Conventional Therapy In Patients Research Articles

Biochemical Modulators of Tight Junctions (TJs): Occludin, Claudin-2 and Zonulin as Biomarkers of Intestinal Barrier Leakage in the Diagnosis and Assessment of Inflammatory Bowel Disease Progression.

Considering the increasing worldwide prevalence of inflammatory bowel disease (IBD), the early diagnosis of this disease is extremely important. However, non-invasive diagnostic methods remain limited, while invasive techniques are the most commonly used in daily practice. Therefore, there is a serious need to find new non-invasive biomarkers of IBD. The serum profiles of occludin, claudin-2, and zonulin were assessed in IBD patients using the ELISA method. The levels of the analyzed biomarkers were measured before and after a year of anti-inflammatory treatment, which was a tumor necrosis factor α (TNF-α) inhibitor (adalimumab) in patients with ulcerative colitis (UC) and conventional therapy in patients with Crohn's disease (CD). In IBD patients, the serum level of occludin (p < 0.001) decreased compared to healthy individuals, while the level of claudin-2 (p < 0.001) increased. Additionally, zonulin (p < 0.01) concentration increased in CD patients compared to the control group. The highest diagnostic ability was presented by occludin measurements with the area under the curve (AUC) of 0.959 (95% CI 0.907-1) in UC and 0.948 (95% CI 0.879-1) in CD. Claudin-2 also demonstrated very good ability in diagnosing UC and CD with AUC values of 0.864 (95% CI 0.776-0.952) and 0.896 (95% CI 0.792-0.999), respectively. The ability of zonulin to diagnose CD was estimated as good with an AUC of 0.74 (95% CI 0.598-0.881). Moreover, a significant correlation was identified between C-reactive protein (CRP), claudin-2 (r = -0.37; p < 0.05), and zonulin (r = -0.44; p < 0.05) in UC patients. Treatment with adalimumab improved the level of occludin, claudin-2, and zonulin in UC patients, while anti-inflammatory conventional therapy decreased the concentration of zonulin in CD. Occludin and claudin-2 measurements present significant utility in diagnosing both UC and CD, while zonulin assessments may be useful in CD diagnosis. Additionally, claudin-2 and zonulin measurements may be helpful in evaluating the intensity of the inflammatory process. Anti-TNF-α treatment improved the value of occludin, claudin-2, and zonulin, indicating its beneficial effect on the integrity of tight junctions in UC.

The change over time in the prescription pattern of the first targeted drug after failure of conventional therapy in patients with rheumatoid arthritis: a 20-year real-world experience.

To evaluate the change over time in the pattern of the first biologic/targeted synthetic drug (b/tsDMARD) prescription and baseline characteristics in patients with rheumatoid arthritis (RA) from 1999 to the present. A retrospective data analysis from RA patients enrolled in an Italian single-center registry was conducted. The analysis was limited to all the patients who received the first b/tsDMARD between October 1999 and December 2022. Patients were stratified according to the date of b/tsDMARD initiation into 4 groups (1999-2004, 2005-2010, 2011-2016, and 2017-2022) and a comparative analysis of prescription patterns and patients' baseline characteristics was performed. The study population included 1206 patients. The characteristics of patients at baseline in the 4 groups were similar overall, with the exception of disease duration (12.26, 10.5, 9.7, 8.1 years, respectively; p<0.0001), mean number of conventional DMARDs used before the first b/tsDMARD (3, 2.5, 2.1, 1.4, respectively; p<0.0001), and mean clinical disease activity index (CDAI) score (30.1, 24.3, 21.8, 20.4, respectively; p<0.0001). A progressive reduction (from 95 to 43% of patients) in the prescription of first-line TNF-α inhibitors toward other mechanisms of action has been observed. The rate of patients treated with b/tsDMARDs as monotherapy progressively increased (from 18 to 26%) especially among those not receiving a TNFα inhibitor. The expansion of the therapeutic armamentarium has changed the management strategy of RA over time towards an earlier introduction of targeted drugs (increasingly often as monotherapy) in patients with progressive lower disease activity and a history of failure with fewer previous conventional drugs.

