Clinical Improvement In Patients Research Articles

Brain activity during reappraisal and associations with psychotherapy response in social anxiety and major depression: a randomized trial.

Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [dlPFC]) foretells CBT response in SAD, it remains unknown if this extends to MDD or is specific to CBT. The current study examined associations between pre-treatment neural activity during reappraisal and clinical improvement in patients with SAD or MDD following a trial of CBT or supportive therapy (ST), a common-factors comparator arm. Participants were 75 treatment-seeking patients with SAD (n = 34) or MDD (n = 41) randomized to CBT (n = 40) or ST (n = 35). Before randomization, patients completed a cognitive reappraisal task during functional magnetic resonance imaging. Additionally, patients completed clinician-administered symptom measures and a self-report cognitive reappraisal measure before treatment and every 2 weeks throughout treatment. Results indicated that pre-treatment neural activity during reappraisal differentially predicted CBT and ST response. Specifically, greater trajectories of symptom improvement throughout treatment were associated with less ventrolateral prefrontal cortex (vlPFC) activity for CBT patients, but more vlPFC activity for ST patients. Also, less baseline dlPFC activity corresponded with greater trajectories of self-reported reappraisal improvement, regardless of treatment arm. If replicated, findings suggest individual differences in brain response during reappraisal may be transdiagnostically associated with treatment-dependent improvement in symptom severity, but improvement in subjective reappraisal following psychotherapy, more broadly.

Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.

Hematologic Abnormalities in Patients With Hidradenitis Suppurativa Receiving Adalimumab

This post hoc analysis of PIONEER I and II randomized clinical trials assesses whether receiving adalimumab is associated with decreased hematologic abnormalities and increased clinical improvement in patients with hidradenitis suppurativa.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies. In this narrative review, we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease, immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following. We focused on the anti-gliadin antibodies, antibodies to different isoforms of tissue transglutaminase (TG) (anti-TG2, 3, and 6 antibodies), anti-glycine receptor antibodies, anti-glutamine acid decarboxylase antibodies, anti-deamidated gliadin peptides antibodies, etc. Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction, presented as different neurological disorders. We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Dupilumab therapy improves gut microbiome dysbiosis and tryptophan metabolism in Chinese patients with atopic dermatitis

BackgroundDupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively contributing to clinical improvement in patients with atopic dermatitis (AD). As the second genome of human body, growing evidence suggests that the gut microbiome might relate to the host response to treatments. Little is known about the association between dupilumab treatment and gut microbiome in AD patients. ObjectiveWe aimed to characterize the gut microbiome among Chinese subjects with or without AD and determine the potential effect of dupilumab on the gut microbiome. ResultsThe 16 s rRNA gene sequencing was conducted on 48 healthy controls (HC), 44 AD patients and 27 AD patients who received dupilumab for 16 weeks. Prior to treatment, we identified the changed beta-diversity, increased Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium and expanded Faecalibacterium among the AD patients compared to HC. After 16 weeks of dupilumab treatment, gut microbiome dysbiosis of the AD patients improved with reversed beta-diversity, closer bacterial connections, increased colonization of Bifidobacterium, Ruminococcus gnavus, and Coprococcus, which were negatively correlated with disease severity indicators. This shift was largely independent of the degree of clinical improvement. Bacterial function analysis revealed further metabolic alterations following dupilumab treatment, including up-regulated expression of genes involved in the indole pathway of tryptophan metabolism, corroborated by quantitative UHPLC-MS/MS analysis. ConclusionDupilumab treatment tends to help shift the gut microbial dysbiosis in AD patients to a healthier state, along with improved intestinal tryptophan metabolism, suggesting the gut flora and its metabolites may mediate part of the synergistic therapeutic effects on the host.

Normalized circulating Tfh and Th17 associates with improvement in myasthenia gravis treated with ofatumumab.

To assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG). 28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed. The frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy. Abnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.

