Acute gout flares cause severe pain and functional impairment, with limited options for patients intolerant to conventional therapies. Firsekibart, a novel anti-IL-1β monoclonal antibody, was approved in China in July 2025, but real-world evidence remains scarce. This multicenter retrospective study enrolled 50 patients with acute gout flares (25 firsekibart 200 mg, 25 compound betamethasone 7 mg). Co-primary endpoints were VAS pain change at 48 h and time to first flare within 12 weeks. Secondary endpoints included pain at other timepoints, CRP change, flare frequency, and time to first flare within 24 weeks. Inverse probability weighting balanced baseline covariates, with weighted log-rank as primary analysis and Firth's penalized Cox regression for sensitivity analysis. Baseline characteristics were balanced. Pain relief was comparable between groups (P > 0.05). No firsekibart patients flared within 12 weeks vs. 11 (44.0%) on betamethasone. Weighted log-rank showed significantly lower flare risk with firsekibart (p < 0.001). Firth's penalized Cox confirmed a 97% risk reduction at 12 weeks (HR: 0.03; 95% CI: 0.01-0.59) and 88% at 24 weeks (HR: 0.12; 95% CI: 0.02-0.78). Median CRP decreased significantly with firsekibart (from 14.20 to 3.85 mg/L, P < 0.0001). Both treatments had acceptable safety profiles. In this real-world study of patients with frequent flares, firsekibart showed comparable analgesic efficacy to compound betamethasone and was associated with superior sustained flare prevention and acceptable safety. These findings suggest firsekibart may be a potential treatment option for patients with limited alternatives, though larger studies are warranted. Key Points • This study provides the first real-world evidence of firsekibart in acute gout flares. • Firsekibart showed comparable pain relief to compound betamethasone at 48 h. • Firsekibart reduced new flare risk by 88% within 24 weeks. • Firsekibart had an acceptable safety profile with no serious infections.
Clinical benefits of oscillating positive expiratory pressure (OPEP) devices have been previously demonstrated in many respiratory diseases, including chronic obstructive pulmonary disease (COPD). This study aimed to provide patient-reported outcomes of OPEP treatment in COPD patients in Québec, Canada. Recruitment took place across 4 sites. Included patients had a COPD Assessment Test (CAT) score greater than 10 and a mucus score of 2 or greater. Aerobika∗ OPEP (TMI) devices were provided, with instructions on usage and technique. CAT assessments were collected at baseline and 6 and 12 weeks. At the final visit, patients were asked whether they would continue to use the device and provided ratings on usability and satisfaction. Data were analyzed from 46 patients. The average CAT score at 6 weeks was significantly lower than baseline (19.02 ± 6.59 vs. 23.65 ± 6.44, p < 0.00001), with 31/44 patients (70.5%) reaching the minimum clinically important difference (MCID). Scores decreased further at 12 weeks (16.15 ± 6.06), a significant improvement from 6 weeks (p = 0.0052). MCID was reached by 39/44 patients (84.8%) after 12 weeks of treatment. Average 6 and 12 week mucus scores (2.59 ± 1.02 and 2.28 ± 1.13, respectively) were both significantly lower than baseline (3.63 ± 0.97; p < 0.00001 at 6 and 12 weeks). Regarding device feedback, 43/44 patients (97.7%) would continue using the device. The proportion of patients that provided 4/5 or 5/5 satisfaction ratings was 40/45 (88.9%), 43/45 (95.6%), and 40/45 (88.9%) for ease of use, quality, and overall satisfaction, respectively. No device-related adverse events were reported. Statistically significant clinical improvements were observed with OPEP therapy. This study supports the use of the Aerobika∗ OPEP in conjunction with standard of care in COPD patients to manage symptoms and enhance quality of life. Patient feedback shows high levels of acceptance and perceived value of the device.
