Future Randomized Clinical Trials Research Articles

Diagnosing Solid Lesions in the Pancreas With Multimodal Artificial Intelligence

Diagnosing solid lesions in the pancreas via endoscopic ultrasonographic (EUS) images is challenging. Artificial intelligence (AI) has the potential to help with such diagnosis, but existing AI models focus solely on a single modality. To advance the clinical diagnosis of solid lesions in the pancreas through developing a multimodal AI model integrating both clinical information and EUS images. In this randomized crossover trial conducted from January 1 to June 30, 2023, from 4 centers across China, 12 endoscopists of varying levels of expertise were randomly assigned to diagnose solid lesions in the pancreas with or without AI assistance. Endoscopic ultrasonographic images and clinical information of 439 patients from 1 institution who had solid lesions in the pancreas between January 1, 2014, and December 31, 2022, were collected to train and validate the joint-AI model, while 189 patients from 3 external institutions were used to evaluate the robustness and generalizability of the model. Conventional or AI-assisted diagnosis of solid lesions in the pancreas. In the retrospective dataset, the performance of the joint-AI model was evaluated internally and externally. In the prospective dataset, diagnostic performance of the endoscopists with or without the AI assistance was compared. The retrospective dataset included 628 patients (400 men [63.7%]; mean [SD] age, 57.7 [27.4] years) who underwent EUS procedures. A total of 130 patients (81 men [62.3%]; mean [SD] age, 58.4 [11.7] years) were prospectively recruited for the crossover trial. The area under the curve of the joint-AI model ranged from 0.996 (95% CI, 0.993-0.998) in the internal test dataset to 0.955 (95% CI, 0.940-0.968), 0.924 (95% CI, 0.888-0.955), and 0.976 (95% CI, 0.942-0.995) in the 3 external test datasets, respectively. The diagnostic accuracy of novice endoscopists was significantly enhanced with AI assistance (0.69 [95% CI, 0.61-0.76] vs 0.90 [95% CI, 0.83-0.94]; P < .001), and the supplementary interpretability information alleviated the skepticism of the experienced endoscopists. In this randomized crossover trial of diagnosing solid lesions in the pancreas with or without AI assistance, the joint-AI model demonstrated positive human-AI interaction, which suggested its potential to facilitate a clinical diagnosis. Nevertheless, future randomized clinical trials are warranted. ClinicalTrials.gov Identifier: NCT05476978.

Effect of low-dose terazosin on arterial stiffness improvement: A pilot study.

Arterial stiffness, a prominent hallmark of ageing arteries, is a predictor of all-cause mortality. Strategies for promoting healthy vascular ageing are encouraged. Here we conducted a pilot study to evaluate the potential effects of low-dose Terazosin on arterial stiffness. We enrolled patients aged over 40 with elevated arterial stiffness, defined as a brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, who were administered Terazosin (0.5 and 1.0 mg/day) from December 2020 to June 2023. Treatment responses were assessed every 3 months. Linear regression analysis was used to characterise the improvement. We matched cases who took Terazosin for 1 year with Terazosin-free controls using propensity score matching (PSM). Our findings demonstrate that Terazosin administration significantly affected arterial stiffness. (1) Arterial stiffness significantly improved (at least a 5% reduction in baPWV) in 50.0% of patients at 3 months, 48.6% at 6 months, 59.3% at 9 months, and 54.4% at 12 months, respectively. (2) Those with higher baseline baPWV and hypertension exhibited a significantly reduced risk of non-response. (3) Terazosin was associated with a reduction of baPWV at 1-year follow-up (linear regression: β = -165.16, p < 0.001). This pilot study offers valuable insights into the potential significance of Terazosin in improving arterial stiffness and paves the way for future randomised clinical trials in combating vascular ageing.

Nonpharmacological Interventions for Treating Breastfeeding Nipple Pain: Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of nonpharmacological topical interventions for treating breastfeeding nipple pain. Methods: Randomized clinical trials (RCTs) assessing lactating women suffering from breastfeeding painful nipples were included. Primary outcomes were pain, healing process, and adverse events. A comprehensive search was conducted on June 02, 2023, without date or language restrictions. Methodological quality was assessed using the Cochrane risk of bias tool and the certainty of the evidence, the GRADE approach. Results: Nineteen RCTs with unclear to high risk of bias were included. There was uncertain evidence regarding the effects of photobiomodulation versus placebo on pain reduction (mean difference [MD] -0.15; 95% confidence interval [95% CI] -1 0.49 to 1.19; 139 participants, 2 RCTs). There are uncertainties concerning the effects of lanolin versus breast milk on pain (MD -1.80; 95% CI -2.43 to -1.17; 1 RCT; 180 participants), wound healing (MD 0.10; 95% CI -0.26 to -0.46; 1 RCT; 180 participants), and any adverse events (zero events in both groups). Similar effects were observed by the other interventions assessed. Conclusion: The evidence of nonpharmacological topical interventions for painful nipples is imprecise, and future RCTs with higher methodological quality are needed to support recommendations. Considering the accessibility and low cost of these alternative treatments, the findings of this evidence synthesis could support clinical decision-making and guide future research. PROSPERO CRD42020170320.