Extracorporeal membrane oxygenation versus conventional therapy in patients with acute respiratory failure: systematic review with meta-analysis

Extracorporeal membrane oxygenation versus conventional therapy in patients with acute respiratory failure: systematic review with meta-analysis

Comparative analysis of therapeutic plasma exchange vs. standard management in hypertriglyceridemia-induced acute pancreatitis: triglyceride reduction and clinical outcomes.

The use of therapeutic plasma exchange (TPE) for treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) remains controversial in the literature. This study compared the clinical outcomes of TPE versus conventional therapy in patients with HTGP. Fifty-five patients with HTGP were included. Patients were retrospectively compared in pairs: those who received TPE treatment and those who did not, those whose triglyceride level fell below 500mg/dL within 48h, and those who did not, those with and without persistent organ failure. The primary outcome was the percentage of triglyceride reduction within 48h. Secondary outcomes were the length of hospital stay, mortality, cost-effectiveness, and persistent organ failure. Percentage decrease in triglyceride levels, medical hospitalization costs, and length of hospital stay were higher in the TPE group compared to the non-TPE group (p < 0.05, for each). However, there was no difference regarding persistent organ failure and mortality (p > 0.05, for each). The length of hospital stay, average cost, persistent organ failure, and mortality were similar in both groups whose triglyceride level fell below 500mg/dL within 48h and those who did not (p > 0.05, for each). Among patients with persistent organ failure, average cost was higher in the TPE group compared to the non-TPE group (p < 0.05). An independent relation was found between the average cost and persistent organ failure, TPE, length of hospital stay, albumin, and urea values in all patients (p < 0.05, for each). The approach of using TPE for treatment of HTGP was not found to be superior to the conventional treatment. Randomized controlled studies with larger number of patients are needed to gain better understanding of this issue.

Effectiveness and safety of biological therapy in patients with severe asthma in a real clinical practice

To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up. We recruited 129 adult outpatients (29% males) aged 18-81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3-6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab - 9 pts, мepolizumab - 8 pts, benralizumab - 11 pts, dupilumab - 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ. The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma (p<0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%. Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.

Gastric cancer with brain metastasis: from molecular characteristics and treatment.

Gastric cancer is one of the cancers with increasing incidence and ranks fourth globally among the most frequent causes of cancer-related mortality. Early gastric cancer is often asymptomatic or presents with atypical symptoms, and the majority of patients present with advanced disease upon diagnosis. Brain metastases are present in approximately 1% of gastric cancer patients at the time of diagnosis, which significantly contributed to the overall mortality of the disease worldwide. Conventional therapies for patients with brain metastases remain limited and the median overall survival of patients is only 8 months in advanced cases. Recent studies have improved our understanding of the molecular mechanisms underlying gastric cancer brain metastases, and immunotherapy has become an important treatment option in combination with radiotherapy, chemotherapy, targeted therapy and surgery. This review aims to provide insight into the cellular processes involved in gastric cancer brain metastases, discuss diagnostic approaches, evaluate the integration of immune checkpoint inhibitors into treatment and prognosis, and explore the predictive value of biomarkers in immunotherapy.

The effectiveness of therapeutic craft-making activities in treating lower-third forearm fracture: study protocol for a randomized controlled trial

