Endoscopic Ultrasound-guided Transmural Biliary Drainage With 6 mm and 8 mm Cautery-enhanced Lumen-apposing Metal Stents: A Multicenter Collaborative Study.

OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) may be unsuccessful in patients with duodenal stenosis or malignant ampullary infiltration. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been proposed as an alternative. We aimed to assess the efficacy and safety of EUS-BD for malignant distal bile duct obstruction using the newly introduced smaller caliber 6 or 8 mm cautery-enhanced lumen-apposing metal stent. METHODS: A multicenter retrospective study was performed on patients with unresectable malignant distal bile duct obstruction who underwent EUS-BD between 2021 and 2022 after unsuccessful ERCP. RESULTS: Thirty-two patients were included [7 (53.13%) males], with a mean age of 72.2 ± 12.5 years. The technical success rate was 100%. Altered anatomy was present in 2 (6.25%). The indication for drainage was biliary obstruction from pancreatic cancer in 26 patients (84.5%), cholangiocarcinoma in 3 (9.4%), and ampullary mass in 3 (9.4%). The procedure was performed mostly in an outpatient setting (n = 19, 59.38%). The clinical success rate was 92.3% [bilirubin: 14.1 (SD: 8.9) preprocedure vs 4.9 (SD: 1.1) postprocedure; P = 0.0001]. There was one early adverse event of a perforation, which was closed endoscopically and drained percutaneously. Delayed adverse events included food impaction of the stent (n = 1), which was resolved with a repeat procedure and insertion of a double pigtail stent. CONCLUSION: This study demonstrates the feasibility of EUS-BD drainage using smaller caliber 6 or 8 mm lumen-apposing metal stent to relieve malignant distal bile duct obstruction in patients who fail conventional ERCP.

Defining patient satisfaction after reverse total shoulder arthroplasty: a systematic review.

BACKGROUND: The prevalence of reverse total shoulder arthroplasty (rTSA) has grown rapidly. As indications for the procedure expand, the proportion of patients who have satisfactory outcomes after rTSA has not been well defined. This systematic literature review explores overall patient satisfaction after rTSA and defines patient satisfaction based on indication for surgery. METHODS: A literature search was performed for studies describing patient satisfaction after rTSA in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Papers were included if they investigated patient satisfaction after rTSA at a minimum of 2-year follow-up. Data were collected on patient demographics, including age, gender, and body mass index. Follow-up duration, indication for surgery, and patient reported outcome measures relating to patient satisfaction were also recorded. RESULTS: There were a total of 5234 patients and 5288 shoulders from the 45 included studies. The overall study population was 61.2% female and the average age was 71.1 years (range 23-99). Satisfaction results were recorded at final follow-up, with average follow-up of 49.1 months (range 24-228). Overall patient satisfaction ranged from 77.7% to 87.8%, depending on patient satisfaction patient reported outcome measures. When stratified by diagnosis, patients with a diagnosis of glenohumeral osteoarthritis (GHOA) rated better satisfaction on all metrics when compared to patients with a diagnosis of cuff tear arthropathy or massive rotator cuff tear. CONCLUSION: This systematic review demonstrated that patients who undergo rTSA for either GHOA, cuff tear arthropathy, or massive rotator cuff tear are generally satisfied with their procedure, with the rate of satisfaction highest in GHOA. Focusing on patient satisfaction may provide the best overall assessment of health care quality in a very understandable and tangible form. Overall satisfaction rate is valuable information for patient education and can be utilized as part of effective surgical counseling.

Low acromial insufficiency fracture rate in reverse shoulder arthroplasty with distal clavicle excision.