Outcomes of patients with intrahepatic cholangiocarcinoma with a focus on the interaction between tumor stage and age on mortality over the past decade.

e16201 Background: Intrahepatic cholangiocarcinoma(iCCA) is the second most prevalent liver tumor and originates from the epithelial cells of the bile duct . The purpose of this study is to assess to the extent independent prognostic factors influence mortality in iCCA. We also investigated the clinical characteristics and survival outcomes of patients with iCCA between 2010 and 2017. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database provided information on 5083 iCCA patients in the USA, between 2010 and 2017. Demographics, clinical features, overall mortality (OM), cancer-specific mortality (CSM), and the interaction between age and tumor stage were analyzed. Variables with p &lt; 0.1 in univariate Cox regression were included in the multivariate model, with a hazard ratio (HR) &gt; 1 indicating adverse prognostic factors. Results: Multivariate Cox proportional hazard regression analyses showed higher OM in males (HR = 1.19), metropolitan counties with 250,000 population (HR = 1.15), and lower in the age groups 40-59 (HR = 0.58) and 60-79 (HR = 0.65). Patients who underwent radiation therapy (HR = 0.78), chemotherapy (HR = 0.54), and surgery (HR = 0.29) had lower OM. Similarly, CSM was higher in males (HR = 1.17) and metropolitan counties (HR = 1.18), but lower in age groups 40-59 (HR = 0.52) and 60-79 (HR = 0.57). Interaction analysis revealed higher OM in stage III tumors with lymph node involvement aged 40-59 (HR = 2.30). CSM was higher in ages 40-59 with stage III iCCA (HR = 2.60) and stage IV (HR = 2.81), as well as in 60-79 with stage III (HR = 2.24) and stage IV tumors (HR = 2.93). OM and CSM were higher in all age groups &gt; 40 compared to the younger population. Conclusions: In this large retrospective study using the SEER database, we unfolded an aspect of iCCA mortality that has not been previously studied. We found a significant interaction between two independent prognostic factors that enhance mortality. This data may assist treating oncologists in selecting patients that would benefit from early aggressive treatment modalities which proved to be beneficial as seen in our study. This study paves the way for future prospective randomized clinical trials to further understand the impact of such interactions in patients with iCCA, especially in the era of precision oncology.

(CDK) 4/6 inhibitors: An effective treatment for homologous recombination deficient (HRD) luminal breast cancers (BC)?

e13100 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) still represents the best 1st-line choice for hormone receptor (HR) positive(+)/HER2 negative(-) metastatic breast cancer (MBC) patients (pts). Approximately 8% of pts with HR+ BC harbors germline BRCA mutation (g BRCAmt). The interaction between Cyclin/CDK pathway, endocrine receptor (ER) and Breast Cancer gene 1/2 (BRCA1/2) is complex and evidence reported so far, await confirmation in the context of future randomized clinical trials. So far, limited data exist about treatment effectiveness of CDK4/6i in homologous recombination deficiency (HRD) Luminal BC. A current frequent question in clinical practice is which additional adjuvant therapy to prioritize for luminal BRCA tumors (tu), considering the approval of both CDK4/6i andpoly ADP ribose polymerase (PARP) inhibitors in this scenario. Considering potential impacts of genetic instability in tu biology, such as potential loss of Rb protein related to Loss of Heterozygosity (LOH) of BRCA2 as a primary resistance mechanism in CDK4/6i, we sought to analyze the clinical results of that drug in tu with genetic instability. Methods: We retrospectively analyzed real-world outcomes of CDK4/6i performance in HR+/HER2- MBC treated in a single institution, with focus in clinical outcomes of HRD BC. germline HR genes status and somatic phosphatidylinositol 3-kinase (PIK3CA) status were also analyzed. Results: A total of 384 consecutive MBC pts treated with CDK4/6i were included in this study. The most used CDK4/6i was palbociclib (40,6%), followed by ribociclib (29,8%) and abemaciclib (29,2%). Considering the whole cohort PFSm 30months (95%IC 26-34) and OSm were 56 months (95%IC 52-60) No differences in PFS or OS was observed among the 3 CDK4/6i. Median age of the cohort was 60 years old. 38.5% were premenopause Pts and 59.9% were postmenopause. A total of 149 (39%) pts performed germline screening. Between 19 pts with gHR mt, 12 were BRCA1/2 mt (just one BRCA1). The other were: 2 PALB2, 2 CHEK2, 1 ATM, 1 RAD51D, 1 RAD51C mt. So far, no differences in PFS ou OS was observed in the presence of BRCA 1/2 or other gHR mt. Nevertheless, PIK3CA mt was tested in 142 pts, 51 were positives. That mt was a predictor of worse OS (55m; 95%IC 45-65) x 63m (95%IC 56-69), p 0,019. Conclusions: The results of this real-world study suggest that treatment outcomes with CDK4/6i may be worse in pts with HRD tu due to potential differences in tu biology. Future exploration in larger samples of patients who have had biomarker testing is ongoing. Patients with Pik3CA mt treated with CDK4/6i presented worse clinical outcomes.