BackgroundOccupational Therapists use craft-making activities as therapeutic interventions to improve physical and psychological functioning of injured people. Despite the therapeutic effects, craft-making is not routinely used in hand rehabilitation as an intervention for patients with upper limb fractures. These patients often experience physical and psychosocial issues; however, without supportive evidence, therapists hesitate to integrate craft-making into upper limb rehabilitation.PurposeThis study aims to determine the effect of a conventional therapy combined with therapeutic craft-making on disability, post-traumatic stress, and physical performance in patients with lower-third forearm fractures.MethodsPriori analysis determined that 38 patients will be needed for this superiority randomized controlled trial to be conducted in a hand and upper limb rehabilitation center. Eligible participants must comprehend English, be diagnosed with lower-third forearm fracture(s) stabilized by open reduction internal fixation, and referred to therapy within 2–4 weeks of surgery. Following the CONSORT guidelines, participants will be randomly assigned to a Control (conventional therapy) group or an Intervention (conventional therapy and craft) group. Twice weekly for 6 weeks, Therapist A will provide both groups with 1-h of conventional therapy while the Intervention group will also receive 15 min of craft-making supervised by the Researcher. The primary outcome of disability will be measured with the Quick-Disabilities of Arm, Shoulder and Hand. The secondary outcome measurements include the Patient-Rated-Wrist-Evaluation; Impact of Event Scale-revised and physical performance, i.e., the Purdue Pegboard Test, AROM, and grip strength. All outcome measures will be obtained by Therapist B prior to the 1st therapy visit and after the 12th visit. Descriptive analysis will be done for the categorical and continuous data and a mixed model ANOVA for analysis of the initial and final assessment scores within and between groups.ResultsThis study is ongoing.DiscussionThe intent of this study is to determine if therapeutic crafts have value as an intervention when used in combination with conventional therapy for patients with lower-third forearm fractures. If the value of crafts is supported, this evidence may reduce hesitancy of therapists to implement craft-making with patients referred to hand therapy after upper limb fracture.ConclusionThis study is ongoing.Trial registrationANZCTR, ACTRN12622000150741. Retrospectively registered on 28 January 2022 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382676&isReview=true..

Effectiveness of Lumbar Stabilization Exercise in Improving Lumbar Spine Endurance by Using Sorenson’s Test and EMG Analysis for People with Chronic Low Back Ache

Background: Strength endurance in lower back region is the most important factor for chronic low - back pain.There are several treatments for strengthening low back muscle. Strength and endurance that have proven benefitin CLBP patients; however, there are very few studies that focus on lumbar stabilization exercises.Purpose: The intention of this study was to improve the strength and endurance more effectively than usualprograms by performing lumbar stabilization exercises.Materials And Methods: This Quasi-Experimental study had 40 participants with persistent LBP, aged 25 to50, divided into lumbar stability (n=20) and lumbar strengthening (n=20) groups. sEMG measured strengthendurance, NPRS scale measured pain, before and after intervention.Results: Lumbar stabilization exercises (Group A) were significantly more effective than static stretching andstrengthening exercises (Group B) in treating persistent low back pain, with p&lt;0.001 in outcome measures.Conclusion: Lumbar stabilization exercises have been demonstrated to be more effective than conventionaltherapies in patients with CLBP.

Survival benefit of resin cartridge extracorporeal blood purification therapy in patients with septic shock.

Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding their effectiveness is lacking. This case-control study aimed to evaluate the 28-day survival benefit of a resin cartridge-based EBP therapy compared to conventional therapies in patients with septic shock. The study sample was collected retrospectively from the medical records of patients admitted to the intensive care unit (ICU) between 2015 and 2020. The study included patients with septic shock aged ≥18 years who had ICU stays >96 h and excluded those lost to follow-up by 28 days or readmitted. First, 28-day survival was compared between EBP patients and 1:1 matched conventionally treated controls. Second, the EBP patients were evaluated for clinical and laboratory improvements within 72 h of EBP therapy. Of 3742 patients, 391 were included in this study, of whom 129 received EBP therapy and had a 28-day survival rate of 44%, compared to 262 matched controls who received conventional therapy alone and had a survival rate of 33% (p = 0.001, log-rank = 0.05, number needed to treat = 8, and odds ratio = 1.7). After receiving EBP therapy for 72 h, improvements were observed in the Sequential Organ Failure Assessment scores (p < 0.05), shock indices (p < 0.05), partial pressure of oxygen in the arterial blood to the fraction of inspiratory oxygen concentration ratios (p < 0.001), vasopressor requirements (p < 0.001), pH (p < 0.05), lactate levels (p < 0.001), and C-reactive protein levels (p < 0.05). The findings suggest that administering resin cartridge-based EBP therapy to patients with septic shock may improve their survival compared to conventional therapies.