Plasma Exchanges: Observational Study at the Mohammed V Rabat Military Training Hospital Blood Transfusion Center from January 2016 to December 2019

Since their initial indications as the ultimate treatment for certain serious pathologies, plasma exchanges (PE) have been utilized as frontline therapies up to lifesaving interventions. In this observational study conducted at the Mohammed V Military Training Hospital Blood Transfusion Center from January 2016 to December 2019, we aimed to elucidate the practical modalities and therapeutic indications of plasma exchanges. Our findings revealed that among the patients treated, the majority suffered from neurological pathologies (37%), followed by autoimmune pathologies such as thrombotic thrombocytopenic purpura and thrombotic microangiopathy (25%), and finally haematological and nephrological pathologies, each representing 19%. These results align with existing literature, emphasizing the prevalence of neurological indications for plasma exchanges.
 Moreover, the study showcased the effectiveness of plasma exchanges in various neurological conditions, with notable sessions for myasthenia, multiple sclerosis, neuromyelitis, polyradiculoneuritis, and meningoencephalitis. For nephrological pathologies, the sessions were primarily conducted for patients with ANCA+ intra-alveolar haemorrhage and Wegener's disease. Additionally, plasma exchanges demonstrated significant clinical improvements in patients with haematological pathologies, such as Waldenstrom's disease and hemolytic anaemia, and autoimmune diseases like thrombotic thrombocytopenic purpura and thrombotic microangiopathy.
 Ultimately, this study underscores the importance of collaboration between the transfusion centre and clinical and biological services for optimal patient management. The insights gained contribute to the broader understanding of plasma exchange applications in various pathologies, emphasizing its role as a crucial therapeutic intervention.

Are the minimally invasive techniques the new gold standard in thymus surgery for myasthenia gravis? Experience of a reference single-site in VATS thymectomy.

The thymus is the primary lymphoid organ responsible for the maturation and proliferation of T lymphocytes. During the first years of our lives, the activation and inactivation of T lymphocytes occur within the thymus, facilitating the correct maturation of central immunity. Alterations in the positive and negative selection of T lymphocytes have been studied as the possible origins of autoimmune diseases, with Myasthenia Gravis (MG) being the most representative example. Structural alterations in the thymus appear to be involved in the initial autoimmune response observed in MG, leading to the consideration of thymectomy as part of the treatment for the disease. However, the role of thymectomy in MG has been a subject of controversy for many years. Several publications raised doubts about the lack of evidence justifying thymectomy's role in MG until 2016 when a randomized study comparing thymectomy via sternotomy plus prednisone versus prednisone alone was published in the New England Journal of Medicine (NEJM). The results clearly favored the group of patients who underwent surgery, showing improvements in symptoms, reduced corticosteroid requirements, and fewer recurrences over 3 years of follow-up. In recent years, the emergence of less invasive surgical techniques has made video-assisted or robotic-assisted thoracoscopic (VATS/RATS) thymectomy more common, replacing the traditional sternotomy approach. Despite the increasing use of VATS, it has not been validated as a technique with lower morbidity compared to sternotomy in the treatment of MG. The results of the 2016 trial highlighted the benefits of thymectomy, but all the patients underwent surgery via sternotomy. Our hypothesis is that VATS thymectomy is a technique with lower morbidity, reduced postoperative pain, and shorter postoperative hospital stays than sternotomy. Additionally, VATS offers better clinical improvement in patients with MG. The primary objective of this study is to validate the VATS technique as the preferred approach for thymectomy. Furthermore, we aim to analyze the impact of VATS thymectomy on symptoms and corticosteroid dosage in patients with MG, identifying factors that may predict a better response to surgery.

P571 The Effect of NLRX1 Activation on Eosinophils in Ulcerative Colitis and Inflammation: Translational Learnings Across Diseases and from Mouse to Human

