Previous Treatment Failure Research Articles

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates.

Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

ПРИЧИНЫ ФОРМИРОВАНИЯ БОЛЬШИХ ОСТАТОЧНЫХ ПОСТТУБЕРКУЛЕЗНЫХ ИЗМЕНЕНИЙ У ДЕТЕЙ И ПОДРОСТКОВ НА СОВРЕМЕННОМ ЭТАПЕ

Objective: to identify factors contributing to the development of large residual changes in children of different age groups with pulmonary TB. Materials and methods. A retrospective comparative nonrandomized study included 455 patients aged 2–17 years admitted to hospital of the Central TB Research Institute. The patients were divided into 3 age groups: group 1 – early age children, group 2 – children of preschool age or young schoolchildren, and group 3 – prepubertal children and adolescents. Each group was divided into two subgroups based on treatment outcomes: subgroup a – patients with large residual changes and subgroup b – children with small residual changes after pulmonary TB. The influence of predictors on the volume of residual changes was assessed based on odds ratio (OR) in subgroups a and b in different age groups. Results. In group 1 the most significant predictors of large residual changes after pulmonary TB were late detection of TB, lack of contact observation and continuous exposure to TB (OR = 14.9, 6.2 and 5.8 respectively); in group 2 – late detection of TB, residence in the area with high prevalence of TB, and previous TB treatment failure (OR = 47.6, 5.8 and 5.6 respectively); in group 3 – concomitant diseases, previous TB treatment failure (OR = 8.4 and 5.8 respectively), residence in the area with high prevalence of TB, and late detection of TB (OR = 4.7 and 4.6 respectively). Conclusions. 1. The main factors influencing the volume of post-tuberculosis residual changes in all age subgroups were time of detection and treatment effectiveness. 2. Less significant predictors influencing residual changes were: lack of contact observation and duration of exposure to TB, concomitant diseases, lack of BCG vaccination, residence with a sociopathic family in a high burden territory or rural area. 3. Defective preventive examinations resulted in both large and small residual changes and contributed to untimely detection, but were not determinant factors of the development of large post-tuberculosis residual changes. 4. Highly informative diagnostic methods (intradermal testing with RTA and chest CT) result in early detection of TB only in cases of timely application.

Migraine Preventive Treatment Failure: A Cross-Sectional Study in a Tertiary Center in Brazil

BackgroundIn Brazil, there is a scarcity of evidence on migraine burden in patients who have experienced previous preventive treatment failure (PPTF). ObjectiveTo evaluate the associations between ≥ 3 PPTF and clinical, psychiatric, and medical history data.MethodsIn a retrospective, cross-sectional study, the medical records of migraine patients who first visited a tertiary specialized clinic were examined. We selected adults of both sexes aged ≥ 18 who attended their first appointment between March and July 2017. Ordinal logistic regression models estimated the associations between number of PPTF (no previous treatment, 1 PPTF, 2, and ≥ 3 PPTF) and chronic migraine, the number of diagnosis exams performed, abortive drugs classes used, and non-pharmacological treatments tried (all categorized as none, 1- 3, and ≥ 4), and severe depression (PHQ-9 ≥ 15) and anxiety (GAD-7 ≥ 15), adjusted for sex, age, and years with disease.ResultsData from 440 patients (72.1 % female) with a mean (SD) age of 37.3 (13.0) years were analyzed. The frequency of no previous treatment was 37.7 % (166/440), while 31.8 % (140/440) showed ≥ 3 PPTF. In patients with ≥ 3 PPTF, 35.7 % (50/140) had episodic, and 64.3 % (90/140) had chronic migraine. Compared to no previous treatment, patients with ≥ 3 PPTF showed higher odds (95 % confidence interval) for chronic migraine [2.10 (1.47, 2.98)], ≥ 4 diagnosis exams [6.59 (3.38, 12.84)], ≥ 4 abortive drug classes [16.03 (9.53, 26.94)], ≥ 4 non-pharmacological treatments [5.91 (3.07,11.35)], and severe depression [1.75 (1.07, 2.88)] and anxiety [1.73 (1.05, 2.85)]. ConclusionPatients first visiting a headache specialist had a high frequency of non-response treatment associated with higher migraine burden in terms of chronification, psychiatric comorbidity, acute medication and non-pharmacological treatment inefficacy, and unnecessary exams.

Success of Helicobacter pylori Guideline-based Treatment of Newly Diagnosed and Previously Treated Patients During 2007-2021 in Edmonton, Alberta.

Updated 2016 Helicobacter pylori consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days. This was a retrospective cohort study to describe and compare the efficacy of anti-Helicobacter treatment regimens over the periods 2007-2015 and 2016-2021 as well as antibiotic resistance. A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed H. pylori treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients. H. pylori-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016-2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) (P < 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7-26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016-2021 and sequential therapy in 2007-2015 (83% [66/80]) (P = 0.535, RD 4%, 95% CI -8.5-16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016-2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007-2015 to 2016-2021 (28% [13/46] to 61% [35/57], P < 0.05, RD 33%, 95% CI 11.6-54.4%). Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures H. pylori in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50-57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in H. pylori is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.

Two-Year Follow-up Results of C-CAR066, a Novel Anti-CD20 Chimeric Antigen Receptor Cell Therapy (CAR-T) in Relapsed or Refractory (r/r) Large B-Cell Lymphoma (LBCL) Patients after Failure of CD19 CAR-T Therapy

Background: Disease recurrence or progression represents a significant challenge in r/r LBCL treated with CAR-T. In a large analysis of r/r LBCL pts who receive further therapy after CD19 CAR-T treatment failure, the overall response rate (ORR) is 39% (CR 20%; PR 19%) and the median post-treatment-OS and post-treatment-EFS are 8.5 months and 1.9 months respectively. C-CAR066 is a novel 2nd generation CAR-T therapy targeting CD20 antigen. We previously reported that C-CAR066 had shown a favorable safety profile and promising efficacy in pts with r/r LBCL following failure to CD19 CAR-T therapy. At a median follow-up of 4.2 months, the ORR was 100%, with 70.0% (7/10) achieving complete response (CR) (Liang et al. ASCO 2021. #2508). Here we present the updated results to include more pts (n=14) and a longer follow-up period. Methods: This first-in-human (FIH) study is an open-label, dose-finding, phase 1 investigator-initiated trial (IIT) to determine the safety and efficacy of C-CAR066 in r/r LBCL (including DLBCL, tFL and PMBCL) after previous CD19 CAR T-cell treatment failure. This study was conducted at two clinical sites in China. C-CAR066 was administered at doses of 2.0x10 6 CAR-T cells/kg and 3.0x10 6 CAR-T cells/kg after a 3-day conditioning chemotherapy. The primary objective was to assess the safety and tolerability of C-CAR066. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT 2019 criteria. The secondary objectives were to evaluate C-CAR066 efficacy and pharmacokinetics (PK). Response was assessed per Lugano 2014 criteria. The study follow-up period was 2 years. Results: Between Oct 16, 2019, and Aug 17, 2021, a total of 14 pts received C-CAR066. 11 pts (78.6%) were DLBCL, 3 pts (21.4%) were tFL. The median age was 54.5 years (range, 37-67) with 2 pts (14.3%) ≥65 years. 12 pts (85.7%) were in Ann Arbor Stage III/IV. 7 pts (50.0%) were double-expressor lymphoma. Median number of prior lines of therapy was 5 (range, 2-7). All pts had prior CAR-T therapy, which included CD19 CAR-T (12 pts), CD19/CD22 bispecific CAR-T (1 pts), and CD19/CD79b bispecific CAR-T (1 pts). 12 pts responded to the prior CAR-T therapy (2 CR and 10 PR), and the median duration of response (DOR) was 1.5 months. Median time from prior CAR-T to C-CAR066 infusion were 5.45 months (range, 3.4-14.2). 7 pts (50.0%) received bridging therapy. As of Jan 15, 2023, 12/14 pts (85.7%) experienced CRS, all were grade 1/2, except for 1 pt dosed at 3.0×10 6 CAR- T cells/kg experienced a grade ≥3 CRS. This pt recovered after receiving corticosteroids and tocilizumab. The median time to CRS onset was 5.5 days (range, 2-15), and the median time to resolution was 4.0 days (range, 1-15). No pts experienced ICANS. Grade ≥3 neutropenia, anemia, thrombocytopenia, and infection were reported in 92.9%, 50.0%, 21.4% and 14.3% of pts, respectively. No new safety signals were observed in this updated 2-year follow-up. Investigator assessed ORR was 92.9%, with 57.1% CR. Median time to first response and CR were 1.0 month (range, 0.9-2.8) and 2.5 month (range, 1.0-2.8), respectively. With the median follow-up of 19.5 months, median PFS and DOR were 9.4 months and 8.3 months, respectively. 5 pts remained in CR 12 months after infusion, and 4 of them remained in CR after 24 months. 6 deaths occurred due to progressive disease. Median post-treatment-OS had not been reached at 24 months. 13 of 14 pts had assessable PK and pharmacodynamic data (one pt dropped out before day 28). The median T max was 11 days (range, 10-23), the median C max was 398,996 copies/µg gDNA (range, 51,667-1,286,932), and the median AUC 0-28day of 4,437,474 copies/µg∙day (range, 431,534-17,842,217), the median T last was 59 days (21~571). We have observed that C-CAR066 can effectively expand and eliminate CD19+/CD20+ B cells in patients. The median time to B cell depletion was 5.5 days (range, 4-11). B cell recovery was observed in 6 (46.2%) pts from 53 to 366 days after the C-CAR066 infusion, 3 of them remained in CR by the data cutoff date. Conclusions: Longer term follow-up demonstrated that C-CAR066 can produce a deep and durable response with a favorable safety profile in pts with r/r LBCL who failed prior CD19 CAR-T therapy.

Outcome of diode laser vaporization for high risk patients with ‎benign prostatic hyperplasia.

Objective: To determine the outcome of laser vaporization of prostate using diode at 980/1470 nm for the treatment of BPH among high risk patients. Study Design: Longitudinal Observational Study. Setting: Shalamar Hospital, Lahore. Period: June 2009 till June 2022. Material &amp; Methods: Total of 500 patients with associated co-morbid illnesses and benign prostate hyperplasia not responding to medical therapy, failed trial without catheter, chronic urinary retention, refusal for TURP were assessed for eligibility to enter the study. Inclusion criteria were patients with refractory urinary retention, chronic urinary retention, failure of previous medical treatment. Exclusion criteria were patients with neurogenic bladder, carcinoma of prostate, carcinoma of bladder, abnormal digital rectal examination, known neurological disorder or history of spinal cord injury also were excluded from study. Results: The patients’ mean age ‎was 68.57 ± 7.98 years, Baseline mean maximum urinary flow rate was 5.57±‎2.44 mL/s, post void residual was 130.91‎±‎24.18 mL, and international prostate symptom score was 26.09 ‎±‎2.40 at preoperative. At 3 months follow-up, Qmax was 23.31±‎8.0, PVR was 22.43±5.21 and IPSS was 7.27‎±‎1.42. On the other hand, mean Qmax was 25.83‎±‎6.84 mL/s, PVR was 18.38‎±‎4.53 mL, and IPSS was 5.29 ±‎0.61 at 6 months follow-up. Conclusion:Treatment of BPH by 980/1470 nm diode laser have effective and safe clinical outcome for high risk patients as we found significant improvements in Qmax, IPSS, and PVR at 3 months and 6 months follow up.

Kognitiv atferdsterapi for spiseforstyrrelser

Background: Few studies have evaluated the effectiveness of enhanced cognitive behaviour therapy (CBT-E) in clinical settings with a transdiagnostic patient population. The current study aimed to evaluate the effectiveness of CBT-E in a specialised outpatient eating disorder clinic in southeastern Norway. Method: The study involved a transdiagnostic sample of 96 patients (age 30.7 (SD = 9.4), 92.7% women) with longstanding eating disorders and previous failed treatment attempts. We used multilevel modelling to examine change in eating disorder pathology from pre-treatment (T1) to post-treatment (T2) and follow-up 25 weeks later (T3). A total of 57 patients had sufficient data at T2 and 35 patients at T3. Results: We found statistically significant reductions in eating disorder pathology from pre- to post-treatment. Of those who completed treatment, 49.1% met criteria for remission at post-treatment. These changes were stable at follow-up. Implications: CBT-E may lead to reductions in eating disorder pathology and should be considered an acceptable form of treatment for adult patients with eating disorders. Keywords: anorexia nervosa, binge eating disorder, bulimia nervosa, cognitive behaviour therapy, eating disorders, effectiveness

Targeting IL-4 and IL-13 Receptors on Eosinophils in CRSwNP Patients: The Clinical Efficacy of Dupilumab.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic respiratory inflammation. 25% of CRSwNP patients relapse after the use of oral glucocorticoids or after surgery and often require several surgeries during their lifetime. In our study we enrolled 14 patients, 11 male and 3 female. The inclusion criteria were: age ≥ 18 years; confirmed diagnosis of chronic rhinosinusitis with severe nasal polyposis; disease severity with NPS Nasal Polyposis Endoscopic Score total score ≥ 5 and/or SNOT-22 ≥ 50; previous treatment failure due to lack of efficacy or discontinuation of systemic corticosteroid therapy and/or non-response or recurrence following surgery. The results presented in this study showed the ability of Dupilumab to improve all the parameters analysed. In particular, statistically significant data were obtained for NPS, SNOT-22, NRS, and IgE in patients exposed to Dupilumab treatment for 24 weeks, highlighting the ability of Dupilumab to produce clinical benefit in CRWwNP patients. In light of these data, the administration of dupilumab every two weeks represents a valid clinical strategy that ENT specialists can adopt for the treatment of adults with inadequately controlled CRSwNP.

P04.01.B MEK INHIBITORS IN PEDIATRIC RECURRENT SYMPTOMATIC UNRESECTABLE LOW-GRADE GLIOMAS HARBORING MAPK ALTERATION: A SINGLE CENTER EXPERIENCE

Abstract BACKGROUND Treatment of inoperable, recurrent, progressive pediatric low-grade gliomas (pLGGs) remains controversial. Recent studies focused on aberrant activation of the mitogen-activated protein kinase (MAPK) pathway, due to gain of function mutations in RAS or BRAF genes or loss or inactivation of NF1. Selumetinib and trametinib, orally bioavailable and selective MEK1/MEK2 inhibitors (MEKi), act on MAPK pathway. In April 2020 the US Food and Drug Administration and in June 2021 the European Medicines Agency approved selumetinib for inoperable plexiform neurofibromas in Neurofibromatosis type 1 (NF1). We evaluated MEKi efficacy and safety in pLLGs harboring MAPK alteration. MATERIAL AND METHODS From July 2021 to February 2023 eight patients (5 females, 3 males, median age 8 years, range 4-18) were admitted to our hospital for symptomatic, recurrent, inoperable pLGGs (location: 3 hypothalamic-optic chiasm region, 2 posterior fossa, 1 temporo-mesial, 1 quadrigeminal plate, 1 diffuse leptomeningeal; MAPK alteration: 3 NF1 inactivation, 4 KIAA1549/BRAF gene fusion, 1 RNF130/BRAF fusion). MEKi were administered (6 selumetinib, 2 trametinib) after disease progression for failure of previous treatments (6 partial resection, 7 multiple chemotherapies, 2 radiotherapy). MRI assessment was performed every 4 months and radiological response was defined in accordance with RAPNO criteria. RESULTS At first evaluation, 3/8 patients (37,5%) showed a partial radiological response (-64,96% mean volume reduction, range 52,61%-77,19%) and 4/8 (50%) stable disease (0-41.67% volume decrease). Disease progression was observed in a patient heavily pretreated for acute leukemia. One patient with leptomeningeal spreading showed progressive disease at second evaluation. Median time to progression has not yet been reached. Six of 8 patients experienced at least one toxicity. The most frequent toxicities reported were mucocutaneus disorders (rash, mucositis, eczema). Three patients presented creatine phosphokinase (CPK) increase (one grade 2 with rapid normalization after therapy discontinuation). All patients on trametinib had to reduce treatment dose (for skin toxicity or increasing blood pressure). CONCLUSION MEKi, selumetinib and trametinib, represent promising strategies in children with recurrent/progressive LGGs harboring MAPK alterations. In our small series, the treatment was effective and well tolerable in patients with localized disease and without other risk factors. The most common toxicities were CPK elevation and rash. Further studies are needed to identify patients who may benefit most from MEKi treatment and to establish whether such treatments are superior to chemotherapy in front line setting for MAPK altered pLGGs.

The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial (RESET BRAIN)

BackgroundWe aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation.MethodsThis was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach.ResultsSixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab.ConclusionErenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped.

Dalbavancin in Bone and Joint Infections: A Systematic Review.

Approved for acute bacterial skin and skin structure infections, dalbavancin (DBV) has gradually acquired over the years a role as an off-label treatment for several infections caused by Gram-positive bacteria even in other anatomical sites. Osteoarticular (OA) infections are one of the most difficult-to-treat infections and, since the absence of recommendations, clinicians use different and heterogenic DBV dosing schedule regimens for the off-label treatment of osteomyelitis, spondylodiscitis, and septic arthritis. Our aim is to systematically review the current literature to describe DBV administration schedules and their outcome in OA infections. According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the use of DBV in OA infections were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. A total of 23 studies and 450 patients were included, prevalently male (144/195, 73.8%) and diabetic (53/163, 32.5%). Overall, 280 (280/388, 72.2%) osteomyelitis, 79 (79/388, 20.4%) spondylodiscitis, and 29 (29/388, 7.5%) septic arthritis were considered. Staphylococcus aureus (164/243, 67.5%) was the most common pathogen isolated. A previous treatment failure (45/96, 46.9%) was the main reason for a switch to a long-acting antibiotic. Most patients were successfully cured with DBV (318/401, 79.3%). A source control was performed in most patients with a favourable outcome (80.4%), while MRSA was prevalently isolated in people with an unfavourable outcome (57%). While a higher percentage of success was found in people who received three doses of DBV 1 week apart (92.3%), a higher rate of treatment failure was recorded in cases of when the DBV cycle was composed of less than two or more than four doses (27.8%). DBV has shown to be effective as a treatment for OA infections. The most favourable outcome was found in patients receiving three doses of DBV and with an adequate surgical management prior to antibiotic treatment. Although a rigorous administration schedule does not exist, DBV is a viable treatment option in the management of OA infections.

Effectiveness and Safety of Eptinezumab in Episodic and Chronic Migraine Headache in the UAE: A Retrospective Study.

Eptinezumab is a humanized IgG1 immunoglobulin monoclonal antibody administered intravenously as a preventative migraine treatment. Previously conducted randomized, double-blind, placebo-controlled trials exhibited significant reductions in monthly migraine frequency among adults experiencing episodic and chronic migraine. The present study seeks to expand upon the current findings and to evaluate eptinezumab's efficacy as a preventative treatment for chronic and episodic migraine patients in the United Arab Emirates. This study is intended to represent the first real-world evidence and will hopefully serve as a valuable complement to the existing literature on the subject. This was a retrospective exploratory study. The participants included within the study were adult (≥18years) patients diagnosed with either episodic or chronic migraine. Patients were categorized according to their history of previous preventative treatment failure. For the final assessment of treatment efficacy, we included only patients with a minimum of 6months of clinical follow-up data. Patients were assessed at baseline for their monthly migraine frequency and assessed again at months 3 and 6. The primary objective was to evaluate the efficacy of eptinezumab in reducing migraine frequency among chronic and episodic migraine patients. A total of 100 participants were identified, of whom 53 completed the study protocol at month 6. Of the total, 40 (75.47%) were female, 46 (86.79%) were Emirati locals, and 16 (30.19%) were pharmaceutically naïve, having never tried any prior preventative therapy. Additionally, 25 (47.17%) patients met the criteria for chronic migraine (CM), whereas the remaining 28 (52.83%) were diagnosed with episodic migraine (EM). The baseline monthly migraine frequency (MMD) was 12.23 (4.97) days across all participants, 15.56 (3.97) for CM patients, and 9.25 (3.76) for EM patients; by month 6, these frequencies reduced to 3.66 (4.21), 4.76 (5.32), and 2.68 (2.61), respectively. Overall, 58.49% of those enrolled experienced>75% reduction in MMD frequency by month 6. Patients enrolled in this trial experienced clinically significant reductions in MMD by month 6. Eptinezumab was well tolerated and with one AE of significance that led to discontinuation from the study.

Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis.

In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties.

Analysing the Impact of Bedaquiline Resistance in Fluoroquinolone-Resistant Clinical Isolates and Investigating the Molecular Interactions of BDQ with the atpE Gene

The progress of the tuberculosis eradication programme is hindered by the global health issue of drug-resistant tuberculosis, which is a significant threat to the population. Resistance-associated mutations vary geographically, so investigate the prevalence of resistance to fluoroquinolone (anti-TB) drugs and its association with resistance-related mutations in clinical isolates of Tamilnadu (north zone) and Puducherry was carried out. And the resultant fluoroquinolone drug-resistant tuberculosis strains will be subjected to the molecular analysis of bedaquiline resistance to study the mutation in the atpE gene. The study includes 430 specimens received at Intermediate Reference Laboratory, State TB training and Demonstration Centre in the Government Hospital for Chest Diseases for Molecular testing between January 2020 and December 2021. Samples were analysed by GenoType MTBDRslV.2 for the molecular detection of mutations in the gyrA and gyrB genes. FQ resistance was observed in 32 samples (7.4%), most of which were naïve and previous treatment failure cases. Twenty-five isolates had mutations in DNA gyrase subunit -A (gyrA), while mutations in gyrB were observed in only 7 isolates. Mutational analysis revealed that the mutations mainly alter codon 94 (replacing aspartic acid with glycine, D94G), and 90 (replacing alanine with valine, A90V). In Isoniazid Resistance, MDR, and treatment failure cases, the resistance to Fluoroquinolones was most commonly associated with the D94G mutation. A molecular stimulation study evaluates the effect of BDQ on atpE gene by docking, using AutoDock 4.2, showing hydrogen, hydrophobic and electrostatic interactions.

Biological treatment for bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects. Therefore, various adjuvant immunosuppressant therapies are used as steroid-sparing agents, with accumulating reports of biological treatments for severely recalcitrant BP. To describe the clinical and immunological features of a series of patients with recalcitrant BP treated with immunobiological therapies. To assess the efficacy and safety of their therapies. Patients receiving biological treatment for BP from two centers were assessed. Here, we described the clinical, immunopathological, and immunofluorescence findings of adult patients with BP and analyzed the clinical response and adverse events associated with various biological therapies. We identified nine eligible patients treated with rituximab (seven), omalizumab (three), or dupilumab (one). The mean age at diagnosis was 60.4 years, the average BP duration before biologic initiation was 1.9 years, and the average previous treatment failure was 2.11 therapies. The mean follow-up period from the first biological treatment to the last visit was 29.3 months. Satisfactory response, defined as clinical improvement, was achieved in 78% (7) of the patients, and total BP clearance was achieved in 55% (5) of the patients at the last follow-up visit. Additional rituximab courses improved the disease outcomes. No adverse events were reported. Efficient and safe novel therapies can be considered in recalcitrant steroid-dependent BP non-responsive to conventional immunosuppressant therapies.

Plain language summary of the MajesTEC-1 study of teclistamab for the treatment of people with relapsed or refractory multiple myeloma.

This is a summary of a phase 1-2 clinical trial called MajesTEC-1. This trial tested the cancer drug teclistamab in people with relapsed or refractory multiple myeloma, a cancer that forms in a certain type of white blood cells known as plasma cells. Most participants who took part in the study had at least 3 prior treatments for multiple myeloma before their cancer came back. A total of 165 participants from 9 countries were included in this study. All participants were given teclistamab once per week and monitored for side effects. Once participants started taking teclistamab, they were checked regularly to monitor if their cancer had no change, improved (responded to treatment), or worsened or spread (known as disease progression). After approximately 14.1months of follow-up (from 2020 to 2021), 63% of participants who were given teclistamab had a decrease in myeloma burden, meaning that they responded to treatment with teclistamab. Participants who responded to teclistamab lived without their myeloma coming back for approximately 18.4months. The most common side effects were infections, cytokine release syndrome, abnormally low white and red blood cell counts (neutropenia, lymphopenia, and anemia), and low platelet cell counts (thrombocytopenia). Approximately 65% of participants experienced serious side effects. Overall, more than half of the participants (63%) in the MajesTEC-1 study responded to treatment with teclistamab despite previous myeloma treatment failures. Clinical Trial Registration: NCT03145181, NCT04557098 (ClinicalTrials.gov).

A Case Series of Large Volume Iii-Degree Hemorrhoidal Disease: A Special Anatomical Condition Requiring Surgical Treatment

Background: Haemorrhoidal Disease (HD) is common and impacts negatively on quality of life with high socio-economic costs. Despite international guidelines aimed to indicate appropriate care in HD, treatment of III-degree HD remains controversial due to the wide range of ambulatory or surgical procedures available. We aimed to analyse treatment options for III-degree HD focusing on special cases characterized by large volume and/or circumferential presentation of intermittent prolapse or recurrence after conservative treatments. Methods: In the period January 2017- December 2018 out of 152 patients treated by excisional haemorrhoidectomy, we collected a case series of 29 patients affected by III-degree symptomatic HD. They showed a very large, single prolapse or circumferential one or failure of previous conservative treatments. Results: 14 (48.2%) patients (median age 45 yrs.) of our series were recurrence of HD following Rubber Band Ligation (RBL) (5pts), Dearterialization (DEART) (5pts), Stapled Haemorrhoidopexy (SH) (4pts). Mean operative time was 35 min. Postoperative severe pain (6.8%) and urinary retention (17.2%) were the main postoperative complications which did not affect the length of stay. All patients showed a good outcome without any complication at follow-up. Conclusion: III-degree HD shows the highest variability in anatomical presentation, and proposed treatment. Thus, the choice of a personalized approach must rely upon objective evaluation of volume of prolapse. Intermittent prolapse, if very large or circumferential, associated or not to large external haemorrhoids, makes a special condition III degree HD, suggesting surgical excision, avoiding conservative approaches.

Resolution of Celiac Artery Compression Syndrome Following Spinal Cord Stimulation: A Case Report

BACKGROUND: Celiac artery compression syndrome is characterized by postprandial epigastric pain, weight loss, and occasional epigastric bruit, and can be difficult to treat because there are no definitive guidelines. We present a case of a 47-year-old man who had postprandial pain, weight loss, and chronic diarrhea for 5 years, which was resolved with spinal cord stimulation (SCS). CASE REPORT: After extensive workup, a diagnosis of celiac artery compression syndrome was confirmed. Due to previous treatment failures, repeat celiac plexus blocks becoming less efficacious, and surgical unsuitability, the patient underwent an SCS trial. They continued having pain relief, so a permanent spinal cord stimulator lead was implanted. CONCLUSION: We highlight complete resolution of celiac artery compression syndrome using SCS. KEY WORDS: Case report, celiac artery compression syndrome, celiac plexus block, median arcuate ligament syndrome, spinal cord stimulation

Use of Medical-Grade Honey to Treat Clinically Infected Heel Pressure Ulcers in High-Risk Patients: A Prospective Case Series.

Management of locally infected heel-pressure ulcers (HPUs) remains challenging, and given the increasing occurrence of infections resistant to antibiotic therapy and patients' unwillingness to surgery, innovative and effective approaches must be considered. Medical-grade honey (MGH) could be an alternative therapeutic approach due to its broad-spectrum antimicrobial activity and healing properties. This study aimed to present the high effectiveness and safety of MGH for the conservative treatment of clinically infected HPUs. In this case series, we have prospectively studied nine patients with local signs of infected HPUs. In all cases, HPUs persisted for more than 4 weeks, and previous treatments with topical antibiotics or antiseptic products were ineffective. All patients were at high-risk to develop HPU infection due to their advanced age (median age of 86 years), several comorbidities, and permanent immobility. All wounds were treated with MGH products (L-Mesitran), leading to infection resolution within 3-4 weeks and complete wound healing without complication. Considering the failure of previous treatments and the chronic nature of the wounds, MGH was an effective treatment. MGH-based products are clinically and cost-effective for treating hard-to-heal pressure ulcers such as HPUs. Thus, MGH can be recommended as an alternative or complementary therapy in wound healing.

Transvesicoscopic Ureteral Reimplantation for Primary Vesicoureteral Reflux in Children: Does Prior Failed Endoscopic Injection Impact Outcome?

Purpose: Transvesicoscopic ureteral reimplantation (TVUR) for vesicoureteral reflux (VUR) is a technically demanding operation. The technical difficulty is further increased by previous failed endoscopic injection, which causes intense fibrosis around the ureter. In this study, we compared primary TVUR with TVUR after previous failed endoscopic injection for VUR. Materials and Methods: The records of all children undergoing TVUR by a single surgeon over a 4-year period were analyzed. The children were divided into group 1 (primary TVUR, n = 50) and group 2 (TVUR after previous failed endoscopic treatment of Dextranomer/Hyaluronic Acid, n = 7). Demographic, clinical, radiologic, operative and follow-up data were compared between the two groups. The results were analyzed by statistical software; Mann-Whitney test and Fisher's exact test were used where appropriate, and P < .05 was considered significant. Results: Both the groups were comparable with respect to age and mean VUR grade. The mean VUR grade was significantly higher in group 1 and mean operative time per ureter was significantly more for group 2 than group 1. The postoperative hospital stay, success of TVUR, and complications were not significantly different between the groups. Conclusions: To our knowledge, this is the first report of its kind. TVUR after previous failed endoscopic injection could be done safely with good success, but with longer operative time than primary TVUR even in expert hands. Hence, previous failed endoscopic injection is not a contraindication to TVUR.