ThTP7.4 Role of transanal irrigation in the management of low anterior resection syndrome: an evidence synthesis by meta-analysis

Abstract Objective Low anterior resection syndrome (LARS) may be a debilitating postoperative anorectal dysfunction causing negative impact on the health-related quality of life in patients undergoing low anterior resection for rectal diseases. The objective of this review is to evaluate the role of transanal irrigation (TAI) in patients with LARS. Methods Randomized controlled trials (RCTs) comparing the effectiveness of TAI against baseline conventional therapies in patients with diagnosed LARS were retrieved from the search of standard medical electronic databases and analysis was conducted by using the principles of meta-analysis on the statistical software RevMan version 5.4. Results Three RCTs reported the effectiveness of TAI on 109 patients with LARS. Two RCTs compared TAI against conventional conservative therapies whereas one RCT reported the comparison of TAI versus tibial nerve stimulation. There were 53 patients in the TAI group and 56 patients were in no-TIA group. In the random effects model analysis, TAI was associated with the reduced low anterior resection score [standardised mean difference -2.32, 95%, CI (-3.98, -0.67), Z = 2.75, P=0.006] and lower faecal incontinence score [standardised mean difference -1.62, 95%, CI (-3.06, -0.17), Z = 2.19, P=0.03] compared to other therapies. There was significant heterogeneity (Tau2 = 1.85; Chi2 = 20.78, df = 2; (p &amp;lt; 0.0001; I2 = 90 %) among included studies. Conclusion TAI has shown clinically proven advantage to improve LARS related anorectal dysfunction. However, due to paucity of the randomised trials, and significant clinical as well methodological diversity among included studies, these findings should be taken cautiously.

Effect of Shaker Exercise and Masako Maneuver on Swallowing Function and Quality of Life in Patients with Dysphagia following Stroke: An Interventional Comparative Study

Background: Dysphagia is a condition that affects the normal deglutition leading to difficulty in swallowing food and liquid. It is a common problem in stroke survivors. Dysphagia after stroke can cause various complications, especially aspiration pneumonia, which can be life-threatening. Some rehabilitation methods reduce the severity of swallowing, improve quality of life, reduce the L-tube intubation period, and reduce the hospital stay duration in patients with dysphagia after stroke. The study compares the effect of the Shaker exercise with conventional therapy and the Masako maneuver with conventional therapy on post-stroke dysphagia. Some studies show the individual effectiveness of the shaker exercise and the Masako maneuver in post-stroke patients. Hence the need arises to evaluate the effectiveness of the Masako maneuver and Shaker exercises in post-stroke dysphagia patients. Aim: To study the effects of the Shaker exercise with conventional therapy and Masako maneuver with conventional therapy in patients with dysphagia following stroke. Methodology: convenient sampling was done for the selection of participants. Thirty patients who met the inclusion criteria were recruited from various hospitals in Vadodara. There were 11 men and 19 women among the 30 participants. The patients were divided into two groups. Group 1 received Shaker exercise along with conventional therapy, and Group 2 was received Masako maneuver along with conventional therapy. Baseline data were collected by EAT-10 scale. After 4 weeks, the participants were evaluated again. Result: The data were analyzed using the paired t-test. During the between-group comparison, group 1 (Shaker Group) showed greater improvement on EAT-10 scale than Group 2 (Masako Group). The SPSS version 23 used for data analysis and the p-value is 0.05. Conclusion &amp; Clinical Implication: the present study concluded that Shaker exercise along with conventional therapy showed greater improvement in swallowing function and quality of life in patients with post stroke dysphagia. Shaker exercise obtained better results with regards to quality of life and swallowing function than Masako maneuver with conventional therapy. KEY WORDS: stroke, dysphagia, Shaker Exercise, Masako Maneuver, EAT-10 scale, swallowing, and quality of life.

