Gastroesophageal reflux disease (GERD) is common and often medically refractory. Abnormal gastric myoelectrical function may contribute to pathogenesis. This prospective observational study with matched controls assessed if myoelectrical abnormalities measured using body surface gastric mapping were correlated with reflux measured by 24-h pH testing and symptom severity. Gastric Alimetry was performed simultaneously on patients undergoing 24-h pH testing for investigation of reflux symptoms, with a standardized 4.5-h test and validated symptom logging. Data were segmented into 15-min epochs. Forty subjects were recruited (mean age 46.5 yr, 60% female): 20 undergoing pH testing (12 with GERD and 8 symptomatic patients without) and 20 controls. Patients with GERD displayed lower gastric rhythm stability measured by the Gastric Alimetry Rhythm Index (GA-RI) when compared with controls (P = 0.011), but not with patients without GERD (P = 0.605). Lower gastric rhythm stability measured by GA-RI was associated with increased esophageal acid exposure (DeMeester score; r = -0.46, P = 0.042). Periods of decreased gastric rhythm stability measured by GA-RI were not temporally correlated with reflux (r = 0.08, P = 0.182) or heartburn severity (r = 0.04, P = 0.309) but were correlated with nausea (r = -0.22, P < 0.001) and excessive fullness (r = -0.28, P < 0.001). We demonstrated that gastric rhythm instability is associated with increased symptom severity and overall acid exposure in patients with GERD. Although there was no temporal link between rhythm instability and heartburn, rhythm instability was temporally associated with increased nausea and fullness. GA-RI therefore offers an emerging biomarker of concurrent gastric neuromuscular dysfunction in patients with GERD.NEW & NOTEWORTHY Gastroesophageal reflux disease (GERD) is common and often medically refractory. We assessed whether gastric myoelectrical function contributes to pathogenesis by simultaneously measuring myoelectrical activity with Gastric Alimetry and reflux events on 24-h pH testing in patients. We demonstrated that gastric rhythm instability is associated with increased symptom severity and acid exposure in patients with GERD. Although there was no temporal link between rhythm instability and heartburn found, rhythm instability was temporally associated with dyspepsia.

Background Abnormal gastric myoelectrical function may contribute to gastroesophageal reflux disease (GERD). We assessed if myoelectrical abnormalities measured using body surface gastric mapping were correlated with reflux measured by 24 hr pH testing, and symptom severity. Methods Gastric Alimetry was performed simultaneously on patients undergoing 24 hr pH testing for investigation of reflux symptoms, with a standardised 4.5 hr test and validated symptom logging. Data were segmented into 15-minute epochs. Correlations between myoelectric activity, reflux events, and symptoms were assessed, including temporal correlations adjusted for repeated measures. Results Forty subjects were recruited (mean age 46.5 years, 60% female): 20 undergoing pH testing (12 with GERD and 8 symptomatic patients without), and 20 controls. GERD patients displayed less stable Gastric Alimetry Rhythm-Index (GA-RI) compared with controls (p=0.011), but not with non-GERD patients (p=0.605). Decreasing GA-RI was associated with esophageal acid exposure (DeMeester score; r=-0.46, p=0.042). Periods of decreased GA-RI were not temporally correlated with reflux (r=0.08, p=0.182), or heartburn severity (r=0.04, p=0.309), but were correlated with nausea (r=-0.22, p<0.001) and excessive fullness (r=-0.28, p<0.001). Conclusion Gastric rhythm instability is associated with increased symptom severity and overall acid exposure in GERD patients, although no temporal link to heartburn was found. Reduced rhythm stability was temporally associated with increased nausea and fullness. GA-RI offers an emerging biomarker of gastric dysfunction in patients with GERD symptomatology. ### Competing Interest Statement Greg OGrady and Armen Gharibans hold grants and intellectual property in the field of gastrointestinal electrophysiology and are the co-founders at Alimetry Ltd. William Xu, Sam Simmonds, Daphne Foong, Chris Varghese, Christopher N Andrews, Gabe Schamberg, Armen Gharibans, Stefan Calder are members of Alimetry Ltd. The remaining authors have no conflicts of interest to declare. ### Funding Statement This study was supported by a New Zealand Health Research Council Program Grant. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for reporting was obtained from the Auckland Health Ethics Research Ethics Committee and Western Sydney Human Research Ethics Committee (ref: AH1130, H15157). All patients provided informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Gastric motility is coordinated, in part, by rhythmic bioelectrical events called slow waves. Dysrhythmic slow waves have been associated with several motility disorders. The current methods for classifying gastric dysrhythmias, via direct-organ mapping, are surgically invasive. To address this limitation, we designed and constructed a minimally invasive, custom gastric mapping device primarily consisting of a 64-electrode spherical-basket mapping catheter, fitted with an internal balloon, which is delivered endoscopically. We successfully deployed this device in n = 13 volunteers, detecting slow waves in n = 12 volunteers, which presented with properties in-line with established physiological ranges confirming device effectiveness. Spatiotemporal propagation maps with >33% electrode coverage were generated in n = 5 volunteers and showed predominantly dysrhythmic activity. This study presents an endoscopic, minimally invasive, high-resolution electrical mapping device complete with first-in-human data from the gastric antrum. With further development, this device could be used to profile and localize gastric dysrhythmias, as a diagnostic tool, and to guide emerging treatments.

Abnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction, but the only tool to evaluate CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. This study aimed to validate body surface colonic mapping (BSCM) through direct correlation with HRCM. Synchronous meal-test recordings were performed in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was performed comparing the meal responses and motility indices (MI). Spatial heat maps were also compared. Post-study questionnaires evaluated participants’ preference and comfort/distress experienced from either test. 11 participants were recruited and 7 had successful synchronous recordings (5 females/2 males; median age: 50 years [range 38–63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range 0.47–0.77). HRCM and BSCM meal response start and end times (Rp = 0.998 and 0.83; both p < 0.05) and durations (Rp = 0.85; p = 0.03) were similar. Heat maps demonstrated good spatial agreement. BSCM is the first non-invasive method to be validated by demonstrating a direct spatio-temporal correlation to manometry in evaluating colonic motility.

Preoperative exclusive enteral nutrition (EEN) improves nutritional status, reduces intestinal inflammation, and likely improves surgical outcomes. Crohn’s disease exclusion diet with partial enteral nutrition (CDED) also reduces intestinal inflammation but its safety preoperatively is unknown. This single-blinded, multicentre, randomised controlled trial of three preoperative nutritional therapies aimed to assess the feasibility of recruiting and retaining patients and collecting primary and secondary effectiveness outcomes. Adults undergoing elective Crohn’s disease surgery with a body mass index (BMI) > 18.5 kg/m2 and without significant weight loss were eligible to participate. Patients were randomly assigned to six weeks of preoperative EEN, CDED, or standard care. Feasibility, nutritional, radiological, and surgical outcomes were recorded. Over 18 months, 48 patients were screened, 17 (35%) were randomised, and 13/17 (76%) patients were retained in the intervention phase. It was feasible to collect primary and secondary effectiveness data; at day 30, three patients had Clavien Dindo Grade 2 complications, and 10 had no complications. Nutritional therapy adherence of patients retained in the study was high. Recruitment and retention of patients who need elective Crohn’s disease surgery for preoperative nutritional therapy is possible, although a shorter duration may improve EEN completion. The impact on surgical outcomes should be assessed in a larger study.

INTRODUCTION:Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years. METHODS:Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200. RESULTS:Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% [117/174]) were in symptomatic remission than those with a history of biologic failure (41.6% [67/161]). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events. DISCUSSION:The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236.