Background: This study investigated the rate of acromial insufficiency fractures (AIF) in patients undergoing reverse shoulder arthroplasty (RSA) with concomitant distal clavicle excision (DCE). Methods: Patients who underwent primary RSA with DCE by a single surgeon from 2010 to 2021 were identified. Exclusion criteria included revision RSA, RSA for fracture, or cases utilizing an augmented baseplate or bone graft. AIF was defined as a radiographically proven acromion or scapular spine fracture. Pain without an identifiable fracture on imaging was defined as an acromial insufficiency reaction. Patient demographics, implant information, and radiograph measurements were compared between patients with and without acromial pathology. Results: One hundred and seventy-five patients were included. Mean age was 72.8 years, and 67% of patients were female. There were 3/174 acromial insufficiency fractures (1.7%). AIF occurred at a mean of 9.3 months after surgery. Twelve patients had insufficiency reactions (6.9%). Patients with acromial pathology were more likely to be female (p = .003) and have a diagnosis of osteoporosis (p = .047) and inflammatory arthritis (p = .049). There was no significant difference between groups in terms of other factors. Conclusion: The AIF rate in patients who underwent RSA with DCE was 1.7%. These findings suggest that DCE in the setting of RSA may have a protective role against AIF.

Nocebo expectations rather than placebo expectations affect topical pain relief: A randomized clinical trial.

Patients' expectations and beliefs regarding the potential benefits and harms of medical interventions may induce placebo and nocebo effects, and affect the response to pain therapies. In a randomized clinical trial, we examined the effect of placebo and nocebo expectations on pain relief and adverse events (AEs) in association with a topical treatment among 65 cancer survivors experiencing chronic musculoskeletal pain. Participants received either a 1% camphor-based topical pain patch or a placebo treatment for 14 days. We measured pain severity with the worst pain item of the Brief Pain Inventory (BPI) at baseline and 14 days and treatment expectations at baseline with validated expectation questionnaires. We found that high vs. low nocebo expectations decreased pain severity improvements by 2.5 points (95% confidence interval [CI] -3.8 to -1.2; p<0.001) on a 0-10 numeric rating scale of the BPI and pain response rate by 42.7% (95% CI 0.2-0.6; p<0.001) at day 14, irrespective of placebo expectation status or treatment arms. Patients with high vs. low nocebo expectations in the true arm reported 22.4% more unwanted AEs. High nocebo expectations were associated with increased AEs by 39.5% (odds ratio: 12.0, 95% CI 1.2, 145.5; p=0.029) and decreased pain response in the true arm vs. placebo. Our study demonstrated that nocebo expectations, rather than placebo expectations, elevate the risk of AEs and compromise the effect of topical pain interventions. The findings raise the possibility that nocebo expectations may worsen somatic symptoms through heightening central pain amplification and should be further investigated.

How does pretreatment expectancy influence pain outcomes with electroacupuncture and battlefield acupuncture in cancer survivors?: Pretreatment expectancy and pain reduction by acupuncture.

Background: Outcome expectancy is an important component of non-specific effect that may play an important role in pain research and clinical care. We sought to evaluate whether pretreatment expectancy predicts pain reduction in cancer survivors receiving electroacupuncture (EA) or battlefield acupuncture (BFA). Methods: We analyzed data from a randomized clinical trial that compared EA and BFA versus wait list control (WLC) for chronic musculoskeletal pain in cancer survivors. Expectancy was measured by the Acupuncture Expectancy Scale (AES) at baseline. Pain severity was assessed using the Brief Pain Inventory (BPI) at baseline and week 12. For each treatment arm, multivariable regression models were used to evaluate the association between pretreatment expectancy and week 12 pain severity, controlling for baseline pain severity, age, sex, race, and education. Results: Among 360 participants enrolled, the mean age was 62.1 years (SD 12.7), with 251 (69.7 %) women and 88 (24.4 %) non-white survivors. Pretreatment expectancy was similar for all groups at baseline (EA: 13.9 ± 3.6; BFA: 13.2 ± 3.7, WLC:12.8 ± 3.3, p = 0.14). Greater pretreatment expectancy was not significantly associated with greater pain reduction in any group, after adjusting for co-variates (EA: Coef. = -0.05, 95 % CI = -0.14 - 0.04, p = 0.28; BFA: Coef. = -0.07, 95 % CI = -0.16 - 0.02, p = 0.15; WLC: Coef. = -0.09, 95 % CI = -0.25 - 0.06, p = 0.23). Conclusions: Pretreatment expectancy did not predict pain reduction for either EA or BFA in cancer survivors. Our study contributes to the interpretation of analgesic effects of EA or BFA, beyond the notion of a mere 'placebo effect'.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Patient-Reported Outcomes as a Recruitment Strategy for Clinical Trial Enrollment.

