Tag: nevin manimala

J Clin Endocrinol Metab. 2023 Jun 30:dgad381. doi: 10.1210/clinem/dgad381. Online ahead of print.

ABSTRACT

CONTEXT: Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).

OBJECTIVE: We report the first clinical studies of an FcRn-inhibitor, batoclimab, in TED.

DESIGN: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials.

SETTING: Multicenter.

PARTICIPANTS: Patients with moderate-to-severe, active TED.

INTERVENTION: In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.

MAIN OUTCOME: Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).

RESULTS: The randomized trial was terminated due to an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P<0.001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab versus placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P<0.03) at 12 weeks, while quality of life (appearance subscale) improved (P<0.03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.

CONCLUSIONS: These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.

PMID:37390454 | DOI:10.1210/clinem/dgad381

Phys Rev Lett. 2023 Jun 16;130(24):248401. doi: 10.1103/PhysRevLett.130.248401.

ABSTRACT

The female reproductive tract (FRT) continuously modulates mammalian sperm motion by releasing various clues as sperm migrate toward the fertilization site. An existing gap in our understanding of sperm migration within the FRT is a quantitative picture of how sperm respond to and navigate the biochemical clues within the FRT. In this experimental study, we have found that in response to biochemical clues, mammalian sperm display two distinct chemokinetic behaviors which are dependent upon the rheological properties of the media: chiral, characterized by swimming in circles; and hyperactive, characterized by random reorientation events. We used minimal theoretical modeling, along with statistical characterization of the chiral and hyperactive trajectories, to show that the effective diffusivity of these motion phases decreases with increasing concentration of chemical stimulant. In the context of navigation this concentration dependent chemokinesis suggests that the chiral or hyperactive motion refines the sperm search area within different FRT functional regions. Further, the ability to switch between phases indicates that sperm may use various stochastic navigational strategies, such as run and tumble or intermittent search, within the fluctuating and spatially heterogeneous environment of the FRT.

PMID:37390449 | DOI:10.1103/PhysRevLett.130.248401

Phys Rev Lett. 2023 Jun 16;130(24):240602. doi: 10.1103/PhysRevLett.130.240602.

ABSTRACT

The task of learning a probability distribution from samples is ubiquitous across the natural sciences. The output distributions of local quantum circuits are of central importance in both quantum advantage proposals and a variety of quantum machine learning algorithms. In this work, we extensively characterize the learnability of output distributions of local quantum circuits. Firstly, we contrast learnability with simulatability by showing that Clifford circuit output distributions are efficiently learnable, while the injection of a single T gate renders the density modeling task hard for any depth d=n^{Ω(1)}. We further show that the task of generative modeling universal quantum circuits at any depth d=n^{Ω(1)} is hard for any learning algorithm, classical or quantum, and that for statistical query algorithms, even depth d=ω[log(n)] Clifford circuits are hard to learn. Our results show that one cannot use the output distributions of local quantum circuits to provide a separation between the power of quantum and classical generative modeling algorithms, and therefore provide evidence against quantum advantages for practically relevant probabilistic modeling tasks.

PMID:37390441 | DOI:10.1103/PhysRevLett.130.240602

Phys Rev Lett. 2023 Jun 16;130(24):241402. doi: 10.1103/PhysRevLett.130.241402.

ABSTRACT

We produce gravitational waveforms for nonspinning compact binaries undergoing a quasicircular inspiral. Our approach is based on a two-timescale expansion of the Einstein equations in second-order self-force theory, which allows first-principles waveform production in tens of milliseconds. Although the approach is designed for extreme mass ratios, our waveforms agree remarkably well with those from full numerical relativity, even for comparable-mass systems. Our results will be invaluable in accurately modeling extreme-mass-ratio inspirals for the LISA mission and intermediate-mass-ratio systems currently being observed by the LIGO-Virgo-KAGRA Collaboration.

PMID:37390425 | DOI:10.1103/PhysRevLett.130.241402

Arthritis Rheumatol. 2023 Jun 30. doi: 10.1002/art.42637. Online ahead of print.

ABSTRACT

OBJECTIVE: Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA), however prior studies have been small and/or uncontrolled; this study aimed to address that gap.

METHODS: This randomized, double-blind, sham-controlled trial enrolled patients aged 18-75 years with active RA who had failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and were naïve to biologic and/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI).

RESULTS: A total of 113 patients (mean age 54 years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation vs 26.9% for sham (difference vs sham [95% CI]: -1.9 [-18.8-14.9], p=0.823). The least square mean (SE) change in DAS28-CRP was -0.95 (0.16) for active stimulation and -0.66 (0.16) for sham (p=0.201); in HAQ-DI it was -0.19 (0.06) for active stimulation and -0.02 (0.06) for sham (p=0.044). Adverse events occurred in 17 patients (15%); all were mild or moderate.

