Clinical Trial Research Articles

Generalizable and replicable brain-based predictions of cognitive functioning across common psychiatric illness

A primary aim of computational psychiatry is to establish predictive models linking individual differences in brain functioning with symptoms. In particular, cognitive impairments are transdiagnostic, treatment resistant, and associated with poor outcomes. Recent work suggests that thousands of participants may be necessary for the accurate and reliable prediction of cognition, questioning the utility of most patient collection efforts. Here, using a transfer learning framework, we train a model on functional neuroimaging data from the UK Biobank to predict cognitive functioning in three transdiagnostic samples (ns = 101 to 224). We demonstrate prediction performance in all three samples comparable to that reported in larger prediction studies and a boost of up to 116% relative to classical models trained directly in the smaller samples. Critically, the model generalizes across datasets, maintaining performance when trained and tested across independent samples. This work establishes that predictive models derived in large population-level datasets can boost the prediction of cognition across clinical studies.

Safety and efficacy evaluation of intracavernosal injection of platelets rich plasma in treatment of vasculogenic erectile dysfunction

ABSTRACT Objectives The study’s objective is to compare platelet-rich plasma (PRP) injections to placebo in terms of effectiveness and safety for patients with vasculogenic erectile dysfunction (ED). Methods This randomized placebo-controlled clinical trial was done on 50 male patients with organic vasculogenic ED and sexually active in a stable heterosexual relationship for a period of over three months. The patients were randomized into two main groups: Group (A) (n = 25) underwent PRP treatment. Group (B) (n = 25) control underwent placebo treatment. Results The two groups under study differed in a statistically significant way regarding the achievement of minimal clinically important differences (MCID) at 3 months and 24 months. Statistically significant variations existed between the mild subgroup and placebo regarding achieving MCID after 3 months and 24 months. The level of satisfaction was statistically significantly higher in the PRP group. A statistically significant variation was present between the mild subgroup and placebo at 3 months and 24 months in terms of changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF-EF) questionnaire score in each subgroup. Conclusions PRP is an effective alternative modality of treatment in cases of ED, and they offer an intermediate stage between pharmaceutical therapy and surgical interventions at least in mild and mild to moderate cases where unsatisfactory results or unpleasant side effects compel the patients to abandon all hope on medical treatment.

Optimization of Timing for Risk-Reducing Salpingectomy and Oophorectomy

Most cases of ovarian cancer are diagnosed at an advanced stage, and long-term survival rates are low. Because no effective ovarian cancer screening has yet been developed, the primary focus to reduce ovarian cancer mortality is surgical prevention. For individuals with a significantly increased risk of ovarian cancer, risk-reducing bilateral salpingo-oophorectomy is highly effective, but uptake at the recommended age is suboptimal, likely because of concerns about premature menopause. Evidence suggests that many “ovarian” cancers originate in the distal fallopian tube, thus making bilateral salpingectomy after completion of childbearing with delayed oophorectomy an attractive but still unproven risk-reduction option for those who decline or are not yet ready for risk-reducing bilateral salpingo-oophorectomy. Two clinical trials (SOROCk [A Non-randomized Prospective Clinical Trial Comparing the Non-inferiority of Salpingectomy to Salpingo-oophorectomy to Reduce the Risk of Ovarian Cancer Among BRCA1 Carriers], NCT04251052; and TUBA-WISP2 [Tubectomy With Delayed Oophorectomy as an Alternative to Risk-Reducing Salpingo-oophorectomy in High-Risk Women to Assess the Safety of Prevention]; NCT04294927) are ongoing to determine whether bilateral salpingectomy with delayed oophorectomy is as effective as risk-reducing bilateral salpingo-oophorectomy to prevent ovarian cancer. The SOROCk trial is a national, prospective nonrandomized trial powered to test the hypothesis that bilateral salpingectomy with delayed oophorectomy is noninferior to risk-reducing bilateral salpingo-oophorectomy to reduce the incidence of ovarian cancer among people with deleterious germline BRCA1 mutations. Gynecologists and gynecologic oncologists in both community-based and academic practices may perform risk-reducing surgeries and have their patients participate in the SOROCk trial. We review key aspects of the SOROCk clinical trial and discuss how surgeons can partner with SOROCk clinical trial sites and facilitate their patients' participation to help answer this important clinical question. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04251052.