Evaluation of the efficacy and safety of Suxiao Jiuxin Pill in the treatment of stable angina: A randomized, double-blind, placebo-controlled, multi-center clinical trial

Ethnopharmacological relevanceThe Suxiao Jiuxin Pill (SJP) has been used for treating chronic stable angina (SA) for more than 40 years in China. SJP is composed of two Chinese herbs and has the effect of activating blood and promoting qi, according to traditional Chinese medicine (TCM) theory. Aim of the studyThe study aims to determine the effects of adjunct SJP on conventional therapy in patients with SA which provides a complementary choice and its evidence for clinical medication for treating SA. Materials and methodsParticipants with SA were recruited and randomized 1:1 to either the SJP group or the control group for 24 weeks. Both groups received conventional treatment according to local tertiary hospital protocols, and the participants received additional SJP (composed of Ligusticum wallichii and Borneol) or placebo in treatment and control groups respectively. The primary outcome was the curative efficacy rate at week 4. Secondary outcomes are the curative efficacy rate, the total score of angina pectoris symptoms, CCS Angina Classification improvement, Seattle Angina Questionnaire (SAQ) score, TCM syndrome scores (TCMSS), and the curative efficacy rate of TCMSS. Adverse events and adverse drug reactions were observed and recorded for safety analysis. ResultsA total of 324 participants with SA from 13 hospitals in China were enrolled in this trial. Compared with the control group, the curative efficacy rate of SA, the curative efficacy rate of TCMSS significantly increased, and the total score of angina pectoris symptoms and TCMSS significantly reduced in the SJP group at week 4, 12, and 24, accompanied by the statistically significant improvement in the curative efficacy rate based on CCS grade reduction (all P < 0.05). Furthermore, the SAQ score (physical limitation, angina stability, and treatment satisfaction) was evaluated as the quality of life significantly improved after treatment (P < 0.05). The medication compliance, concomitant medication, and rates of adverse events were similar between the two groups (P > 0.05). ConclusionThe present prospective, multicenter, randomized, double-blind, placebo-controlled, clinical trial confirms that adjunct SJP to conventional treatment increased the curative efficacy and life quality of SA patients with no significant adverse drug reactions during the clinical application. Clinical trial registration(ID, ChiCTR1900021876, URL = http://www.chictr.org.cn/showproj.aspx?proj=34955).

Additional Effects of Medial Wedge Insole Coupled with Conventional Therapy in Patients with Bilateral Lateral Compartmental Knee Osteoarthritis: A Clinical Trial Study

Background: Osteoarthritis (OA) is the most prevalent disorder of the locomotor system, and involves the largeweight bearing joints of the lower limb such as knee joint. The progression of OA knee is typically affected bymechanical stress created by varus and valgus malalignment, which in turn overloads the medial and lateralcompartments, respectively. The rationale of wedged insoles is to transfer the load from the affected kneecompartment to the joint contralateral compartment. So, the aim of the study was to compare the effectiveness ofconventional therapy plus medial wedge insole in the footwear and conventional therapy alone on pain, physicalfunction and alignment in lateral compartmental knee osteoarthritic patients.Method: Study included 30 patients with bilateral lateral compartmental knee OA, aged 40-60 years anddivided into 2 groups: Group A received conventional therapy plus medial wedge insole and Group B receivedconventional therapy alone for 6 weeks (3 sets of 10 repetitions daily). Inter-group analysis by unpaired t-testshowed statistically significant improvement in Lequesne index score and tibiofemoral angle (P value ≤ 0.05).Conclusion: In patients with lateral compartmental knee OA, conventional therapy plus medial wedge insole weremore effective than conventional therapy alone in reducing pain, improving functional disability and tibiofemoralangle.

BRUIN CLL-321: A phase 3 open-label, randomized study of pirtobrutinib versus investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab in BTK inhibitor pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma.