Importance: Clinical trials are critical for progress in oncology; however, only 5% of the adult cancer population participates. Harnessing data that are routinely collected (ie, electronic patient-reported outcomes [ePROs]) may serve as a method to promote trial enrollment. Objective: To evaluate if an ePRO-prompted recruitment strategy is associated with increased clinical trial enrollment. Design, Setting, and Participants: A randomized substudy was conducted from September 2022 to March 2023 at a multisite tertiary cancer center as part of an ongoing clinical trial that was testing a symptom-intervention for cancer-related fatigue. Patients with breast cancer who were undergoing radiotherapy who completed at least 1 ePRO questionnaire during the study period were included. Physician-level cluster randomization assigned fatigue-eligible patients to either receive a portal message invitation to a symptom-intervention trial or standard of care (SOC; physician-based referral). Exposure: ePRO questionnaires distributed in routine practice were queried weekly and screened for moderate or greater fatigue, the principle inclusion criterion for the primary trial. To assess the association of the portal message source with response and enrollment, every other patient received a message from the primary radiation oncology team or the referral service. Main Outcomes and Measures: Clinical trial response/referral and enrollment. Results: A total of 1041 patients completed ePRO questionnaires, of whom 394 (38%; 53 Asian [13.6%], 43 Black [11.0%], 29 Hispanic [7.4%], and 262 White individuals [66.5%]; median [IQR] age, 55 [47-65] years) endorsed moderate or greater fatigue while receiving treatment. A total of 210 patients (53.3%) were assigned to receive a portal message and 184 (46.7%) patients, SOC. In the portal message group, 73 patients (35%) responded and 41 (20%) enrolled compared with 1 patient (0.5%) referred and 0 enrolled in the SOC group (P < .001). The response rate to portal messages favored the referral service vs the primary radiation oncology service (44% vs 26%; P = .01), but there was no significant difference in enrollments. Conclusions and Relevance: The study results suggest that use of routine care ePROs was associated with greater enrollment in a symptom-intervention trial compared with physician-based referral. Messaging directly from the referral service may support enrollment and help reduce oncology physician-level barriers to trial enrollment for studies testing symptom interventions.

Clinical and radiographic outcomes of shoulder hemiarthroplasty for patients with glenoid medialization.

BACKGROUND: Glenoid bone loss in shoulder arthroplasty is a difficult problem that is prone to complications because of challenges with achieving glenoid component fixation and stability. The purpose of this study was to evaluate the outcomes of primary shoulder hemiarthroplasty for patients with severe glenoid medialization precluding placement of a glenoid component. METHODS: This was a retrospective case series evaluating patients who underwent shoulder hemiarthroplasty for severe glenoid erosion and medialization between 2010 and 2020. Patients were evaluated via chart review and phone survey to determine if there were any reoperations at final follow-up and to obtain Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Simple Shoulder Test (SST) scores. Preoperative and postoperative radiographs were evaluated and compared to determine glenoid morphology, version, medialization, acromiohumeral distance, and humeral offset. Final postoperative films were also evaluated for anterosuperior migration and signs of mechanical failure, including loosening or periprosthetic fracture. RESULTS: Overall, there were 28 patients during this period who underwent shoulder hemiarthroplasty for severe glenoid medialization. Eight patients were deceased at the time of the study, 2 were unable to complete surveys because of dementia, and 7 were lost to follow-up. The final cohort included 11 shoulders and 11 patients with a mean age of 71 ± 7.1 years and mean follow-up of 6.7 years (range 1.6-13.0 years). Mean postoperative SANE, ASES, and SST scores were 80.6 ± 17.6, 71.5 ± 29.3, and 7.6 ± 2.0, respectively. There were no reoperations or revision surgeries at final follow-up. Radiographic evaluation demonstrated severe glenoid medialization and decreased lateral humeral offset, which was unchanged postoperatively. There were 2 patients with signs of anterosuperior migration at final radiographic follow-up but no signs of implant failure. CONCLUSION: Shoulder hemiarthroplasty for severe medial glenoid bone loss provides modest clinical outcomes and low rates of reoperation at mid- to long-term follow-up and is an option worth considering in cases where placement of a glenoid component is challenging because of deficient bone stock and high risk for complications.