Liver cyst penetration of antibiotics at the target site of infection: a randomized pharmacokinetic trial

Abstract Background The EASL cystic liver disease guideline states that drug penetration at the site of infection (liver cyst) is essential for successful treatment, but pharmacokinetic (PK) data on cyst penetration are limited. Objectives This study aims to investigate tissue penetration of four antibiotics in non-infected liver cysts and explores influencing factors. Methods We performed a prospective, randomized single-dose PK-study. Before percutaneous drainage of a non-infected liver cyst, an intravenous (IV) dose of either ciprofloxacin and piperacillin/tazobactam (group 1); or co-trimoxazole (trimethoprim/sulfamethoxazole) and doxycycline (group 2) was given. Cyst fluid was collected during drainage. Blood samples were obtained before, during and after drainage (within 12 h). Drug concentrations were measured with a validated LC-MS/MS. Primary outcome was liver cyst penetration, defined as the cyst-fluid-to-plasma concentration ratio (%) expressed as median (IQR). Results We included 20 patients, and 21 liver cysts were drained (group 1: n = 11, group 2: n = 10). Median drained cyst volume was 700 mL. Median time between infusion and drainage was 139 min (IQR 120–188 min). Median cyst-fluid-to-plasma concentration ratio was 4.2% (IQR 1.6%–8.9%) for ciprofloxacin, 0.3% (IQR 0.0%–1.3%) for piperacillin, 0.2% (IQR 0.0%–1.3%) for tazobactam, 12.2% (IQR 6.3%–16.1%) for trimethoprim, 0.4% (IQR 0.2%–3.8%) for sulfamethoxazole and 1.6% (IQR 0.9%–2.3%) for doxycycline. Time between trimethoprim infusion and cyst drainage was correlated with increased cyst-fluid-to-plasma concentration ratio (P < 0.01). Conclusions Trimethoprim and ciprofloxacin have the highest penetration ratios amongst antibiotics tested. We found that liver cyst penetration varies widely between drugs after a single IV dose. Clinical trial number NTR8499 The trial was originally registered in the Netherlands Trial Register (ID: NL7290), which was converted to the International Clinical Trials Registry Platform in 2022.

Recombinant Human Thyrotropin Plus Radioactive Iodine Among Patients With Thyroid Cancer

ImportanceRadioactive iodine (131I or RAI) therapy has long been the standard of care for most patients with differentiated thyroid cancer (DTC) after primary surgery. However, no multicenter prospective studies have identified the optimal administered activity and stimulation method for RAI therapy in patients with intermediate-risk DTC.ObjectiveTo compare the efficacy and safety of recombinant human thyrotropin (SNA001) with thyroid hormone withdrawal (THW) plus 3.7 GBq RAI in patients with intermediate-risk DTC.Design, Setting, and ParticipantsThis noninferiority, open-label, phase 3 randomized clinical trial was conducted at 19 sites in China from April 16, 2020, to September 9, 2021, with a follow-up period of 8 months. Patients aged 18 to 70 years with DTC who had undergone a total or near-total thyroidectomy and had no distant metastasis were enrolled in the trial. Statistical analysis followed the full analysis and per-protocol analysis sets and was performed between November 18, 2021, and April 18, 2022.InterventionPatients were randomly assigned 1:1 to receive SNA001, 0.9 mg, intramuscular injection daily for 2 days or to undergo thyroid hormone withdrawal for 3 to 6 weeks.Main Outcomes and MeasuresThe primary end point was the success rate after 6 to 8 months of RAI therapy. Success was defined as a negative diagnostic whole-body scan result and a stimulated thyroglobulin level less than 1.0 ng/mL.ResultsA total of 307 patients (192 females [62.5%]; median [range] age, 40 [19-69] years) were randomized: 154 to the SNA001 group and 153 to the THW group. Baseline characteristics were evenly matched between the 2 groups. Noninferiority in the success rate of RAI therapy between groups was met, with success rates of 43.8% in the SNA001 group and 47.1% in the THW group (risk difference, −3.3; 95% CI, −14.8 to 8.3 percentage points). Forty-six patients (29.9%) in the SNA001 group reported adverse events compared with 90 (58.8%) in the THW group during RAI therapy (P < .001). No treatment-related adverse events leading to discontinuation and drug modification occurred in the SNA001 group.Conclusions and RelevanceThis randomized clinical trial showed that SNA001 was noninferior to THW plus 3.7 GBq RAI in patients with predominantly intermediate-risk DTC. SNA001 also demonstrated a favorable safety profile compared with THW and had a lower incidence of adverse events.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2100046907