TPS7582 Background: Covalent (c) Bruton tyrosine kinase inhibitors (BTKi) have transformed the management of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but these agents are not curative. cBTKi share pharmacologic liabilities such as low oral bioavailability and a short half-life that may lead to suboptimal BTK target coverage, especially in rapidly proliferating tumors with high BTK protein turnover, which can manifest as acquired resistance to cBTKi. Novel therapeutic agents addressing both intolerance and resistance while also improving efficacy are needed. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, inhibits both wildtype and C481-mutant BTK with equal low nM potency, and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval, regardless of intrinsic rate of BTK turnover. In the phase 1/2 BRUIN study, pirtobrutinib demonstrated promising durable overall response rates (ORR) and was well tolerated in patients with CLL/SLL regardless of prior therapy (including cBTKi), number of prior lines of therapy, BTK C481 mutation status, or reason for prior cBTKi discontinuation. The objective of this study is to determine whether pirtobrutinib is superior to conventional therapy in patients previously treated with cBTKi. Methods: BRUIN CLL-321 (NCT04666038) is a randomized, open-label, global phase 3 study comparing pirtobrutinib monotherapy (200mg QD) to investigator’s choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR). Approximately 250 CLL/SLL patients previously treated with a covalent BTKi will be randomized 1:1 and stratified by both del(17p) status (yes/no) and prior venetoclax treatment (yes/no). Patients on the control arm can crossover to pirtobrutinib monotherapy if they experience progressive disease per iwCLL 2018 as confirmed by an independent review committee (IRC). Adults with CLL/SLL who require therapy per iwCLL 2018 criteria and have received prior covalent BTKi are eligible. An unlimited number of prior lines of therapy, including venetoclax, are allowed. Key exclusion criteria include CNS involvement by CLL/SLL, a major bleeding event on prior cBTKi, Richter’s Transformation at any time, prior therapy with a non-covalent BTKi, or a history of either allogeneic or autologous stem cell transplant (SCT), or chimeric antigen receptor (CAR) T-cell therapy within 60 days prior to randomization. The primary end point is progression-free survival (PFS) per iwCLL 2018 criteria as assessed by IRC. Secondary endpoints include investigator assessed PFS, overall survival, ORR, duration of response, safety and tolerability, and patient reported outcomes. Enrollment for this study is ongoing. Clinical trial information: NCT04666038 .

Cost-Effectiveness of Bariatric Surgery in Tunisia.

Obesity is a growing global issue with evidence linking it to an increase in loss of disease-free years, reduced quality of life, increased mortality, and additional economic burden. This study sought to establish the cost-effectiveness of gastric bypass and sleeve gastrectomy, compared to conventional therapy in patients with obesity, from a Tunisian healthcare payor perspective. A Markov model compared lifetime costs and outcomes of bariatric surgery with conventional treatment among patients with body mass index (BMI) ≥ 40 kg/m2, BMI ≥ 35 kg/m2 with obesity-related co-morbidities (Group 1), or BMI ≥ 35 kg/m2 with type 2 diabetes mellitus (T2DM) (Group 2). Inputs were sourced from the Tunisian Health Examination Survey, local clinician data and literature sources. Health states were associated with different cost and utility decrements. Changes in body mass index, systolic blood pressure, lipid ratio and diabetes remission rates were modelled on a yearly basis. The incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs) and net monetary benefit (NMB) were key outcomes. Sensitivity and scenario analyses were performed to test the model's robustness. The model showed that the benefits of bariatric surgery were favorable compared to conventional treatment, with an ICER of 1844 TND/QALY in Group 1 patients and 2413 TND/QALY in Group 2 patients. Bariatric surgery resulted in a QALY gain of 3.26 per patient in Group 1 and a gain of 1.77 per patient in Group 2. At a willingness to pay threshold of 31,379 TND/QALY, the incremental NMB was 96,251 TND and 51,123 TND for Group 1 and Group 2, respectively. From the Tunisian healthcare payor perspective, bariatric surgery is cost-effective for patients with obesity and those with T2DM and obesity-related comorbidities. These findings may have impact on future decision-making on funding and reimbursement of bariatric surgery in Tunisia.

