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Purpose: To compare the treatment time of digital and conventional workflows for single-implant crowns, as well as prostheses made of polymer-infiltrated ceramic-network (PICN; Vita Enamic, Vita Zahnfabrik) and lithium disilicate (LS2; n!ce, Straumann). Materials and Methods: A total of 40 patients who needed a single-implant crown in posterior regions were considered and randomly divided into digital workflows (n = 20) that used an intraoral scanner (IOS; iTero Element 5D, Align Technologies) and conventional workflows (n = 20) that used polyether impressions (3M ESPE Impregum Penta). Then, each group was again distributed into two subgroups based on the crown material used: PICN (n = 10) and LS2 (n = 10). Treatment time was calculated for both digital and conventional workflows. Analysis was done at a 5% confidence interval (P < .05). An independent two-sample t test was used to compare treatment time between the groups. The Kruskal--Wallis test was used to compare clinical try-in time among subgroups. Any of the implant crowns that had to be remade in each subgroup were evaluated using the Fisher exact test. Results: The entire process of digital and conventional workflows required 104.31 ± 20.83 and 153.48 ± 16.35 minutes, respectively. Digital workflows saved 39.2% more time than the conventional protocol for the single-implant crown treatment (P < .0001). Conclusions: Both digital and conventional workflow protocols can achieve a successful outcome for single-implant monolithic crowns in posterior areas. The digital protocol yielded greater timesaving over the conventional procedure in data acquisition and laboratory steps, while the time for clinical try-in and delivery were similar. [ABSTRACT FROM AUTHOR]

Endurance exercise can disturb intestinal epithelial integrity, leading to increased systemic indicators of cell injury, hyperpermeability, and pathogenic translocation. However, the interaction between exercise, diet, and gastrointestinal disturbance still warrants exploration. This study examined whether a 6-day dietary intervention influenced perturbations to intestinal epithelial disruption in response to a 25-km race walk. Twenty-eight male race walkers adhered to a high carbohydrate (CHO)/energy diet (65% CHO, energy availability = 40 kcal·kg FFM−1·day−1) for 6 days prior to a Baseline 25-km race walk. Athletes were then split into three subgroups: high CHO/energy diet (n = 10); low-CHO, high-fat diet (LCHF: n = 8; <50 g/day CHO, energy availability = 40 kcal·kg FFM−1·day−1); and low energy availability (n = 10; 65% CHO, energy availability = 15 kcal·kg FFM−1·day−1) for a further 6-day dietary intervention period prior to a second 25-km race walk (Adaptation). During both trials, venous blood was collected pre-, post-, and 1 hr postexercise and analyzed for markers of intestinal epithelial disruption. Intestinal fatty acid-binding protein concentration was significantly higher (twofold increase) in response to exercise during Adaptation compared to Baseline in the LCHF group (p =.001). Similar findings were observed for soluble CD14 (p <.001) and lipopolysaccharide-binding protein (p =.003), where postexercise concentrations were higher (53% and 36%, respectively) during Adaptation than Baseline in LCHF. No differences in high CHO/energy diet or low energy availability were apparent for any blood markers assessed (p >.05). A short-term LCHF diet increased intestinal epithelial cell injury in response to a 25-km race walk. No effect of low energy availability on gastrointestinal injury or symptoms was observed. [ABSTRACT FROM AUTHOR]

Clinical Scenario: Knee osteoarthritis (KOA) is a complex progressive synovial joint disease that results in impaired muscle function, including a considerable loss of maximal strength and power. Exercise therapies, such as sensorimotor or balance training and resistance training, are frequently used to improve muscle function, mobility, and quality of life, but their impact on maximal muscle strength in patients with KOA is not well understood. Focused Clinical Question: Does sensorimotor or balance training improve knee-extensor and knee-flexor maximal muscle strength compared with strength training or no intervention in patients with KOA? Summary of Key Findings: Results from 4 fair- to good-quality randomized controlled/clinical trials (level 1b) revealed inconsistent grade B evidence regarding the effect of sensorimotor or balance training to improve knee-extensor and knee-flexor maximal muscle strength in patients with KOA. Two studies, one good-quality study and one fair-quality study, showed significant strength improvements, and 2 good-quality studies demonstrated no significant strength enhancements. Clinical Bottom Line: Sensorimotor or balance training may be useful to improve maximal strength of quadriceps and hamstring muscle groups in patients with KOA; however, it seems that this depends on a training duration of at least 8 weeks and the use of unstable devices to induce destabilization of patients' balance, initiating neuromuscular adaptations. Strength of Recommendation: Due to inconsistent evidence (grade B), the true effect of sensorimotor or balance training to improve knee-extensor and knee-flexor maximal muscle strength in patients with KOA remains unclear and needs to be further investigated. [ABSTRACT FROM AUTHOR]

Focused ultrasound ablation provides a truly noninvasive tumor treatment option with clinically proven feasibility and safety. However, the frequently required long treatment duration hinders its clinical applicability. In this work, we compared the thermal ablation induced by conventional focused ultrasound (cFUS), split-focus ultrasound (sFUS), and acoustic vortex (AV) in tissue phantoms containing phase-change nanodroplets and mouse tumors. The results indicated that AV could substantially enhance the thermal ablation efficiency compared with cFUS, which was attributed to the larger focal region in the former. Additionally, the ablation region appeared as a unique cylindrical area with a smaller length-to-width ratio in AV than that in cFUS. Though the efficiency could also be improved in sFUS compared with cFUS, the ablation region was irregular and non-ablated tissues were present. Furthermore, in vivo experiments demonstrated that the tumor volume decreased faster and the mice survived longer after AV treatment compared with cFUS. The cavitation activity was also found to be more intense in AV ablation. The proposed method may solve the general issue of low efficiency often observed in cFUS ablation and further promote the development of other ultrasound treatments. [ABSTRACT FROM AUTHOR]

Purpose Procalcitonin (PCT) levels may play a role in decreasing the duration of antimicrobial therapy in institutions that have long durations of therapy for management of community-acquired pneumonia. We assessed the impact of the combination of pharmacist stewardship interventions assisted by a clinical decision support (CDS) tool and PCT assessment on the antimicrobial days of therapy (DOT) prescribed for respiratory tract infections (RTIs). Methods We conducted a quasi-experimental study in which patients in the preintervention group were admitted between April and June 2021 and patients in the intervention group were admitted between April and June 2022. In the intervention phase, a CDS tool was utilized to alert clinical pharmacists when patients met specific criteria. This alert was programmed to activate for individual patients when a reported PCT level was less than 0.25 ng/mL and the patient was on antimicrobials prescribed for an RTI as indicated by providers in the electronic health record. Stewardship interventions were made by pharmacists via prospective audit and feedback. The primary endpoint was inpatient antimicrobial DOT for RTIs. Results There were 90 patients in the preintervention group and 104 patients in the intervention group. Although baseline characteristics were not well matched between the groups, favoring the preintervention group, the median DOT was lower in the intervention group, at 3 days (interquartile range [IQR], 2-4 days), compared to 4 days (IQR, 2.8-5 days) in the preintervention group (P = 0.001). Conclusion The results of our study demonstrate the utility of pharmacist interventions coupled with CDS and PCT in reducing antimicrobial DOT prescribed for RTIs. Antimicrobial stewardship programs may benefit from implementing a PCT bundle. [ABSTRACT FROM AUTHOR]