Pentoxifylline improves anemia through its novel effect on hypoxia-inducible factor-2 alpha in hemodialysis patients: a randomized, double-blind, placebo-controlled clinical trial

ABSTRACT Objectives This randomized, double-blind, placebo-controlled clinical trial aimed to prospectively examine the effect of pentoxifylline (PTX) on hypoxia-inducible factor-2 alpha (HIF-2α) and its role in controlling anemia in hemodialysis (HD) patients. Methods Eighty patients on HD were randomized to receive 400 mg of PTX or placebo twice daily for 6 months. The hemoglobin (Hb) and other hematologic parameters, the weekly erythropoiesis-stimulating agents (ESAs), and the ESA resistance index (ERI) were assessed monthly during the study. The HIF-2α, transforming growth factor-β1 (TGF-β1), and high-sensitivity C-reactive protein (hs.CRP) were measured before and after the intervention. Results In the pentoxifylline group, an appreciable increase in Hb from 9.7 (9.3, 10.3) g/dl to 10.5 (9.3, 11.4) g/dl and hematocrit (Hct) from 31.3 (29.6, 32.4)% to 33.2 (29.4, 35.9)% was observed after one month of PTX administration, and this effect was maintained over the study time (p < 0.001). This was along with a decrease in the ESA doses required from 8000 (8000, 11500) IU/wk to 4000 (2000, 8000) IU/wk (p < 0.001), and an improvement in the ERI from 11.6 (8.07, 16.97) IU/kg/wk/g/dl to 5.79 (2.01, 10.09) IU/kg/wk/g/dl (p < 0.001). Additionally, the HIF-2α increased significantly at the end of the intervention in patients who received PTX from 3245.35 (2886.8, 4691.56) pg/ml to 7208.75 (5382, 9182.7) pg/ml, while TGF-β1 and hs.CRP decreased significantly from 657.78 (539.78, 1146.62) pg/ml and 88.08 (39.93, 100.4) mg/l to 329.94 (228.67, 793.18) pg/ml and 48.65 (34.44, 84.61) mg/l, respectively. The percent changes in HIF-2α, TGF-β1, and hs.CRP levels in the pentoxifylline group were also statistically significant in comparison with the placebo group. Conclusions PTX could be a promising agent for correcting anemia in HD patients via increasing HIF-2α levels. Clinical trial registration Clinicaltrials.gov, February 2023, registry number: NCT05708248.

Cardio-rheumatology: present and future. Part I

Patients suffering from rheumatic diseases are at high risk of the development and accelerated progression of cardiovascular due to inflammation as one of the etiological factors of atherogenesis and heart failure. To choose the rational and safe treatment, especially in comorbid patients, it is necessary to have a comprehensive and complete understanding of the mechanisms of these relationships, as well as the most accurate determination of cardiovascular risk using modern validated scales. The first part of the review presents the results of current experimental and clinical studies on the effect of the chronic inflammatory and its biomarkers on the development, course and prognosis of cardiovascular diseases.