Effects of Upper Limb Robot-Assisted Rehabilitation Compared with Conventional Therapy in Patients with Stroke: Preliminary Results on a Daily Task Assessed Using Motion Analysis

Robotic rehabilitation of the upper limb has demonstrated promising results in terms of the improvement of arm function in post-stroke patients. The current literature suggests that robot-assisted therapy (RAT) is comparable to traditional approaches when clinical scales are used as outcome measures. Instead, the effects of RAT on the capacity to execute a daily life task with the affected upper limb are unknown, as measured using kinematic indices. Through kinematic analysis of a drinking task, we examined the improvement in upper limb performance between patients following a robotic or conventional 30-session rehabilitation intervention. In particular, we analyzed data from nineteen patients with subacute stroke (less than six months following stroke), nine of whom treated with a set of four robotic and sensor-based devices and ten with a traditional approach. According to our findings, the patients increased their movement efficiency and smoothness regardless of the rehabilitative approach. After the treatment (either robotic or conventional), no differences were found in terms of movement accuracy, planning, speed, or spatial posture. This research seems to demonstrate that the two investigated approaches have a comparable impact and may give insight into the design of rehabilitation therapy.

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer.

The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.

Nuclear receptor modulators inhibit osteosarcoma cell proliferation and tumour growth by regulating the mTOR signaling pathway

Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Chemoresistance leads to poor responses to conventional therapy in patients with osteosarcoma. The discovery of novel effective therapeutic targets and drugs is still the main focus of osteosarcoma research. Nuclear receptors (NRs) have shown substantial promise as novel therapeutic targets for various cancers. In the present study, we performed a drug screen using 29 chemicals that specifically target 17 NRs in several different human osteosarcoma and osteoblast cell lines. The retinoic acid receptor beta (RARb) antagonist LE135, peroxisome proliferator activated receptor gamma (PPARg) antagonist T0070907, liver X receptor (LXR) agonist T0901317 and Rev-Erba agonist SR9011 significantly inhibited the proliferation of malignant osteosarcoma cells (U2OS, HOS-MNNG and Saos-2 cells) but did not inhibit the growth of normal osteoblasts. The effects of these NR modulators on osteosarcoma cells occurred in a dose-dependent manner and were not observed in NR-knockout osteosarcoma cells. These NR modulators also significantly inhibited osteosarcoma growth in vivo and enhanced the antitumour effect of doxorubicin (DOX). Transcriptomic and immunoblotting results showed that these NR modulators may inhibit the growth of osteosarcoma cells by regulating the PI3K/AKT/mTOR and ERK/mTOR pathways. DDIT4, which blocks mTOR activation, was identified as one of the common downstream target genes of these NRs. DDIT4 knockout significantly attenuated the inhibitory effects of these NR modulators on osteosarcoma cell growth. Together, our results revealed that modulators of RARb, PPARg, LXRs and Rev-Erba inhibit osteosarcoma growth both in vitro and in vivo through the mTOR signaling pathway, suggesting that treatment with these NR modulators is a novel potential therapeutic strategy.

Comparison of Physical Activity Training Using Augmented Reality and Conventional Therapy on Physical Performance following a Total Knee Replacement: A Randomized Controlled Trial

There is growing interest in using augmented reality (AR)-based training for rehabilitation programs, while it remains unclear whether physical exercises using AR can be more effective than conventional therapy for patients with total knee replacement (TKR). This study, therefore, aimed to compare the effects of AR-based training to conventional therapist-based training on the physical performance of early-stage rehabilitation in patients after a TKR. It was a double-blind randomized controlled trial with repeated measures (pre-surgery, post-surgery, and post-intervention). Twenty-four participants with TKR were allocated to either AR-based training or therapist-based training. Both groups received a training program for 30 min per session, three sessions per week, for four weeks. The outcome measures included the range of motion (ROM), muscle strength, balance, and perceived pain. The results showed significant improvements in all measured outcomes in both groups (p &lt; 0.05). However, despite our hypothesis that ART would be more effective than the TKR, no significant differences in all the outcomes were found between the two groups. While there was some evidence showing that performing physical exercises using AR could improve physical performance in patients with TKR after surgery, a comparison with conventional therapy did not show superior effectiveness. However, AR could be used to provide real-time feedback and motivation appropriate for home-training programs.

