Clinical Improvement In Patients Research Articles

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.

THU041 Clinical Improvements In Patients With Cushing’s Disease Treated With Osilodrostat According To Urinary And Late-night Salivary Cortisol Levels: Pooled Analysis From LINC 3 And LINC 4

Abstract Disclosure: B.M. Biller: Consulting Fee; Self; HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Research Investigator; Self; served on the LINC 3 steering committee. M. Fleseriu: Consulting Fee; Self; HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Research Investigator; Self; served on the LINC 3 steering committee. R. Pivonello: Consulting Fee; Self; Novartis Pharmaceuticals, Recordati, Corcept Therapeutics, Pfizer, Inc., Bresmed Health Solutions, Damor farmaceutici, S&amp;R Farmaceutici SpA, Organon Italia Srl, Siunergos Pharma, Biohealth Italia Srl. Research Investigator; Self; Novartis Pharmaceuticals, Recordati, Xeris Pharmaceuticals (Strongbridge), Corcept Therapeutics, Takeda, Neurocrine Biosciences, Camurus AB, Pfizer, Inc., Merk Serono, Ibsa. R. Feelders: Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; Corcept Therapeutics. M. Gadelha: Advisory Board Member; Self; Novo Nordisk, Recordati, Crinetics Pharmaceuticals. Speaker; Self; Recordati, Ipsen, Pfizer, Inc., Crinetics, Novo Nordisk. A. Lacroix: Consulting Fee; Self; Novartis Pharmaceuticals, Recordati, Corcept Therapeutics, Ipsen, Novo Nordisk. Grant Recipient; Self; Novartis Pharmaceuticals, Recordati, Corcept Therapeutics, Ipsen, Novo Nordisk. P. Witek: Grant Recipient; Self; Novartis Pharmaceuticals, Ipsen, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge), Lilly. Speaker; Self; Novartis Pharmaceuticals, Ipsen, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge), Lilly. A.P. Heaney: Advisory Board Member; Self; Xeris Pharmaceuticals (Strongbridge), Novo Nordisk, Lundbeck Pharma. Speaker; Self; Chiasma, Ipsen. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. J. Newell-Price: Consulting Fee; Self; Crinetics, Diurnal, HRA Pharmaceuticals, Recordati Rare Diseases. Grant Recipient; Self; Crinetics, Diurnal, HRA Pharmaceuticals, Recordati Rare Diseases. Introduction: In two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734), osilodrostat, a potent oral 11β-hydroxylase inhibitor, led to rapid, sustained reductions in mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC), as well as improvements in clinical signs of hypercortisolism and health-related quality of life (HRQoL), in patients (pts) with Cushing’s disease (CD). mUFC and LNSC are recommended for monitoring treatment response. Objective: We assessed if pts with control of both mUFC and LNSC experienced greater improvements in clinical signs of hypercortisolism and HRQoL, compared to control of mUFC alone. Methods: LINC 3 comprised a 48-week (W) core phase, including an 8W randomized-withdrawal period. LINC 4 included a 12W, double-blind, placebo-controlled period followed by 36W of open-label osilodrostat. Both studies had an optional extension. mUFC (mean of 2–3 samples; normal range [NR] 11–138 nmol/24h [4–50 µg/24h]) and LNSC (one sample; NR ≤2.5 nmol/L [≤0.9 µg/L]) were measured by liquid chromatography-tandem mass spectrometry. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism and HRQoL were assessed in the pooled population according to mUFC and LNSC control status: both controlled (C) mUFC + LNSC (mUFC ≤ULN + LNSC ≤ULN), C-mUFC (mUFC ≤ULN + LNSC &amp;gt;ULN) and uncontrolled (UC) mUFC + LNSC (mUFC &amp;gt;ULN + LNSC &amp;gt;ULN). Pts with C-LNSC (mUFC &amp;gt;ULN + LNSC ≤ULN) were not analyzed as very few pts had control of LNSC without UFC control. This analysis includes pts in core and extension phases with both mUFC and LNSC assessments available. Periods where pts received placebo were excluded. Results: 136 (85.0%) of 160 pts with available assessments had UC mUFC + LNSC at baseline (BL). At W48 (n=133) and W72 (n=111), respectively, 59 (44.4%) and 54 (48.6%) pts had C mUFC + LNSC, 49 (36.8%) and 44 (39.6%) had C-mUFC, and 19 (14.3%) and 11 (9.9%) had UC mUFC + LNSC. Pts with C mUFC + LNSC had greater percentage improvements from BL to W72 in cardiovascular/metabolic-related parameters than pts with C-mUFC or UC mUFC + LNSC, respectively: fasting plasma glucose, –5.0%, –4.8%, 1.9%; glycated hemoglobin, –5.1%, –4.8%, –1.3%; weight, –6.5%, –6.5%, –4.5%; waist circumference, –7.2%, –6.3%, –4.9%. Physical manifestations of hypercortisolism generally improved from BL to W72 regardless of mUFC/LNSC control. Pts with C mUFC + LNSC or C-mUFC had the greatest improvement from BL to W72 in HRQoL. Conclusions: The greatest improvements in cardiovascular/metabolic-related parameters and HRQoL were observed in pts with C mUFC + LNSC or C-mUFC, compared to pts with UC mUFC + LNSC. Improvements in most physical manifestations of hypercortisolism were observed regardless of mUFC/LNSC control. Data are limited by small patient numbers in some groups. Normalization of both mUFC and LNSC can improve long-term treatment outcomes in pts with CD. Presentation: Thursday, June 15, 2023