Current management practices of de novo oligometastatic breast cancer: Real-world data from a physician survey.

1104 Background: De novo oligometastatic breast cancer (oligo-mBC) is generally defined as &lt; 5 lesions at the time of diagnosis and represent a steadily increasing subset of metastatic cancers. Several retrospective studies demonstrated prolonged overall survival (OS) for select patients with oligo-mBC when treated with multimodality therapy (chemotherapy, surgery, and radiation). However, randomized trials that tested surgical resection of the primary tumor, or radiation of oligometastases (including recurrent and de novo disease) showed no OS benefit. No randomized trials to date have tested all 3 treatment modalities combined (as used with curative intent in early-stage disease). Current NCCN guidelines do not include specific recommendations for de novo oligo-mBC, the St Gallen International guidelines allow multimodality therapy for carefully selected patients. We surveyed practicing medical oncologists through the ASCO survey pool regarding their use of multimodality therapy in de novo oligo-mBC. Methods: An online survey was sent to the ASCO Research survey pool (N=999) between 11/14/23 – 12/29/23, 193 ASCO members completed the survey. Data was confidential and anonymous. Results: The majority (76-79%) of respondents recommend starting with palliative systemic chemotherapy. If patients have a response to initial chemotherapy, 42-54% recommend ablative radiation to all residual lesions, and 38-52% recommended surgical resection of the primary tumor. Overall, multimodality therapy is recommended sometimes by 29-36%, often by 19-29%, almost never by 32-41%, and never by 2-7% of respondents. Recommendations varied by disease subtype (Table). Conclusions: These survey data indicate varied practices in the treatment of de novo oligo-mBC. This highlights the need for future randomized clinical trials to investigate whether there may be survival benefit by receptor subtype in de novo oligo-mBC treated with curative intent multimodality therapy as used in locally advanced cancers. [Table: see text]

Using virtual multiteam systems to conduct a multisite randomized clinical trial in the part C early intervention system: Benefits, challenges, and lessons learned

Background/AimsCOVID-19 necessitated a shift to virtual data collection for many research projects, providing the opportunity for novel approaches to carrying out multi-site clinical trials. Virtual multiteam systems (VMTS) are a type of team structure in which multiple geographically dispersed teams collaborate using technology-mediated communication. The article presents a case study of our use of VMTS, in response to COVID-19, to carry out a multisite randomized hybrid effectiveness-implementation trial of a caregiver-implemented intervention. MethodsWe describe how we modified our team structure from predominantly site-specific, co-located teams to predominantly cross-site, virtual teams. We then present examples of how we have conducted the two primary data collection activities virtually. To demonstrate the feasibility of this approach, we present participant demographic information, the percent of cross-site data collection activities, and fidelity data. ResultsIn the first 20 months of data collection, we have enrolled 108 EI providers and 132 families, with 17% and 9% attrition respectively. The family sample is highly diverse in terms of race/ethnicity, parent education, and household income. The majority of provider training activities and roughly 50% of family assessment activities have been conducted cross-site. Fidelity is high, with no differences across site. ConclusionsOur data illustrate the feasibility of using virtual teams, training, and assessment in a multisite clinical trial in the Part C system. We discuss the strengths and challenges of this approach, as well as lessons learned to facilitate the planning of future multisite randomized clinical trials which may benefit from this approach. Clinical TrialsNCT05114538