Same-day discharge vs. inpatient total shoulder arthroplasty: an age stratified comparison of postoperative outcomes and hospital charges.

BACKGROUND: As the number of total shoulder arthroplasty (TSA) procedures increases, there is a growing interest in improving patient outcomes, limiting costs, and optimizing efficiency. One approach has been to transition these surgeries to an outpatient setting. Therefore, the purpose of this study was to conduct an age-stratified analysis comparing the 90-day postoperative outcomes of primary TSA in the same-day discharge (SDD) and inpatient (IP) settings with a specific focus on the super-elderly. METHODS: This retrospective study included all patients who underwent primary anatomic or reverse TSA between January 2018 and December 2021 in ambulatory and IP settings. The outcome measures included length of stay (LOS), complications, hospital charges, emergency department (ED utilization), readmissions, and reoperations within 90 days following TSA. Patients with LOS ≤8 hours were considered as SDD, and those with LOS >8 hours were considered as IP. P < .05 was considered statistically significant. RESULTS: There were 121 and 174 procedures performed in SDD and IP settings, respectively. There were no differences in comorbidity indices between the SDD and IP groups (American Society of Anesthesiologists score P = .12, Elixhauser Comorbidity Index P = .067). The SDD cohort was younger than the IP group (SDD 67.0 years vs. 73.0 IP years, P < .001), and the SDD group higher rate of intraoperative tranexamic acid use (P = .015) and lower estimated blood loss (P = .009). There were no differences in 90-day overall minor (P = .20) and major complications (P = 1.00), ED utilization (P = .63), readmission (P = .25), or reoperation (P = .51) between the SDD and IP groups. When stratified by age, there were no differences in overall major (P = .80) and minor (P = .36) complications among the groups. However, the LOS was directly correlated with increasing age (LOS = 8.4 hours in ≥65 to <75-year cohort vs. LOS = 25.9 hours in ≥80-year cohort; P < .001). There were no differences in hospital charges between SDD and IP primary TSA in all 3 age groups (P = .82). CONCLUSION: SDD TSA has a shorter LOS without increasing postoperative major and minor complications, ED encounters, readmissions, or reoperations. Older age was not associated with an increase in the complication profile or hospital charges even in the SDD setting, although it was associated with increased LOS in the IP group. These results suggest that TSA can be safely performed expeditiously in an outpatient setting.

Participation in Virtual Prehabilitation and Outcomes Following Thoracic Cancer Surgery.

This cohort study evaluates the association of a virtual synchronized prehabilitation program with perioperative outcomes among patients undergoing thoracic cancer surgery.

In Situ Formation of Fibronectin-Enriched Protein Corona on Epigenetic Nanocarrier for Enhanced Synthetic Lethal Therapy.

PARP inhibitors (PARPi)-based synthetic lethal therapy demonstrates limited efficacy for most cancer types that are homologous recombination (HR) proficient. To potentiate the PARPi application, a nanocarrier based on 5-azacytidine (AZA)-conjugated polymer (PAZA) for the codelivery of AZA and a PARP inhibitor, BMN673 (BMN) is developed. AZA conjugation significantly decreased the nanoparticle (NP) size and increased BMN loading. Molecular dynamics simulation and experimental validations shed mechanistic insights into the self-assembly of effective NPs. The small PAZA NPs demonstrated higher efficiency of tumor targeting and penetration than larger NPs, which is mediated by a new mechanism of active targeting that involves the recruitment of fibronectin from serum proteins following systemic administration of PAZA NPs. Furthermore, it is found that PAZA carrier sensitize the HR-proficient nonsmall cell lung cancer (NSCLC) to BMN, a combination therapy that is more effective at a lower AZA/BMN dosage. To investigate the underlying mechanism, the tumor immune microenvironment and various gene expressions by RNAseq are explored. Moreover, the BMN/PAZA combination increased the immunogenicity and synergized with PD-1 antibody in improving the overall therapeutic effect in an orthotopic model of lung cancer (LLC).