Objectives: Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients. Background: SM is defined as a debilitating migraine attack lasting more than 72 h. There is no standard of care for SM, including whether a 72‐h duration is required before the attack can be treated as SM. Methods: The Refractory Headache Special Interest Group from AHS developed a four‐question survey distributed to AHS members enquiring (1) whether they treat severe refractory migraine attacks the same as SM regardless of duration, (2) what their first step in SM management is, (3) what the top three medications they use for SM are, and (4) whether they are United Council for Neurologic Subspecialties (UCNS) certified. The survey was conducted in January 2022. Descriptive statistical analyses were performed. Results: Responses were received from 196 of 1859 (10.5%) AHS members; 64.3% were UCNS certified in headache management. Respondents treated 69.4% (136/196) of patients with a severe refractory migraine attack as SM before the 72‐h period had elapsed. Most (76.0%, 149/196) chose "treat remotely using outpatient medications at home" as the first step, 11.2% (22/196) preferred procedures, 6.1% (12/196) favored an infusion center, 6.1% (12/196) sent patients to the emergency department (ED) or urgent care, and 0.5% (1/196) preferred direct hospital admission. The top five preferred medications were as follows: (1) corticosteroids (71.4%, 140/196), (2) nonsteroidal anti‐inflammatory drugs (NSAIDs) (50.1%, 99/196), (3) neuroleptics (46.9%, 92/196), (4) triptans (30.6%, 60/196), and (5) dihydroergotamine (DHE) (21.4%, 42/196). Conclusions: Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management. Plain Language Summary: In this research study, we asked members of the American Headache Society how they treat status migrainosus, a very severe migraine attack lasting more than 3 days. Out of the 196 people who answered the survey, most used stronger treatments before the headache lasted 72 h, and the majority preferred to use home‐based treatments to avoid the hospital. The five most common treatments they use are corticosteroids (like dexamethasone), nonsteroidal anti‐inflammatory drugs (like ketorolac), neuroleptics (like prochlorperazine), triptans (like naratriptan), and dihydroergotamine. [ABSTRACT FROM AUTHOR]

The multiple benefits of family-based treatment (FBT) used in substance use disorder (SUD) treatment include increased treatment engagement, better treatment outcomes, and cost-effectiveness compared to other behavioral health treatment modalities. However, the prevalence and types of FBTs offered among SUD treatment facilities are largely unknown. The present study used data collected during 2009–2010 from 325 treatment centers in the United States to (1) explore the prevalence in the utilization of FBT in SUD treatment, and (2) identify differences between treatment facilities that do and do not offer FBT. Results indicated that the adoption of FBT was negatively associated with the percentage of clients who were unemployed or involved in the criminal justice system at time of intake, and positively related to the number of hours of individual therapy and treatment center emphasis on utilizing the 12 Steps. Additionally, the majority of treatment centers that followed the American Society of Addiction Medicine (ASAM) clinical guidelines offered FBT. Lastly, the percentage of families involvement was negatively associated with centers' proportion of revenues from Medicaid (i.e., health insurance for those with limited income) and positively associated with treatment center revenues from private insurance. The impact of having FBT in SUD treatment centers is discussed. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to improve the efficiency of daytime surgery for gastrointestinal polyp and ensure the safety of patients. We tried an information management method based on WeChat platform in patients undergoing daytime gastrointestinal polypectomy and to explore the feasibility and effectiveness of a full management model. Methods: Five hundred and ninety‐three patients were randomly divided into two groups: the control group was treated with traditional management methods and the experimental group was treated with the whole‐process management mode based on the WeChat platform. The WeChat platform‐based full management model included establishing a day surgery management WeChat group, developing multidisciplinary, full‐management protocols and processes for day surgery, establishing an information‐based surgical scheduling system and adopting diverse forms of day surgery education and continuity of care. This feature included illustrated brochures, vivid verbal presentations, WeChat public numbers and Internet management platforms. The treatment time, hospitalization cost and patient satisfaction of the two groups were counted. Results: In the experimental group, 408 patients were enrolled. The preoperative waiting time and patients' length of stay were 3 days and 1 day, respectively. The medical and nursing intake time was 7 min. The procedure cancellation rate and postoperative complications rate was 0.07% and 0.02%. In the control group, 185 patients were enrolled in the study, The preoperative waiting time and patients' length of stay was 7 days and 3 days. The medical and nursing intake time was 28 min. The procedure cancellation rate and postoperative complications rate were 0.13% and 0.05%, respectively. The hospitalization costs were reduced by an average of $140/person and the satisfaction scores were higher than the control group. In summary, the preoperative waiting time, medical reception time, surgical cancellation rate, length of hospital stay and hospitalization cost in the observation group were less than those in the control group (p < 0.05). Patient satisfaction scores were significantly higher than those in the control group (p < 0.05). Conclusion: Through the full management model based on WeChat, the preoperative waiting time, medical reception time, surgical cancellation rate, length of hospital stay and hospitalization cost in the experimental group were less than those in the control group. Patient satisfaction scores were significantly higher than those in the control group and the difference was statistically significant. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis is the most common rheumatic disorder in childhood and adolescence posing a significant threat of short-term and long-term disability if left untreated. Methotrexate is a folic acid analog with various immunomodulatory properties. It has demonstrated significant efficacy for the treatment of juvenile idiopathic arthritis, often considered the preferred first-line disease-modifying anti-rheumatic drug given as monotherapy or in combination with biological drugs. Despite this, there is a considerable risk for treatment disruptions owing to the high prevalence of methotrexate intolerance, with symptoms such as nausea, stomach ache, vomiting, and behavioral symptoms. Many different risk factors for the intolerance have been proposed including gender, age, disease activity, treatment duration, dosing and administration, and genetic and psychological factors. As the studies have shown contradictory results, many questions are left unanswered. Therefore, a consensus regarding outcome measures and reporting is crucial. In this review, we describe the identification and assessment of methotrexate intolerance and evaluate potential risk factors, genetic associations as well as management strategies. [ABSTRACT FROM AUTHOR]

Introduction: Medullary thyroid carcinoma constitutes 5% to 10% of all thyroid cancers. Metastatic adenopathies may pose challenges in intricate anatomical locations, such as the parapharyngeal space. A rare case of metastatic medullary thyroid carcinoma in the parapharyngeal space has been treated in our unit using combined trans-cervical trans-oral robotic surgery. Our objective was to provide a detailed description of the surgery performed on this patient. Method: We reported a singular case report worth of interest. Result: A 42-year-old woman was addressed in our unit for the management of a medullary thyroid carcinoma adenopathy located in the right parapharyngeal space. A parapharyngeal 40.0 mm × 25.0 mm × 12.0 mm adenopathy was removed using a combined trans-cervical and trans-oral robotic approach without sacrifice or injury of vascular or nervous structure. Neither the tracheostomy nor the feeding tube was implemented. Feeding was resumed on postoperative day 1 and hospitalization spanned 7 days. Conclusion: An innovative combined trans-cervical and trans-oral robotic surgery approach was conducted to address a metastatic medullary thyroid carcinoma in the parapharyngeal space. This surgical technique allowed us to circumvent the need for a trans-mandibular approach, tracheostomy, and feeding tube and enabling successful tumor removal without fragmentation. Postoperative care was significantly eased. The sole complication observed was dysphonia, likely resulting from intra-operative stretching of the vagus nerve during the dissection of the carotid artery. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the risk factors for delayed chemotherapy–induced vomiting (DCIV) in pediatric oncology patients. We collected data on pediatric patients from a tertiary care pediatric hospital in an Asian urban center. We analyzed the risk factors for DCIV in patients by univariate analysis and logistic regression. Patients were grouped according to age by the Youden index, and differences in clinical features between the high-risk and low-risk groups were calculated. In the univariate analysis, the number of chemotherapy days, pH, and blood glucose levels were significantly associated with DCIV. In the logistic regression analysis, patient age was an independent risk factor (odds ratio [OR] = 1.013, 95% confidence interval [CI] = 1.005-1.021, P =.002). Children in the high-risk group had a higher grade of vomiting (P <.05). Age is an important risk factor for DCIV in pediatric patients, with older children tending to experience more frequent and more severe vomiting. [ABSTRACT FROM AUTHOR]

The number needed to treat (NNT) is the inverse of the absolute risk difference, which is used as a secondary outcome to clinical trials as a measure relevant to a positive trial, supplementing statistical significance. The NNT requires dichotomous outcomes and is influenced by the baseline disease or symptom severity, the particular population, the type and intensity of the interventional, the duration of treatment, the time period to assessment of response, and the comparator response. Confidence intervals should always accompany NNT for the precision of its estimate. In this review, three meta-analyses are reviewed, which included the NNT in the analysis of response. [ABSTRACT FROM AUTHOR]