Efficacy of systemic therapy on adults with depressive disorders: A meta-analysis

Objective This meta-analysis evaluates the efficacy of systemic therapy approaches on adult clients with depressive disorders. Methods The illness-specific systematic review updates a previous meta-analysis on the efficacy of systemic therapy on psychiatric disorders in adulthood. It integrates the results of 30 randomized controlled trials (RCTs) comparing systemic psychotherapy for depression with an untreated control group or alternative treatments. Studies were identified through systematic searches in relevant electronic databases and cross-referencing. A random-effects model calculated weighted mean effect sizes for each type of comparison (alternative treatments, control group with no alternative treatment/waiting list) on two outcomes (depressive symptoms change, drop-out rates). Results On average, systemic interventions show larger improvements in depressive symptoms compared to no-treatment controls at post-test (g = 1.09) and follow-up (g = 1.23). Changes do not significantly differ when comparing systemic interventions with alternative treatments (post-test g = 0.25; follow-up g = 0.09). Results also vary, in part, by participant age, publication year, and active control condition. Conclusion This meta-analysis indicates the potential benefits of systemic interventions for adult patients with depression. Future randomized clinical trials in this area should enhance study quality and include relational and other relevant outcome measures.

Orbital radiotherapy with combined intravenous methylprednisolone and mycophenolate mofetil in moderate-to-severe thyroid eye disease

PurposeTo report the clinical outcomes of orbital radiotherapy (ORT) with combined intravenous methylprednisolone (IVMP) and mycophenolate mofetil (MMF) in thyroid eye disease (TED) patients with restrictive myopathy. DesignProspective comparative case series of patients managed at The Chinese University of Hong Kong from 2015 to 2021. MethodsThe primary outcome was the change in Gorman diplopia score at 52 weeks. Secondary outcomes were the changes in extraocular muscle motility (EOMy), area of extraocular muscle (EOM) on MRI, exophthalmos, and marginal reflex distance (MRD) 1 and MRD2 at 52 weeks. ResultsA total of 40 (29 females) TED patients, medium age 56 years, were treated with the double regimen: combined IVMP and MMF (17) or triple regimen: IVMP, MMF, and ORT (23). The triple group has a higher age (P = 0.028). Sex, smoking history, thyroid, and pre-treatment orbital status were comparable between the 2 groups. EOMy improved more after the triple regimen(P = 0.026). Nine patients from the triple group showed a significant reduction in the size of the inferior rectus (both eyes: P < 0.05), while five from the double group showed no significant reduction of any EOM on MRI. The improvement of CAS, diplopia score, exophthalmos, MRD1, and MRD2 were similar. No patient reported any severe or organ-threatening side effects from IVMP, MMF, or ORT requiring discontinuation of treatment. ConclusionThe triple regimen demonstrates better structural and functional outcomes in TED-related restrictive myopathy. Future randomized clinical trials are warranted to clarify the adjuvant role of ORT in this specific indication of TED management.

Transdermal bisoprolol for prevention of postoperative atrial fibrillation: A systematic review and meta‐analysis

AbstractBackgroundThe transdermal patch of bisoprolol available in Japan has been reported to demonstrate superior efficacy in preventing postoperative atrial fibrillation, possibly surpassing its oral counterpart. However, there has been no systematic review and meta‐analysis assessing the efficacy of transdermal bisoprolol.MethodsA comprehensive systematic literature search was conducted on PubMed, Embase, and Cochrane to identify all relevant studies assessing the efficacy of transdermal bisoprolol in preventing postoperative atrial fibrillation. The search covered studies from inception up to December 4, 2023. For data analysis, Review Manager (RevMan) 5.4 software was employed, using a random‐effects model to calculate risk ratios (RR) and 95% confidence intervals (CI).ResultsThree studies, comprising a total of 551 patients (transdermal bisoprolol 228 and control 323), were included. There was a decreased risk of postoperative atrial fibrillation or atrial tachyarrhythmias in patients treated with transdermal bisoprolol (RR 0.43, 95% CI 0.27–0.67, p = .0002, I2 = 0%).ConclusionTransdermal administration of bisoprolol has consistently shown efficacy, and this pooled analysis supports its effectiveness. The heterogeneity of the included studies limits certain interpretations. Future randomized clinical trials may elucidate the superiority of transdermal administration over oral administration.

Posterior Positioning of Levator Veli Palatini with Intact Nasal Layer and Side-by-Side Bilateral Buccinator Flaps: Modified Approach for Palatal Lengthening.