Estimated frequency and economic burden of incident fragility fractures during 2023 in Mexico.

Osteoporosis and its fractures impose a high clinical and economic burden. The objective of this analysis was to estimate the frequency and costs owing to incident fragility fractures (FFs) during the year 2023 in Mexico. This is an incidence-based cost-of-illness study. The target population is adults ≥ 50years old sustaining a fracture related to osteoporosis (caused by a fall on the same level). The model estimates the costs and productivity losses associated with their treatment within 1year post-fracture. National epidemiologic databases supplemented with information, derived from literature when appropriate, were used to estimate the frequency of new FFs during 2023 in the study population. Resource use included surgical and non-surgical inpatient or ambulatory care the patients received immediately after fracture plus the outpatient physiotherapy post-discharge and the eventual follow-up with a specialist who may prescribe pharmacotherapy. Sick days taken in employed patients were estimated from the literature. Local unitary costs of services and drugs for both public and private settings as well as average income in those occupied were applied. All costs are reported in Mexican pesos (MXN) from 2023. The model estimated a total of 229,239 FFs, among which 63% were classified as a major osteoporotic fracture, including 53,842 and 41,459 fractures located at the hip and vertebral, respectively. The total costs were estimated at 15,593 million MXN; most of them (75.2%) were attributable to acute-phase care. Fragility fractures represent a serious health problem for Mexico. Better preventive/therapeutic strategies may help to mitigate their significant financial toll.

Compressive force and valgus torque are the predominant applied loads during the pivot shift exam: An in vitro study.

Despite the clinical utility of the pivot shift exam, the requisite applied forces and torques to elicit a pivot shift remain unclear. The purposes of this study are (1) to identify the greatest forces and torques applied to the knee during the pivot shift exam and (2) to evaluate if the applied loads differ among experienced surgeons. Three cadaveric hemipelvis-to-toe specimens (ages 53, 36 and 31 years; two males and one female) with no history of knee or hip injury were utilized. The experimental setup consisted of securing the hemipelvis to a mounting frame via an external fixator to simulate patient positioning during the clinical exam. The hemipelvis, femur, and tibia were spatially tracked by motion capture and the applied loads were measured using a 6-axis force-torque sensor. After sectioning the anterior cruciate ligament (ACL), three board-certified sports medicine surgeons then performed the pivot shift exam on each specimen utilizing their preferred technique. Forces (compression-distraction, anterior-posterior, and medial-lateral) and torques (varus-valgus, internal-external rotation, and flexion-extension) applied to the knee joint immediately preceding the reduction of the proximal lateral tibia during each pivot shift exam were calculated. Compression was the largest applied force averaging 95 N ± 15 N for all surgeons and knees, which was at least 4.5 times greater, on average, than the applied anterior and applied medial tibial forces (p < 0.0001). Valgus was the largest of the three applied torques, averaging 8.5 ± 2.1 Nm. Internal rotation torque was 3.7 times less, on average, than the applied valgus torque (p < 0.0001). Each surgeon applied compressive force. However, anterior force was more variable among surgeons, with one of the three surgeons applying minimal anterior force (p ≤ 0.024). The magnitude of applied torques was similar among examiners (n.s). Compressive force and valgus torque were the predominant applied loads during the pivot shift exam. A lower magnitude of internal rotation torque was also applied. The anterior force was not consistently applied among examiners. These data can better inform clinical, cadaveric, and computational studies utilizing the pivot shift exam to assess knee biomechanics and can be used to educate trainees in conducting this complex manoeuvre. An in vitro biomechanic study.