Background: Many patients critically ill with COVID-19 develop acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation and proning. Although proning is lifesaving, it has been linked to the occurrence of facial pressure injuries (PIs). Objectives: To evaluate the incidence and use of prevention strategies and identify predictors of facial PIs in patients who received ventilator and proning treatments in COVID-designated intensive care units at 2 large quaternary medical centers in the Midwest. Method: This was a retrospective cohort study using data extracted from an electronic health record between October 2020 and February 2022. Demographics, clinical and care variables, and PI outcomes were analyzed to identify predictors of PI using logistic and Cox regression. Results: The cohort (N = 150) included patients from 2 units, unit a (n = 97) and unit b (n = 53) with a mean age of 60 years, with 68% identifying as male. Patients were vented for an average of 18 (SD, 16.2) days and proned for an average of 3 (SD, 2.5) days. Many (71%) died. Over half (56%) developed facial PI with a proning-exposure-adjusted incidence rate of 18.5%. Patients with PI were significantly different in several factors. Logistic regression showed predictors of PIs were duration of mechanical ventilation (in days; P = .02) and head turned (P = .01). Cox regression also identified head turn as predictive (P < .01), with Black/African American race as protective (P = .03) Discussion: Critically ill patients with COVID-19 receiving ventilator and proning therapy developed facial PIs despite the use of recommended prevention practices. Further research on effective PI prevention strategies is needed. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the influence of supervision, athlete age and sex and programme duration and adherence on exercise-based injury prevention programme effectiveness in sport. Databases were searched for randomized controlled trials evaluating exercise-based injury prevention programme effectiveness compared to "train-as-normal". A random effects meta-analysis for overall effect and pooled effects by sex and supervision and meta-regression for age, intervention duration and adherence were performed. Programmes were effective overall (risk ratio (RR) 0.71) and equally beneficial for female-only (0.73) and male-only (0.65) cohorts. Supervised programmes were effective (0.67), unlike unsupervised programmes (1.04). No significant association was identified between programme effectiveness and age or intervention duration. The inverse association between injury rate and adherence was significant (β=-0.014, p = 0.004). Supervised programmes reduce injury by 33%, but there is no evidence for the effectiveness of non-supervised programmes. Females and males benefit equally, and age (to early middle age) does not affect programme effectiveness. [ABSTRACT FROM AUTHOR]

Despite total shoulder arthroplasty (TSA) and reverse TSA (rTSA) being fundamentally different procedures, and indicated in different pathologies (rTSA for rotator cuff deficiency [RCD] and proximal humeral fractures [PHFx] and anatomic TSA [aTSA] for glenohumeral osteoarthritis [GHOA]), they have the same Current Procedural Terminology (CPT) code (23472). This paper's aim is to investigate differences in operative time and work-related value units (wRVUs) per hour among these pathologies, and ultimately determine if there is a need to assign separate CPTs for aTSA and rTSA. A retrospective cohort of data from the American College of Surgeons–National Surgical Quality Improvement Program was collected, all patients who underwent aTSA or rTSA (CPT: 23472) between the years of 2006 and 2019 for diagnoses of GHOA, RCD, and PHFx were included. Data collected included patient age, body mass index, operative time, and wRVUs per hour. Compared to GHOA (reference group), the average operative time for the RCD cohort was 12.242 minutes shorter (P <.001), while the wRVUs were higher by 1.627 (P <.001). The average operative time for rTSAs in the PHFx cohort were 17.615 minutes longer (P <.001), while the wRVUs were lower by 2.205 (P <.001). The average operative time for rTSAs for both RCDs and PHFx were longer than that for aTSAs for GHOA. Additionally, wRVUs were lower for rTSAs for RCD and PHFx compared to aTSAs for GHOA. This elucidates inconsistency in reimbursement structure for the procedures, which should be revisited. [ABSTRACT FROM AUTHOR]

Parents have long been concerned with the transition to adulthood of their children with intellectual and developmental disability (IDD) particularly with financial issues. The purpose of this study was to explore the financial concerns of mothers of adults with IDD. Five mothers of adults with IDD participated in a focus group to share their experiences, opinions, concerns, and challenges related to finances. Five themes emerged from the qualitative data analysis: (a) job-related difficulties, (b) living expenses, (c) access to essential services, (d), skills deficits and/or challenging behavior, and (e) long-term care. Mothers in general indicated tremendous financial burdens, loss of income, and expressed concerns about long-term care of their children with IDD. These themes are discussed and implications for practice and research are provided. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of Sanjie Analgesic Capsule (SAC) in Chinese patients with endometriosis-associated pain. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in China. Eligible 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group (241 cases) and placebo group (82 cases) by stratified block randomization. Patients in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day, orally, respectively since the first day of menstruation for 3 consecutive menstrual cycles. The primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 months. The secondary endpoint was the pain score evaluated by VAS (chronic pelvic pain, defecation pain, and dyspareunia) at 3 and 6 months, and the pain recurrence rate at 6 months. Adverse events (AEs) were recorded during the study. Results: A total of 241 women were included in the SAC group, and 82 were in the placebo group. Among these women, 217 (90.0%) and 71 (86.6%) completed the intervention, respectively. At 3 months, overall response rate (ORR) was significantly higher in women administered SAC (80.1%) compared with those who received a placebo (30.5%, P<0.01). Six months after treatment, the ORR for dysmenorrhea was 62.7% in the SAC group and 31.7% in the placebo group (P<0.01). Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo (both P<0.05). The incidence rates of total AEs events in the SAC and placebo groups were 6.6% and 9.8%, respectively, and no significant difference was shown between the two groups (P=0.339). Conclusion: SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain. (Trial registration: ClinicalTrials.gov, No. NCT02031523) [ABSTRACT FROM AUTHOR]

Introduction: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. Methods: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. Results: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9–98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. Conclusion: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. ClinicalTrials.gov Registration: NCT03892655. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. Methods: This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011–30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan–Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs). Results: Among 93 patients selected, median age at index was 67 years (interquartile range [IQR] 60–72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3 months (IQR 8.7–25.4 months), and median time from end of 1L therapy to 1LM initiation was 35.0 days (IQR 25.0–53.9 days). Median TTD was 9.3 months (95% CI 6.1–11.3 months). Median TTNT was 12.9 months (95% CI 11.5–19.0 months). Conclusions: This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC. [ABSTRACT FROM AUTHOR]

Polygonum minus Huds. has massive potential to be commercialized following many current discoveries of its medicinal properties. We investigated the growth and physiology changes of P. minus under different shading and treatment durations. The effects of four shading levels: 0% (T1), 30% (T2), 50% (T3) and 70% (T4) and two treatment durations of 10 weeks and 20 weeks were studied. Significant effects of shading levels and treatment durations were observed on the transpiration rate (E), leaf resistance, pigment content in leaves (Chl a, Chl b and Car), carbohydrate, ascorbic acid, total anthocyanin, phenolic and flavonoid contents. Enzyme activity of superoxide dismutase and ascorbate peroxidase were also significantly affected by shading levels and treatment durations. The highest antioxidant activities were recorded under T4 of both treatment durations along with the high content of Chl a, Chl b and Car. The leaf, stem and root extracts of P. minus were also subjected to HPLC analysis for quantification of selected flavonoid compounds. It was observed that longer treatment duration of 20 weeks reduced the amount of flavonoid. [ABSTRACT FROM AUTHOR]

Background: In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. Methods: This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. Results: The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P < 0.001). The VAS scores decreased over time, reaching 0 in all groups by 10 weeks. The mean scores in groups A and B were higher than those in the other groups at 2 and 4 weeks (P < 0.001), whereas the opposite was true at 8 weeks (P < 0.001). ATRS and the AOFAS Ankle-Hindfoot scale score increased across all groups over time, showing significant between-group differences from weeks 6 to 16 (P < 0.001) and weeks 6 to 12 (P < 0.001). The mean scores were better in groups A and B than in groups C and D. Thirty-eight complications (3.5%) were observed, including 20 re-ruptures and 18 superficial infections. All complications were resolved at the last follow-up, with no significant between-group differences. Conclusions: Immobilisation for 2 weeks after open surgery for ATR repair may be the optimal strategy for early rehabilitation with relatively minimal pain and other complications. Trial registration: ClinicalTrials.gov (NCT04663542). [ABSTRACT FROM AUTHOR]