CONCLUSION: Auricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility. This article is protected by copyright. All rights reserved.

PMID:37390360 | DOI:10.1002/art.42637

Ann Am Thorac Soc. 2023 Jun 30. doi: 10.1513/AnnalsATS.202212-1062OC. Online ahead of print.

ABSTRACT

RATIONALE: Clinical care guidelines advise lung volume recruitment (LVR) be performed routinely by people with neuromuscular disease (NMD), to maintain lung and chest wall flexibility and slow lung function decline. However, the evidence-base is limited and no randomised controlled trials (RCT) of regular LVR in adults have been published.

OBJECTIVE: To evaluate the effect of regular LVR on respiratory function and quality of life in adults with NMD.

METHODS: Randomised controlled trial with assessor blinding, conducted between September 2015 and May 2019. People (>14 years old) with NMD and vital capacity (VC) <80% predicted were eligible, stratified by disease sub-group (amyotrophic lateral sclerosis/motor neurone disease or Other NMDs) and randomised to three months of twice-daily LVR or breathing exercises. The primary outcome was change in maximum insufflation capacity (MIC) from baseline to 3-months, analysed using a linear mixed model approach.

RESULTS: 76 participants (47% female, median age 57 (31-68) years, mean baseline VC 40±18% predicted) were randomised (LVR=37). 73 participants completed the study. There was a statistically significant difference in MIC between groups (linear model interaction effect p=0.002; observed mean difference = 0.19 [0.00 to 0.39] L). MIC increased by 0.13 [0.01 to 0.25] L in the LVR group, predominantly within the first month. No interaction or treatment effects were observed in secondary outcomes of lung volumes, respiratory system compliance or quality of life. No adverse events were reported.

CONCLUSIONS: Regular LVR increased MIC in a sample of LVR-naïve participants with NMD. We found no direct evidence that regular LVR modifies respiratory mechanics or slows the rate of lung volume decline. The implications of increasing MIC are unclear, and the change in MIC may represent practice. Prospective long-term clinical cohorts with comprehensive follow-up, objective LVR usage, and clinically meaningful outcome data are needed.

CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000565549 (anzctr.org.au) Primary Source of Funding: National Health and Medical Research Council/Motor Neurone Disease Research Institute of Australia co-funded Postgraduate Scholarship (2014/GNT1093831); Mavis Gallienne MND Victoria grant (GIA 1703); Institute for Breathing and Sleep grants (2014, 2018); Physiotherapy Research Foundation grant (S14-013).

PMID:37390359 | DOI:10.1513/AnnalsATS.202212-1062OC

J Crohns Colitis. 2023 Jun 30:jjad110. doi: 10.1093/ecco-jcc/jjad110. Online ahead of print.

ABSTRACT

BACKGROUNDS AND AIMS: Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis (UC). The PICaSSO Histological remission Index (PHRI) is a new simple index for UC based only on the detection of neutrophils. We evaluate PHRI’s correlation with endoscopy and its prognostic value compared to other established indices.

METHODS: Consecutive patients with UC underwent colonoscopy at 2 referral centres (Birmingham, UK and Milan, Italy) and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI] and Robarts [RHI]) and endoscopy (Mayo Endoscopic Score [MES]; Ulcerative Colitis Severity Endoscopic Index of Severity [UCEIS], and PICaSSO score) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with ROC curves and outcome stratification with Kaplan-meier curves.

RESULTS: 192 patients with UC were enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI’s correlation with MES, UCEIS and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils (PHRI = 0) with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar (p>0.05) across indexes (2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively).

CONCLUSION: PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.

PMID:37390319 | DOI:10.1093/ecco-jcc/jjad110

J Am Acad Orthop Surg. 2023 Jun 30. doi: 10.5435/JAAOS-D-23-00239. Online ahead of print.

ABSTRACT

INTRODUCTION: Replicating native knee kinematics remains the ultimate goal of total knee arthroplasty (TKA). Technology, such as robotics, provides robust intraoperative data; however, no evidence-based targets currently exist for improved clinical outcomes. Furthermore, some surgeons target a rectangular flexion space in TKA unlike the native knee. This study evaluated the effect of in vivo flexion gap asymmetry on patient-reported outcome measures (PROMs) in contemporary TKA.

METHODS: In vivo tibiofemoral joint space dimensions were measured during 129 TKAs using a calibrated tension device before and after complete posterior cruciate ligament resection. PROMs were compared based on the final dimensions and the change in flexion gap dimensions at 90° of flexion: (1) equal laxity, (2) lateral laxity, and (3) medial laxity. Groups did not differ by demographics (P ≥ 0.347), clinical follow-up (P = 0.134), tibiofemoral alignment (P = 0.498), or preoperative PROMs (P ≥ 0.093). Mean follow-up for the cohort was 1.5 years (range, 1-3).