Neuroesthetics and its Excitatory Sensitization of the Cerebral Cortex

The human mind receives, perceives, and processes visual and auditory input daily from the everyday world of art and culture as an esthetic neural experience involving several regions of the cerebrum. It is important to comprehend how this process of neuroesthetics works and how it affects each individual’s emotions and behavior. This article will incorporate various clinical scanning techniques and methods to examine the anatomical cerebral structures where the effects of external neuroesthetic stimuli can be correlated with its resultant neural cognitive response. The effects of neuroesthetic stimuli on the clinical improvement in patients experiencing depression, cognitive decline, and other forms of behavioral manifestations will be reviewed. The results of these studies (including international examples, along with various comparative analyses) demonstrate the beneficial effects of art on the pleasure centers of the brain and its consequent positive effects on patients’ behavior and emotions, thus exemplifying the short- and long-term importance of incorporation of neuroesthetics in not only the clinical setting but also in our global society.

Baseline Left Ventricle Longitudinal Strain as a Predictor for Clinical Improvement Following Coronary Sinus Reducer Implantation

Coronary sinus narrowing device (reducer) implantation has emerged as an effective treatment to improve the quality of life and functional capacity in patients suffering from disabling refractory angina. Left ventricle global longitudinal strain (LV-GLS) is a useful tool for early diagnosis of subclinical cardiac injury and an independent predictor for coronary artery disease. We aimed to investigate whether LV-GLS could help predict clinical improvement after coronary sinus reducer implantation. LV-GLS assessments were performed at baseline and 6months after reducer implantation in consecutive patients treated for refractory angina. Patients were divided into 2 groups based on reduced (<17% absolute value) or preserved baseline LV-GLS. Clinical improvement was defined as an increase of ≥25m in the 6-minute walk test (6MWT) at follow-up. Overall, 41 patients were included, 31 in the reduced LV-GLS group and 10 in the preserved LV-GLS group. The mean age was 68±8years, with only 2 female patients (5%). Baseline characteristics did not differ significantly between the 2 groups. Univariable analysis revealed that LV-GLS was the only significant predictor for 6MWT improvement. Baseline preserved LV-GLS reduced the likelihood of 6MWT improvement by 82% (odds ratio 0.18 [0.04 to 0.83], p=0.029). A significant increase in 6MWT (307±97m to 343±92m, p=0.017) was observed in the reduced LV-GLS group, compared with a decrease in the preserved LV-GLS group (378±86m to 361±123m, p=0.651). In conclusion, reduced LV-GLS may serve as a marker for potential clinical improvement in patients with refractory angina treated with reducer. Larger clinical trials are needed to establish its role.

