Preoperative Crohn's Disease Exclusion Diet and Exclusive Enteral Nutrition in Adults with Crohn's Disease: A Feasibility Randomised Controlled Trial.

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.

Validation of body surface colonic mapping (BSCM) against high resolution colonic manometry for evaluation of colonic motility.

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.

Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance 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.

Hyperactive Distal Colonic Motility and Recovery Patterns Following Right Colectomy: A High-Resolution Manometry Study.

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 RECUPERACIN DESPUS DE COLECTOMA DERECHA UN ESTUDIO DE MANOMETRA DE ALTA RESOLUCIN: 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 ).

Early Symptomatic Improvement After Ustekinumab Therapy in Patients With Ulcerative Colitis: 16-Week Data From the UNIFI Trial.

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.

Efficacy and Safety of Maintenance Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension.

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.

The role of a novel self-expanding metal stent in variceal bleeding: a multicenter Australian and New Zealand experience.

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.

Potential causes of the preoperative increase in the rectosigmoid cyclic motor pattern: A high-resolution manometry study.

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.

High-Resolution Colonic Manometry Pressure Profiles Are Similar in Asymptomatic Diverticulosis and Controls.

BACKGROUND: Elevated colonic pressures and increased colonic activity have been thought to contribute to the pathophysiology of diverticulosis. However, evidence for this has been limited to low-resolution manometry, which is of limited accuracy. AIMS: This study aimed to evaluate the contraction pressures, counts, and distance of propagation recorded by high-resolution colonic manometry in diverticulosis vs control patients. METHODS: High-resolution colonic manometry was used to record descending and sigmoid colon activity pre- and post-meal in patients with established, asymptomatic diverticulosis and in healthy controls. Antegrade and retrograde propagating contractions, distance of propagation (mm), and mean contraction pressures (mmHg) in the descending and sigmoid colon were compared between patients and controls for all isolated propagating contractions, the cyclic motor pattern, and high-amplitude propagating contractions independently. RESULTS: Mean manometry pressures were not different between controls and diverticulosis patients (p > 0.05 for all comparisons). In the descending colon, diverticulosis patients had lower post-meal mean distance of propagation for all propagating contractions [10.8 (SE1.5) mm vs 20.0 (2.0) mm, p = 0.003] and the cyclic motor pattern [6.0 (2.5) mm vs 17.1 (2.8) mm, p = 0.01]. In the sigmoid colon, diverticulosis patients showed lower post-meal mean distance of propagation for all propagating contractions [10.8 (1.5) mm vs 20.2 (5.9) mm, p = 0.01] and a lower post-meal increase in retrograde propagating contractions (p = 0.04). CONCLUSIONS: In this first high-resolution colonic manometry study of patients with diverticular disease, we did not find evidence for increased manometric pressures or increased colonic activity in patients with diverticular disease.

Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial.

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. ACTRN: 12615000249550.

Altered colonic motility is associated with low anterior resection syndrome.

AIM: Patients frequently suffer from low anterior resection syndrome (LARS) after distal colorectal resection. The pathophysiology of LARS has not been clearly elucidated. We hypothesized that rectosigmoid resection could impair motility patterns in the distal colon, such as the rectosigmoid brake, which contribute to control of stool form and frequency. METHOD: High-resolution colonic manometry was performed in patients who had previously undergone distal colorectal resection (mean 6.8 years after resection) and non-operative controls before and after a standardized meal. Symptoms were assessed using the LARS score. Propagating contractions were compared between patients with and without LARS, and controls. RESULTS: Data were analysed from 23 patients (11 no-LARS; 12 LARS) and nine controls. All groups demonstrated a significant meal response. LARS patients had fewer post-prandial antegrade propagating contractions than controls (P = 0.028), and fewer retrograde propagating contractions both pre- (P = 0.005) and post-prandially (P = 0.004). Post-prandially, the LARS group had a significantly lower percentage of propagating contractions that met the criteria for the cyclic motor pattern compared to the control group (26% vs. 58%; P = 0.009). There were significant differences in antegrade and retrograde amplitude (P = 0.049; P = 0.018) and distance of propagation (P = 0.003; P = 0.002) post-prandially between LARS patients and controls. CONCLUSION: Rectosigmoid resection alters the meal response following anterior resection, including impairment of the rectosigmoid brake cyclic motor pattern. These findings help to quantify the impaired functional motility after rectosigmoid resection and offer new insights into the mechanisms of LARS.

Ustekinumab is effective and safe for ulcerative colitis through 2 years of maintenance therapy.