Erratum in: IMI – Defining and Classifying Myopia: A Proposed Set of Standards for Clinical and Epidemiologic Studies

Erratum in: IMI – Defining and Classifying Myopia: A Proposed Set of Standards for Clinical and Epidemiologic Studies

Use of follow-up psycho-oncology consultations in urological cancer after transition from inpatient to outpatient care

Background: In urological oncology, the physical and psychological effects of cancer and its treatment post-discharge highlight the importance of follow-up psycho-oncology consultations. This study examines their utilisation and identifies predictors in urological cancer patients after inpatient care. Methods: A prospective, single-centre clinical observational study was conducted. Inpatients with urological cancer and ≥ 5 points on the Distress Thermometer and/or request for psycho-oncological support were recruited, offered an initial psycho-oncology consultation, and up to five online or on-site appointments within three months of discharge. The following variables were collected: socio-demographics, psycho-oncological baseline documentation (PO-BADO), psychosocial distress (Distress Thermometer with problem list), anxiety and depressive symptoms (GAD-2 &amp; PHQ-2), and performance status (ECOG). Results: A total of 501 patients were screened, 139 were included, and 108 were analysed. 25 patients used psycho-oncological follow-up care (n = 16 online). The final hierarchical model predicting the use of follow-up psycho-oncological support included the two predictors: age (OR 0.93, 95% CI 0.90-0.96) and anxiety (OR 1.60, 95% CI 1.11-2.44). Discussion: Nearly one in four urological cancer patients use follow-up psycho-oncology consultations, mostly online. Predictors for this usage are younger age and higher levels of anxiety. To improve care: 1) online services reduce barriers; 2) older patients require support with these services; and 3) screening specifically for depression is crucial to ensure that follow-up appointments are scheduled as a mandatory part of hospitalisation.

Effect of Interrupting Prolonged Sitting with Frequent Activity Breaks on Postprandial Glycemia and Insulin Sensitivity in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Crossover Pilot Trial.

Objective: This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). Method: In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m2) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (SiSP) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Results: Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L-1; P = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L-1; P < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU-1; P = 0.03). SiSP was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Conclusion: Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Trial Registration: Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).

Impact of platelet-rich fibrin derivatives on patient morbidity and quality of life in palatal donor sites following free gingival graft surgery: a randomized clinical trial.

Platelet concentrates are biomaterials with significant potential in tissue regeneration, functioning as scaffolds with greater leukocyte inclusion and a flexible fibrin mesh. However these concentrates have different preparation methods and biological properties. The objective of this clinical investigation was to evaluate the effects of utilizing platelet-rich fibrin (PRF) materials (L-PRF and A-PRF) as a palatal bandage following free gingival graft (FGG) on patients' morbidity and oral health-related quality of life. Thirty-nine participants received FGG to promote keratinized tissue and treat gingival recession. Participants were randomly assigned to L-PRF, A-PRF, and control groups, with 13 participants in each. They used a visual analog scale (VAS) to rate their pain, analgesic medication use, dietary changes, discomfort, and bleeding at 1-7 days, 14 days and 1 month during the healing process. Patients' quality of life was assessed using the Oral Health Impact Profile (OHIP-14) at baseline, 1-7 days, 14 days, 1 month, and 6 months. There was no difference in anxiety levels between the all groups. (p > 0.05). The control group had higher OHIP-14 total scores than the other groups, but the differences were not statistically significant, especially in the first seven days (p > 0.05). In addition, the PRF groups showed an improvement in quality of life after 14 days, 1 month, and 6 months (p < 0.05). Patients' pain and suffering decreased with healing. The control group took more postoperative analgesics than PRF groups. In addition, there was a significant decrease in patient complaints about medicine intake, bleeding, pain, perceived sensitivity, and dietary modifications in all groups during follow-up. PRF palatal bandages may improve patient's quality of life, donor site healing, postoperative pain and morbidity. This study found that preserving the palate in FGG and employing PRF materials that speed palate healing reduce discomfort and morbidity.

Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma

ImportanceEquecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.ObjectiveTo evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.Design, Setting, and ParticipantsThe FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.InterventionsPatients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion.Main Outcomes and MeasuresEfficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.ResultsOf 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10−5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell–associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell–associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.Conclusions and RelevanceIn this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000033946

Laser hemorrhoidoplasty versus hemorrhoidectomy in the treatment of surgically indicated hemorrhoids in inflammatory bowel patients: a randomized comparative clinical study

Abstract Background This study aims to assess and compare the outcomes of traditional surgery and laser surgery for anal hemorrhoids in patients with inflammatory bowel disease. Methods This is a single-center prospective randomized comparative clinical trial performed at Zagazig University Hospitals from September 2023 to September 2024. The study comprised 48 patients who were admitted during this period and had inflammatory bowel disease along with hemorrhoids. The patients were randomly allocated into two groups: Group I consisted of 24 patients who underwent laser hemorrhoidoplasty, selected based on odd numbers, while Group II consisted of 24 patients who underwent traditional surgery, selected based on even numbers. Results Group I, which underwent laser treatment for hemorrhoids in inflammatory bowel patients, demonstrated significantly better outcomes than traditional surgery (p &lt; 0.001) regarding operation time, pain score and duration, postoperative anal discharge, return to work time, and patient satisfaction. Moreover, laser treatment was found to be more effective than traditional surgery for treating hemorrhoids in inflammatory bowel patients in terms of postoperative bleeding and anal stenosis. Additionally, there was a higher frequency of residual hemorrhoids in laser group. Conclusion Laser treatment is mostly superior to traditional surgery for hemorrhoids in inflammatory bowel patients. Trial registration Clinical Trial.gov (NCT06216223), registered on December 27, 2023, last updated in May 12, 2024. Protocol registration ID #101080-5-9-2023

Effects of dexamethasone combined with vitamin B12 on percutaneous endoscopic interlaminar discectomy early outcomes: a randomized controlled trial.

Residual low back and leg pain can occur after percutaneous endoscopic interlaminar discectomy (PEID) and compromise early surgical outcomes. This study aimed to determine the efficacy of combining dexamethasone with vitamin B12 (VB12) via epidural injection in improving the symptoms of low back and leg pain after PEID, and the underlying mechanism of action. Patients who underwent PEID for lumbar disc herniation (LDH) were enrolled and randomly assigned to the single surgery (SS) group, where disc removal was performed via PEID alone, or the combined treatment (CT) group, which received epidural injections of dexamethasone and VB12 alongside surgery. The outcome measures were the Visual Analog Scale (VAS), Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), serum inflammatory factor expression, adverse surgical events, duration of postoperative hospitalization, and modified MacNab criteria. Compared with the SS group, the CT group exhibited lower VAS scores for low back and leg pain at 1, 3, and 7 days post-surgery (P < 0.05). JOA and ODI scores were significantly improved in the CT group than in the SS group 7 days post-surgery (P < 0.05); however, no significant differences were observed at other time points. Serum inflammatory factors were lower in the CT group than in the SS group 3 days post-surgery (P < 0.05). The duration of postoperative hospitalization was shorter in the CT group (P < 0.05). Both groups had similar good outcomes (89.3% vs. 92.2%, P = 0.945). Epidural injection of dexamethasone and VB12 effectively reduces early postoperative low back and leg pain, lowers postoperative inflammatory factor expression, and improves early PEID outcomes. Its clinical adoption merits consideration. This trial was registered with the China Clinical Trial Registration Center (Identifier: ChiCTR2400088854).

Retention rate of giomer S-PRG filler containing pit and fissure sealant applied with or without etching: a randomized clinical trial