Abstract Background Although the precise role of eosinophils in IBD is debated, elevated eosinophils may influence response to therapy and clinical outcomes1. Thus, therapeutic agents which affect both neutrophil and eosinophil recruitment may provide more robust clinical improvement in patients with UC. NLRX1 is an immunometabolic protein which reduces oxidative stress, shifts cellular metabolism, and decreases inflammation in multiple cell types implicated in ulcerative colitis (UC). Studies of NLRX1 agonists (gut-selective NX-13 & systemic LABP-73) in diverse disease models identified novel cellular targets of NLRX1 activation. We compared NLRX1’s effect on eosinophils in 2 disease states, UC and the more prototypical eosinophilic disease, asthma, and evaluated the findings. Methods In the 4-week NX-13 Phase 1b, a double-blind trial of 36 patients with active UC (Total Mayo Score 4-10; Mayo endoscopic subscore 2-3) who were randomly assigned to NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks, histology was assessed using the Geboes score by a blinded pathologist2. For allergic asthma models, mice were immunized with ovalbumin or house dust mite followed by antigen challenge concurrent with LABP-73 or vehicle. Cells isolated from the lung were analyzed by flow cytometry using the BD FACS Celesta/Diva. Data are represented as means (standard error). Results In the 1b clinical trial, both the Geboes score and neutrophil subscores were reduced in the IR NX-13 group compared to placebo, consistent with the effects seen in preclinical IBD models. Upon examination, eosinophil infiltration was reduced in both the IR dose cohorts compared to placebo (Fig1A). In the subset of patients with active eosinophil infiltration at baseline (defined as Geboes subscore ≥2A.1), eosinophil reduction was seen in all NX-13 doses (Fig1B). Importantly, a numerically increased clinical response rate (decrease in total Mayo score of ≥3 or ≥30%) was seen in patients that demonstrated effective eosinophil reduction, compared to patients without improvement (75% versus 29%; Fisher’s Exact Test, p=0.08). In two allergic asthma models, NLRX1 activation by LABP-73 significantly reduced the fraction of eosinophils within the lung relative to vehicle control (n=7-8; p< 0.05), confirming NLRX1 activation can regulate eosinophilic inflammation in Th2-mediated responses. Conclusion Neutrophil and eosinophil infiltration were reduced in UC patients treated with the gut selective NLRX1 agonist, NX-13, and was coupled with better clinical outcomes. The effect of NX-13 on eosinophils will be evaluated further in the ongoing phase 2 NEXUS trial in patients with UC. 1 A Mookhoek, et al. JCC (16). 2 L Peyrin-Biroulet, et al. JCC (17) Supp

Can the Initial Parameters of Functional Scales Predict Recovery in Patients with Complete Spinal Cord Injury? A Retrospective Cohort Study.

Regaining greater independence in performing daily activities constitutes a priority for people with tetraplegia following spinal cord injury (SCI). The highest expectations are connected with the improvement of hand function. Therefore, it is so important for the clinician to identify reliable and commonly applicable prognostic factors for functional improvement. The aim of this study was to conduct an analysis to assess the impact of initial functional factors on the clinical improvement in patients during early neurological rehabilitation (ENR). This study assessed 38 patients with complete SCI aged 17-78 who underwent ENR in 2012-2022. The analysis included the motor score from the AIS (MS), the Barthel Index (BI) and the SCIM scale values at the beginning of the ENR program and after its completion. During ENR, patients achieved a statistically significant improvement in MS, BI and SCIM. The initial MS and the level of neurological injury constituted the predictors of functional improvement during ENR. Significant statistical relationships were observed primarily in the correlations between the initial MS and BI, and the increase in the analyzed functional scales of SCI patients. Higher initial MS may increase the chances of a greater and faster functional improvement during ENR.

Alveolar macrophage lipid burden correlates with clinical improvement in patients with pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a life-threatening, rare lung syndrome for which there is no cure and no approved therapies. PAP is a disease of lipid accumulation characterized by alveolar macrophage foam cell formation. While much is known about the clinical presentation, there is a paucity of information regarding temporal changes in lipids throughout the course of disease. Our objectives were to define the detailed lipid composition of alveolar macrophages in PAP patients at the time of diagnosis and during treatment. We performed comprehensive mass spectrometry to profile the lipid signature of alveolar macrophages obtained from three independent mouse models of PAP and from PAP and non-PAP patients. Additionally, we quantified changes in macrophage-associated lipids during clinical treatment of PAP patients. We found remarkable variations in lipid composition in PAP patients, which were consistent with data from three independent mouse models. Detailed lipidomic analysis revealed that the overall alveolar macrophage lipid burden inversely correlated with clinical improvement and response to therapy in PAP patients. Specifically, as PAP patients experienced clinical improvement, there was a notable decrease in the total lipid content of alveolar macrophages. This crucial observation suggests that the levels of these macrophage-associated lipids can be utilized to assess the efficacy of treatment. These findings provide valuable insights into the dysregulated lipid metabolism associated with PAP, offering the potential for lipid profiling to serve as a means of monitoring therapeutic interventions in PAP patients.

Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis.

(1) Background: In this study, we evaluated the modulation of urine glycosaminoglycans (GAGs), which resulted from etanercept (ETA) therapy in patients with juvenile idiopathic arthritis (JIA) in whom methotrexate therapy failed to improve their clinical condition. (2) Methods: The sulfated GAGs (sGAGs, by complexation with blue 1,9-dimethylmethylene), including chondroitin-dermatan sulfate (CS/DS) and heparan sulfate (HS), as well as non-sulfated hyaluronic acid (HA, using the immunoenzymatic method), were determined in the blood of 89 children, i.e., 30 healthy children and 59 patients with JIA both before and during two years of ETA treatment. (3) Results: We confirmed the remodeling of the urinary glycan profile of JIA patients. The decrease in the excretion of sGAGs (p < 0.05), resulting from a decrease in the concentration of the dominant fraction in the urine, i.e., CS/DS (p < 0.05), not compensated by an increase in the concentration of HS (p < 0.000005) and HA (p < 0.0005) in the urine of patients with the active disease, was found. The applied biological therapy, leading to clinical improvement in patients, at the same time, did not contribute to normalization of the concentration of sGAGs (p < 0.01) in the urine of patients, as well as CS/DS (p < 0.05) in the urine of sick girls, while it promoted equalization of HS and HA concentrations. These results indicate an inhibition of the destruction of connective tissue structures but do not indicate their complete regeneration. (4) Conclusions: The metabolisms of glycans during JIA, reflected in their urine profile, depend on the patient's sex and the severity of the inflammatory process. The remodeling pattern of urinary glycans observed in patients with JIA indicates the different roles of individual types of GAGs in the pathogenesis of osteoarticular disorders in sick children. Furthermore, the lack of normalization of urinary GAG levels in treated patients suggests the need for continued therapy and continuous monitoring of its effectiveness, which will contribute to the complete regeneration of the ECM components of the connective tissue and thus protect the patient against possible disability.

Radiographic and Clinical Outcomes After Stand-Alone Anterior Lumbar Interbody Fusion for Symptomatic L5-S1 Retrolisthesis.

Degenerative lumbar spondylolisthesis is associated with significant pain and disability. The literature on the treatment options and clinical outcomes for lumbar anterolisthesis is robust, but very few reports specifically evaluate lumbar retrolisthesis. This study investigated surgical outcomes for symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 anterior lumbar interbody fusion (ALIF). All patients with symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 ALIF at a single institution over a 7-year period were identified. Exhaustive nonoperative management had failed for all patients. Patients with previous lumbar fusion were excluded. Preoperative and postoperative radiographic images and patient-reported outcome measures for 20 patients (14 males and 6 females; mean [SD] age, 50.3 [13.7] years) were analyzed. The mean (SD) follow-up was 43.0 (23.7) months (range, 12.1-102.5 months). Patients experienced postoperative improvements in L5-S1 retrolisthesis (P = .048), L5-S1 disk height and angle (P < .001), L5 foraminal height (P < .001), L5-S1 lordosis (P < .001), and lumbar lordosis (P = .01). There were no significant changes in spinopelvic parameters. At the most recent follow-up, minimal clinically important differences in Oswestry Disability Index score, 36-Item Short-Form Survey (SF-36), and numerical rating scale score for leg pain were achieved in 11 of 20 (55%), 7 of 14 (50%), and 7 of 13 (54%) patients, respectively. All patients demonstrated fusion with no graft subsidence at up to 32 months. No patient experienced intraoperative complications, was readmitted, or required a subsequent posterior decompression or fusion because of refractory symptoms. In our cohort, stand-alone L5-S1 ALIF was associated with radiographic and clinical improvement in patients with symptomatic L5-S1 retrolisthesis.

Mechanism underlying polyvalent IgG-induced regulatory T cell activation and its clinical application: Anti-idiotypic regulatory T cell theory for immune tolerance.