Central nervous system (CNS) involvement in multidrug-resistant tuberculosis (MDR-TB) is associated with high morbidity, and evidence guiding the use of standardized all-oral regimens in intracranial disease is limited. We describe radiographic evolution of a presumed cerebellar tuberculoma during BPaLM-based therapy for MDR-TB. We report the clinical course, microbiologic data, treatment regimen, and serial neuroimaging of a man in his 30s with pulmonary MDR-TB, pleural involvement, and a small peripherally enhancing cerebellar lesion compatible with a tuberculoma. The patient presented with respiratory symptoms and mild headache, and was diagnosed with cavitary pulmonary tuberculosis, pleural involvement, and a small left cerebellar lesion. Further evaluation showed no ataxia, dizziness, or focal neurologic deficits. Sputum acid-fast culture was positive for Mycobacterium tuberculosis, and rapid molecular testing demonstrated rifampin resistance. Whole-genome sequencing confirmed resistance to rifampin, isoniazid, and ethambutol, and did not identify mutations associated with resistance to pyrazinamide, fluoroquinolones, linezolid, clofazimine, or bedaquiline. Treatment was transitioned to BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) with adjunctive corticosteroids early in the course. Sputum cultures converted to negative approximately 6 weeks after treatment initiation. Serial brain MRI demonstrated progressive reduction in lesion size at 9 weeks, residual punctate enhancement at 21 weeks, near-complete resolution by 44 weeks, and complete radiographic resolution on subsequent imaging. The patient completed 52 weeks of therapy and remained clinically stable, without neurologic deficits or relapse more than 2 years after treatment completion. This case describes radiographic resolution of a small presumed cerebellar tuberculoma during extended BPaLM/BPaL-based therapy for disseminated MDR-TB, highlighting the evidence gap for standardized all-oral regimens in CNS drug-resistant tuberculosis.
To review postoperative rehabilitation protocols after surgery for patellar instability, including medial patellofemoral ligament reconstruction (MPFLR), tibial tubercle osteotomy (TTO), trochleoplasty, and combined procedures. A secondary aim was to compare published recommendations with guidance generated by selected artificial intelligence (AI) platforms. Sixty three protocol entries were included: 35 isolated MPFLR, 9 isolated TTO, 4 isolated trochleoplasty, and 15 combined procedures. Isolated MPFLR showed the most consistent rehabilitation pattern, favoring immediate weight bearing as tolerated (66%, p < 0.001), locked bracing for up to 6 weeks (63%, p < 0.001), and full ROM by 6 to 12 weeks (51%, p = 0.002). Isolated TTO protocols recommended delayed or non weight bearing (56%), locked brace duration greater than 6 weeks (67%), and full ROM by 6 to 12 weeks (44%), with no significant predominance (all p > 0.05). Trochleoplasty protocols were too few and heterogeneous. Combined procedures were mostly protective but variable overall. RTS criteria were mostly time, functional, and strength based (76%-89%), whereas psychological readiness (43%) and physician approval (22%) were infrequent. AI generated protocols broadly reproduced MPFLR rehabilitation principles but lacked procedure specific differentiation. Rehabilitation protocols following patellar instability surgery remain highly variable, particularly for non MPFLR procedures. Isolated MPFLR protocols generally follow a more structured and accelerated pathway, whereas rehabilitation after TTO, trochleoplasty, and combined procedures remains less clearly defined and more protective. RTS decisions rely mainly on time, strength, and functional based criteria, whereas psychological readiness remains underutilized. AI based tools may serve as supportive decision making aids but currently require integration with clinical judgment and procedure-specific expertise.
Renal ischemia-reperfusion injury (IRI) contributes to acute kidney injury (AKI) and is a major driver of progression to chronic kidney disease (CKD). A reproducible animal model is necessary to facilitate the evaluation of maladaptive repair and fibrosis mechanisms. Herein is reported a standard mouse model of renal fibrosis established by unilateral ischemia-reperfusion injury (uIRI) followed by contralateral nephrectomy (CNx). This strategy ensures long-term animal survival during disease progression while enabling the precise assessment of residual renal function of the injured kidney at the time of harvest. Male C57BL/6 mice were subjected to warm ischemia for 28 min at 37 °C, and a CNx was performed 24 h prior to each study endpoint. Mice were sacrificed for histological and immunohistochemical evaluations at the following time points: 2 days, 5 days, 1 week, 2 weeks, 3 weeks, and 4 weeks post-IRI. On postoperative days 2 and 5, the kidneys primarily exhibited tubular necrosis, particularly at the corticomedullary junction, without evidence of interstitial fibrosis. Starting one week after surgery, these pathological features were replaced by inflammatory cell infiltration and early tubular atrophy; interstitial fibrosis also emerged and reached its peak severity by the second week. During the third and fourth weeks after surgery, the kidneys showed widespread tubular atrophy consistent with disuse atrophy. Notably, interstitial fibrosis was reduced compared to the second week, indicating progression to the quiescent, hypocellular scarring phase. This model effectively reproduces the clinical scenarios of the AKI-to-CKD transition and provides a reliable platform for exploring fibrotic mechanisms and screening therapeutic interventions.