RESULTS: Pain with climbing stairs, pain while standing upright, and knees “always feeling normal” scores were superior for patients with equal or lateral laxity compared with medial laxity (P ≤ 0.064). Pain with level walking, University of California Los Angeles activity level, KOOS JR, and satisfaction scores also tended to be superior for patients with equal or lateral laxity, although it lacked statistical significance (P ≥ 0.111).

DISCUSSION: Results of this study suggest that patients with either an equally tensioned rectangular flexion space or with later-flexion lateral laxity after posterior cruciate ligament resection may achieve superior PROMs. Findings support the clinical benefit of facilitating posterolateral femoral roll back in flexion, which mimics native knee kinematics and further helps define targets for advanced technology.

PMID:37390317 | DOI:10.5435/JAAOS-D-23-00239

Medicine (Baltimore). 2023 Jun 30;102(26):e34128. doi: 10.1097/MD.0000000000034128.

ABSTRACT

The coronavirus disease 2019 has become a threat to global healthcare because of its rapid spread and evolution. In severe cases, the initial management of the disease is mainly supportive therapy and mechanical ventilation. Therefore, we investigated whether a modified emergency department workflow affects the efficacy will influence the efficacy and patient outcomes of traumatic brain injury (TBI) in Taiwan. This retrospective observational study used the Chang Gung Research Database in Taiwan from 7 hospitals in the Chang Gung Memorial Hospital System. Clinical index parameters and treatment efficiencies were analyzed between the locally transmitted period (January 20, 2020-June 7, 2020, period 2) and the community spread period (May 19, 2021-July 27, 2021, period 4) with the same interval of the pre-pandemic in 2019 as a reference period. During the locally transmitted period, only the time interval for patients who had to wait for a brain CT examination was, on average, 7.7 minutes shorter, which reached statistical significance. In addition, the number of TBI patients under 18 years of age decreased significantly during the community spread period. The “Door to the operating room (OR),” with polymerase chain reaction (PCR) testing, was on average 109.7 minutes slower than without the PCR testing in the reference period 2019. TBI treatment efficiency was delayed because of the PCR test. However, the surgical volume and functional outcome during these 2 periods were statistically insignificant compared to the pre-pandemic period because the spread of the virus was well controlled and hospital capacity was increased.

PMID:37390292 | DOI:10.1097/MD.0000000000034128

Medicine (Baltimore). 2023 Jun 30;102(26):e34107. doi: 10.1097/MD.0000000000034107.

ABSTRACT

This study aims to review the 1481 cases of medical complaints from Fujian Provincial Jinshan Hospital in the past 5 years for providing a reference for new hospitals to deal with medical complaints, optimize medical procedures, improve medical quality, and enhance patient experience. The medical complaint information received by the hospital’s medical department and service center accepted and transferred by the health administrative department in the past 5 years was systematically reviewed and statistically analyzed by using hierarchical clustering method. The transfer of the health administration department (61.5%) and the acceptance of the service center (28.9%) were the main sources of medical complaints in hospital. The incidence of medical complaints per 10,000 patients in the hospital was between 3 and 6. The maximum number of complaints was 2017 (5.28 cases/10,000 population), and the least was in 2019 (3.2 cases/10,000 population). The median of complaints was 25, and May to Sep was the period of high incidence of medical complaints each year. In 5 years, the month with the largest number of complaints was May 2020 (41 cases), followed by August 2017(40 cases), and the month with the least number was November 2020 (11 cases). In the past 5 years, the hospital’s medical complaints were mainly in 4 aspects: medical process (n = 329, 22.2%), medical environment (n = 282, 19%), humanistic care (n = 277, 18.7%), and medical management (n = 209, 14.1%). The most frequent complaints were in clinical departments, among which the emergency, outpatient, and pediatric departments accounted for more than 50%. The top 3 complaints were doctors (n = 778, 53%), logistics (n = 284, 19%), and nurses (n = 239, 16%). The main way to resolve complaints was letter and telephone feedback (n = 1372, 92.6%). Our research recommends that new hospitals change their concepts, pay more attention to the services and quality of medical resources and logistical support, follow the best practices of patient-centered, perfect various medical complaint channels, and establish multiple methods. They should also properly accept and dispose medical complaints, improve the timeliness and feedback efficiency of responding to medical complaints, strengthen communication, exchange, and dialogue, and improve patients’ medical experience and sense of gain.

PMID:37390291 | DOI:10.1097/MD.0000000000034107