BACKGROUND: The ongoing UNIFI long-term extension evaluates subcutaneous ustekinumab for moderate-to-severe ulcerative colitis (UC) from weeks 44 through 220. AIMS: To assess efficacy (through week 92) and safety (through week 96) during the long-term extension METHODS: Overall, 399 responders to intravenous ustekinumab induction and who were randomised to maintenance therapy were treated in the long-term extension (115 received subcutaneous placebo, 141 received ustekinumab 90 mg every 12 weeks [q12w], and 143 received ustekinumab 90 mg q8w). Placebo treatment was discontinued at unblinding after week 44. Partial Mayo scores were collected every 12 weeks and at each dosing visit after unblinding. Safety was evaluated throughout. RESULTS: Among all patients randomised in maintenance, symptomatic remission rates (stool frequency = 0/1; rectal bleeding = 0) at week 92 were, 64.5% and 67.6% in the ustekinumab q12w and q8w groups, respectively. Among randomised patients treated in the long-term extension, 78.7% and 83.2% of patients receiving q12w and q8w, respectively, attained symptomatic remission at week 92; >95% of patients in symptomatic remission at week 92 were corticosteroid-free. Both ustekinumab groups maintained efficacy through week 92. From weeks 44 to 96, adverse events (AEs) per hundred patient-years (PY) of follow-up for combined ustekinumab vs placebo were: 255.68 vs 267.93; serious AEs, 9.34 vs 12.69; malignancies (including non-melanoma skin cancers), 0.93 vs 1.49; and serious infections, 2.33 vs 2.99. One patient with multiple comorbidities who received one ustekinumab dose after dose adjusting from placebo experienced a fatal cardiac arrest. CONCLUSIONS: The efficacy of ustekinumab in patients with UC was sustained through 92 weeks. No new safety signals were observed (ClinicalTrials.gov number, NCT02407236).

Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma.

Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity. We discover a region of focal amplification at chromosome 1q32.1 encompassing the ELF3 locus in LUAD which is absent in the squamous subtype. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. ELF3 expression was required for tumor growth and a pan-cancer expression network analysis supports its subtype and tissue specificity. We further show that ELF3 displays strong prognostic value in LUAD but not LUSC. We conclude that, contrary to many other tumors of epithelial origin, ELF3 is an oncogene and putative therapeutic target in LUAD.

Screening acute cholangitis patients for sepsis.

BACKGROUND: Acute cholangitis (AC) complicated by septic shock is associated with 40% mortality. The best screening method for diagnosing sepsis in patients with AC is unknown. In this study, we aimed to compare the discriminative powers of systemic inflammatory response syndrome criteria (SIRS test) and the 2018 Tokyo Guidelines for moderate cholangitis (TG18 test) in screening AC patients for sepsis and to estimate their predictive abilities. METHODS: This was a retrospective diagnostic accuracy study in which the TG18 and SIRS tests were applied to two groups of patients; 52 patients with 70 hospital admissions had AC with shock index ≥0.7 and 46 patients with 57 hospital admissions had AC with shock index <0.7, uncomplicated choledocholithiasis, obstructive jaundice and biliary stent removal. RESULTS: The sensitivity and specificity for the TG18 test in identifying AC patients with sepsis were 69% and 68%, respectively. The SIRS test applied to the same patient cohort yielded 93% sensitivity and 79% specificity. The SIRS test had a larger area under the receiver operating characteristic curve, 86% and 69%, respectively (P = 0.0004). With a sepsis prevalence of 23% in patients with biliary tract infections, the positive predictive value (PPV) for the SIRS test was 57% (95% confidence interval (CI) 44-69%) and the negative predictive value was 97% (95% CI 94-99%). The PPV and negative predictive value for the TG18 criteria were 39% (95% CI 30-50%) and 88% (95% CI 83-92%), respectively. CONCLUSION: The SIRS test had better discriminative power in identifying AC patients with sepsis than the TG18 criteria, but had a low PPV.

Predictors of non-attendance at outpatient endoscopy: a five-year multi-centre observational study from New Zealand.

AIMS: Outpatient endoscopy non-attendance leads to diagnostic delay and increasing wait times. We aimed to analyse endoscopy non-attendance rates and factors associated with it at the Canterbury and Auckland District Health Boards during a five-year period. METHODS: Consecutive appointments between April 2012 and March 2017 were assessed. The following procedures were included: gastroscopy, colonoscopy and endoscopic retrograde cholangiopancreatography. Predictors of non-attendance were assessed using univariate and multivariate binary logistic regression. RESULTS: A total of 58,434 appointments were offered (Canterbury-33,697, Auckland-24,737), of which 2,694 (4.6%) were not attended. Maori (OR 3.0, 95%CI 2.63-3.42) and Pacific Peoples (OR 3.1, 95%CI 2.7-3.55) were significantly more likely to miss appointments compared with Europeans. Patients from socioeconomically most deprived areas (NZDep10) had higher rates of non-attendance (OR 2.13, 95%CI 1.72-2.63) compared with NZDep1. Males (OR 1.43, 95%CI 1.32-1.56) and the Auckland District Health Board patients (OR 2.28, 95%CI 2.08-2.50) had higher non-attendance rates. CONCLUSION: Overall, 4.6% patients did not attend endoscopy appointments. Maori, Pacific Peoples and patients from socioeconomically deprived areas had higher non-attendance rates. Targeted interventions for at-risk groups would potentially lessen health inequalities and optimise utilisation of endoscopy resources.