Hook of hamate fractures are relatively common injuries in baseball players, often occurring during batting due to repetitive contact between the bat handle and the hypothenar region. Excision of the fractured hook is frequently performed in athletes for whom nonoperative treatment fails or who require expedited return to sport. To evaluate return-to-play (RTP) rates, time to RTP, and postoperative complications and reoperation rates after hook of hamate excision in baseball players. Systematic review; Level of evidence, 4. A systematic search of 5 databases was performed to identify studies reporting clinical outcomes and complications after hook of hamate excision in baseball players. Extracted variables included patient characteristics, level of play, time from injury to surgery, RTP rate, time to RTP, complications, and reoperations. Overall outcomes and outcomes stratified by level of performance were analyzed. Study quality was assessed using the Methodological Index for Non-Randomized Studies criteria. Ten studies consisting of 624 athletes were included. RTP ranged from 81% to 100%, with a weighted mean of 90.7%. The median RTP time was 5.7 weeks. The weighted RTP rate for professional athletes was 88.1%, with a weighted mean RTP time of 7 weeks. In nonprofessional and mixed-level cohorts, the weighted RTP rate was 98.2%, with a weighted mean RTP time of 5.3 weeks. A total of 43 (11.8%) complications were reported, most of them consisting of transient ulnar nerve symptoms or scar-related pain. Three (0.5%) athletes underwent reoperation. Hook of hamate excision in baseball players is associated with high RTP rates and short RTP time, typically occurring between 5 and 7 weeks after surgery. Postoperative complications are infrequent and generally minor and temporary, and reoperations are rare.
Glycated hemoglobin (HbA1c) and average glucose (AG) can show discordance due to personal variations in red blood cell (RBC) physiology, creating management difficulties. Our aims were to understand the size of the problem and refine this glycemic metric by adjusting for personal differences in RBC characteristics. A 26-week prospective study was conducted in individuals with type 1 diabetes (T1D) or type 2 diabetes across four racial groups with HbA1c collected every 2 weeks and continuous glucose monitoring (CGM) used throughout. Personal glycation ratio (PGR) was derived from HbA1c and AG data (weeks 0-12), allowing calculation of personalized HbA1c (pA1C) and subsequent testing (weeks 20-26). The relationship between AG and HbA1c or pA1C was then analyzed, documenting a clinically meaningful discordance of ≥0.5%. In addition, we used real-world data sets to further validate the accuracy of pA1C at reflecting glucose exposure. Of 257 participants (19% T1D) with complete CGM and HbA1c data sets, mean age (±SD) was 53 ± 14 years (45% females). The racial background was 35% Asian, 30% White, 22% Black, and 14% other/mixed. Of the total study population, 33% showed ≥0.5% HbA1c-AG discordance, with the Black population affected most (41% discordance). Use of pA1C reduced the discordance in the whole population to 14% (58% reduction), while this was reduced in the Black population to 12% (71% reduction). HbA1c-AG discordance is common, particularly in the Black population, with pA1C improving alignment with glucose levels, potentially helping to optimize clinical management and reduce health disparities.
Gallic acid, a catechin polyphenol in tea, completely inhibited angiogenesis in assays of human tissue at 10-3 M. Psoriasis is a skin disease caused by excessive secretion of angiogenenic factors by keratinocytes and stromal skin cells. In a double-blind pilot study, six subjects with bilateral plaque psoriasis were treated with 10-2 M gallic acid in a cream base or with a cream base placebo over 8 weeks, four times a day, and treatments were randomly assigned to either the left or the right side. The gallic acid cream was well tolerated, but it did not reduce the psoriasis more than the placebo. One subject wanted to extend treatment for an additional 8 weeks. At the end of 16 weeks, the subject had complete resolution of the psoriatic plaque treated with gallic acid cream. In contrast, the plaque treated with placebo cream was not reduced and stayed equivalent to week six. Gallic acid is inexpensive and does not cause side effects. A longer trial evaluating 10-2 M gallic acid cream for the treatment of psoriasis seems indicated.