BACKGROUND: Postoperative ileus results in morbidity, prolonged hospitalization, and increased health care expenditure. However, the underlying abnormalities in motility remain poorly understood. Recent high-resolution manometry studies demonstrated that the distal colon becomes hyperactive with a cyclic motor pattern postoperatively, but they did not track this activity beyond 16 hours after surgery. OBJECTIVE: This study used high-resolution manometry to evaluate distal colonic motility during the first 4 days after right-sided colectomy. DESIGN: An observational study of perioperative high-resolution colonic manometry using a 36-sensor catheter with 1-cm resolution. SETTING: A single tertiary hospital. PATIENTS: Adult patients undergoing elective laparoscopic or open right-sided colonic resection. MAIN OUTCOME MEASURES: Occurrence of distal colonic motor patterns during the perioperative period, defined according to a published classification system. Clinical markers of gut recovery included time to first stool, oral diet, and prolonged postoperative ileus. RESULTS: Seven patients underwent perioperative manometry recordings. Hyperactive cyclic motor patterns emerged intraoperatively and peaked in the first 12 hours postoperatively, occupying 81.8% ± 3.9% of the recording. This gradually returned to normal during the first 4 days, reaching 19.0% ± 4.4% (p = 0.002). No patient had a bowel movement before this hyperactivity resolved. High-amplitude propagating sequences were absent in early postoperative recordings, and their return temporally correlated with the passage of stool. Abnormal high-amplitude repetitive 0.5 to 1 cycle per minute activity was observed in the left colon of 1 patient with prolonged ileus. LIMITATIONS: The invasive nature of recordings limited this study to a small sample size. CONCLUSIONS: Cyclic motor patterns are markedly hyperactive in the distal colon after right-sided colectomy and resolve during the first 4 postoperative days. High-amplitude propagating sequences are inhibited by surgery and gradually recover. Bowel function may not return until these changes resolve. Other abnormal repetitive hyperactive patterns could contribute to the development of prolonged ileus. See Video Abstract at http://links.lww.com/DCR/B967. MOTILIDAD HIPERACTIVA DEL COLON DISTAL Y PATRONES DE RECUPERACIÓN DESPUÉS DE COLECTOMÍA DERECHA: UN ESTUDIO DE MANOMETRÍA DE ALTA RESOLUCIÓN ANTECEDENTES: El íleo post-operatorio produce una morbilidad significativa, una hospitalización prolongada y un aumento del gasto sanitario. Sin embargo, las anomalías subyacentes en la motilidad siguen siendo poco conocidas. Estudios recientes de manometría de alta resolución demostraron que el colon distal se vuelve hiperactivo con un patrón motor cíclico en el post-operatorio, pero no registraron esta actividad más allá de las 16 horas posteriores a la cirugía. OBJETIVO: Utilizar la manometría de alta resolución para evaluar la motilidad del colon distal durante los primeros cuatro días después de la colectomía del lado derecho. DISEÑO: Estudio observacional de pacientes sometidos a manometría colónica perioperatoria de alta resolución mediante catéter de 36 sensores con 1 cm de resolución. AJUSTE: Un solo hospital terciario. PACIENTES: Pacientes adultos sometidos a resección laparoscópica o abierta de colon del lado derecho de forma electiva. PRINCIPALES MEDIDAS DE RESULTADO: AAparición de patrones motores del colon distal durante el período perioperatorio, definidos según un sistema de clasificación publicado. Los marcadores clínicos de recuperación intestinal incluyeron, tiempo hasta la primera evacuación, dieta oral e íleo posoperatorio prolongado. RESULTADOS: Siete pacientes fueron sometidos a registros de manometría perioperatoria. Los patrones motores cíclicos hiperactivos emergieron intraoperatoriamente y alcanzaron su punto máximo en las primeras 12 horas post-operatorias, ocupando 81,8 ± 3,9% del registro. Esto volvió gradualmente a la normalidad durante los primeros cuatro días, alcanzando el 19,0 ± 4,4% (p = 0,002). Ningún paciente tuvo una evacuación intestinal antes de que se resolviera esta hiperactividad. Las secuencias de propagación de alta amplitud estaban ausentes en las grabaciones post-operatorias tempranas y su retorno se correlacionó temporalmente con el paso de las heces. Se observó actividad anormal de alta amplitud repetitiva de 0,5-1 ciclo / minuto en el colon izquierdo de un paciente con íleo prolongado. LIMITACIONES: La naturaleza invasiva de las grabaciones limitó este estudio a un tamaño de muestra pequeño. CONCLUSIONES: Los patrones motores cíclicos son marcadamente hiperactivos en el colon distal después de la colectomía del lado derecho y se resuelven gradualmente durante los primeros cuatro días posoperatorios. Las secuencias de propagación de gran amplitud se inhiben mediante cirugía y se recuperan gradualmente. Es posible que la función intestinal no regrese hasta que estos cambios se resuelvan. Otros patrones hiperactivos repetitivos anormales podrían contribuir al desarrollo de íleo prolongado. Consulte Video Resumen en http://links.lww.com/DCR/B967. (Traducción—Dr. Mauricio Santamaria)

Abstract Background and Aims The UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy. Methods Patients randomised to ustekinumab every 12 weeks [q12w] or every 8 weeks [q8w] at maintenance baseline [N = 348] and randomised ustekinumab-treated patients in the LTE [N = 284] were evaluated. Symptomatic remission [Mayo stool frequency = 0/1, rectal bleeding = 0] was assessed. Safety included all LTE patients [N = 188 placebo and N = 457 ustekinumab]. Results Among patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma [BCC] reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes. Conclusions Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.

Introduction: Ustekinumab (UST) is an IL-12/23p40 inhibitor approved for treatment of Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients (pts) with moderate to severe UC, > 90% of pts who achieved clinical response or remission at week (wk) 44 were not receiving corticosteroids, an important therapeutic goal. In this analysis, we describe the corticosteroid-sparing effects of UST treatment through 4 years (yrs) among pts who were treated in the UNIFI long-term extension (LTE). Methods: Overall, 523 intravenous UST induction responders were randomized to subcutaneous (SC) maintenance therapy (placebo [PBO], n=175; UST 90mg every 12 wks [q12w], n=172; or UST 90mg q8w, n=176). A total of 284 UST pts completed wk44 and were treated in the LTE. PBO pts were discontinued after study unblinding. Based on investigator’s clinical judgement of UC disease activity, pts in the LTE were eligible to receive a dose adjustment starting at wk56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Pts in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Efficacy was evaluated using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0). During the maintenance study, all pts receiving corticosteroids at maintenance baseline were required to initiate tapering. Through wk200 of the LTE, symptomatic remission endpoints were calculated with treatment failure and missing data nonresponder imputation, and dose adjustment was not considered to be a treatment failure. Missing corticosteroid dose data were managed using last observation carried forward. Results: Of the 284 pts randomized to UST and treated in the LTE, 139 were receiving corticosteroids at maintenance baseline. Of these, 79.1% (n=110) were no longer receiving corticosteroids at wk200. Rates of corticosteroid-free symptomatic remission at wk200 were generally similar for the q8w and q12w maintenance doses (Table). Of the UST-treated pts in symptomatic remission at wk200, 94/96 (97.9%) in the q12w group and 91/96 (94.8%) in the q8w group were corticosteroid free. Conclusion: UST maintenance therapy, with both q8w and q12w dosing regimens, was effective in reducing and eliminating the use of corticosteroids in pts with UC through 4 yrs. The majority of pts in symptomatic remission were corticosteroid free through 4 yrs of treatment with UST. Table 1. - Symptomatic remission and corticosteroid-sparing effects in patients who were randomized to UST in maintenance and were treated in the long-term extension Analysis 90 mg UST SC q12w a 90 mg UST SC q8w a Combined UST a Randomized patients in maintenance who were treated in the LTE, N 141 143 284 Patients in symptomatic remission, n/N (%) d,e,f Week 44 117/141 (83.0) 119/143 (83.2) 236/284 (83.1) Week 200 96/141 (68.1) 96/143 (67.1) 192/284 (67.6) Patients in symptomatic remission and not receiving corticosteroids, n/N (%) b,d,e,f Week 44 111/141 (78.7) 115/143 (80.4) 226/284 (79.6) Week 200 94/141 (66.7) 91/143 (63.6) 185/284 (65.1) Patients in symptomatic remission and not receiving corticosteroids among patients receiving corticosteroids at maintenance baseline, n/N (%) b,c,d,e,f Week 44 49/68 (72.1) 56/71 (78.9) 105/139 (75.5) Week 200 39/68 (57.4) 47/71 (66.2) 86/139 (61.9) Patients who were able to eliminate the use of corticosteroids, n/N (%) b,c Week 44 61/68 (89.7) 64/71 (90.1) 125/139 (89.9) Week 200 53/68 (77.9) 57/71 (80.3) 110/139 (79.1) LTE, long-term extension; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; UST, ustekinumab.aRandomized group at maintenance Week 0 regardless of whether patients had a dose adjustment during the LTE.bPatients who had a missing value in corticosteroid use at the designated visit had their last available value carried forward to the designated visit.cDenominator is the number of patients who were receiving concomitant corticosteroids at maintenance baseline.dSymptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0.ePatients who had both stool frequency and rectal bleeding subscores missing at a visit were considered not to be in symptomatic remission for that visit.fPatients who had an ostomy or colectomy, or discontinued study agent due to lack of therapeutic effect or due to an adverse event of worsening of ulcerative colitis prior to the designated visit were considered not to be in symptomatic remission.

BACKGROUND & AIMS:Rapid symptomatic relief is an important treatment goal for patients with ulcerative colitis (UC). We aimed to characterize early response with ustekinumab in patients with moderate-to-severe UC during the initial 16 weeks of treatment. METHODS:We performed a post hoc analysis of data from A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis trial. Patients (N = 961) were randomized (1:1:1) to receive intravenous 130 mg ustekinumab, approximately 6 mg/kg ustekinumab, or placebo at week 0. Symptomatic remission, absolute stool number, Mayo stool frequency and rectal bleeding subscores, partial Mayo score, C-reactive protein, and fecal calprotectin were assessed in the overall population and for patients in the biologic-naïve or prior biologic failure subgroups. RESULTS:A significantly greater percentage of patients in the 130-mg ustekinumab (20.0%; P = .015) or approximately 6-mg/kg ustekinumab (20.2%; P = .012) groups achieved symptomatic remission at week 2 vs placebo (12.9%). Mean [SD] changes from baseline in daily stool number on day 7 were greater in the ustekinumab groups (-1.1 [2.6] in 130 mg [P = .065] and -1.2 [2.5] in ∼6 mg/kg [P = .017]) vs placebo (-0.7 [2.7]). The percentage of patients with Mayo stool frequency subscore of 1 or less and rectal bleeding subscore of 0 increased from baseline through week 16 for both ustekinumab groups. Significant improvements in partial Mayo scores were observed by week 2 in both ustekinumab groups vs placebo (P ≤ .001). Significantly more patients in the ustekinumab groups had normalized C-reactive protein levels from week 2 to week 8 vs placebo (P ≤ .05). Similar results were observed with normalized fecal calprotectin levels between week 2 and week 4 (P ≤ .05). CONCLUSIONS:Ustekinumab improved symptoms in patients with UC compared with placebo in as early as 7 days, indicating rapid onset of effect after induction. CLINICAL TRIAL REGISTRY NUMBER:ClinicalTrials.gov: NCT02407236.

Growing mammary epithelial cells as organoids in a three-dimensional (3D) cell culture environment represents a more physiological model system than conventional 2D adherent cell culture systems for studying many different aspects of mammary epithelial cell biology. We have developed MammoCult™ Organoid Growth Medium (Mouse), a serum- and phenol red-free medium for the long-term propagation of organoids from mouse mammary tissue. To initiate the cultures, mouse mammary glands are resected and enzymatically dissociated sequentially in Gentle Collagenase/Hyaluronidase, trypsin, and dispase/DNase I to generate a single-cell suspension, and 4.5 x 103 of the liberated cells are then embedded in Corning® Matrigel® and maintained in MammoCult™ Organoid Growth Medium (Mouse). Alternatively, freshly dissociated mammary cells can be expanded in adherent culture in EpiCult™ Plus Medium prior to seeding into Matrigel®. Approximately 8.4 ± 0.6% (mean ± SEM; n=10) of the freshly dissociated cells seeded in the Corning® Matrigel® will proliferate and generate organoids that are typically > 200 µm in diameter and have a highly branched morphology, although organoids with a cystic morphology are also observed. Immunostaining of these branched organoids reveals that they are composed of a polarized epithelium made up of keratin (K) 8-expressing luminal cells and K5/14-expressing basal cells (n=7). Organoids upregulate transcripts for caseins (Csn1s1, Csn2), whey acidic protein (Wap), and lactoferrin (Ltf) upon stimulation with prolactin, hydrocortisone, and insulin (n=4). These multilineage organoids can be established from multiple inbred mouse strains, including C57Bl6/J, FVB, BALB/c, and CD-1. Organoids can be passaged every 10 - 14 days as small fragments at a 1:3 to 1:4 split ratio, and can be maintained for a minimum of 10 passages while still maintaining multilineage potential and a normal karyotype. These results demonstrate that MammoCult™ Organoid Growth Medium (Mouse) efficiently generates and expands mammary epithelial cell-derived organoids and offers researchers a novel tool for in vitro mammary studies. Citation Format: David Rowbotham, Samantha Rothwell, Allen C. Eaves, Sharon A. Louis, John Stingl. Expansion of mouse mammary epithelial stem cells in serum-free organoid growth medium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6018.

Background and study aims  Refractory variceal bleeding is associated with high mortality in patients with chronic liver disease. A fully-covered self-expanding metal stent (SEMS) has been reported to have excellent rates of technical success and initial bleeding control; however, studies to date are small and limited to Europe and Asia. Our aim was to evaluate the efficacy and safety of this SEMS for control of refractory variceal bleeding (VB). Patients and methods  A retrospective analysis was undertaken of all patients who received the SX-ELLA Danis SEMS for management of VB at 9 tertiary centers across Australia and New Zealand. A total of 32 SEMS had been deployed in 30 patients (median age 53.3). Results  Technical success of SEMS placement was achieved in 100 % of cases, resulting in immediate control of bleeding across 31 of 32 cases (96.9 %). Re-bleeding with SEMS in situ occurred in three of 32 cases (9.4 %). Mean SEMS in-dwelling time was 6.4 days. Delayed SEMS migration occurred in 6.3 % of cases. Interventional radiological therapy for management of varices within 6 weeks was performed in 12 of 30 patients (40 %). Death with SEMS in situ occurred in seven of 30 patients (23.3 %). Seven-day bleeding-related mortality was 16.7 %, 14-day mortality 23.3 %, and 6-week mortality 33.3 %. Three of 30 patients (10 %) received orthotopic liver transplantation following SEMS insertion, including two patients within 6 weeks. Conclusions  SX-Danis Ella SEMS is highly effective for immediate control of refractory VB and bridging to definitive therapy because it has excellent technical success rates, appears to be relatively easy to use, and has low rates of serious adverse events.

Abstract Background Ustekinumab (UST) is an IL-12/23p40 antagonist used to treat pts with moderate-to-severe ulcerative colitis (UC). The ongoing UNIFI long-term extension (LTE) evaluates subcutaneous (SC) 90mg UST maintenance therapy, with efficacy (wk152) and safety (wk156) results reported here. Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (175 SC placebo [PBO]; 172 UST 90mg every 12 weeks [q12w]; 176 UST 90mg q8w). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Starting at wk56, randomized pts with UC worsening could adjust to q8w. Symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) was evaluated in randomized pts. Safety was evaluated for all 588 pts treated in the LTE, including the randomized and nonrandomized populations; 188 received PBO and 457 received UST. The nonrandomized population included responders to PBO induction and UST induction nonresponders at wk8 who received SC UST, responded 8 wks later and received UST 90mg q8w. Results Among all pts randomized to UST at maintenance baseline (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 55.2% were in symptomatic remission at wk152 (biologic naïve, 66.1%; biologic failures, 43.5%; Table 1); 96.4% (185/192) of pts in symptomatic remission at wk152 were corticosteroid-free. Overall, 20.1% (39/149 biologic failure, 16/149 biologic naïve) of pts who were randomized to UST and treated in the LTE discontinued treatment between wks44 and 156. Among randomized pts treated with UST in the LTE, 67.6% were in symptomatic remission at wk152; 76.4% of those in clinical remission at wk44 were in symptomatic remission at wk152; and 84.1% of pts with observed data at wk152 were in symptomatic remission. From maintenance wk0-156, combined UST and PBO pts had 1281.6 and 425.0 pt-years of follow-up, respectively; and safety events per 100 pt-years of follow-up for combined UST vs PBO were AEs: 235.81 vs 204.48, SAEs: 7.73 vs 7.53, and serious infections: 2.34 vs 2.35 (Table 2). From wks96-156, there were no reported deaths or major adverse cardiovascular events. One UST-treated pt with fair skin and a prior history of basal cell carcinoma (BCC) reported 2 BCC. One 90 mg q8w UST pt receiving concomitant 6-MP reported SAEs of neutropenic sepsis and oral herpes SAE; the latter events were considered potential opportunistic infections. The dose of 6-MP was reduced, pt recovered and continued UST. Conclusion The efficacy of UST in pts with UC was sustained through 3 years. No new safety signals were observed.

BACKGROUND & AIMS: Antibiotic treatment is the standard care for patients with uncomplicated acute diverticulitis. However, this practice is based on low-level evidence and has been challenged by findings from 2 randomized trials, which did not include a placebo group. We investigated the non-inferiority of placebo vs antibiotic treatment for the management of uncomplicated acute diverticulitis. METHODS: In the selective treatment with antibiotics for non-complicated diverticulitis study, 180 patients hospitalized for uncomplicated acute diverticulitis (determined by computed tomography, Hinchey 1a grade) from New Zealand and Australia were randomly assigned to groups given antibiotics (n = 85) or placebo (n = 95) for 7 days. We collected demographic, clinical, and laboratory data and answers to questionnaires completed every 12 hrs for the first 48 hrs and then daily until hospital discharge. The primary endpoint was length of hospital stay; secondary endpoints included occurrence of adverse events, readmission to the hospital, procedural intervention, change in serum markers of inflammation, and patient-reported pain scores at 12 and 24 hrs. RESULTS: There was no significant difference in median time of hospital stay between the antibiotic group (40.0 hrs; 95% CI, 24.4-57.6 hrs) and the placebo group (45.8 hrs; 95% CI, 26.5-60.2 hrs) (P = .2). There were no significant differences between groups in adverse events (12% for both groups; P = 1.0), readmission to the hospital within 1 week (1% for the placebo group vs 6% for the antibiotic group; P = .1), and readmission to the hospital within 30 days (11% for the placebo group vs 6% for the antibiotic group; P = .3). CONCLUSIONS: Foregoing antibiotic treatment did not prolong length of hospital admission. This result provides strong evidence for omission of antibiotics for selected patients with uncomplicated acute diverticulitis.

Background: Cyclic motor patterns (CMPs) are the most common motor pattern in the distal colon. This study used high-resolution (HR) colonic manometry to quantify trends in distal colonic motor activity before elective colonic surgery, determine the effect of a preoperative carbohydrate load, and compare this with a meal response in healthy controls. Methods: Fiber-optic HR colonic manometry (36 sensors, 1 cm intervals) was used to investigate distal colonic motor activity in 10 adult patients prior to elective colonic surgery, 6 of whom consumed a preoperative carbohydrate drink (200 kCal). Data were compared with nine healthy volunteers who underwent HR colonic manometry recordings while fasted and following a 700 kCal meal. The primary outcome was the percentage of recording occupied by CMPs, defined as propagating contractions at 2-4 cycles per minute (cpm). Secondary outcomes included amplitude, speed, and distance of propagating motor patterns. Results: The occurrence of CMPs progressively increased in time periods closer to surgery (p = 0.001). Consumption of a preoperative drink resulted in significantly increased CMP occurrence (p = 0.04) and propagating distance (p = 0.04). There were no changes in amplitude or speed of propagating motor patterns during the preoperative period. The increase in activity following a preoperative drink was of similar magnitude to the colonic meal response observed in healthy controls, despite the lesser caloric nutrient load. Conclusion: Distal colonic CMP increased in occurrence prior to surgery, amplified by ingestion of preoperative carbohydrate drinks. We hypothesize that anxiety, which is also known to rise with proximity to surgery, could play a contributing role.