To introduce a modified surgical method using bilateral buccinator flaps with posterior positioning of levator veli palatini muscles to treat velopharyngeal insufficiency. Cross-sectional clinical study. Non-syndromic patients with velopharyngeal insufficiency. We performed a modified surgical method using posterior positioning of levator veli palatini muscles and side-by-side bilateral buccinator flaps. Patients' characteristics, severity of hypernasality, palatal lengthening size, and operative complications were recorded and described. The severity of hypernasality was determined by a speech therapist before and after the operation. A total of 26 non-syndromic patients, with a median age of 8.5 years, were enrolled. All patients presented with severe hypernasality. Following the operation and during the follow-up period, 12 patients showed a complete resolution of hypernasality, while 9, 3, and 2 patients exhibited mild, moderate, and severe hypernasality, respectively. In addition, the mean palatal lengthening was measured to be 25.3 ± 3.5 mm. Overall, three patients experienced partial flap loss in one flap, which was successfully repaired with a secondary intention without the development of a fistula. In five cases, complete closure of the donor sites couldn't be achieved and thus were treated with secondary intention. Additionally, postoperative food restrictions were observed in seven cases but were resolved within one month. No other complications were noted in the remaining patients. This modified palatal lengthening technique results in a significant lengthening of the palate while maintaining favorable speech outcomes. Future randomized clinical trials are warranted to validate our findings.

P050 Determining the feasibility of a multi-centre randomised clinical trial to test the effectiveness of integrated symptom tracking for managing rheumatoid arthritis

Abstract Background/Aims In a series of studies, we co-developed and piloted the remote monitoring of rheumatoid arthritis (REMORA) system. REMORA enables patients to daily track symptoms via their smartphone and integrates this data into their electronic health record for discussion during routine clinic visits. This offers the opportunity to make better, and shared, treatment decisions and improve disease management. The effectiveness of integrated daily symptom tracking on clinical and patient-reported outcomes will be tested in a multi-centre stepped wedge randomised clinical trial (RCT). Here, we present the results of the REMORA feasibility study to test trial procedures and intervention delivery. Methods Across two NHS sites in the Northwest of England we aimed to recruit 60 patients, aged ≥18 years with rheumatoid arthritis (RA) or inflammatory arthritis (IA), and access to an Android/iOS smartphone with daily internet access. Participants were asked to complete a baseline web-survey and use the REMORA app to collect daily symptom reports for up to six months. Clinical care teams extracted data from participants’ medical records for all baseline and follow-up appointments, including disease activity scores. To assess feasibility, we reported recruitment rates, participants’ uptake of and adherence to daily symptom tracking, and outcome data completeness. We also compared characteristics of a) those who consented vs. trackers (defined as submitting ≥1 symptom report, i.e., successful intervention uptake), and b) high adherers (symptoms reported on &amp;gt; 60% days) vs. low adherers (symptoms reported on &amp;lt; 25% days). Results A total of 130 patients were screened across study sites, and 52 were eligible and provided consent to take part (40.0%). Of those, 32 (61.5%) initiated symptom tracking; their demographic characteristics were broadly similar to those who consented, though more people of white ethnicity appeared higher in the tracker group (93.8% (95% CI 79.2-99.2) vs 86.5% (74.2-94.4), respectively). Participants completed at least one symptom report on 63.2% of study days (2384/3771 days). We observed few differences between low vs high adherers, though low adherers (n = 6) were younger (median (IQR) years: 41.5 (34.5-55.3)) than the high engagers (n = 20; 61.0 (50.5-65.3)) and had a shorter disease duration (years: 1.0 (0-5.8) vs 3.0 (0.8-10.8)). In total, 48 consented participants had at least one follow-up appointment during the study window; 46 (95.8%) had complete primary outcome data. Conclusion Across two clinical sites, we determined that the procedures and intervention delivery designed for use within a future multi-centre stepped wedge RCT of the REMORA system were feasible for recruitment, adherence to the intervention and completion of the primary outcome. However, uptake of the intervention was lower than we hoped. To enhance intervention uptake in the main trial, we clarified inclusion criteria, improved patient information on what is required to initiate symptom tracking and modified our supporting materials. Disclosure K.L. Druce: None. M. Parkes: None. R. Bravo: None. D. Griffiths-Jones: None. S.N. van der Veer: None. W. Dixon: Consultancies; consultancy fees from Google unrelated to this work. J. McBeth: None.

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Chest Tube Size Selection: Evaluating Provider Practices, Treatment Efficacy, and Complications in Management of Thoracic Trauma.