An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway.

Animals sense and respond to nutrient availability in their environments, a task coordinated in part by the mTOR complex 1 (mTORC1) pathway. mTORC1 regulates growth in response to nutrients and, in mammals, senses specific amino acids through specialized sensors that bind the GATOR1/2 signaling hub. Given that animals can occupy diverse niches, we hypothesized that the pathway might evolve distinct sensors in different metazoan phyla. Whether such customization occurs, and how the mTORC1 pathway might capture new inputs, is unknown. Here, we identify the Drosophila melanogaster protein Unmet expectations (CG11596) as a species-restricted methionine sensor that directly binds the fly GATOR2 complex in a fashion antagonized by S-adenosylmethionine (SAM). We find that in Dipterans GATOR2 rapidly evolved the capacity to bind Unmet and to thereby repurpose a previously independent methyltransferase as a SAM sensor. Thus, the modular architecture of the mTORC1 pathway allows it to co-opt preexisting enzymes to expand its nutrient sensing capabilities, revealing a mechanism for conferring evolvability on an otherwise conserved system.

A psychoeducational intervention to improve sexual functioning in male rectal and anal cancer patients: A pilot randomized controlled trial study.

OBJECTIVES: Male rectal and anal cancer patients demonstrate high rates of sexual dysfunction. This pilot randomized controlled trial tested a psychoeducational intervention designed to improve psychosexual adjustment. METHODS: Rectal or anal cancer patients were randomized to a Sexual Health Intervention for Men (intervention) or to a referral and information control (control). The intervention included control activities plus 4 sexual health intervention sessions every 4-6 weeks and 3 brief telephone calls timed between these sessions. Assessments were completed pre-intervention (baseline) and 3 months (follow-up 1) and 8 months (follow-up 2) post-intervention. Differences were assessed with statistical significance and Cohen's d effect sizes (d = 0.2, small effect; d = 0.5, moderate effect; d = 0.8, large effect). RESULTS: Ninety subjects enrolled. Forty-three participants completed at least 1 follow-up assessment (intervention, n = 14; control n = 29). At follow-up 1, men in intervention, compared to control, improved on all domains of the International Index of Erectile Function (IIEF) (p < 0.001 to p < 0.05) and demonstrated large effects (d = 0.8 to d = 1.5). Similarly, at follow-up 2, changes in all domains of the IIEF except the orgasm domain were either statistically significant or marginally statistically significant (p = 0.01 to p = 0.08) and demonstrated moderate to large treatment effects for intervention versus control (d = 0.5 to d = 0.8). Men in the intervention, compared to control, demonstrated decreased sexual bother at follow-up 1 (p = 0.009, d = 1.1), while Self-Esteem and Relationship (SEAR) total scores and the SEAR sexual relationship subscale demonstrated moderate increases for intervention versus control (d = 0.4 to d = 0.6). SIGNIFICANCE OF RESULTS: This study provides initial evidence for combining a psychoeducational intervention with medical interventions to address sexual dysfunction following rectal and anal cancer. Trials register number: NCT00712751 (date of registration: 7/10/2008).

Adaption of novel clip-closure technique for large mucosal defects after EMR of a colon laterally spreading tumor using standard hemostatic clips.

Video 1EMR of a large colonic polyp with defect closure using Resolution 360 ULTRA Clips (Boston Scientific, Boston, Mass, USA) and the Anchor, Mobilize, and Close approach.

Active narcotic use and post-peroral endoscopic myotomy outcomes in esophageal motility disorders.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a minimally invasive technique used to treat esophageal motility disorders. Opioid use has been demonstrated to adversely affect esophageal dysmotility and is associated with an increased prevalence of esophageal motility disorders. Our aim was to investigate the effect of narcotic use on success rates in patients undergoing POEM. METHODS: This was a single-center, retrospective study of patients undergoing POEM between February 2017 and September 2021. Primary outcomes were post-POEM Eckardt score (ES), distensibility index, and length of procedure. Secondary outcomes included technical success, myotomy length, length of stay, adverse events, reintervention rates, and postprocedure GERD. RESULTS: During the study period, 90 patients underwent POEM for treatment of esophageal dysmotility disorders. Age, sex, race, indications for POEM, and body mass index were not significant between those with or without narcotic use. There were no differences in procedure time, preprocedure ESs, or length of stay. Postprocedure ESs were higher in the group with active narcotic use compared to the group with no prior history (2.73 vs 1.2, P = .004). Distensibility indexes measured with EndoFLIP (Medtronic, Minneapolis, Minn, USA) were not different in patients using narcotics compared with opioid-naïve patients. CONCLUSION: Active narcotic use negatively affects symptom improvement after POEM for the treatment of esophageal motility disorders.