Subtrochanteric femur fractures account for 4% to 10% of all pediatric femur fractures. In adults, managing these fractures can be challenging due to loss of reduction and nonunion. Limited data exist on pediatric outcomes related to implant selection. This study evaluates the radiographic and functional outcomes of subtrochanteric femoral fracture fixation strategies. Patients ≤18 years old treated operatively for subtrochanteric femoral fractures, defined as fracture lines starting ≤10% of the femoral length distal to the lesser trochanter, between 2015 and 2023, were included. Medical records provided demographics, fracture characteristics, management, radiographic measurements, and outcomes. Radiographic healing was defined as bridging callus formation in 3 of 4 cortices. Angulation and displacement were measured at presentation and at follow-up visits. Complications, including painful hardware and malalignment (>10 degrees angulation in AP or lateral planes), were noted. Patient-Reported Outcomes Measurement Information System (PROMIS) scores were collected. We included 31 operatively managed subtrochanteric femur fractures with a median follow-up of 13.0 months (range: 0.6 to 127.0). Flexible nails were used in 48% of cases, rigid nails in 32%, and plating in 19%. Average ages were 6, 13, and 9 years, respectively (P<0.001). Initial fracture translation and angulation were similar across treatment groups. At 6 weeks postoperatively, malalignment >10 degrees was most common in the flexible nail group (P=0.046). Radiographic healing was not different across treatment methods. After 4 weeks postoperatively, PROMIS pain and mobility scores were similar across treatment groups (P>0.05). At 3 months postoperatively, malalignment >10 degrees was present in 31% of flexible nail cases, 33% of plate cases, and 0% of rigid nail cases (P=0.25). Rigid nails, flexible nails, and plate fixation all result in radiographic healing and functional improvement in pediatric subtrochanteric femur fractures. Although flexible nails are associated with higher malalignment rates at 6 weeks, these rates were comparable across treatment groups by 3 months. Flexible nails remain a viable option in this population. Ultimately, the fixation strategy should be guided by patient-related factors rather than the subtrochanteric pattern alone. Level III-therapeutic studies; investigating the results of treatment.
Based on randomized clinical trials, bupropion and nicotine replacement therapy (NRT) are recommended as equally effective first-line pharmacotherapies for smoking cessation. However, long-term real-world observational data comparing these two treatment options are scarce. This study aimed to evaluate 12 months smoking cessation success rates among adult smokers attending a community health center-affiliated Smoking Cessation Clinic in Giresun, Turkey, comparing bupropion with nicotine replacement therapy (NRT) in a real-world clinical setting. This prospective observational cohort study included 235 adult smokers who visited a single-center, community health center-affiliated Smoking Cessation Clinic in Giresun, Turkey, between October 2022 and October 2023. All participants received physician-led counseling and were prescribed either bupropion (n=45) or NRT (n=190; NRT 15 mg, n=118, and NRT 25 mg, n=72). Both treatments were provided free of charge for 12 weeks, during which six scheduled clinical visits were conducted over a 90-day period. Telephone follow-up assessments were conducted at weeks 16, 24 and 52. The primary outcome was the self-reported continuous abstinence at week 52. The mean age of participants was 40.74 ± 12.42 years, with 59.6% (n=140) being men. The overall 12 months continuous abstinence rate was 69.4% (n=163). The independent predictors of sustained abstinence at 52 weeks were high adherence to treatment, regular attendance at scheduled follow-up visits, counseling along with bupropion or high-dose NRT (25 mg), and fewer adverse effects during treatment. In real-world clinical practice, bupropion or high-dose NRT (25 mg), combined with structured counseling yielded high long-term abstinence rates and acceptable side effect profiles.