The standard for managing traumatic pneumothorax (PTX), hemothorax (HTX), and hemopneumothorax (HPTX) has historically been large-bore (LB) chest tubes (>20-Fr). Previous studies have shown equal efficacy of small-bore (SB) chest tubes (≤19-Fr) in draining PTX and HTX/HPTX. This study aimed to evaluate provider practice patterns, treatment efficacy, and complications related to the selection of chest tube sizes for patients with thoracic trauma. A retrospective chart review was performed on adult patients who underwent tube thoracostomy for traumatic PTX, HTX, or HPTX at a Level 1 Trauma Center from January 2016 to December 2021. Comparison was made between SB and LB thoracostomy tubes. The primary outcome was indication for chest tube placement based on injury pattern. Secondary outcomes included retained hemothorax, insertion-related complications, and duration of chest tube placement. Univariate and multivariate analyses were performed. Three hundred and forty-one patients were included and 297 (87.1%) received LB tubes. No significant differences were found between the groups concerning tube failure and insertion-related complications. LB tubes were more frequently placed in patients with penetrating MOI, higher average ISS, and higher average thoracic AIS. Patients who received LB chest tubes experienced a higher incidence of retained HTX. In patients with thoracic trauma, both SB and LB chest tubes may be used for treatment. SB tubes are typically placed in nonemergent situations, and there is apparent provider bias for LB tubes. A future randomized clinical trial is needed to provide additional data on the usage of SB tubes in emergent situations.

Association between beta-blocker utilization and heart failure mortality in the peritoneal dialysis population: a cohort study.

The prognostic significance of beta(β)-blocker therapy in patients at end-stage renal disease, specifically those receiving peritoneal dialysis (PD) and presenting with heart failure, remains inadequately elucidated due to limited research conducted thus far. A retrospective analysis was performed on a cohort comprising 608 patients receiving PD between September 2007 and March 2019, with a subsequent follow-up period extending until December 2020. Cox regression and propensity score matching weighted analysis was used to model adjusted hazard ratios for β-blocker use with heart failure-related mortality. Competing risk analysis and subgroup analysis were carried out to further elucidate the correlation. β-blockers were prescribed for 56.1% of the peritoneal dialysis patients. Heart failure occurred in 43.4% of the total population and 15.5% of deaths were due to heart failure. The prescription of β-blockers was associated with a 43% lower adjusted hazard ratio (HR) for heart failure death within the cohort (95% confidence interval [CI] = 0.36-0.89; P=0.013). Even after accounting for competing risk events, patients in the group using β-blockers demonstrated a significantly lower cumulative risk of heart failure-related mortality compared to those not using β-blockers (P=0.007). This protective effect of β-blockers was also observed in subgroup analyses. Conversely, β-blocker use had no statistically significant associations with all-cause mortality. The use of β-blockers was associated with a reduced risk of heart failure-related mortality in the PD population. Future randomized clinical trials are warranted to confirm the beneficial effect of β-blockers in the context of PD.

Clinical Trial Racial and Ethnic Disparities in Minimally Invasive Gynecologic Surgery

Study ObjectiveTo study racial and ethnicity disparities in randomized clinical trials (RCT) in Minimally Invasive Gynecologic Surgery (MIGS). DesignCross sectional study. SettingOnline review of all published MIGS RCTs in high-impact journals from 2012 to 2023. PatientsJournals included all Q1 Obstetrics & Gynecology journals, as well as The New England Journal of Medicine, The Lancet, The British Medical Journal, and The Journal of the American Medical Association. The National Institutes of Health's PubMed and the ClinicalTrials.gov websites were queried using the following search terms from the American Board of Obstetrics and Gynecology's certifying examination bulletin 2022 to obtain relevant trials: adenomyosis, adnexal surgery, abnormal uterine bleeding, cystectomy, endometriosis, fibroids, gynecology, hysterectomy, hysteroscopy, laparoscopy, leiomyoma, minimally invasive gynecology, myomectomy, ovarian cyst, robotic surgery InterventionsThe United States (US) Census Bureau data was used to estimate the expected number of participants. We calculated the enrollment ratio (ER) of actual to expected participants for US trials with race and ethnicity data available. Measurements and Main ResultsA total of 352 RCTs were identified. Of these, race and/or ethnicity data were available in 65 studies (18.5%). We analyzed the 46 studies that originated in the US, with a total of 4,645 participants. Of these RCTs only 8 (17.4%) reported ethnicity in addition to race. When comparing published RCT data to expected proportions of participants, White participants were overrepresented [70.8% versus 59.6%, ER 1.66, 95% confidence interval (CI) 1.52-1.81], as well as Black or African American participants (15.4% versus 13.7%, ER 1.15, 95% CI 1.03-1.29). Hispanic (6.7% versus 19.0%, ER 0.31, 95% CI 0.27-0.35), Asian (1.7% versus 6.1%, ER 0.26, 95% CI 0.20-0.34), Native Hawaiian or Other Pacific Islander (0.1% versus 0.3%, ER 0.21, 95% CI 0.06-0.74), and Indian or Alaska Native participants (0.2% versus 1.3%, ER 0.16, 95% CI 0.08-0.32) were underrepresented. When comparing race/ethnicity proportions to the 20 states where the RCTs were conducted, Black or African American participants were underrepresented. ConclusionIn MIGS RCTs conducted in the US, White and Black or African American participants are overrepresented compared to other races, and ethnicity is characterized in fewer than one fifth of trials. Efforts should be made to improve racial and ethnic recruitment equity as well as reporting in future MIGS RCTs.

Patterns of Care in the Diagnosis and Management of Intracranial Atherosclerosis‐Related Large‐Vessel Occlusion: The Rescue‐LVO Survey

Background We aimed to determine the current practice patterns among neurointerventional practitioners frequently involved in treating intracranial atherosclerosis‐related large‐vessel occlusion (ICAS‐LVO) during mechanical thrombectomy. Methods We conducted an international online survey of neurointerventionalist members of the Society of Vascular and Interventional Neurology and Society of Neurointerventional Surgery. The 28‐question poll evaluated the preferences on diagnosis, treatment, and endovascular approach to ICAS‐LVO. Results A total of 184 individual survey responses were obtained from practicing neurointerventional physicians. Overall, 38.3% reported an incidence of 6% to 10% of ICAS‐LVO during mechanical thrombectomy. Most neurointerventionalists (91%) diagnose ICAS‐LVO after a continued or recurrent occlusion or by the presence of fixed focal stenosis after multiple mechanical thrombectomy attempts. Most respondents (86%) preferred acute treatment of ICAS‐LVO with rescue stenting (RS)±angioplasty. However, in patients who achieved recanalization with a severe fixed focal stenosis, most (58%) recommended primary medical management. The preferred medication during acute RS was intravenous antiplatelet therapy (65%), and after acute RS, it was dual oral antiplatelet therapy (65%). Fear of hemorrhagic complications (74%) was the most compelling reason not to perform RS±angioplasty. Of respondents, 24% were hesitant to randomize patients to acute RS versus medical therapy in a future randomized trial because of the lack of sensitive and specific biomarkers to diagnose ICAS‐LVO before mechanical thrombectomy treatment. Conclusions The findings of this survey highlight the variations in practice in the medical and endovascular management of ICAS‐LVO. In addition, it informs the situation of equipoise in the treatment decision in ICAS‐LVO, which can then be incorporated into the design of future randomized clinical trials.

Prognostic factors for overall survival in patients with advanced digestive neuroendocrine carcinoma treated with first-line cisplatin-based chemotherapy: A post-hoc analysis of JCOG1213.

594 Background: Advanced digestive neuroendocrine carcinoma (ADNEC) is a rare and aggressive malignancy without evidence of prognostic factors assessed in prospective studies. We aimed to evaluate prognostic factors in patients with ADNEC receiving first-line cisplatin-based chemotherapy. Methods: This is a post-hoc analysis of JCOG1213, which is a phase 3 randomized trial showing equivalent overall survival (OS) for cisplatin plus etoposide versus cisplatin plus irinotecan as first-line chemotherapy for patients with ADNEC. The primary endpoint of JCOG1213 was OS. For this post-hoc analysis of prognostic factors, patients who had ineligible histology based on the central pathological review or who lacked the necessary clinical data for analysis were excluded. A Cox proportional hazard model was used to assess the effect of independent variables on OS. Priori variables selected on previous reports (performance status (PS), Ki-67 index, and serum LDH level), as well as variables that remained at a level of p-value &lt;0.20 by backward stepwise selection, were incorporated in the final model of OS. Results: Among 170 patients enrolled in JCOG1213, a total of 129 patients with ADNEC were included in this analysis. In multivariable analysis, serum LDH level (&gt; upper normal limit vs. normal) was identified as a significant prognostic factor for OS (HR = 1.721, 95% CI: 1.144–2.589, p = 0.009). Other clinicopathological factors were not found to be significant, including PS (1 vs. 0; HR = 0.784, 95% CI: 0.507–1.214, p = 0.276), Ki-67 (≥ 55% vs. &lt; 55%; HR = 1.475, 95% CI: 0.588–3.698, p = 0.407), liver metastasis (present vs. absent; HR = 1.434, 95% CI: 0.968–2.124, p = 0.072), sex (female vs. male; HR = 1.387, 95% CI: 0.937–2.053, p = 0.102), and serum ALP level (&gt; upper normal limit vs. normal; HR = 0.948, 95% CI: 0.639–1.406, p = 0.789). OS of patients with elevated serum LDH levels was shorter than those with normal serum LDH levels (median: 9.5 months vs. 15.6 months, p = 0.0019). No statistically significant differences were observed between the two groups regarding objective response rate (58.8% vs. 54.1%, p = 0.594) and progression-free survival (median: 4.5 months vs. 5.9 months, p = 0.141). A numerically lower proportion of patients with elevated serum LDH levels received second-line chemotherapy than those with normal serum LDH levels (76.5% vs. 88.3%). Conclusions: Serum LDH level may serve as a prognostic factor in the daily practice of patients with ADNEC and as a risk stratification factor in future randomized clinical trials. Clinical trial information: UMIN000014795 .

Association of cardiovascular disease management drugs with Lewy body dementia: a case-control study.

Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer's disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with the risk of developing Lewy body dementia, we performed a population-based case-control study of 148 170 US Medicare participants diagnosed with Lewy body dementia between 1 January 2008 and 31 December 2014 and of 1 253 043 frequency-matched controls. We estimated odds ratios and 95% confidence intervals for the association of Lewy body dementia risk with 1017 prescription drugs overall and separately for the three major racial groups (Black, Hispanic and White Americans). We identified significantly reduced Lewy body dementia risk associated with drugs used to treat cardiovascular diseases (anti-hypertensives: odds ratio = 0.72, 95% confidence interval = 0.70-0.74, P-value = 0; cholesterol-lowering agents: odds ratio = 0.85, 95% confidence interval = 0.83-0.87, P-value = 0; anti-diabetics: odds ratio = 0.83, 95% confidence interval = 0.62-0.72, P-value = 0). Notably, anti-diabetic medications were associated with a larger risk reduction among Black Lewy body dementia patients compared with other racial groups (Black: odds ratio = 0.67, 95% confidence interval = 0.62-0.72, P-value = 0; Hispanic: odds ratio = 0.86, 95% = 0.80-0.92, P-value = 5.16 × 10-5; White: odds ratio = 0.85, 95% confidence interval = 0.82-0.88, P-value = 0). To independently confirm the epidemiological findings, we looked for evidence of genetic overlap between Lewy body dementia and cardiovascular traits using whole-genome sequence data generated for 2591 Lewy body dementia patients and 4027 controls. Bivariate mixed modelling identified shared genetic risk between Lewy body dementia and low-density lipoprotein cholesterol levels, Type 2 diabetes and hypertension. By combining epidemiological and genomic data, we demonstrated that drugs treating cardiovascular diseases are associated with reduced Lewy body dementia risk, and these associations varied across racial groups. Future randomized clinical trials need to confirm our findings, but our data suggest that assiduous management of cardiovascular diseases may be beneficial in this understudied form of dementia.

The association between migraine and Parkinson's disease: a nationwide cohort study.

Clinical studies have suggested an association between migraine and the occurrence of Parkinson's disease (PD). However, it is unknown whether migraine affects PD risk. We aimed to investigate the incidence of PD in patients with migraine and to determine the risk factors affecting the association between migraine and PD incidence. Using the Korean National Health Insurance System database (2002-2019), we enrolled all Koreans aged ≥40 years who participated in the national health screening program in 2009. International Classification of Diseases (10th revision) diagnostic codes and Rare Incurable Diseases System diagnostic codes were used to define patients with migraine (within 12 months of enrollment) and newly diagnosed PD. We included 214,193 patients with migraine and 5,879,711 individuals without migraine. During 9.1 years of follow-up (55,435,626 person-years), 1,973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were newly diagnosed with PD. Following covariate adjustment, patients with migraine showed a 1.35-fold higher PD risk than individuals without migraine. The incidence of PD was not significantly different between patients with migraine with aura and those without aura. In males with migraine, underlying dyslipidemia increased the risk of PD (p=0.012). In contrast, among females with migraine, younger age (<65 years) increased the risk of PD (p=0.038). Patients with migraine were more likely to develop PD than individuals without migraine. Preventive management of underlying comorbidities and chronic migraine may affect the incidence of PD in these patients. Future prospective randomized clinical trials are warranted to clarify this association.