Outcomes of Cold Snare Endoscopic Mucosal Resection of Nonampullary Duodenal Adenomas ≥1 cm: A Multicenter Study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.

Evaluating Immune-Related Adverse Events Using PRO-CTCAE in a Phase II Study of Ipilimumab for Hormone-Sensitive Prostate Cancer.

Introduction: Use of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) during chemotherapy is associated with decreased hospitalization rates, improved quality of life, and longer survival. Limited data exist on the benefit of this symptom assessment tool for monitoring immune-related adverse events (irAEs). Methods: We incorporated irAE-related items from the National Cancer Institute's (NCI) PRO-CTCAE in a trial evaluating ipilimumab in combination with androgen deprivation therapy in 16 patients with hormone-sensitive prostate cancer. For comparison, NCI's CTCAE version 4.0 was used by clinicians. Results: IrAE-related PRO-CTCAE surveys and matched CTCAEs (184 pairs) reporting abdominal pain, diarrhea, fatigue, anorexia, nausea, vomiting, rash, and pruritus were collected at each treatment administration and during follow-up. Fatigue, diarrhea, rash, and pruritus were the symptoms most frequently reported by both patients and clinicians. Agreement was lowest for pruritus (κ = 0.10) and highest for rash (κ = 0.64). IrAEs were more commonly reported and of higher grade with PRO-CTCAE scores compared with CTCAE grades. Conclusion: PRO-CTCAEs focused on irAEs capture the patient's immunotherapy experience while complementing the clinician's toxicity assessment measures. Further study is needed to assess PRO-CTCAE's utility in identifying and managing irAEs.

Acupuncture vs Massage for Pain in Patients Living With Advanced Cancer: The IMPACT Randomized Clinical Trial.

Importance: Pain is challenging for patients with advanced cancer. While recent guidelines recommend acupuncture and massage for cancer pain, their comparative effectiveness is unknown. Objective: To compare the effects of acupuncture and massage on musculoskeletal pain among patients with advanced cancer. Design, Setting, and Participants: A multicenter pragmatic randomized clinical trial was conducted at US cancer care centers consisting of a northeastern comprehensive cancer center and a southeastern cancer institute from September 19, 2019, through February 23, 2022. The principal investigator and study statisticians were blinded to treatment assignments. The duration of follow-up was 26 weeks. Intention-to-treat analyses were performed (linear mixed models). Participants included patients with advanced cancer with moderate to severe pain and clinician-estimated life expectancy of 6 months or more. Patient recruitment strategy was multipronged (eg, patient database queries, mailings, referrals, community outreach). Eligible patients had English or Spanish as their first language, were older than 18 years, and had a Karnofsky score greater than or equal to 60 (range, 0-100; higher scores indicating less functional impairment). Interventions: Weekly acupuncture or massage for 10 weeks with monthly booster sessions up to 26 weeks. Main Outcomes and Measures: The primary end point was the change in worst pain intensity score from baseline to 26 weeks. The secondary outcomes included fatigue, insomnia, and quality of life. The Brief Pain Inventory (range, 0-10; higher numbers indicate worse pain intensity or interference) was used to measure the primary outcome. The secondary outcomes included fatigue, insomnia, and quality of life. Results: A total of 298 participants were enrolled (mean [SD] age, 58.7 [14.1] years, 200 [67.1%] were women, 33 [11.1%] Black, 220 [74.1%] White, 46 [15.4%] Hispanic, and 78.5% with solid tumors). The mean (SD) baseline worst pain score was 6.9 (1.5). During 26 weeks, acupuncture reduced the worst pain score, with a mean change of -2.53 (95% CI, -2.92 to -2.15) points, and massage reduced the Brief Pain Inventory worst pain score, with a mean change of -3.01 (95% CI, -3.38 to -2.63) points; the between-group difference was not significant (-0.48; 95% CI, -0.98 to 0.03; P = .07). Both treatments also improved fatigue, insomnia, and quality of life without significant between-group differences. Adverse events were mild and included bruising (6.5% of patients receiving acupuncture) and transient soreness (15.1% patients receiving massage). Conclusions and Relevance: In this randomized clinical trial among patients with advanced cancer, both acupuncture and massage were associated with pain reduction and improved fatigue, insomnia, and quality of life over 26 weeks; however, there was no significant different between the treatments. More research is needed to evaluate how best to integrate these approaches into pain treatment to optimize symptom management for the growing population of people living with advanced cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT04095234.

Expression of the vesicular GABA transporter within neuromedin S+ neurons sustains behavioral circadian rhythms.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of a central circadian clock that orchestrates overt rhythms of physiology and behavior. Circadian timekeeping requires intercellular communication among SCN neurons, and multiple signaling pathways contribute to SCN network coupling. Gamma-aminobutyric acid (GABA) is produced by virtually all SCN neurons, and previous work demonstrates that this transmitter regulates coupling in the adult SCN but is not essential for the nucleus to sustain overt circadian rhythms. Here, we show that the deletion of the gene that codes for the GABA vesicular transporter Vgat from neuromedin-S (NMS)+ neurons-a subset of neurons critical for SCN function-causes arrhythmia of locomotor activity and sleep. Further, NMS-Vgat deletion impairs intrinsic clock gene rhythms in SCN explants cultured ex vivo. Although vasoactive intestinal polypeptide (VIP) is critical for SCN function, Vgat deletion from VIP-expressing neurons did not lead to circadian arrhythmia in locomotor activity rhythms. Likewise, adult SCN-specific deletion of Vgat led to mild impairment of behavioral rhythms. Our results suggest that while the removal of GABA release from the adult SCN does not affect the pacemaker's ability to sustain overt circadian rhythms, its removal from a critical subset of neurons within the SCN throughout development removes the nucleus ability to sustain circadian rhythms. Our findings support a model in which SCN GABA release is critical for the developmental establishment of intercellular network properties that define the SCN as a central pacemaker.

Closure of Mucosal Defects Using Endoscopic Suturing Following Endoscopic Submucosal Dissection: A Single-Center Experience.

Background and Aims: Endoscopic submucosal dissection (ESD) is a therapeutic technique for en-bloc resection of both large (>20 mm) and smaller, complex gastrointestinal neoplasms. ESD has a higher success rate of en-bloc resection and a lower rate of local recurrence compared to endoscopic mucosal resection (EMR). Removal of lesions via ESD can leave large mucosal defects, raising unique challenges leading to adverse events. We aimed to determine clinical outcomes including delayed bleeding, perforation and hospitalization in patients undergoing endoscopic suturing following ESD. Methods: Single-center retrospective study of a prospectively collected database of consecutive adult patients who underwent ESD with mucosal defect closure using endoscopic suturing. Primary outcomes were adverse events, specifically, delayed bleeding or perforation. Secondary outcomes included need for hospitalization and suturing complications. Results: 55 patients (mean age: 67 years) were included with a mean lesion size of 27.4 mm ± 15. Defect closure occurred in the esophagus (6), gastroesophageal junction (2), stomach (30), cecum (2), sigmoid colon (2) and rectum (13). A mean of 1.8 ± 1.0 sutures were required for defect closure. Hospital admission rates were 14% (8/55) with an average length of stay 2 days (range: 1-3 days). Intra-procedure perforation occurred in two patients and both were successfully treated with endoscopic suturing. There was one case of delayed bleeding and no cases of delayed perforation or suturing complications. Conclusion: The use of endoscopic suturing following ESD is a safe and clinically reliable method to close mucosal defects. This approach is associated with minimal adverse events and need for hospitalization. Larger studies are needed to further validate these findings.