Recently, it has been reported that dual agonists of the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor (GCGR) have important functions in regulating glucose metabolism and energy expenditure. However, the usefulness of these dual agonists for the treatment of type 2 diabetes remains unclear. This systematic review and meta-analysis of randomized controlled trials aimed to assess the impact of GLP-1/GCGR dual agonists on glycemic markers. The search process was performed in PubMed, Scopus, ClinicalTrials.gov, and Cochrane Library databases. Randomized controlled trials assessing the impact of GLP-1/GCGR agonists on glycemic parameters were included. The meta-analysis was performed with the random-effects model and the generic inverse variance method, and the leave-one-out method was used for the sensitivity analysis. The meta-analysis of 14 randomized controlled trials demonstrated that GLP-1/GCGR agonists significantly decrease fasting glucose (WMD: -0.79 mmol/l, 95% CI: -1.14, -0.45, p<0.0001, I2 = 92%) and HbA1c (WMD: -0.50%, 95% CI: -0.67, -0.32, p<0.0001, I2 = 93%). However, these dual agonists had no significant impact on insulin levels (WMD: -14.78 pmol/l, 95% CI: -35.89, 6.34, p=0.17, I2 = 87%). The subgroup analysis by treatment duration exhibited that GLP-1/GCGR agonists significantly reduced fasting glucose and HbA1c in randomized controlled trials ≤12 weeks and >12 weeks, as well as insulin levels in those studies >12 weeks of treatment. In conclusion, the results of our meta-analysis indicated that GLP-1/GCGR dual agonists have a positive effect by decreasing fasting glucose and HbA1c concentrations.
Emergency department (ED) patients exhibit higher rates of depression than those in primary care and the general population, but it is unclear whether these symptoms reflect chronic conditions or transient responses to acute stress. Our objective in this study was to evaluate the longitudinal trajectory of depression and anxiety identified in the ED to inform evidence-based screening and intervention strategies. Adult, English-speaking ED patients with adequate literacy who presented to two urban academic EDs with somatic (non-psychiatric) chief complaints completed six mental health screening assessments at enrollment. Of 262 approached patients, 188 were enrolled, representing approximately 0.5% of all adult ED visits (188/37,898) during the study period. Follow-up assessments were completed through a secure phone app at one, two, and four weeks after ED discharge. The primary outcome was the longitudinal stability of depression and anxiety symptoms. The secondary outcome was differences in follow-up completion rates by baseline mental health status. Among 188 patients with baseline assessments, 44 (23%) screened positive for major depressive disorder, 17 (9%) for moderate/severe depression, and 34 (18%) for moderate/severe anxiety at baseline. Overall, 50 patients (27%) screened positive for at least one of these conditions. Follow-up responses at weeks 1 (n = 42, 22%), 2 (n = 41, 22%), and 4 (n = 27, 14%) showed no significant changes in levels of depression as measured by the Computerized Adaptive Test-Depression Inventory or severity of anxiety as per the Computerized Adaptive Test for Anxiety severity. High intraclass correlation coefficients (0.76-0.84) for all measures indicated inter-individual differences accounted for most variance. Stability of the Computerized Adaptive Diagnostic Test for Major Depressive Disorder ranged from moderate to substantial (Cohen kappa: 0.74 at week 1 to 0.46 at week 4). Patients who were positive for major depressive disorder had significantly higher follow-up completion rates at weeks 2 and 4 (P = .04). High baseline rates of depression and anxiety highlight the substantial mental health burden in ED patients. Among those who completed follow-up assessments, severity scores remained stable, suggesting these symptoms reflect ongoing conditions rather than transient stress. Future work should improve follow-up responses and assess whether ED-based identification and treatment improve outcomes.
The mechanisms by which exercise modulates liver metabolism are poorly understood. Leveraging data from molecular transducers of physical activity consortium (MoTrPAC), we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omics approaches. Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) protein complexes, while male livers showed an increased acetylation of OXPHOS, tricarboxylic acid cycle, and fatty acid oxidation enzymes. Mechanistic examination revealed that these sex-specific acetylation events are partially mediated by carnitine acetyltransferase. Exercise enhanced liver cholesterol and bile acid synthesis, reducing liver lipid metabolites in males after 8 weeks of exercise. Male rats had higher fecal cholesterol and cholic acid levels, indicating a sex-specific mechanism of lipid excretion with exercise. Eight weeks of training reduced markers related to hepatic stellate cell activation and fibrosis in both sexes. This study highlights the sexual dimorphic and temporal molecular signatures by which exercise modulates liver metabolism to provide hepatoprotective effects.
Cognitive impairment is a core symptom of schizophrenia, severely affecting patients' prognosis and quality of life. Repetitive transcranial magnetic stimulation (rTMS) and occupational therapy (OT) show potential efficacy alone, while their combined effects on cognitive function remain to be explored. A retrospective analysis was conducted on 131 hospitalized schizophrenia patients from September 2024 to June 2025. Based on the treatment regimens documented in their medical records, patients were divided into two groups: cohort A (n=67), who received only regular drug treatment and psychological rehabilitation; and cohort B (n=64), who received additional rTMS combined with OT. The Positive and Negative Symptom Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (rBANS) scores were collected at baseline, week 4, and week 8. Independent t-tests, chi-square tests, repeated-measures analysis of variance, and linear regression were used to compare differences in symptoms and cognitive function between cohorts and across time points, to assess symptom and cognitive function improvement. There was no significant difference in general data, initial scores of PANSS and rBANS between the two cohorts (P > 0.05). After 4 weeks and 8 weeks of treatment, the total scores of PANSS in both cohorts were significantly decreased (P < 0.05), and the total scores of rBANS were significantly increased (P < 0.05) compared with week 0/4, where cohort B had a larger change than cohort A (P < 0.05). Moreover, after 8 weeks of treatment, there were significant differences in all subscale scores of PANSS and rBANS between cohort B and cohort A (P < 0.05). In summary, rTMS combined with OT is able to improve the symptoms and cognitive function in schizophrenia patients. Moreover, the effect of an 8-week intervention is greater than that of a 4-week intervention.
To evaluate bowel ultrasound (BUS) findings and the diagnostic and prognostic performance of international bowel ultrasound segmental activity score (IBUS-SAS) in children with moderate ulcerative colitis (UC), including its accuracy for assessing endoscopic activity and predicting clinical remission and colectomy within 12 months. This was a single-center retrospective study conducted at Meyer Children's Hospital IRCCS. All patients who underwent a BUS performed for moderate UC (defined as pediatric ulcerative colitis activity index 35-60, either at disease onset or at relapse) between January 2019 and December 2023 were included. Where available, data on ileocolonoscopy performed within 4 weeks before or after BUS were retrieved, if no changes in medical management were performed during this period. Seventy-seven patients were included; 35/77 (45.5%) underwent ileocolonoscopy within 4 weeks from BUS. The most common BUS finding was increased colonic wall thickness (74/77, 96.1%), followed by enhanced vascularization (70/77, 90.9%). Loss of wall stratification was observed in 15 of 77 BUS (19.5%). The discriminative ability of IBUS-SAS in identifying moderate endoscopic activity was appraised through a receiver operating characteristic curve, showing a good area under the curve (0.75, 95% confidence interval [CI]: 0.58-0.90, p = 0.021) with an optimal cut-off of 48.5. IBUS-SAS ≥ 49 (as nominal variable) was identified as independent predictor of clinical remission (adjusted hazard ratio:0.42, 95% CI: 0.23-0.78) and colectomy within 12 months (adjusted odds ratio:4.18, 95% CI: 1.03-16.91). BUS is a non-invasive, repeatable tool for monitoring disease activity and stratifying pediatric UC with moderate activity. IBUS-SAS showed good discriminative ability for endoscopic activity, supporting its use for ultrasound-based risk-stratification in this setting.
Improved understanding of late gestation fetal growth patterns and postnatal outcomes in fetuses with single ventricle heart disease may inform decisions about elective delivery timing. This was a retrospective cohort analysis of patients in the National Pediatric Cardiology Quality Improvement Collaborative database from 2016 to 2019 anticipated to need stage 1 palliation (S1P) and had a gestational age (GA) of ≥ 36 weeks. Birthweight (BW) and BW z-scores were compared across GA. Survival to stage 2 palliation (S2P), post-S1P length of stay, and duration of mechanical ventilation were compared by GA. In 1290 infants, the mean BW increased with increasing GA (p < 0.001). Mean BW z-scores were below zero in late gestation (p < 0.001), with declining growth velocity 38 to > 40 weeks GA. Of 1216 patients with mechanical ventilation data, those at later GA had shorter durations of ventilation (p < 0.001). Among 1083 survivors to discharge or S2P if not discharged, infants born at later GA had shorter S1P hospitalizations (p = 0.015) and were more likely to undergo S2P (p = 0.003). Infants with single ventricle heart disease requiring S1P have decreased late gestation growth velocity, but growth continues. Infants born after longer gestation have shorter duration of ventilation and greater likelihood of undergoing S2P.
Midkine (MDK) could enhance neuron survival through its endocytosis receptor, lipoprotein receptor-related protein-1 (LRP-1). This study was designed to investigate whether body weight-supported treadmill training (BWSTT) promotes motor function and ameliorates neuronal injury following T10 incomplete contusive spinal cord injury (SCI) through the MDK/LRP-1 signaling pathway. T10 incomplete contusive SCI rats underwent two weeks of BWSTT. LRP-1-siRNA was utilized during the intervention to inhibit the MDK/LRP-1 signaling pathway. The Basso, Beattie, and Bresnahan (BBB) score, three-dimensional gait analysis, Nissl and NeuN staining of the spinal cord, and protein expression of MDK/LRP-1 were evaluated. Downstream activation of PI3K/Akt and BDNF expression was analyzed in vivo and in vitro. Two weeks of BWSTT significantly improved the BBB score after spinal cord injury (SCI) and ameliorated neuronal injury in the lumbar spinal cord. Immunofluorescence co-staining of MDK with NeuN indicates that BWSTT promoted the neuronal localization of MDK. The use of LRP-1-siRNA significantly inhibited the effectiveness of exercise training in enhancing motor function and ameliorating neuronal injury. Additionally, LRP-1-siRNA also hindered the neuronal localization of MDK following exercise training. Furthermore, exercise-induced Akt activation and BDNF upregulation were diminished in vivo by LRP-1-siRNA. In vitro results demonstrated that MDK activates Akt and BDNF, while RAP, an LRP-1 inhibitor, notably inhibited this effect. The neuroprotective effect of exercise training after SCI may be mediated, at least in part, through the MDK/LRP-1 signaling pathway, which promotes Akt activation and BDNF upregulation, contributing to neuronal survival and motor recovery after BWSTT in T10 incomplete spinal cord-injured rats.
To explore the cost-effectiveness of mavacamten + beta-blocker/calcium channel blocker therapy (BB/CCB) versus BB/CCB monotherapy for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM). A 5-state Markov model (New York Heart Association classes I-IV, death) that included treatment sequencing was developed. It used a Dutch societal perspective and lifetime horizon stratified into short-term (mavacamten + BB/CCB: 30 weeks; BB/CCB: 46 weeks) and long-term (i.e. post short-term) periods. The model population reflected the EXPLORER-HCM trial intention-to-treat population. Model parameters were aligned with 2016 Zorginstituut Nederland guidelines, including annual discount rates of 4.00% and 1.50% for costs and health outcomes. Costs (2022/2023 Euros), life-years (LYs) and quality-adjusted LYs (QALYs) per patient, incremental costs and LYs/QALYs, and incremental cost-utility ratios were estimated. Sensitivity and scenario analyses were conducted to evaluate the robustness of the results. Treatment with mavacamten + BB/CCB resulted in an incremental discounted gain of 3.09 QALYs and 3.17 LYs versus the BB/CCB monotherapy strategy. Incremental discounted costs were €49,388 over a lifetime; the additional costs of mavacamten were driven by increased treatment acquisition costs but partly offset by savings in healthcare resource utilization and indirect costs, particularly informal care costs. Mavacamten + BB/CCB was cost-effective at a €50,000 per QALY threshold versus BB/CCB monotherapy at €15,961 per QALY gain. The deterministic and probabilistic sensitivity and scenario analyses supported the robustness of the model results. In the Netherlands, mavacamten + BB/CCB is a cost-effective treatment strategy for symptomatic obstructive HCM compared to BB/CCB