The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases. In vitro studies have demonstrated that purified polyvalent immunoglobulin G (IgG) from multiple healthy blood donors can exert immunomodulatory effects on Treg cells. Incubation of polyvalent human IgG with purified CD4+CD25high T cells increased the intracellular expression of interleukin (IL)-10. Intravenous administration of polyvalent human IgG induced significant expansions of CD4+ Foxp3+ Treg cells and clinical improvements in patients with autoimmune diseases. In human clinical trials, intramuscular administration of autologous total IgG significantly increased the percentage of IL-10-producing CD4+ Treg cells in the peripheral blood of healthy subjects and provided significant clinical improvements in patients with atopic dermatitis. These results suggest a clinical usefulness of polyvalent IgG-induced activation of Treg cells in human subjects. This review proposes a new hypothesis for immune tolerance mechanism by integrating the pre-existing "idiotypic network theory" and "Treg cell theory" into an "anti-idiotypic Treg cell theory." Based on this hypothesis, an "active anti-idiotypic therapy" for allergic and autoimmune diseases using autologous polyvalent IgG (as immunizing antigens) is suggested as follows: (1) Intramuscular or subcutaneous administration of autologous polyvalent IgG produces numerous immunogenic peptides derived from idiotypes of autologous IgG through processing of dendritic cells, and these peptides activate anti-idiotypic Treg cells in the same subject. (2) Activated anti-idiotypic Treg cells secrete IL-10 and suppress Th2 cell response to allergens and autoimmune T cell response to self-antigens. (3) These events can induce a long-term clinical improvements in patients with allergic and autoimmune diseases. Further studies are needed to evaluate the detailed molecular mechanism underlying polyvalent IgG-induced Treg cell activation and the clinical usefulness of this immunomodulatory therapy for autoimmune and allergic diseases.

Can a structured home-based rehabilitation program reduce dorsal central wrist pain?

ObjectivesDorsal central wrist pain, often a consequence of peri-scapholunate ligament injury, can result in a decline in functional performance. There is a scarcity of clinical data evaluating the effectiveness of conservative management on peri-scapholunate ligament injury. Conservative management includes education, immobilization with orthotic devices, scapholunate-stabilizing muscle strengthening, and proprioception training. The identification of the ligamento-muscular reflex and scapholunate-stabilizing muscles formed the rationale for a rehabilitation training program. We have devised an innovative standardized 16-week treatment program for patients with dorsal central wrist pain associated with acute peri-SL ligament injury. We hypothesized that the program can effectively reduce dorsal wrist pain and improve functional performance. Materials and methodsRecruited subjects underwent the 16-week home-based program, which included immobilization and rehabilitation exercises, to improve their wrist stability. Follow-up was arranged every 4 weeks for progress monitoring. The Short-Form 12 item questionnaire version 2, power grip, pinch grip, wrist range of motion, total performance score and total pain score when performing activities of daily living were used to evaluate the effectiveness of the program. An exercise adherence questionnaire was used to evaluate adherence to the home rehabilitation program. ResultsTwenty-three subjects (26 wrists) completed the program. Pain on visual analog scale improved by 5.1 cm and total pain score improved from 14.4/20 to 19.5/20. Total performance score reached 39/40, which indicated near-normal wrist function. Power grip and pinch grip increased by 22.3% and 17.8%, respectively. The physical component scale of the Short-Form 12 item questionnaire showed significant improvement, while the mental component scale did not. Overall adherence was fair. DiscussionConservative management, including immobilization and rehabilitation training, can provide significant clinical improvement in patients with dorsal central wrist pain associated with acute peri-scapholunate ligament injury. ConclusionStandardized wrist rehabilitation can be taken as a reference treatment modality. It is an evidence-based non-invasive treatment option for clinicians and therapists.

Pharmacodynamic effects of filgotinib treatment driving clinical improvement in patients with active psoriatic arthritis enrolled in the EQUATOR trial

ObjectivesThe goal of this study was to identify protein and transcriptional biomarkers and pathways associated with baseline disease state, the effect of filgotinib (FIL) treatment on these biomarkers, and to...