Abstract Background Pit and fissure sealant is a micro-invasive modality for treating deep and retentive pits and fissures to prevent and/or stop occlusal caries. Every effort needs to be done to enhance sealant retention and survival. The aim of this research is to assess the retention rate of giomer S-PRG filler containing pit and fissure sealant applied with or without etching. Methods Overall, 52 patients were included in this trial and they were allocated randomly in 2 groups (n = 26). Group 1 (control group) received giomer sealant (Beautisealant, Shofu, Kyoto, Japan) without an etching step, and group 2 (intervention group) received the same but with a separate preparatory etching step before the sealant application. The retention rate of the sealant was assessed over one year at 3 months, 6 months, and 12 months. Intergroup comparison between categorical variables was done using the chi square test, while intragroup comparison was done using Cochran’s q test followed by multiple comparisons. Relative risk was used to evaluate the clinical significance. Survival rate was analyzed using Kaplan-meier and Log-rank test. Results Intergroup comparison between both techniques revealed statistically significant difference within different follow up periods (P &lt; 0.05). Intragroup comparison within both giomer sealant with etching group and giomer sealant without etching group revealed statistically significant difference between different follow-up periods (P &lt; 0.001). There was 69% less risk for total loss or partial loss of giomer sealant with etching when compared to giomer sealant without etching after 12 months. Conclusion An initial preparatory step of etching to the enamel surface is crucial before giomer sealant application to enhance its bonding, increase its retention and promote its survival. Trial registration Trial registration ClinicalTrials.gov, NCT04929782. Registered 14 July 2024 - Retrospectively registered, https://clinicaltrials.gov/study/NCT06509451

Dermatomal spread in lateral quadratus lumborum blocks versus transversus abdominus plane blocks after laparoscopic colorectal surgery: a randomized clinical trial

IntroductionPostoperative pain after laparoscopic abdominal surgery remains complex. While lateral quadratus lumborum (QL) block and transversus abdominus plane (TAP) block are similar techniques, no studies have examined if one technique has greater dermatomal spread.MethodsLaparoscopic colorectal surgical patients were randomized to lateral QL or TAP blocks. Dermatomal anesthetic spread, as measured by loss of sensation to temperature in the postanesthesia care unit, was the primary outcome. If a clear level of dermatomal anesthesia could not be defined, the block was categorized as “indeterminate.” Secondary outcomes included opioid consumption, pain scores, and opioid-related side effects.Results153 patients completed the study (75 QL and 78 TAP). Mean (95% CI) number of dermatomes with loss of sensation to ice was greater in subjects randomized to QL (4.2 (3.7 to 4.8)) versus TAP (2.7 (2.2 to 3.2); p=0.0001), and the QL group was more likely to have loss of sensation above T8 (p=0.01) and T10 (p=0.02). Indeterminate block was more often noted with TAP blocks (p&lt;0.0001). Opioid consumption at 24 hours, pain scores, and opioid-related side effects did not differ.DiscussionCompared with TAP blocks, QL blocks had greater dermatomal anesthesia spread and lower rates of an indeterminate block. However, differences in pain and opioid consumption were not noted. The clinical importance of these findings should be investigated in future trials.Trial registration numberNCT03490357.

Patient considerations when using ritlecitinib for alopecia areata in adolescents: Guidance for the clinicians

Background: Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss that can affect children, adolescents, and adults. Ritlecitinib, an orally administered Janus kinase (JAK) 3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family inhibitor, is the first and currently the only treatment approved by the United States Food and Drug Administration for adolescents (aged 12-17 years) with severe AA. Summary: The ALLEGRO Phase 2b–3 trial demonstrated that 25% and 50% of adolescents with a Severity of Alopecia Tool (SALT) score ≥50 at baseline achieved a SALT score ≤20 at week 24 and week 48 after receiving 50mg ritlecitinib daily, respectively. The most common adverse events were headache, acne, and nasopharyngitis in adolescents. This review summarizes the mechanism of action, clinical trial evidence on efficacy and safety profile, factors associated with treatment response to JAK inhibitors for AA, and vaccination considerations for adolescents. Key Messages: This review aims to facilitate the risk-benefit assessment and shared decision-making between clinicians and patients and provide clinical considerations and management recommendations for ritlecitinib use in adolescents with AA.

Correction: An open‑label, parallel‑group, randomized clinical trial of different silver diamine fluoride application intervals to arrest dental caries

Correction: An open‑label, parallel‑group, randomized clinical trial of different silver diamine fluoride application intervals to arrest dental caries