Regulatory T Cell-Targeted Immunomodulatory Therapy for Long-Term Clinical Improvement of Atopic Dermatitis: Hypotheses and Perspectives.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disorder characterized by itching and eczematous lesions. It is often associated with a personal or familial history of allergic diseases. Allergic inflammation induced by immunoglobulin E and T-helper type 2 (Th2) cell responses to common environmental agents has been suggested to play an essential role in AD pathogenesis. The standard therapies for AD, including topical or systemic agents, focus on controlling skin inflammation. Recently developed monoclonal antibody to interleukin-4 receptor alpha or Janus kinase inhibitors can provide significant clinical improvements in patients with AD by inhibiting Th2 cell-mediated skin inflammation. However, the clinical efficacy of the Th2 cell-targeted therapy is transient and incomplete in patients with AD. Patients with AD are seeking a permanent cure. Therefore, the development of novel immunomodulatory strategies that can improve a long-term clinical outcome and provide a long-term treatment-free clinical remission of AD (disease-modifying therapy) is needed. Regulatory T (Treg) cells play a critical role in the maintenance of immune tolerance and suppress the development of autoimmune and allergic diseases. This review provides three working hypotheses and perspectives for the treatment of AD by Treg cell activation. (1) A decreased number or function of Treg cells is a critical event that causes the activation of Th2 cells, leading to the development and maintenance of AD. (2) Activation of Treg cells is an effective therapeutic approach for AD. (3) Many different immunomodulatory strategies activating Treg cells can provide a long-term clinical improvement of AD by induction of immune tolerance. The Treg cell-targeted immunomodulatory therapies for AD include allergen immunotherapy, microbiota, vitamin D, polyvalent human immunoglobulin G, monoclonal antibodies to the surface antigens of T cell or antigen-presenting cell, and adoptive transfer of autologous Treg cells or genetically engineered Treg cells expanded in vitro.

Can inspiratory muscle training benefit patients with COVID-19? A systematic review and meta-analysis.

The possible benefits of inspiratory muscle training (IMT) on mechanical and clinical outcomes in patients with Coronavirus disease-2019 (COVID-19) remain controversial. We conducted a meta-analysis to evaluate the effect of IMT in the rehabilitation strategy of patients with COVID-19. The Pubmed, Embase, Web of Science (WOS), and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify trials evaluating the efficacy of IMT in the treatment of patients with COVID-19. The primary outcome included change from baseline of VO2 max, maximal inspiratory pressure (PImax), 6-min walk test(6MWT), forced expiratory volume in the first second predicted (FEV1%pred), and quality of life (QOL). Six studies with 349 participants were analyzed. Significant improvements were found in change from baseline of VO2 max (MD: 4.54, 95% confidence interval [CI]: 1.79-7.30, Z = 3. 32, I2 = 0, p = 0.001), PImax (MD: 21.43, 95% CI: 1.33-41.52, Z = 2.09, I2 = 90%, p = 0.04), 6MWD (MD: 40.13, 95% CI: 24.92-55.35, Z = 5.17, I2 = 0, p < 0.00001) and FEV1%pred (MD: 8.73, 95% CI 3.07-14.39, Z = 3.02, p = 0.002) while no statistical improvements were found in QOL (SMD: 0.70, 95% CI: 0.37-1.03, Z = 4.15, I2 = 89% p = 0.32) between IMT group and control group. The application of IMT might elicit mechanical and clinical improvement in patients with COVID-19. IMT could be recommended as an effective strategy of pulmonary rehabilitation for COVID-19. However, the proper timing, optimal duration, as well as appropriate frequency and intensity of IMT remain uncertain and further studies are needed.

Hydroxyurea treatment for adult sickle cell anemia patients in Kinshasa.