ABSTRACT Neutropenia is a common chemotherapy‐associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 109/L or pretreatment ANC <1.5 × 109/L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%–69%) evaluable NEs, a nadir ANC of ≥0.75 × 109/L and pretreatment ANC of ≥1.5 × 109/L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%–48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%–70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%–69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%–27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%–25.8%) vincristine DRs. Seventy‐three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11). [ABSTRACT FROM AUTHOR]

Sepsis is a common cause of neonatal mortality and morbidity. Though antibiotics are the mainstay of treatment in culture‐positive neonatal sepsis, the dilemma persists for the optimum duration of antimicrobial therapy. The present study aimed to evaluate the efficacy of short‐course antibiotics for uncomplicated culture‐positive neonatal sepsis. This systematic review and meta‐analysis (PROSPERO: CRD42023444899) identified, appraised, and synthesised the available evidence from randomised and quasi‐randomised controlled trials related to the efficacy of short‐course (7–10 days) versus standard‐course (14 days) antibiotics for uncomplicated culture‐positive neonatal sepsis on the rate of treatment failure, mortality, duration of hospitalisation, morbidities including antibiotics‐related adverse events, long‐term neurodevelopmental outcomes and cost analysis. Data were pooled using RevMan 5.4 software. Certainty of evidence (COE) for predefined outcomes was analysed by GRADE. Available evidence showed no significant difference in the rate of treatment failure between 7‐ to 10‐day versus 14‐day antibiotics courses [risk ratio (95% confidence interval, CI), 2.45 (0.93–6.47), I2 = 0%, six studies, n = 573, very low COE]. No incidence of death was reported in either treatment arm in the two included studies. Duration of hospitalisation was significantly shorter with the short‐course antibiotics arm compared to standard‐course [mean difference (95% CI), −3.88 (−4.22 to −3.54) days, I2 = 0%, five studies, n = 507, low COE]. Morbidities reported in the three studies were similar. Other outcomes were not reported. To conclude the evidence is very uncertain about the effect of short‐course antibiotic regimen, compared to a standard‐course, on the treatment failure rate in uncomplicated culture‐positive neonatal sepsis. Adequately powered trials with outcomes including death and long‐term neurodevelopmental impairment are needed. [ABSTRACT FROM AUTHOR]

Background: In recent years, the utilization of autogenous vascularized iliac crest flap for repairing jaw defects has seen a significant rise. However, the visual monitoring of iliac bone flaps present challenges, frequently leading to delayed detection of flap loss. Consequently, there's a urgent need to develop effective indicators for monitoring postoperative complications in iliac crest flaps. Methods: A retrospective analysis was conducted on 160 patients who underwent vascularized iliac crest flap transplantation for jawbone reconstruction from January 2020 to December 2022. We investigated the changes in D-dimer levels among patients with or without postoperative complications. Additionally, multivariable logistic regression analysis was performed to explore potential individual risk factors, including surgical duration, age, pathology type, absolute and relative D-dimer levels, and gender, culminating in the development of a nomogram. Results: On the first day following surgery, patients who experienced thrombosis exhibited a substantial increase in plasma D-dimer levels, reaching 3.75 mg/L, 13.84 times higher than the baseline. This difference was statistically significant (P < 0.05) compared to patients without postoperative complications. Furthermore, the nomogram we have developed and validated effectively predicts venous thrombosis, assigning individual risk scores to patients. This predictive tool was assessed in both training and validation cohorts, achieving areas under the curve (AUC) of 0.630 and 0.600, with the 95% confidence intervals of 0.452–0.807 and 0.243–0.957, respectively. Conclusions: Our study illustrates that postoperative plasma D-dimer levels can serve as a sensitive biomarker for monitoring thrombosis-induced flap loss. Moreover, we have developed a novel prediction model that integrates multiple factors, thereby enhancing the accuracy of early identification of patients at risk of thrombosis-associated flap loss. This advancement contributes to improving the overall management and outcomes of such procedures. [ABSTRACT FROM AUTHOR]

Background and Aims: Systematic reviews and medical guidelines are widely used in clinical practice. However, these are often not up-to-date and focussed on the average patient. We therefore aimed to evaluate a guideline add-on, TherapySelector (TS), which is based on monthly updated data of all available high-quality studies, classified in specific patient profiles. Methods: We evaluated the TS for the treatment of hepatitis C (HCV) in an international cohort of patients treated with direct-acting antivirals between 2015 and 2020. The primary outcome was the number of patients receiving one of the two preferred treatment options of the HCV TS, based on the highest level of evidence, cure rate, absence of ribavirin-associated adverse effects, and treatment duration. Results: We enrolled 567 patients. The number of patients treated with one of the two preferred treatment options according to the HCV TS ranged between 27% (2015) and 60% (2020; p < 0.001). Most of the patients received a regimen with a longer treatment-duration (up to 34%) and/or addition of ribavirin (up to 14%). The effect on the expected cure-rate was minimal (1–6% higher) when the first preferred TherapySelector option was given compared to the actual treatment. Conclusions: Medical decision-making can be optimised by a guideline add-on; in HCV its use appears to minimise adverse effects and cost. The use of such an add-on might have a greater impact in diseases with suboptimal cure-rates, high costs or adverse effects, for which treatment options rely on specific patient characteristics. [ABSTRACT FROM AUTHOR]

Background: This study aims to comprehend the levels of dry mouth and thirst in patients after general anesthesia, and to identify the factors influencing them. Methods: The study included all patients transferred to the Post Anesthesia Care Unit (PACU) at the Second Affiliated Hospital of Dalian Medical University between August 2021 and November 2021 after undergoing general anesthesia. A thirst numeric rating scale was utilized to conduct surveys, enabling the assessment of thirst incidence and intensity. Statistical analysis was performed to explore patient thirst levels and the associated factors. Results: The study revealed a thirst incidence rate of 50.8%. Among the thirst intensity ratings, 71.4% of patients experienced mild thirst, 23.0% reported moderate thirst, and 5.6% expressed severe thirst. Single-factor statistical analysis of potential risk factors among the enrolled cases indicated that gender, history of coronary heart disease, surgical duration, intraoperative fluid volume, intraoperative blood loss, intraoperative urine output, and different surgical departments were linked to post-anesthetic thirst in patients undergoing general anesthesia. Multifactorial Logistic regression analysis highlighted age, gender, history of coronary heart disease, fasting duration, and intraoperative fluid volume as independent risk factors for post-anesthetic thirst in patients undergoing general anesthesia. Moreover, age, gender, history of coronary heart disease, and intraoperative fluid volume were also identified as risk factors for varying degrees of thirst. Conclusion: The incidence and intensity of post-anesthetic thirst after general anesthesia are relatively high. Their occurrence is closely associated with age, gender, history of coronary heart disease, fasting duration, and intraoperative fluid volume. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the clinical efficacy of minimally invasive endoscopic treatment of children with congenital muscular torticollis (CMT). Methods: In total, 72 children (41 male, 31 female) with CMT who underwent endoscopic surgery at the Department of Orthopedics, Xi'an Children's Hospital, between January 2021 and January 2023 were included. Their mean age was 54 ± 36.1 (range, 12–141) months. Of these, 29 (40.3%) cases involved the left side while 43 (59.7%) involved the right side. Preoperative preparation involved precise body surface markings of the sternocleidomastoid muscle(SCM), clavicle, and important nerve and blood vessels, followed by the establishment of surgical channels through passive separation techniques. An arthroscope and a low-temperature plasma knife were utilized for accurate localization and surgical release of the clavicular and sternal heads of the SCM. The duration of surgery, blood loss, postoperative hospital stay, neck range of motion measurements, and any intraoperative or postoperative complications were analyzed using the rank sum test. Cervical and thoracic braces were applied for three months postoperatively, with follow-up assessments conducted using Cheng's scoring system. Results: All patients successfully underwent endoscopic surgery, without the need for conversion to open surgery. No intra- or postoperative complications were observed. The average surgical duration was 56.4 ± 15.7 min, with minimal intraoperative bleeding (1–5 mL) and no need for blood transfusion. The mean postoperative hospital stay was 2.7 ± 0.8 days. Over a mean follow-up period of 22.2 ± 5.5 (range, 14–32) months, significant improvements were observed in neck rotation (from 20.2° [17.7° to 25°] to only 3.6° [2° to 6.7°]) and lateral flexion (from 19° [17° to 22.6°] to only 3° [2° to 7.8°]) restrictions (p < 0.05). According to Cheng's scoring system, 70 (97.2%) patients achieved excellent or good clinical outcomes, while 2 (2.8%) had average outcomes. The torticollis deformity was corrected during the follow-up period, and all surgical incisions healed without noticeable scarring. Conclusion: Endoscopic release is a safe, effective, and minimally invasive treatment option for CMT in children. [ABSTRACT FROM AUTHOR]