monotherapy. Obstructive hypertrophic cardiomyopathy (HCM) is a heart condition where the heart muscle becomes thick and blocks blood flow, impacting quality of life. Patients can have various symptoms including shortness of breath and fatigue.In recent years, a drug class called cardiac myosin inhibitors (CMI), has been tested in patients with symptomatic obstructive HCM, leading to approval for mavacamten (the first CMI) by the European Medicines Agency in 2024.This study aimed to compare mavacamten in combination with standard of care (SoC) vs SoC alone for patients with symptomatic obstructive HCM in the Netherlands. A model to assess cost-effectiveness was developed, to compare costs and health benefits, including length and quality of life, for these interventions over a patient’s lifetime. These cost-effectiveness estimates assist decision makers in selecting the treatment providing the best health outcomes for the lowest cost (i.e. good value for money). The model inputs are aligned with the Dutch guidelines.This study found patients live longer and have a better quality of life when treated with mavacamten compared to with SoC alone. Although treatment with mavacamten results in additional costs (€49,388 over a lifetime), patients should expect to live on average 3.17 years longer (3.09 when adjusting for quality of life). The cost per quality-adjusted life year gained is €15,961, which is considered good value for money in the Netherlands.The results of this study imply mavacamten offers meaningful health benefits for a reasonable cost, making it a valuable addition to the healthcare system in the Netherlands.
Starvation ketosis in pregnancy, though rare, is increasingly recognized, underscoring the need for a better understanding of its pathophysiology. Prolonged fasting or inadequate carbohydrate intake leads to elevated ketone levels, which can adversely affect maternal and fetal health. Early diagnosis via ketone monitoring and clinical assessments, is essential. The clinical presentation and laboratory profile of starvation ketosis overlap with euglycemic diabetic ketoacidosis (DKA), often creating a diagnostic dilemma. A 28-year-old female with gestational diabetes presented at 37 weeks of gestation with a 3-day history of nausea, vomiting, and abdominal pain. She had been unable to eat for 60 hours, consuming only small sips of water. Laboratory workup revealed high-anion gap metabolic acidosis with elevated β-hydroxybutyrate. Other causes of high-anion gap metabolic acidosis were ruled out, leading to a diagnosis of starvation ketosis versus euglycemic DKA. The patient was treated with dextrose supplementation to meet caloric needs, along with an insulin infusion. As her nausea improved, she tolerated an oral diet and was gradually weaned off intravenous dextrose. She recovered well and delivered a healthy infant at 38 weeks of gestation via spontaneous vaginal delivery. During starvation, the body transitions from glucose to lipid metabolism, producing ketone bodies as an alternative energy source. While ketoacidosis typically develops after 10 to 14 days in nonpregnant individuals, pregnancy-induced insulin resistance increases susceptibility, allowing ketoacidosis to develop within 24 hours, particularly in the third trimester. Treatment of starvation ketosis in pregnancy involves aggressive caloric replacement through dextrose infusions and insulin supplementation. Early intervention and maintaining a high index of clinical suspicion are crucial to prevent adverse complications for both mother and fetus.
Injuries at the medial gastrocnemius-soleus junction are common among athletes and physically active individuals. They typically result from sudden overstretching or repetitive microtrauma, leading to significant calf pain and functional limitations. Diagnosis is primarily clinical, with ultrasound or MRI used to assess injury severity. Most cases are managed conservatively, including rest, cryotherapy, anti-inflammatory therapy, and structured rehabilitation focusing on gradual stretching, eccentric strengthening, and proprioceptive training. Recovery generally occurs within 6-12 weeks, with return to activity guided by functional recovery rather than symptom resolution alone. A thorough understanding of the anatomy, pathophysiology, and evidence-based management strategies is essential to prevent complications, reduce recurrence, and facilitate a safe return to sport. ABSTRACT(CONCISE VERSION): Despite their prevalence in athletes, medial gastrocnemius-soleus junction injuries respond well to early conservative care, with most patients regaining full function. Diagnosis is based on clinical evaluation, supported by imaging when needed. Most cases are treated conservatively with rest, anti-inflammatory measures, and structured rehabilitation. Recovery typically occurs within 6-12 weeks, allowing safe return to activity while minimizing recurrence.