Background: Despite a high incidence of sickle cell anemia, hydroxyurea (HU) treatment is rarely used in the DR Congo. This study aims to assess the efficacy of HU, the incidence of side effects that may limit its use in adults and to determine the dose needed for clinical improvement in patients. Methods: In a prospective study, patients received an initial dose of 15mg/kg/day which was increased by 5mg/kg every 6 months, up to a maximum of 30mg/kg/day. The response and side effects to HU were evaluated biologically and clinically every 3 months during a 2-year period. Results: Seventy adult patients with a moderate or severe clinical phenotype initiated treatment. Only minor side effects were reported. At the end of the 2-year treatment phase, 45 (64.3%) had dropped out, of whom 33 were without a clear reason. Clinical and biological improvement was more marked during the first year. There was a reduction in severe vaso-occlusive crises (p<0.001), need for transfusion (p<0.001), and hospitalization days (p=0.038). Fetal hemoglobin (HbF) levels increased on average 2.9 times after 12 months (p<0.001). The increase in mean corpuscular volume was greater in the first year (p<0.001) than in the second year (p=0.041). The decrease in leukocytes (p<0.001) was significant during the first year. In 70% of patients, the 20mg/kg/day dose was needed to reach the 20% HbF threshold. Conclusion: HU is effective and well tolerated. The magnitude of the response varies from one patient to another. Improvement of clinical manifestations is achieved in most patients with a relatively low dose. Effective implementation of HU treatment will require improved adherence to treatment.

Evaluation of Serum Levels of Cytokines in Acute Apical Abscess: A Longitudinal Observational Study

IntroductionCytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection. MethodsIn total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P < .05). ResultsAAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P < .05); there were similar levels of interferon gamma, IL-1β, IL-4, and IL-17 between groups (P > .05). IL-6 and IL-10 levels decreased after antibiotic treatment (P < .05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment. ConclusionsIn conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment.

Knee Osteoarthritis: Clinical and MRI Outcomes After Multiple Intra-Articular Injections With Expanded Autologous Adipose-Derived Stromal Cells or Platelet-Rich Plasma.

To directly compare clinical and MRI outcomes of multiple intra-articular injections of adipose-derived stromal cells (ASCs) or platelet-rich plasma (PRP) in patients with knee osteoarthritis (OA). We retrospectively compared 24-month outcomes in (1) 27 patients receiving 3-monthly intra-articular injections with a total of 43.8 million ASCs and (2) 23 patients receiving 3-monthly injections of 3-ml preparation of PRP. All patients had Kellgren-Lawrence grade 1, 2, or 3 knee OA with failed conservative medical therapy. The Numeric Pain Rating Scale (NPRS) scores; Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline, 6, 12, and 24 months after the first injection; and the MRI Osteoarthritis Knee Score (MOAKS) at 12 and 24 months were considered as outcomes. No major complications occurred in any patient. Both groups significantly improved in pain NPRS score and KOOS at 6 months. At 12- and 24-month evaluations, the ASC group significantly decreased scores to a greater degree (P < 0.001) than the PRP group. MOAKS scores indicated a decrease in disease progression in the ASC group. Both ASCs and PRP were safe and resulted in clinical improvement in patients with knee OA at 6 months; however, at 12 and 24 months, ASCs outperformed leukocyte-poor PRP in clinical and radiological outcomes.

Physiotherapy Management in Postoperative Anterior Cruciate Ligament

Stabilization of the tibia when moving forward and rotational movements of the knee joint will be assisted by one of the ligaments in the knee joint, namely the Anterior Cruciate Ligament (ACL). This study aims to present physiotherapy management strategies to help reduce pain, prevent stiffness, increase muscle strength, decrease muscle spasms, increase the joint scope of motion, and overcome edema. The method used in this study is a case report. Primary data are obtained through auto anamnesis and physical examination. Holistic diagnosis assessment is carried out quantitatively from the study's beginning, process, and end. The result is that a 33-year-old male patient with a postoperative diagnosis of ACL underwent surgery on November 14, 2022, and has done therapy 7 times; the patient has experienced significant changes. It can be concluded that postoperative ACL rehabilitation can reduce edema and pain, increase muscle strength, and increase ROM. Finding interventions that can be applied to learning and modification of interventions is also recommended to assist in post-ACL reconstruction recovery to return to daily activities. The diagnosis and treatment of physiotherapy in patients are by the latest theories and research. In the evaluation, clinical improvement of patients and increased knowledge were obtained