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Lung ultrasound (LU) and clinical parameters evaluated during the first postnatal hour potentially predict the length of CPAP therapy in newborns with respiratory distress.In a single‐centre, prospective observational pilot study, 130 newborns ≥36 weeks gestational age were assessed using standardised LU at 30 and 60 min postnatally. Various clinical parameters were evaluated influencing CPAP duration (<1 vs. ≥1 h) using univariate and multivariate analyses.Lung ultrasound score >5, FiO2 > 0.21 and respiratory acidosis 30 min postnatally were associated with CPAP ≥1 h. Our model showed good diagnostic quality (ROC AUC = 0.87) and was confirmed by classification and regression tree (CART) analysis. Additional LU findings like double lung point and pleural line abnormalities were frequently observed, with good interrater reliability for LU interpretation (ICC = 0.76–0.77).Newborns with postnatal respiratory distress at risk for prolonged CPAP therapy can be identified based on specific LU and clinical parameters assessed 30 min postnatally. Despite the need for validation in an independent sample, these findings may lay the groundwork for a prediction tool. LU proved feasible and reliable for assessing respiratory status in this population, highlighting potential utility in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Respiratory distress and failure is a complication of the coronavirus disease (COVID-19) and tracheostomy may be necessary in cases of prolonged intubation in order to reduce mechanical ventilation duration. However, according to the Canadian Society of Otolaryngology-Head and Neck Surgery guidelines, which our institution applies, patients should not undergo tracheostomy unless cleared of the virus to reduce its spread among healthcare workers because tracheostomy is an aerosolized procedure. This study aimed to identify the outcomes of prolonged intubation in patients with and without COVID-19 who underwent tracheostomy and to determine the morbidity and mortality rates in both groups. Methods: This retrospective cohort study included adult patients admitted to the intensive care unit of King Fahad Hospital of the University, Alkhobar, Saudi Arabia, between March 1 and October 31, 2020. This study compared and analyzed the outcomes of delayed tracheostomy in patients with and without COVID-19 in terms of complication, morbidity, and mortality rates. Results: Of the 228 study participants, 111 (48.68%) had COVID-19. The mean age of the study participants was 58.67 years (SD = 17.36, max.=93, min.=20), and the majority were males (n = 149, 65.35%). Regarding tracheostomy in patients with COVID-19, 11 (9.91%) patients underwent tracheostomy; however, four (36.36%) of them had prolonged intubation. The mean intensive care unit admission length of stay for tracheostomy patients was 37.17 days, while it was 12.09 days for patients without tracheostomy (t(226)=-9.32, p < 0.001). Regarding prolonged intubation among patients with COVID-19 (n = 7, 6.31%), the complications were as follows: six people (85.71%) had dysphonia, one (14.29%) had vocal cord granuloma, and two (28.57%) had subglottic tracheal stenosis. The mortality rate among our study participants was 51.32%, and the risk was significantly higher in older people (Odds ratio = 1.04, 95% Confidence Interval [CI] = 1.02–1.06) and in delayed tracheostomy cases (OR = 2.95, 95% CI = 1.31–6.63). However, COVID-19 status was not significantly related to the risk of mortality. Conclusions: Delaying tracheostomy increases the risk of mortality. Therefore, we recommend weighing the risks and benefits for each patient to benefit both healthcare workers and patients with COVID-19. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study is to show how sodium nitrite alters the histology of submandibular salivary glands and livers of Albino rats, as well as how chlorogenic acid may have therapeutic benefits. Methods: A sample size of thirty male Sprague Dawley Albino rats weighing between 100 and 150 g (5-6 weeks old) was randomly allocated into 3 equal groups. Group I: rats were used as controls and were given phosphate buffer solution, whereas Group II: rats were given an 80 mg/kg sodium nitrites (SN) daily dissolved in distilled water. The rats in Group III were given a daily dose of 80 mg/kg SN dissolved in distilled water and after 6 hours each rat received 50 mg/mL freshly prepared chlorogenic acid (CGA) every other day. For 12 weeks, all treatment modalities will be administered orally, every day. After the experiment, all rats were euthanized. Samples from salivary glands and livers were processed and stained with H&E and interleukin 6 (IL 6). Malondialdehyde (MDA) and superoxide dismutase (SOD) enzymes were detected using an ELISA assay. Results: Groups III had nearly comparable findings to Group I regarding histological pattern with normal submandibular glands and livers features. Group III salivary gland treated with CGA exhibited higher SOD levels (20.60±4.81 U/g) in comparison to the SN group, and lower MDA levels (111.58±28.28 nmol/mg) in comparison to the SN treated samples. In comparison to the SN group, CGA treatment significantly reduced MDA levels in liver samples (167.56±21.17 nmol/mg) and raised SOD (30.85±6.77 U/g). Conclusions: Chlorogenic acid has a protective effect against salivary gland and liver toxicity induced by SN in rats. This was mediated via the anti-inflammatory and antioxidative properties of CGA and the restoration of oxidant/antioxidant balance in rat salivary gland and liver. [ABSTRACT FROM AUTHOR]

Background: Outpatient parenteral antimicrobial treatment (OPAT) is a safe and effective therapy used in several settings across Australia. As OPAT services expand their inclusion criteria to include complex patient populations, there is an increased need for selecting appropriate patients to receive either healthcare‐administered OPAT (H‐OPAT) or self‐administered OPAT (S‐OPAT). Aims: To describe patient demographics, diagnosis, microbiology and outcomes of patients treated by H‐OPAT and S‐OPAT within the Sunshine Coast Hospital and Health Service, Australia. Methods: Data on demographics, diagnoses, treatment and outcomes on all patients treated by H‐OPAT and S‐OPAT from March 2017 to December 2019 were collected retrospectively. Results: One hundred and sixty‐five patients (62.26%) were enrolled in H‐OPAT and 100 patients (37.74%) in S‐OPAT. S‐OPAT patients were significantly younger. H‐OPAT patients were more comorbid. Bone and joint infections were the most treated infections and were more likely to be treated by S‐OPAT. There was no difference in treatment duration, cure and complication rates between S‐OPAT and H‐OPAT. Longer duration of therapy was associated with more complications. Treatment failure was associated with infections due to multiple organisms, number of comorbidities and treatment of surgical site, skin and soft tissue infections. Conclusions: There were significant differences in demographics between H‐OPAT and S‐OPAT without any difference in outcomes. Overall failure and complication rates were low. Higher rates of treatment failure were predicted by the diagnosis, number of comorbidities and number of organisms treated. [ABSTRACT FROM AUTHOR]

Purpose: Paraprobiotics are a non-viable form of probiotics that are reported to provide significant health benefits. Nevertheless, little is known about the beneficial effects of paraprobiotics on inflammatory bowel disease. Although probiotics show potential as therapeutic agents for a range of diseases, including inflammatory bowel disease (IBD), there are certain risks associated with their use. These risks include toxin production, hemolytic potential, antibiotic resistance, and the need to analyze metabolic activities. Hence Using paraprobiotic with the lower aforementioned risk would therefore be the preferable option. Here, we conducted an in vivo study to evaluate the preventive effect of our native paraprobiotic cocktail against dextran sulfate sodium (DSS)-induced murine colitis by affecting the autophagy signaling pathway. Methods: Four-week-old male C57Bl/6 mice were randomly divided into three groups after a two-week acclimation period with normal standard laboratory food diet. Mice were administered PBS (PBS group as control), PBS along with DSS (DSS group, as a control), and a cocktail of paraprobiotics along with DSS (Para group). The severity of colitis, length and histopathology of the colon were evaluated. In addition, the expression of autophagy was assessed using real-time PCR. Results: The results showed that administration of the paraprobiotic cocktail to DSS-treated mice inhibited the severity of colitis symptoms, as evidenced by the inhibition of weight loss and DAI, as well as histopathological scores in the study colon, as well as shortening of colon length caused by DSS. In contrast to the DSS group, the cocktail was able to modulate inflammation through upregulation of autophagy-related genes (becline 1, atg5, atg7, atg12, and atg13). Conclusion: Although there are some limitations in our investigation, such as the dosage and duration of treatments, our native paraprobiotic blend effectively prevented the advancement of colitis. This suggests that it plays a vital role in regulating inflammation and preventing colitis by promoting the autophagy mechanism in cases where the consumption of probiotics may have negative consequences. [ABSTRACT FROM AUTHOR]

Background: Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval‐prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high‐quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil. Methods: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age ≥18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non‐fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random‐effects meta‐analyses were performed with a treatment‐arm continuity correction for single and double zero event studies. Results: Sixty RCTs (n = 12,463) were included. Twenty‐five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow‐up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88–1.33, I2 = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88–1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow‐up ≥52 weeks (RR: 1.32, 0.98–1.79). Conclusions: This systematic review with meta‐analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices. [ABSTRACT FROM AUTHOR]

Simple Summary: A model predicting responders to corticosteroid switch during abiraterone therapy in patients with metastatic castration-resistant prostate cancer is warranted. The model using logistic regression was developed in a cohort of 67 and validated in another cohort of 42 patients. The use of this model is easy and all needed parameters are available from routine laboratory and history of patients. The overall accuracy was 92%. Multivariate analysis revealed that responsiveness was a marker of longer treatment duration and overall survival. For non-responders a new systemic treatment was indicated. Background: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients' history was used to find the best model in a cohort of 67 patients. The model was validated in another cohort of 42 patients. Results: The model provided 92.5% and 90.5% accuracy in the testing and the validation cohorts, respectively. Overall the accuracy was 91.7%. The AUC of ROC curve was 0.92 (95% CI 0.85–0.96). After a median follow-up of 27.9 (26.3–84) months, the median AA+dexamethasone treatment duration (TD) in non-responders and responders was 4.7 (3.1–6.5) and 11.1 (8.5–12.9) months and the median overall survival (OS) was 23.2 (15.6–25.8) and 33.5 (26.1–38) months, respectively. Multivariate Cox regression revealed that responsiveness was an independent marker of TD and OS. Conclusions: A high accuracy model was developed for mCRPC patients in predicting cases which might benefit from the switch. For non-responders, induction of the next systemic treatment is indicated. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients diagnosed with gynecological and breast cancer undergo multimodal treatments leading to estrogen deprivation and vaginal damage in case of radiotherapy, resulting in significant impairments of vulvo-vaginal function. Non-ablative intravaginal CO2 laser is a promising technique for VVA (vulvo-vaginal atrophy) in breast cancer, gynecological and other pelvic cancer survivors. In this study we explored the effectiveness and the long-term effects of repeated cycles of laser therapy. This therapeutic regimen could represent an effective treatment option for patients with limited therapeutic alternatives due to the hormone-sensitivity frequently showed by these cancers. This study aimed to investigate the efficacy and duration of multiple non-ablative intravaginal CO2 laser (V-lase®) cycles in breast cancer patients, gynecological and other pelvic cancers previously subjected to multiple oncological treatments. This prospective study enrolled women under the age of 65 years who reported vaginal symptoms. Data on the Vaginal Health Index (VHI), vaginal length (VL), vaginal pain measured using a Visual Analog Scale (VAS), and the Female Sexual Function Index (FSFI) were collected at baseline and before each laser application, and at subsequent follow-up visits. A total of 170 laser applications were performed on 113 women with various types of cancer. Most patients (57.5%) had received radiotherapy-based treatments before receiving laser treatment. Vaginal health parameters and sexual function improved significantly with each laser application. However, a temporary decline in these improvements occurred during the intervals between cycles. Such worsening was reversed with the subsequent cycle in all groups of patients, irrespective of the type of oncological treatments they had undergone. Multiple course vaginal laser therapy showed promising results as a potential treatment for vaginal atrophy in heavily treated gynecological and breast cancer patients, necessitating further research to determine the optimal time interval between cycles to ensure sustained positive effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide receptor radionuclide therapy using 177Lu-DOTATATE is a standard therapy for patients with metastatic neuroendocrine tumors. Many patients with liver-dominant disease undergo liver embolization as an earlier line of treatment. It is unclear whether prior embolization impacts the safety and efficacy of subsequent 177Lu-DOTATATE treatment. We analyzed 171 patients who underwent treatment with 177Lu-DOTATATE, among whom 61 underwent prior embolization. There was no significant difference in serious liver toxicity or radiographic progression of liver tumors between the group that had undergone prior embolization and the group that had not. The conclusion is that peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients who had prior liver embolization is both safe and effective. Rationale: Evaluating the long-term safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumors (mNETs) who have undergone prior bland hepatic transarterial embolization (TAE). Methods: Retrospective review of mNET patients who received PRRT with 177Lu-DOTATATE between 4/2018 and 02/2022 with and without prior TAE. The most recent clinical, imaging, and laboratory findings, including hepatic Common Terminology Criteria for Adverse Events v5.0, were compared to pre-PRRT. Results: 171 patients (95 M, 76 F, median age = 66) with mNET of different primary sites (9 foregut, 100 midgut, 9 hindgut, 44 pancreas, 9 unknown) received at least 1 cycle of PRRT with at least 6 months of follow-up, 110 of whom were embolization-naïve and 61 who had prior TAE. The median follow up was 22 months (range: 6–43). Patients with prior TAE had higher liver tumor burden on average than patients without prior TAE; however, the difference was not statistically significant (p = 0.06). There was no significant difference in the rates of G3 or G4 hepatotoxicity (p = 0.548 and p = 0.999, respectively) in patients who underwent prior TAE and those who were TAE-naïve. The hepatic progression-free survival was 22.9 months in TAE-naïve patients and 25.7, 20.2, and 12.8 months in patients with 1, 2, and 3 prior TAE treatments, respectively. Conclusion: Peptide receptor radionuclide therapy following transarterial bland embolization for mNET is safe and effective. [ABSTRACT FROM AUTHOR]

Background/Objectives: Data on the long-term effects of oxybutynin in patients with neurogenic bladder (NGB) due to spinal cord injury (SCI) are limited. This study aimed to evaluate the long-term effects of oxybutynin and the combination of oxybutynin with trospium in these patients, under real-world medical conditions. Methods: A total of 107 patients with NGB due to SCI were included. The mean treatment duration was 2.8 years ± 0.8 years. The patients were categorized into three groups: (1) low-dose oxybutynin (5–15 mg/day), (2) high-dose oxybutynin (20–40 mg/day), and (3) oxybutynin combined with trospium. The main outcomes were maximal detrusor pressure (MDP) and cystometric bladder capacity (CBC). Both were assessed at baseline and at three subsequent follow-up visits. Generalized estimation equation models were used to estimate the overall mean reduction in MDP and CBC for each group. Results: The overall adjusted mean reduction from baseline of MDP in groups 1, 2, and 3 were 2.5 (95% CI: −5.4 to 10.4; p = 0.540), 16.9 (95% CI: 4.4 to 29.4; p = 0.008), and 21.9 (95% CI: 4.1 to 39.8; p = 0.016) cmH2O, respectively. For the CBC, the mean reduction was not significant in any group at any visit, nor were the overall mean reductions. Conclusions: These findings suggest that high-dose oxybutynin and oxybutynin–trospium combination achieve a significant long-term reduction in MDP in patients with NGB after SCI. The effects were sustained across all three follow-up periods. [ABSTRACT FROM AUTHOR]

Long-term use of anabolic-androgenic steroids (AAS) might lead to distressing withdrawal symptoms following cessation. This paper aims to share challenges in recruiting patients to a pilot intervention study with parallel substance use disorder (SUD) treatment and to explore barriers to participation among AAS forum members. Eligible AAS-dependent men were recruited to receive hormone therapy for 16 weeks, and exclusion reasons were registered. Audience engagement from social media advertisements was measured. Information about the study was posted in an AAS online forum, and discussion among forum members was thematically analyzed. Twelve of 81 potential participants were included, whereas ten completed the intervention. Participants were excluded due to residency outside the study area, illicit substance use or severe medical conditions. Challenges in recruitment were linked to the COVID-19 pandemic, funding and advertisements on social media. AAS forum members suggested modifications to the intervention, were skeptical to the SUD-patient requirement, feared prosecution or other negative outcomes and/or preferred to seek online advice on self-initiated testosterone replacement therapy or post cycle therapy. AAS-related online recommendations among peers, criminalized AAS use setting and obligatory SUD treatment might have affected recruitment. Based on lessons learned, recommendations for future similar studies are presented. [ABSTRACT FROM AUTHOR]

Objective To determine whether persistent complete B cell (BC) depletion was associated with a better clinical response in rheumatoid arthritis (RA) patients long-term treated with rituximab (RTX). Methods We conducted a retrospective study including RA patients admitted for a new infusion between 2019 and 2021. The primary endpoint was the comparison of the mean disease activity score based on 28 joints (DAS28)-CRP at each of the four last infusion visits between patients with persistent complete BC depletion (mean CD19 counts <18/µl at each of the last four visits) or without persistent complete BC depletion (mean CD19 counts of the last four visits ≥18/µl). Secondary endpoints included DAS28, pain/fatigue visual analogue scale, CRP, gammaglobulins and the frequency of self-reported RA flares. Results Of the 126 patients in maintenance therapy with RTX [exposure period: 76 (5) months, 14 (7) infusions received], 43 (34%) had persistent complete BC depletion at each of the four last infusions. The mean DAS28-CRP calculated at each of the four last infusion visits did not significantly differ according to persistence or not of complete BC depletion. This result remained unchanged after adjusting for antibody status, number of previous therapies, number of RTX infusion and cumulative RTX dose. All secondary outcomes were also not significantly different between the two groups. Conclusion Maintaining complete BC depletion does not appear to be a therapeutic target to achieve in RA patients in long-term maintenance therapy with RTX. There is a limited benefit of monitoring CD19 in RA patients long-term treated with RTX and having achieved low disease activity/remission. [ABSTRACT FROM AUTHOR]

Objectives Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (i) drug survival and (ii) disease activity at 6 months and 12 months, compared with those who remain on the originator. Methods Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving the originator, based on gender, age, disease duration and originator start year. Drug survival was calculated; Cox-proportional hazard models assessed differences in drug persistence between those who switched vs remaining on originator. Change in DAS28 after 6 months and 12 months was compared between cohorts. Multiple imputation was used. Results A total of 1024 adults with RA switching from etanercept originator to biosimilar were included, with a matched cohort of patients remaining on the originator. Patients who switched onto a biosimilar product were no more likely to discontinue etanercept treatment vs those who remained on the originator; hazard ratio 1.06 (95%CI 0.89–1.26), with 65% of patients remaining on treatment at three years. Ninety-five (9%) patients switched back to the originator within the first year. After 6 months and 12 months, biosimilar patients were no more likely to have a worsening of DAS28 (>0.6 units) compared with those who remained on the originator. Conclusions This is the largest matched comparative effectiveness analysis showing patients switching from etanercept originator to biosimilar appearing to do just as well with regard to disease activity and drug persistence compared with those who remained on the originator. These data will be reassuring to clinicians and patients regarding non-medical switching. [ABSTRACT FROM AUTHOR]

Objectives: The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long‐acting regimens in a 'real world' Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non‐adherence. Methods: JABS was a 12‐month, single‐centre, single‐arm, open‐label phase IV study of long‐acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV‐1 infection. The primary endpoint was the proportion of attendances and administration of injections within a 14‐day dosing window over 12 months, out of the total prescribed doses. Secondary endpoints included proportions of missed appointments, use of oral bridging, discontinuations, virological failures, adverse events and participant‐reported outcomes. A multidisciplinary adherence programme embedded in the clinical service known as REACH provided support to JABS participants. Results: Of 60 participants enrolled by May 2022, 60% had one or more complexity or vulnerability factors identified, including absence of social supports (50%), mental health issues, alcohol or drug use (30%) and financial hardship or instability (13%), among others. Twenty‐seven per cent of participants had historical non‐adherence to antiretroviral therapy. Out of 395 prescribed doses, 97.2% of injections were administered within correct dosing windows at clinic visits. Two courses of short‐term oral bridging were required. The rate of injection site reactions was 29%, the majority being grade 1–2. There were no virological failures, no serious adverse events and only one injection‐related study discontinuation. High baseline treatment satisfaction and acceptability of injections increased by month 12. Those with vulnerability factors had similar adherence to injections as those without such factors. Ninety‐eight per cent of the participants who completed 12 months on the study have maintained long‐acting therapy, virological suppression and retention in care. Conclusions: Long‐acting cabotegravir plus rilpivirine was associated with very high adherence, maintenance of virological suppression, safety and treatment satisfaction in a diverse Australian clinic population, comparable to results of phase III randomized clinical trials. Individuals with vulnerability factors can achieve adherence to injections with individualized support. Long‐acting therapies in this group can increase the subsequent engagement in clinical care. [ABSTRACT FROM AUTHOR]

To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies. Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4–10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score. Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7–24) years. Median duration of TCZ therapy was 15 (range, 5–32) months. Mean CST reduced from 373 ± 101.0 μm to 298.2 ± 40.3 μm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases. IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis. [ABSTRACT FROM AUTHOR]

Registry-based observational prospective study aimed at describing the use of biologic drugs in pediatric-onset scleritis. Data were collected at baseline, at 3-, 6-, 12-month follow-up and at last assessment. Scleral inflammation was graded according to Sen classification. Five patients (9 eyes) treated with adalimumab, infliximab, abatacept and secukinumab were included. All patients were previously treated with conventional immunosuppressors and glucocorticoids. Median biologic treatment duration was 28 (IQR = 118) months. At 6-months, scleritis resolved in all eyes. At 12-months, complete disease control was observed in 7/9 eyes (77.8%). The number of relapses 12 months before and after treatment initiation was 17 and 2, respectively. Mean BCVA was 0.83 (range 0.3–1.0) at baseline and 1.0 for all eyes after 12 months. Glucocorticoids had been withdrawn in 4/5 patients. In conclusion, biological agents proved to be effective in pediatric-onset scleritis, allowing a noticeable steroid-sparing effect and preserving visual function and bulbar integrity. [ABSTRACT FROM AUTHOR]

Context.--: Extracorporeal membrane oxygenation (ECMO) is increasingly used in the treatment of respiratory and cardiac failure, but data describing lung histopathology in ECMO recipients are limited. Objective.--: To examine pulmonary histopathologic findings in patients who underwent venovenous (VV) ECMO for pulmonary reasons or venoarterial (VA) ECMO for cardiac indications shortly before death, and to determine if the pulmonary changes provided insights into therapy that may prevent complications and improve outcome. Design.--: We conducted a retrospective study of lung autopsies, from VV and VA ECMO recipients and patients with acute respiratory distress syndrome (ARDS) and non-ECMO treatment, between 2008 and 2020 in Silesia Center for Heart Diseases in Zabrze, Poland. Results.--: Among 83 ECMO patients (42-64 years; men, 57 [68.7%]), the most common histopathologic findings were bronchopneumonia (44 [53.0%]), interstitial edema (40 [48.2%]), diffuse alveolar damage (DAD; 32 [38.6%]), hemorrhagic infarct (28 [33.7%]), and pulmonary hemorrhage (25 [30.1%]). DAD was associated with longer ECMO treatment and longer hospital stay. The use of VV ECMO was a predictor of DAD in patients with ARDS and undergoing ECMO, but it also occurred in 21 of 65 patients (32.3%) in the VA ECMO group, even though VA ECMO was used for heart failure. Conclusions.--: Although DAD was significantly more common in lung autopsies of VV ECMO patients, one-third of VA ECMO patients had histopathologic changes characteristic of ARDS. The presence of DAD in lung autopsies of patients treated with VA ECMO indicates that in these patients, protective lung ventilation should be considered. [ABSTRACT FROM AUTHOR]

Objective: Posterior left atrial wall isolation (PWI) plus traditional pulmonary vein isolation (PVI) has been proposed as a promising intervention to decrease atrial fibrillation (AF) recurrence. We aim to investigate the efficacy and safety of adding PWI to the traditional PVI in patients with AF. Methods: A systematic review and meta‐analysis was conducted using synthesizing randomized controlled trials (RCTs) retrieved by systematically searching PubMed, Web of Science, SCOPUS, EMBASE, and Cochrane through June 14, 2023. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023446227). Results: We included 11 RCTs with a total number of 1534 patients. Combined ablation with PWI + PVI was not associated with any significant difference over PVI only regarding the recurrence of clinical AF (RR: 0.86 with 95% CI [0.70–1.06]), all atrial arrhythmia (RR: 0.93 with 95% CI [0.82–1.07]), nonatrial fibrillation arrhythmia (RR: 1.22 with 95% CI [0.97–1.53]), early AF (RR: 0.89 with 95% CI [0.62–1.27]), and antiarrhythmic drugs at discharge (RR: 0.83 with 95% CI [0.67–1.04]). However, it was associated with increased total ablation duration (minutes) (MD: 12.58 with 95% CI [6.80–18.37]) and total procedure duration (minutes) (MD: 16.77 with 95% CI [9.63–23.91]), without any significant difference regarding adverse events (RR: 1.05 with 95% CI [0.63–1.74]). Conclusion: While the pooled data from PWI + PVI using point‐by‐point radiofrequency did not suggest a benefit in the recurrence of various atrial arrhythmias compared to PVI alone, PWI+PVI using direct posterior wall ablation, especially with cryoballoon, demonstrated a significant reduction in recurrence of AF/atrial arrhythmias. Also, PWI + PVI significantly increased the ablation and total procedure durations. [ABSTRACT FROM AUTHOR]

This study was to evaluate and compare the efficacy and safety of endoscopic mucosal resection (EMR), clip-and-snare assisted endoscopic mucosal resection (CS-EMR), and endoscopic submucosal dissection (ESD) for the endoscopic resection of rectal NETs. A retrospective analysis was performed on 47 patients with rectal NETs who underwent endoscopic treatment in The Second Affiliated Hospital of Soochow University. Manifestations of clinic pathological characteristics, complications, procedure time and hospitalization costs were studied. The complete resection rates with CS-EMR and ESD were significantly higher than those with EMR (CS-EMR vs. EMR, p = 0.038; ESD vs. EMR, p = 0.04), but no significant difference was found between the CS-EMR and ESD groups (p = 0.383). The lateral margin was less distant in the CS-EMR group than in the ESD group and there was no difference with regard to vertical margin (lateral margin distance, 1500 ± 3125 vs.3000 ± 3000 μm; vertical margin distance, 400 ± 275 vs.500 ± 500 μm). Compared to ESD, CS-EMR required less operation time (p < 0.01) and money (p < 0.01) and reduced the length of hospital stays (p < 0.01). The CS-EMR technique is more effective and efficient than EMR for small rectal NETs. In addition, CS-EMR reduces procedure time, duration of post-procedure hospitalization and decreases patients' cost compared to ESD while ensuring sufficient vertical margin distances. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively evaluate the feasibility and safety of a polyetheretherketone (PEEK) polymer transpedicular vertebral system to treat vertebral compression fracture (VCF). Methods: Nine consecutive patients (4 men and 5 women; median age 59 [interquartile range: 58-64 years]) were included. The procedure duration, length of hospital stay, and complications were reported. Visual analog scale (VAS) and the Oswestry disability index (ODI) for pain and disability were assessed before and at 2, 6, and 12-month after the procedure. Results: The procedure was technically feasible in all patients. The median procedural time was 64 minutes [45-94]. Only minor adverse events were reported (5 clinically asymptomatic cement leakages) but no severe complications. No post procedural adjacent fracture was reported during follow-up (median: 193 days [147-279]). The median VAS score decreased from 55 mm [50-70] before the procedure to 25 mm [5-30] at 2-month (P =.0003) and 30 mm [15-40] at 6-month follow-up (P =.14). The median ODI decreased from 23% [19-26] before the procedure to 12% [10-14] at 2-month (P =.03) and 12% [9-20] at 6-month follow-up (P =.47). Conclusion: Percutaneous transpedicular fixation of VCF by PEEK implants appears feasible and safe. [ABSTRACT FROM AUTHOR]

Background: This study aims to compare three commonly used energy devices for dissection during Video-Assisted Thoracoscopic Surgery (VATS) lobectomy: monopolar hook, advanced bipolar, and ultrasonic device, in terms of duration of the surgical procedure and clinical intra- and post-operative outcomes. Materials and methods: In this prospective single-center study, 75 patients undergoing VATS lobectomy for non-small cell lung cancer between January 2022 and May 2023 were enrolled and divided into 3 groups based on the device used during the surgical procedure (Group 1: Ultrasonic Device, Group 2: Advanced Bipolar, Group 3: Monopolar Hook). The duration of the surgical procedure, daily pleural fluid production, post-operative pain, length of hospital stay, and occurrence of post-operative complications were compared for each group. In a subgroup of 20 patients (10 from Group 1 and 10 from Group 3), concentrations of inflammatory cytokines in pleural fluid at 3 h and 48 h post-surgery were analyzed. Results: Pleural fluid production on the first and second post-operative days was significantly lower in patients treated with the Ultrasonic device compared to the other two groups (p < 0.001). The duration of the surgical procedure was significantly shorter when using the Ultrasonic device (p < 0.001). There were no significant differences in length of hospital stay (p = 0.975), pain on the first and second post-operative days (p = 0.147 and p = 0.755, respectively), and blood hemoglobin levels on the first post-operative day (p = 0.709) and at discharge (p = 0.795). No differences were observed in terms of post-operative complications, although the incidence of post-operative cardiac arrhythmias was borderline significant (p = 0.096), with no cases of arrhythmias recorded in Group 1. IL-10 levels in pleural fluid of patients in Group 3 peaked at 3 h post-surgery, with a significant reduction at 48 h (p = 0.459). Discussion: The use of the ultrasonic device during VATS lobectomy may reduce pleural fluid production and shorten the duration of the surgical procedure compared to using a monopolar hook or advanced bipolar device. The choice of energy device may influence the local inflammatory response, although further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopic liver surgery has advanced significantly, offering benefits, such as reduced intraoperative complications and quicker recovery. However, complex laparoscopic hepatectomy (CLH) is technically demanding, requiring skilled surgeons. This study aims to share technical aspects, insightful tips, and outcomes of CLH at our center, focusing on the safety and learning curve. Methods: We reviewed all patients undergoing liver resection at our center from July 2017 to December 2023, focusing on those who underwent CLH. Of 135 laparoscopic liver resections, 63 (46.7%) were CLH. The learning curve of CLH was also assessed through linear and piecewise regression analyses considering the operation time and intraoperative blood loss. Results: Postoperative complications occurred only in 4.8% of patients, with a 90-day mortality rate of 3.2%. The mean operation time and blood loss significantly decreased after the first 20 operations, marking the learning curve's optimal cut-off. Significant improvements in R0 resection (p = 0.024) and 90-day mortality (p = 0.035) were noted beyond the learning curve threshold. Conclusion: CLH is a safe and effective approach, with a relatively short learning curve of 20 operations. Future large-scale studies should further investigate the impact of surgical experience on CLH outcomes to establish guidelines for training programs. [ABSTRACT FROM AUTHOR]