Changes in electrophysiological findings of spinal muscular atrophy type I after the administration of nusinersen and onasemnogene abeparvovec: two case reports

BackgroundRecently, there have been significant advances in the treatment of spinal muscular atrophy (SMA). Although clinical improvement in patients with SMA after the treatment has been reported, changes in electrophysiological findings, especially needle electromyography (EMG), have rarely been reported. Herein, we report the posttreatment changes in EMG and nerve conduction study findings over time in two patients with SMA type I.Case presentationPatient 1: A 2.5-year-old girl was diagnosed with SMA type I at 1 month of age. She received nusinersen four times and onasemnogene abeparvovec (OA) was administered at 6 months of age. The compound muscle action potential (CMAP) amplitudes of the median and tibial nerves increased over time. The needle EMG after the treatment showed high-amplitude motor unit potentials (MUPs) suggestive of reinnervation during voluntary contraction, which were not seen before the treatment. However, fibrillation potentials at rest were still seen after the treatment. Patient 2: A 2-year-old girl was diagnosed with SMA type I at 6 months of age. She had received nusinersen two times and OA was administered at 7 months of age. The CMAP amplitudes and the MUPs presented similar changes as presented in Case 1.ConclusionThis is the first report on the changes in needle EMG findings after treatment in patients with SMA type I. These findings suggested that peripheral nerve reinnervation occurred after the treatment, although active denervation was still present. The accumulation of these findings will be important for evaluating the effectiveness of treatment for SMA in the future.

A Report of Two Cases of the Use of Korean Medicine Treatment of Patients with Post-COVID-19 Conditions

The purpose of this study is to report clinical improvement in patients who have received Korean medicine treatment for post-COVID-19 conditions. After COVID-19 infection, two people complaining of symptoms, such as fatigue and indigestion, were treated with Korean medicine, such as acupuncture and herbal medicine. The C19-YRS questionnaire and heart rate variability (HRV) were used to assess the treatment outcomes. After treatment, the patients reported improvements in their symptoms on the YRS questionnaire, with some improvement in the HRV test results. According to the results of this study, Korean medicine can be used to treat post-COVID-19 conditions in clinical practice.

Association between SARS-CoV-2 viral kinetics and clinical score evolution in hospitalized patients.

The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS-2) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23) randomly assigned to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS-2 score lower than 3 (in patients with NEWS-2 <7 at hospitalization) or 5 (in patients with NEWS-2 ≥7 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large interindividual variability. Remdesivir antiviral activity was 22% and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS-2. However, simulations predicted that antiviral activity greater than 99% could reduce by 2 days the time to clinical improvement in patients with high viral load, irrespective of the NEWS-2 score at hospitalization, whereas no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.

Short-term Outcome of Peroral Endoscopic Myotomy Performed by the Same Endoscopist on Achalasia and Nonachalasia Esophageal Motility Disorders.

Peroral endoscopic myotomy (POEM) is a relatively new but increasingly therapeutic option for achalasia. In recent years, POEM has been used for nonachalasia esophageal motility disorders (NAEMDs), such as diffuse esophageal spasm, esophagogastric junction outlet obstruction, and hypercontractile disorder, with some clinical success. No studies thus far compare the outcomes of these two groups. We perform the first head-to-head comparison of outcomes after POEM in patients with achalasia and NAEMD. A retrospective analysis of all patients undergoing POEM at one university hospital by a single expert endoscopist from July 2021 to December 2022 was performed. All patients were symptomatic, and the presence of esophageal motility disorders was confirmed using multiple diagnostic modalities. These patients were then divided into 2 groups, achalasia and NAEMD, based on the underlying diagnosis. Statistical analysis of different clinical outcomes, including effectiveness and safety, was performed. Thirty-seven patients (mean age: 59.55, females: 22) underwent POEM in the study period. Twenty patients had achalasia and 17 patients had NAEMD. The median myotomy length was 5.5 cm for the achalasia group and 10 cm for the NAEMD group. This excluded patients with esophagogastric junction outlet obstruction in which the median myotomy length was 3 cm. The procedure time, the duration of hospital stays, the rates of same-day discharge, and complications were similar between the two. Short-term outcomes of POEM for the two groups were similar with improvement in 94% of patients in the achalasia group and 93.75% in the NAEMD group. Contrary to prior observations, our study highlights that POEM is equally effective in achieving clinical improvement in patients with NAEMD as achalasia over 6 months of follow-up. In addition, POEM has a comparable safety profile in both patient groups making it a feasible therapeutic option for these debilitating and challenging disorders.