A Prospective Study of Short-Term Chemotherapy Bridging Allogeneic-SCT in High Risk Peripheral T-Cell Lymphoma

Background: Results of conventional therapy in patients with peripheral T-cell lymphoma (PTCL) are dismal. Current guidelines recommend consolidation with autoSCT after 6 course of induction for most PTCL patients, but one third of new diagnosed patients progressed before autoSCT. Allogeneic hematopoietic stem cell transplantation (alloSCT) can cure relapsed/refractory patients, even those failured to HDT/ASCT. We hypothesized that AlloSCT as first-line consolidation post short course of induction could improve outcome in high-risk PTCL patients. Patients and Methods: A prospective study was conducted in high-risk PTCL patients (except ALK+ ALCL, and stage 1 with aaIPI 0) who were scheduled to undergo upfront allo-SCT after 3 x CHOEP(or -like) induction chemotherapy (registered in Clinical Trials, NCT03672084). Matched sibling donor(MSD) was the first choice, an unrelated donor or haploidentical family donor(Haplo-donor) search was performed in patients without MSD. From Jan.2018 to June 2022, 23 newly diagnosed patients enrolled, 8 PTCL-NOS, 1 ALK-negative ALCL, 6 AITL and 9 HSTL. After 1st line induction, 12 proceeded upfront alloSCT(10 in CR,1 in PR and 1 in SD), 9 of 11 with progressive disease received transplant after 2nd line chemotherapy (salvage alloSCT), the other 2 (diagnosed with PTCL-NOS) did not undergo transplantation because of PD. All patients received myeloablative conditioning and antithymocyte globulin was administered for Haplo-SCT (with 2.5mg/kg daily on days -5 to -2). All patients received cyclosporineA, MMF and short-term MTX as GVHD prophylaxis (Patients characters were in Table 1). Results: Untill July 30,2022，we had an interim results with the median follow up of 367(38-1237)d. For all transplanted patients, the median age was 38(4-63) years old, five had a MSD and the other 16 had a haplo-donor. Before alloSCT, 11 patients (52.4%) were in CR and 6 (28.6%) in PR, 1 (4.7%) in SD, and 3(14.3%) in PD. All but one patients had CR post alloSCT, 1 in PR received donor lymphocyte infusion(DLI) on D30 then had got CR on D60. One patient received a second alloSCT from another haplo-donor because of secondary graft failure. Acute GVHD of grade II-IV occurred in 9 of 21 patients (42.9%) (6 of grade III-IV). Thirteen of 20 (65%) evaluable patients developed chronic GVHD, which was extensive in 4 cases(20%). Four patients, all diagnosed with HSTL, experienced with post-SCT relapse on day 60,75, 180 and 455 respectively. Two had response to salvage chemotherapy with DLI, and stay in CR at last follow-up. Three patients died, 2 of lymphoma and 1 of pneumonia on day 280. The estimated 1- and 2-year event-free survival (EFS) in all transplanted cases were 78% and 67%, and those of overall survival(OS) were all 83%. The D100 and 1-y toxicity-related mortality(TRM) were 0% and 6.4%, respectively. There were no differences in PFS and OS between upfront and salvage alloSCT. The patients who diagnosed with HSTL had a significant poor PFS compared to other types of PTCL, with the 1y PFS of 56% vs 92% (p=.017), and had a comparable 1-y OS ,78% vs 92% (p=.337). This result may due to the higher relapsed rate of HSTL (44% vs 0%, p=0.003). So we involved a prophylaxis DLI in HSTL patients recently. Conclusions: Upfront AlloSCT in high-risk PTCLs was feasible with low TRM, and it could provide long-term disease control. And the strategy of haplo-donor SCT can bring more patients to AlloSCT. However, half of patients had progressed disease after 1st line induction, due to the strong anti-lymphoma effect of allograft, salvage alloSCT had been shown increased response rate in this group of refractory patients. The treatment strategy of short-term induction followed by alloSCT may improve the outcome for high-risk PTCL patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal