Months Of Treatment Research Articles

Patterns and cofactors of polyfunctional mycobacteria-specific T cell response restoration following 6-month antiretroviral treatment in children living with HIV.

Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children living with HIV (CLHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CLHIV. CD4 and CD8 T cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells (PBMCs) from CLHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya. T cell expression of cytokines and activation induced markers (AIM) were measured following stimulation of PBMCs with a pool of 300 peptides from TB (MTB300) or staphylococcal enterotoxin B (SEB). Among 47 CLHIV of median age 1.5 years, SEB-induced Th1 cytokine+ and AIM+ CD4 cell frequencies increased significantly after 6 months ART. Although MTB300-specific CD4 and CD8 cell frequency did not increase after ART, polyfunctional capacity of MTB300-specific CD4 cells expressing combinations of Th1 cytokines with CD40L increased significantly after ART. Baseline age, immune activation, and effector memory CD4 levels were associated with less restoration of MTB300-specific polyfunctional CD4 cells, whereas CD4% and levels of naïve CD4 cells following ART were associated with improved MTB300-specific polyfunctional capacity. Despite increases in Th1 cytokine production, deficits in mycobacteria-specific CD4 cells persisted 6 months after ART, with higher deficits in older CLHIV with more immunosuppression, higher immune activation, and lower proportion of naïve CD4 cells. These findings may explain persistent TB risk during early ART among CLHIV and identify those at highest risk.

Clinical study of two mandibular advancement devices in the treatment of Obstructive Sleep Apnea: a pilot randomized controlled trial

ObjectiveA preliminary clinical evaluation of the efficacy, comfort, and adverse reactions of two mandibular advancement devices (MADs) in the treatment of Obstructive Sleep Apnea (OSA).MethodsForty patients with mild-to-severe OSA were recruited and randomly divided into two groups. They were treated with Shark-fin or Silensor MAD, respectively. Treatment efficacy was evaluated by home sleep apnea tests, the snoring scale, Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). A comfort scale questionnaire was applied. Cone beam computed tomography (CBCT), cephalometric radiography, and intraoral scanning were made before and after 3-month treatment to detect temporomandibular joints (TMJ), dental and skeletal changes. All data were assessed as normal distributed and analyzed by t test. The significance level was defined as α = 0.05.ResultsThe effective rate, defined as a decrease in Respiratory Event Index (REI) to less than 5 events per hour or a decrease of more than 50%, was 70% in the Shark-fin MAD group and 50% in the Silensor MAD group. REI, lowest oxygen saturation and maximum apnea and hypoventilation time were significantly improved in Shark-fin MAD group (P < 0.01), and the proportion of non-rapid eye movement (REM) sleep stage 3 was higher than before use (P < 0.05), while only REI and lowest oxygen saturation were significantly improved in Silensor MAD group (P < 0.05). The loudness of snoring was significantly decreased after one day using Shark-fin MAD (P < 0.05), and further decreased after one month (P < 0.01). Conversely, Silensor MAD exhibited inferior efficacy in mitigating snoring compared to Shark-fin MAD. Upon wearing the Shark-fin MAD, ESS were significantly improved after one month and three months (P < 0.05), and PSQI improved after three months (P < 0.05). Additionally, the Shark-fin MAD group had a significantly better comfort score compared to the Silensor MAD group (P < 0.05). There was no significant difference in TMJ, dental and skeletal structures in the two groups before and after treatment (P > 0.05).ConclusionBoth two MADs were effective in reducing REI and increasing lowest oxygen saturation on OSA patients, and Shark-fin MAD has better improvement effect and faster onset of action. In addition, Shark-fin MAD was superior to Silensor MAD in improving snoring loudness, daytime sleepiness, sleep quality and wearing comfort. There were no significant dental or skeletal changes, and no alterations in occlusion or temporomandibular joint function in the short term.Trial registrationClinical Trials.gov Registration ID ChiCTR2400086628. Registered 08/07/ 2024-Retrospectively registered, https://register.clinicaltrials.gov.

Risk Factors and Postoperative Outcomes in Pouchitis Following Restorative Proctocolectomy: An 18-Year Single-Center Study

Background/Objectives: Restorative proctocolectomy with ileo-anal pouch anastomosis (IPAA) remains the preferred surgical treatment for ulcerative colitis (UC). However, complications like pouchitis can occur. This study aimed to describe patients who underwent IPAA for inflammatory bowel disease (IBD) at Padua Hospital from 2005 to 2023 and identify risk factors for pouchitis. Secondary objectives included evaluating the effectiveness of biological therapy in chronic antibiotic-refractory pouchitis (CARP), Crohn’s disease of the pouch (CDP), and Crohn’s-like inflammation of the pouch (CDLPI), and assessing risk factors for pouch failure. Methods: This retrospective, observational study included 109 patients whose data were collected from medical records. Univariate logistic regression was used to analyze associations between preoperative and postoperative factors and outcomes such as acute pouchitis and pouch failure. The effectiveness of biological therapy was assessed by measuring changes in the Pouchitis Disease Activity Index (PDAI) and the Modified Pouchitis Disease Activity Index (mPDAI) over a 12-month treatment period. Results: Univariate logistic regression revealed significant associations between preoperative extraintestinal manifestations (OR 3.569, 95% CI 1.240–10.720), previous diagnosis of Crohn’s disease (OR 10.675, 95% CI 1.265–90.089), and transmural inflammation at cross-sectional imaging before surgery (OR 3.453, 95% CI 1.193–9.991) with an acute pouchitis risk. Pouch failure was significantly associated with a previous diagnosis of Crohn’s disease (OR 9.500, 95% CI 1.821–49.571) and post-surgical fistulas (OR 41.597, 95% CI 4.022–430.172). Biological therapy led to a significant reduction in the PDAI score in patients with CARP, decreasing from a median of 10 to 4 (p = 0.006). Similarly, in patients with CDP or CDLPI, the mPDAI score was significantly reduced from a median of 9 to 1 (p = 0.034), with remission achieved in 5/6 (83.3%) of these patients. Conclusions: This study provides valuable insights into the management of IPAA patients and highlights the importance of early identification and treatment of risk factors for pouchitis and failure. Biological therapy demonstrated significant effectiveness in reducing disease activity in patients with CARP, CDP, and CDLPI, suggesting its role as a crucial component in managing these complications.

Therapeutic Efficacy of Tirofiban Combined With Thrombus Aspiration and Stent Thrombectomy in the Treatment of Large Vessel Occlusion Ischemic Stroke.

This research aimed to ascertain the effects of tirofiban combined with thrombus aspiration and stent thrombectomy on large vessel occlusion ischemic stroke (LVO-IS). Sixty patients with acute ischemic stroke (AIS) caused by LVO were randomized into the control group and the intervention group (n=30). Patients in the control group received thrombus aspiration combined with stent thrombectomy, while those in the intervention group were treated with tirofiban combined with thrombus aspiration and stent thrombectomy. General data, perioperative-related indicators, cerebral blood flow perfusion, coagulation function indicators, and neurological function indicators were collected, and the prognosis was observed after 3-month treatment. A comparison of symptomatic cerebral hemorrhage rate and hospital mortality rate between the 2 groups displayed no significant difference (P>0.05). The rate of revascularization in the intervention group (90.00%) was higher versus the control group (66.67%). After treatment, the mean blood flow and cerebral blood volume of the intervention group were higher and the time to peak cerebral blood flow was less versus the control group. The prothrombin time, activated partial thromboplastin time, and prothrombinogen time of the intervention group were higher, and fibrinogen was lower versus the control group. A lower National Institutes of Health Stroke Scale score was observed in the intervention group versus the control group. Tirofiban combined with thrombus aspiration and stent thrombectomy has good efficacy in LVO-IS patients.

Relationship among ultrasound features, pus Mycobacterium tuberculosis load, and efficacy of antituberculosis drugs in patients with necrotizing tuberculous lymphadenitis

For patients with necrotizing cervical tuberculous lymphadenitis (CTL) who have formed abscesses and are unwilling to undergo surgery, early and accurate assessment of drug therapy should be performed to guide subsequent clinical adjustments. This study investigated 22 patients with necrotizing CTL who underwent chemotherapy at our hospital from February 2020 to December 2022. They were diagnosed based on the positive results of pathogen detection methods (acid-fast bacillus smear, mycobacteria culture, Gene X-pert, and next-generation sequencing). Based on the 6-month treatment outcomes, the relationship among prechemotherapy ultrasound features, pus Mycobacterium tuberculosis (MTB) load, and treatment efficacy was assessed. In this study, the maximum lymph node (LN) area, maximum necrotic area, and pus MTB load in patients with necrotizing CTL were associated with poor prognosis and showed significant differences between the effective and ineffective groups (P < 0.05). However, no statistical difference was observed in the maximum longitudinal diameter, short diameter, and necrosis rate between the two groups (P > 0.05). The maximum necrotic area of the LNs was not associated with the pus MTB load. Furthermore, maximum LN area, maximum necrotic area, and pus bacterial load may be potential radiological markers for predicting the therapeutic response of CTL.

Demographic and clinical characteristics associated with utilization of alcohol use disorder treatment in a multicenter study of patients with alcohol-associated cirrhosis.

Alcohol use disorder (AUD) treatment can help improve clinical outcomes among patients with alcohol-associated cirrhosis but is underutilized. Among socioeconomically disadvantaged patients with alcohol-associated cirrhosis, we examined rates of lifetime and past 12-month AUD treatment utilization and associated demographic and clinical characteristics. Racial/ethnically diverse patients with alcohol-associated cirrhosis who had at least one hepatology clinic visit in the prior 6 months were recruited from three Northern California medical centers serving veterans and safety-net populations. Participants self-reported their AUD treatment utilization, liver disease quality of life (LDQoL), history and current symptoms of anxiety and depression, and problematic drinking as measured by the Alcohol Use Disorders Identification Test (AUDIT). Clinical measures including liver disease severity were captured from medical records. Among 196 participants, the majority were male (88%) with a mean age of 62 years. Two-thirds of participants (67%) reported ever utilizing AUD treatment and 32% reported utilizing AUD treatment in the past 12 months. Compared with those who did not utilize AUD treatment, participants who utilized lifetime or past 12-month AUD treatment were younger, had lower LDQoL scores, and had higher scores on current symptoms of anxiety, depression, and problematic drinking. In multivariable analyses, the odds of ever utilizing pharmacological treatment alone or both behavioral and pharmacological treatment (vs. none) were lower with older age or higher LDQoL, and higher among those with a history of anxiety/depressive disorder. For past 12-month treatment utilization, odds were lower with older age, and higher among those with current clinically significant anxiety/depression or problematic drinking. Patients with alcohol-associated cirrhosis who were younger or had anxiety/depression and problematic drinking were more likely to utilize AUD treatment. To improve AUD treatment utilization, targeted outreach to patients less likely to receive care and the provision of integrated ALD and AUD treatment is warranted.

Evidence for therapeutic use of cannabidiol for nail-patella syndrome-induced pain in a real-world pilot study

Nail-patella syndrome (NPS) is a rare genetic disease characterized by dysplastic nails, patella abnormalities, skeletal malformation, and chronic pain. Although chronic pain in NPS is mainly due to bone and musculoskeletal symptoms, it can also result from neurological dysfunction. Conventional analgesics are often insufficient to relieve NPS-associated chronic pain. Cannabinoids, which act on the serotonergic and/or noradrenergic pain systems, may therefore represent valuable non-psychoactive alternatives for managing pain in these patients. The effectiveness and safety of synthetic cannabidiol (CBD) for the management of NPS-associated pain was assessed using real-world data from a pilot cohort of patients with NPS who received a 3-month treatment with oral CBD. The treatment (median dose of 900 mg/day) was associated with a significant reduction in pain intensity (mean score of 7.04 ± 0.24 at initiation versus 4.04 ± 0.38 at 3 months, N = 28, p < 0.0001), which correlated with changes in the peripheral concentration of noradrenaline (r = 0.705, 95% CI [0.44–0.86], p < 0.0001). Health-related quality of life and other NPS-associated symptoms also improved in most patients. CBD treatment was well tolerated and no elevations in liver enzyme levels were reported. Synthetic CBD therefore appears to be a safe and effective treatment option for managing NPS-associated chronic pain.

Improvement of biological and physicochemical quality of agricultural soil after three years of ultra-high dilutions treatment

Soil health is crucial for healthy crops, but pesticides, fertilizers, fungicides, and soil disinfectants can harm beneficial organisms and increase harmful ones. Agricultural practices can also damage soil, disrupting nutrient release and absorption. An economical, side-effect-free solution for soil revitalization is needed [1]. Ultra-high diluted supplements are now used for plant treatment, offering a cost-effective and easy method often added to water. This study examines the effects of ultra-high diluted supplements on soil detoxification and restoration over three years. It measured soil respiration, water absorption, residual toxins, active nitrogen, heavy metals, rheological characteristics, and bacterial diversity [2]. This study investigates the impact of ultra-high diluted supplements on detoxifying and restoring soil's biological and physicochemical characteristics after three years of treatment. For this soil respiration, water absorption, elemental and toxins contents, rheological and bacterial diversity stadied. Treatmet starts by two 6-month detox treatments with 200C sulfur and 30C petroleum. The soil was then irrigated toxin-free for 6 months and recovered for two 4-month periods with Carbo Vegetabilis 30C. After a 4-month rest, a 2-month rotation with silica 200C and calcarea carbonica 30C was applied, followed by another 4-month rest. The final treatment involved three courses of Sulfur 200C, Berberis 6C, and Carbo Vegetabilis 30C over 6 months. The soil was irrigated and rested for the last 4 months, then sampled for new characteristics. Results showed increased essential elements and decreased toxic elements after three years. Soil microbial population decreased by 2 units, gas exchange improved by 6 units, and soil pH became more acidic by one unit. Beneficial bacteria for plant growth, metabolism, fertility, and health were present.

Efficacy and safety profile of 2nd line Anti TB drugs in DRTB patients in a tertiary care hospital of South Punjab.

The objective of the study was to assess the efficacy and safety profile of 2nd line Anti TB drugs in DR TB patients in a tertiary care hospital of South Punjab. This retrospective cohort study included patients who received therapy for multidrug-resistant tuberculosis (MDR-TB) between March 2018 and June 2021 at the Pulmonology Department of Sheikh Zayed Hospital, Rahim Yar Khan. Sociodemographic data, TB treatment history, treatment schemes, safety profiles, weight measures, and sputum smear results were obtained from medical records. Outcome variables of interest included body weight, sputum smear grading for treatment efficacy, and ADRs for safety assessment. The study showed a progressive decline in positive sputum smear results over the 24-month treatment for MDR-TB, with an increase in negative smear results from 33 (9.50%) at baseline to 97 (28.0%) by Month 24. Furthermore, the mean body weight significantly increased every three months throughout the trial. Beginning at 43.83 kg at baseline, the mean weight increased to 50.02 kg by the end of 24 months. ADRs were mostly mild to moderate, including depression (18.4%), arthralgia (17.1%), anxiety (16.5%), and Qtc prolongation (11.0%). The treatment adhered to international guidelines, using a tailored combination of second-line drugs and adjusting regimens based on drug resistance patterns from sputum culture and DST. The study findings suggest the efficacy of second-line anti-TB drug regimens in achieving sputum smear conversion and positive treatment outcomes in patients with MDR-TB. However, the occurrence of ADRs highlights the need for careful monitoring and management during treatment.

A mindfulness-based, cognitive, social, digital relapse-prevention intervention for youth with depression in Australia: study protocol for a randomised controlled trial of Rebound

IntroductionMajor depressive disorder (MDD) causes significant disease burden and functional impairment during adolescence and young adulthood. While most young people recover from their first episode, around two-thirds will experience one...

Effects of 3-month liraglutide treatment on oxidative stress and inflammation in type 2 diabetes patients with different urinary albumin-to-creatinine ratio categories

This study evaluates the effects of liraglutide on albuminuria, oxidative stress, and inflammation in type 2 diabetes (T2D) patients with different urinary albumin-to-creatinine ratio (UACR) categories. We enrolled 107 patients with T2D who were initiating liraglutide for glycemic control. Patients were categorized into 3 groups: group I (UACR &lt; 30 mg/g); group II (30 mg/g ≤ UACR ≤ 300 mg/g); group III (UACR &gt; 300 mg/g). We observed the changes in body mass index, fasting plasma glucose, glycated hemoglobin, lipid profile, serum liver enzymes, creatinine, uric acid, cystatin C, UACR, as well as oxidative stress and inflammation biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase before and after 3 months of liraglutide treatment. After 3-month liraglutide treatment, fasting plasma glucose, glycated hemoglobin, and body mass index significantly decreased in all 3 groups regardless of the baseline UACR (all P &lt; .05). UACR significantly decreased in groups II (P = .005) and III (P = .001). Patients with higher UACR at baseline showed significantly greater albuminuria reduction (P &lt; .001). Compared with baseline, TNF-α, IL-6, MCP-1, and MDA were remarkably decreased, while SOD and glutathione peroxidase were significantly increased in all 3 groups (P &lt; .05). UACR at baseline showed a positive correlation with TNF-α, IL-6, and MDA, and a negative correlation with SOD at baseline. The change in UACR was negatively correlated with UACR, TNF-α, and MDA at baseline, while it was positively correlated with SOD at baseline, and also positively correlated with the change in MCP-1. Liraglutide ameliorated albuminuria in T2D patients with microalbuminuria and macroalbuminuria. The renoprotective effect of liraglutide was associated with the alleviation of oxidative stress and inflammation. These findings may provide new therapeutic strategies for patients with diabetic kidney disease.

Predicting survival, neurotoxicity and response in B-cell lymphoma patients treated with CAR-T therapy using an imaging features-based model

BackgroundThis multicentre retrospective observational study aims to develop imaging-based prognostic and predictive models for relapsed/refractory (R/R) B-cell lymphoma patients undergoing CAR-T therapy by integrating clinical data and imaging features. Specifically, our aim was to predict 3- and 6-month treatment response, overall survival (OS), progression-free survival (PFS), and the occurrence of the immune effector cell-associated neurotoxicity syndrome (ICANS).ResultsSixty-five patients of R/R B-cell lymphoma treated with CAR-T cells in two centres were included. Pre-infusion [18F]FDG PET/CT scans and clinical data were systematically collected, and imaging features, including kurtosis, entropy, maximum diameter, standardized uptake value (SUV) related features (SUVmax, SUVmean, SUVstd, SUVmedian, SUVp25, SUVp75), total metabolic tumour volume (MTVtotal), and total lesion glycolysis (TLGtotal), were extracted using the Quibim platform. The median age was 62 (range 21–76) years and the median follow-up for survivors was 10.47 (range 0.20–45.80) months. A logistic regression model accurately predicted neurotoxicity (AUC: 0.830), and Cox proportional-hazards models for CAR-T response at 3 and 6 months demonstrated high accuracy (AUC: 0.754 and 0.818, respectively). Median predicted OS after CAR-T therapy was 4.73 months for high MTVtotal and 37.55 months for low MTVtotal. Median predicted PFS was 2.73 months for high MTVtotal and 11.83 months for low MTVtotal. For all outcomes, predictive models, combining imaging features and clinical variables, showed improved accuracy compared to models using only clinical variables or imaging features alone.ConclusionThis study successfully integrates imaging features and clinical variables to predict outcomes in R/R B-cell lymphoma patients undergoing CAR-T. Notably, the identified MTVtotal cut-off effectively stratifies patients, as evidenced by significant differences in OS and PFS. Additionally, the predictive models for neurotoxicity and CAR-T response show promising accuracy. This comprehensive approach holds promise for risk stratification and personalized treatment strategies which may become a helpful tool for optimizing CAR-T outcomes in R/R lymphoma patients.

Comparative Efficacy and Safety of Baricitinib Against Traditional Therapies in Severe Alopecia Areata: ARetrospective Cohort Study.

Alopecia areata is a common autoimmune disease which results in reversible hair loss. Janus kinase inhibitors are prescribed for severe alopecia areata with encouraging results. There are no studies comparing the efficacy and safety of Janus kinase inhibitors to traditional treatment options, such as topical immunomodulators and traditional immunosuppressants. To retrospectively compare the efficacy and safety of baricitinib, an approved Janus kinase inhibitor, to other treatments for severe AA during a 6-month treatment period. We included patients with newly presenting, relapsing or treatment-resistant alopecia areata with Severity of Alopecia Tool (SALT) score ≥ 50, for the period between July 2021 and July 2023. Medical histories were reviewed and possible side effects were recorded. Primary endpoints were SALT ≤ 20 and SALT ≤ 10 after 6 months of treatment. Seventy-five patients (53 females) were divided into three groups: topical immunomodulators (51 patients); baricitinib (19 patients); and a group receiving pulsed intramuscular corticosteroids or traditional immunosuppressants (11 patients). Twenty-one patients received more than one treatment options within 2 years. After 6 months, the baricitinib group showed superior efficacy with 32% and 26% of patients achieving SALT ≤ 20 and SALT ≤ 10, compared to 12% and 9% in both other groups. Baricitinib demonstrated better secondary outcomes (50% and 90% reduction from initial SALT scores). All treatments exhibited mild-to-moderate and expected side effects. Weight gain, which had not been reported in clinical trials for alopecia areata, was observed in three baricitinib-treated patients. Baricitinib was superior to traditional treatments for severe alopecia areata after 6 months. Weight gain concerned 16% of patients receiving baricitinib.

Rivaroxaban for 18 Months Versus 6 Months in Patients With Cancer and Acute Low-Risk Pulmonary Embolism: An Open-Label, Multicenter, Randomized Clinical Trial (ONCO PE Trial).

The optimal duration of anticoagulation therapy for patients with cancer and acute low-risk pulmonary embolism (PE) is clinically relevant, but evidence is lacking. Prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 32 institutions in Japan, we randomly assigned patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, in a 1:1 ratio, to receive either an 18-month or a 6-month rivaroxaban treatment. The primary end point was recurrent venous thromboembolism (VTE) at 18 months. The major secondary end point was major bleeding at 18 months according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that an 18-month treatment was superior to a 6-month treatment in terms of the primary end point. From February 2021 to March 2023, 179 patients were randomized, and after the exclusion of one patient who withdrew consent, 178 were included in the intention-to-treat population: 89 patients in the 18-month rivaroxaban group and 89 in the 6-month rivaroxaban group. The mean age was 65.7 years; 47% of the patients were men, and 12% had symptoms of PE at baseline. The primary end point of recurrent VTE occurred in 5 of the 89 patients (5.6%) in the 18-month rivaroxaban group and in 17 of the 89 (19.1%) in the 6-month rivaroxaban group (odds ratio, 0.25 [95% CI, 0.09-0.72]; P=0.01). Among 22 recurrent VTE, 5 patients presented with a symptomatic recurrent VTE; recurrent PE occurred in 11 patients, including 2 with main and 4 with lobar PEs; and recurrent deep vein thrombosis was seen in 11 patients, including 3 with proximal deep vein thromboses. The major secondary end point of major bleeding occurred in 7 of the 89 patients (7.8 %) in the 18-month rivaroxaban group and in 5 of the 89 patients (5.6%) in the 6-month rivaroxaban group (odds ratio, 1.43 [95% CI, 0.44-4.70]; P=0.55). In patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, the 18-month rivaroxaban treatment was superior to the 6-month rivaroxaban treatment with respect to recurrent VTE events.

Comparative Analysis of Medical Interventions to Alleviate Endometriosis-Related Pain: A Systematic Review and Network Meta-Analysis.

Background/Objectives: Endometriosis is a chronic condition that affects 6-10% of women of reproductive age, with pain and infertility being its primary symptoms. The most common aspects of pain are overall pelvic pain, dysmenorrhea, and dyspareunia. Our aim was to compare the available medical treatments for endometriosis-related pain. Methods: A systematic search was conducted in three medical databases to assess available drug options for pain management. Randomized controlled trials (RCTs) investigating various medical treatments for endometriosis-related pain on different pain scales were included. Results were presented as p-scores and, in cases of placebo controls, as mean differences (MD) with 95% confidence intervals (CI). From the available data, a network meta-analysis was carried out. Results: The search yielded 1314 records, of which 45 were eligible for data extraction. Eight networks were created, and a total of 16 treatments were analyzed. The highest p-score, meaning greatest pain relief (p-score: 0.618), for the treatment of dysmenorrhea was achieved using gonadotropin-releasing hormone (GnRH) agonists for 3 months on a scale of 0-100. Additionally, a p-score of 0.649 was attained following a 6-month treatment with GnRH agonists combined with hormonal contraceptives (CHCs). In the case of dyspareunia on a scale of 0-100 following 3 months of treatment, CHCs (p-score: 0.805) were the most effective, and CHCs combined with aromatase inhibitors (p-score: 0.677) were the best treatment option following 6 months of treatment. In the case of overall pelvic pain, CHCs (p-score: 0.751) yielded the highest p-score on a scale of 0-100 following 3 months of treatment, and progestins combined with aromatase inhibitors (p-score: 0.873) following 6 months of treatment. Progestins (p-score: 0.901) were most effective in cases of overall pelvic pain on a scale of 0-3 following 3 months of treatment. Conclusions: Our network meta-analysis showed that in cases of dysmenorrhea, GnRH agonists supplemented with CHCs reduced pain the most following 3 months of treatment. Regarding dyspareunia CHCs were most effective, and in the case of overall pelvic pain, CHCs or progestins combined with aromatase inhibitors yielded the most desirable results.

Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies

BackgroundThe role of circulating endothelial progenitor cells (cEPCs) in vascular repair and their association to cardiovascular protection is well established. ObjectivesWe examined the effect of proprotein convertase subtilisin kexin type 9 monoclonal antibodies (PCSK9 mAb) on cEPCs in adults with hypercholesterolemia and cardiovascular disease, aiming to establish a pleotropic class effect. MethodsNon-interventional prospective study in patients with cardiovascular disease treated with either evolocumab or alirocumab. Patients were sampled for cEPCs at baseline, 1- and 3-months following initiation of PCSK9 mAb. cEPCs were assessed using flow cytometry by expression of CD34/CD133 and vascular endothelial growth factor receptor (VEGFR)-2, and functionally by formation of colony forming units (CFUs) and by Mitochondrial Tetrazolium (MTT) assay, indicative of cEPCs viability. Results51 patients (median age 67 (IQR 63,74) years;63 % male, median low-density lipoprotein-cholesterol (LDL-C) 125 (102,165) mg/dL) were initiated on PCSK9 mAb therapy (evolocumab n = 22, alirocumab n = 29) for secondary prevention. Following 3-month treatment with PCSK9 mAb, there was an increase in CD34(+)VEGFR-2(+) and CD133(+)VEGFR-2(+) levels (0.50 % [IQR 0.30,1.04] to 1.36 % [0.89, 1.73], p < 0.001 and 0.57 % [0.25,0.88] to 1.18 % [0.74,1.66], p < 0.001, respectively). Functionally, increase in EPCs-CFUs was evident (0.5 [0.0,1.0] to 2.0 [1.5,2.5], p < 0.001) with concomitant increase in MTT (0.11 [0.09,0.15] to 0.17 [0.12,0.21], p < 0.001). Stratifying by PCSK9 mAb, both agents were associated with an increase in cEPCs level and function. ConclusionsIn hypercholesterolemic patients with cardiovascular disease treated with PCSK9 mAb, there is an increase in cEPCs levels and function from baseline levels. These findings, which persist in both evolocumab and alirocumab, might suggest a novel pleiotropic class effect.

Association of Antibiotic Route and Outcomes in Children with Methicillin-Resistant Staphylococcus aureus Bacteremic Osteomyelitis.

There remains uncertainty about whether transitioning to oral antibiotic therapy is appropriate for the management of children with methicillin-resistant Staphylococcus aureus (MRSA) bacteremic osteomyelitis. We compared clinical outcomes for children with MRSA osteomyelitis with associated bacteremia who were transitioned to discharge oral antibiotic therapy to those discharged on outpatient parenteral antibiotic therapy (OPAT). We performed a retrospective, multicenter, cohort study of children ≤ 18 years hospitalized with MRSA bacteremic osteomyelitis across four children's hospitals from 2007 to 2018 discharged on oral antibiotic therapy versus OPAT. The primary outcome was treatment failure within 6 months of discharge, defined as any of the following: diagnosis of chronic osteomyelitis, conversion from oral to IV antibiotic route, an operative procedure after the index hospitalization (abscess drainage, bone biopsy, arthrocentesis, or pathologic fracture) and/or recrudescence of MRSA bacteremia. Outcomes were analyzed in an inverse propensity score weighted (IPW) cohort. A total of 106 cases of MRSA bacteremic osteomyelitis were included; 44 (42%) were discharged in the oral antibiotic therapy group and 62 (59%) patients were discharged in the OPAT group. In the IPW cohort, treatment failure within 6 months of discharge occurred in 3.4% of children in the discharge oral therapy group and 16.3% in the OPAT group (P = 0.03). The odds of 6-month composite treatment failure between discharge oral therapy and OPAT were 0.18 (95% CI 0.05-0.61). Discharge oral therapy was not associated with higher rates of treatment failure compared to OPAT for children with MRSA bacteremic osteomyelitis.

Abstract 4141496: Methylation changes in monocytes of type 2 diabetes patients with cardiovascular disease are associated with apoptosis and inflammation pathways.

Background: Monocytes have been implicated in the initiation and progression of cardiovascular (CV) complications of type 2 diabetes (T2D). Aim: We investigated diabetes-induced methylation changes and enriched pathways in circulating monocytes of T2D patients. We compared T2D vs. non-T2D participants and analyzed T2D patients according to diabetes control. Further, we assessed methylation changes in a subset of patients with poor diabetes control and high CV risk following a 6-month treatment intensification. Methods: We recruited consecutively 200 participants, 160 with T2D and 40 non-diabetes controls. Circulating monocytes were sorted using the FACSAria2 ™ cell sorter. Samples were sequenced using enhanced reduced representation bisulfite sequencing. Methylation data was processed with Lumi and limma R packages to obtain batch and covariate corrected differential expression values for the indicated comparisons. Ingenuity Pathway Analysis (Qiagen) was used to identify enriched pathways for each tested condition. Differentially methylated genes used for pathway analysis were those with a p-value &lt; 0.05 and an absolute logFC value ≥ 0.5. Results: There were 1122 differentially methylated genes when comparing T2D to non-T2D patients. Among the top five enriched canonical pathways, apoptosis signaling was predicted to be activated, while the RHO GTPase cycle and LPS-stimulated MAPK signaling pathways were predicted to be inhibited. Within patients with diabetes, there were 1670 differentially methylated genes comparing those with poor control (HbA1c ≥ 7%) vs. good control (HbA1c&lt;7%). Among the top five enriched pathways, synthesis of DNA, DNA replication signaling, and cell cycle checkpoints were activated while inhibition of ARE-mediated mRNA degradation pathway was inhibited. In patients who responded to treatment intensification (Δ HbA1c = -1.5%, p= 0.02), 1377 differentially methylated genes and differentially inhibited pathways such as non-homologous end-joining and cellular response to heat stress were identified. In non-responders, we identified 1582 differentially methylated genes and activated pathways, including inhibition of mRNA degradation pathways and p14/p19 ARF signaling. Conclusion: Treatment intensification in T2D patients with CVD and poor control showed the presence of differentially methylated genes affecting pathways regulating cell proliferation and inflammation and are known to be associated with diabetic CVD complications.

NCOG-39. EXPLORING THE POTENTIAL OF STEREOTACTIC RADIOSURGERY IN THE MANAGEMENT OF MENINGIOMAS

Abstract INTRODUCTION Meningiomas present complex therapeutic challenges due to their potential impact on neurological function and quality of life. While the standard of care involves observation and surgical resection, stereotactic radiosurgery (SRS) is an alternative treatment modality. This study aimed to compare the relative efficacy of SRS and surgical resection in the management of meningiomas to inform evidence-based decision-making in this clinical context. METHODS A retrospective cohort study was conducted using the TriNetX database, comparing patients undergoing treatment for meningiomas with either stereotactic radiosurgery (SRS) or surgical resection. Cohorts were matched on comorbidities. Rates of mortality and malignant neoplasms of the brain within 5-years of treatment with either modality were compared. In addition, short-term outcomes were assessed at 3 months post-treatment. RESULTS After matching, there were 1,898 patients in each cohort. Patients receiving SRS exhibited a significantly lower risk of mortality (95% CI: 0.76-1.07) and a decreased risk of developing malignant neoplasms of the brain (RR: 0.68, 95% CI: 0.54-0.85) over 5 years, compared to surgical resection. At 3-months post treatment, patients treated with SRS demonstrated significantly lower relative risks for several outcomes, including cerebral infarction (RR: 0.27, 95% CI: 0.18-0.39), hydrocephalus (RR: 0.19, 95% CI: 0.11-0.32), cerebral edema (RR: 0.13, 95% CI: 0.10-0.18), seizures (RR: 0.27, 95% CI: 0.21-0.34), neurological deficits (RR: 0.19, 95% CI: 0.13-0.28), and post-procedural infection (RR: 0.14, 95% CI: 0.07-0.28). CONCLUSION This retrospective cohort study suggests that in the management of meningiomas, SRS may be associated with lower mortality rates, decreased risks of malignant neoplasms of the brain, and improved short-term outcomes compared to surgical resection. Further research is warranted to validate these results and explore long-term outcomes and potential adverse effects.

Approaches and processes for paediatric chest X-ray classification used in the SHINE TB treatment-shortening trial.

<sec><title>INTRODUCTION</title>SHINE (Shorter Treatment for Minimal Tuberculosis in Children) was the first Phase 3 paediatric TB treatment-shortening trial. Robust chest X-ray (CXR) classification methods were integral to excluding severe disease for trial eligibility and to retrospectively adjudicating TB status at baseline. We describe and critically evaluate the CXR classification approaches and processes used in the SHINE trial.</sec><sec><title>METHODS</title>Children with non-severe TB were randomised to 4- vs 6-months anti-TB treatment. Radiologically non-severe TB was defined on CXR. CXRs were systematically interpreted by on-site clinicians prospectively for eligibility determination and retrospectively by experts to inform adjudication of baseline TB status and disease severity.</sec><sec><title>RESULTS</title>A screening CXR was successfully obtained from all 1,204 enrolled children; 1,134 CXRs from children with intra-thoracic TB were reviewed by expert readers. Compared with the expert panel, enrolling clinicians classified more CXRs as abnormal and 'typical TB' and all as radiologically non-severe. The expert panel retrospectively classified 71/1,134 (6%) CXRs as severe. Of these, 4 (5.6%) had unfavourable outcomes compared with 34 (3.0%) in the trial overall.</sec><sec><title>DISCUSSION</title>Using CXRs to classify radiological disease severity and inform eligibility decisions in real-time by local enrolling clinicians was feasible and safe in this large paediatric TB trial. Retrospective central expert CXR review was successful. Refinement of the CXR methods for the classification of both disease severity and TB status could support standardised implementation in routine care and research.</sec>.