the regulation of DNA hydroxymethylation. We postulate that nutritional co-deficiencies in MASH, such as low VitC, may accelerate disease progression and deserve further attention.

Efficacy and safety of post-discharge oral nutritional supplements for patients with gastric cancer undergoing gastrectomy: a meta-analysis of randomized controlled trials.

To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluated the efficacy and safety of post-discharge oral nutritional supplements (ONS) for patients with gastric cancer undergoing gastrectomy. Systematic review and meta-analysis. RCT which evaluated the efficacy and/or safety of post-discharge ONS for patients with gastric cancer undergoing gastrectomy. We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2023 for relevant RCTs. Outcomes of meta-analysis included absolute change of body weight, % change of body weight, absolute change of body composition, absolute change of laboratory parameters and adverse events. All the relevant data were analyzed by Review Manager 5.4.1 and Stata 15.1. 5 RCTs including 1,586 patients (804 in ONS group versus 782 in control group) were included for meta-analysis. The two groups were comparable in age, gender (male), weight at baseline, BMI at baseline, albumin at baseline, and hemoglobin at baseline. Meta-analysis revealed a significant lower absolute body weight loss (WMD: 0.75; 95% CI: 0.11, 1.40; p = 0.02) and % body weight loss (WMD: 1.15; 95% CI: 0.20, 2.11; p = 0.02) in the ONS group compared with the control (regular diet/dietary advice) group. Moreover, this study did not observe a significant difference between the two groups for adverse events rate (RR: 1.11; 95% CI: 0.81, 1.53; p = 0.52). ONS was significantly effective and safe in improving postoperative weight loss for patients with gastric cancer undergoing gastrectomy. Identifier, CRD42023414678, https://www.crd.york.ac.uk/PROSPERO/.

Low Bone Mineral Density and Associated Factors Among People Living With HIV in Kerman, Iran: A Cross-Sectional Study in 2021-2022.

Chronic diseases such as osteoporosis and low bone mineral density (BMD) are significant public health concerns for people living with HIV (PLWH), especially with the increased life expectancy because of antiretroviral therapy (ART). This study evaluated the prevalence and associated factors of low BMD among 94 PLWH in Kerman, Iran, from September 2021 to February 2022. Using dual-energy X-ray absorptiometry, BMD was measured, with low BMD defined by specific T-scores and Z-scores. Predictors were assessed through interviews, medical records, and blood tests. Bivariable and multivariable logistic regression models identified associations between low BMD and various factors. The study found a 51.1% prevalence of low BMD, with significant associations with hypogonadism (adjusted odds ratio [aOR]: 3.19), longer ART duration (aOR per month: 1.02), and lower body mass index (aOR per unit: 0.83). The findings highlight the need for regular screening and timely intervention for low BMD among PLWH, particularly with prolonged ART use.