Diagnostic inflammatory markers in acute cholangitis.

BACKGROUND: The 2018 Tokyo guidelines for acute cholangitis (AC) use white cell count (WCC) as one of the diagnostic criteria. However, the 2018 Tokyo guidelines grading does not provide guidance for AC patients with normal WCC. In this situation, other inflammatory biomarkers also can be used to diagnose AC and grade severity, but their diagnostic values are yet undetermined. The aims of this study were to evaluate the discriminative powers of common inflammatory markers compared with WCC for diagnosing AC and to determine their diagnostic cutoff levels. METHODS: This was a retrospective cohort study. Over 2 y, 96 patients who underwent endoscopic biliary decompression were identified from the Auckland City Hospital Radiology Department database. Only patients with a confirmed diagnosis of AC were included in the study. Thirty-four patients with AC and 18 controls met eligibility criteria. RESULTS: Comparing areas under the receiver operating characteristic curves, it was the lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP) that had the highest discriminative powers in diagnosing AC. Values of WCC for diagnosing AC were equal to or above 9.6 × 109/L, neutrophil count equal to or exceeding 4.9 × 109/L, lymphocyte count equal to or below 1.3 × 109/L, NLR 5.3 and above, albumin equal to or below 30.5 g/L, and CRP concentration 23.5 mg/L or above. CONCLUSIONS: Lymphocyte count, NLR, and CRP have superior discriminative powers to WCC, albumin, and neutrophil count and can be useful in the diagnosis of AC.

Clozapine induced gastrointestinal hypomotility: A potentially life threatening adverse event. A review of the literature.

OBJECTIVE: The haematological and cardiac complications of clozapine have been well documented. Recent evidence from pharmacovigilance databases suggests that gastrointestinal (GI) complications are the leading cause of clozapine related deaths. This review aims to describe clinical features along with preventative and treatment options. METHOD: A review of MEDLINE via PubMed searching for all articles published up to February of 2016. Inclusion criteria were articles that provided clinical or epidemiological information relating to the diagnosis, outcome, management or pathophysiology of clozapine related gastrointestinal disorders in humans. RESULTS: Three large case series were identified with 104 cases, 20 of these reported clinical details. A further 52 cases reports were included. Median age was 40, with 79% being male, mean daily clozapine dose was 453 mg. Mortality was 38% with survivors being younger (39 vs. 42), on lower daily doses (400 mg vs. 532 mg), more likely to be female (32% vs. 6%). Four patients were re-challenged with clozapine following CIGH, two suffered a recurrence. CONCLUSION: Risk factors for CIGH appear to be older age, male gender, patients in the first four months of treatment, co-prescription of constipating agents, higher daily dose of clozapine, and previous CIGH. Risk factors for death were older age and male gender. Patients receiving clozapine should be counselled about the dangers of constipation and to report new GI symptoms. Once severe CIGH has occurred clozapine should be halted and reviewed with bowel symptoms managed promptly. Re-challenging with clozapine may present substantial risks due to the severity of CIGH and a paucity of evidence. From the available evidence a treatment strategy has been proposed. Further prospective data regarding CIGH are needed to allow a better assessment of the scale of the problem with the development and testing of treatment strategies.

Uncomplicated Acute Diverticulitis: Identifying Risk Factors for Severe Outcomes.

BACKGROUND: The management of uncomplicated (Modified Hinchey Classification Ia) acute diverticulitis (AD) has become increasingly conservative, with a focus on symptomatic relief and supportive management. Clear criteria for patient selection are required to implement this safely. This retrospective study aimed to identify risk factors for severe clinical course in patients with uncomplicated AD. MATERIALS AND METHODS: Patients admitted to General Surgery at two New Zealand tertiary centres over a period of 18 months were included. Univariate and multivariate analyses were carried out in order to identify factors associated with a more severe clinical course. This was defined by three endpoints: need for procedural intervention, admission >7 days and 30-day readmission; these were analysed separately and as a combined outcome. RESULTS: Uncomplicated AD was identified in 319 patients. Fifteen patients (5%) required procedural intervention; this was associated with SIRS (OR 3.92). Twenty-two (6.9%) patients were admitted for >7 days; this was associated with patient-reported pain score >8/10 (OR 5.67). Thirty-one patients (9.8%) required readmission within 30 days; this was associated with pain score >8/10 (OR 6.08) and first episode of AD (OR 2.47). Overall, 49 patients had a severe clinical course, and associated factors were regular steroid/immunomodulator use (OR 4.34), pain score >8/10 (OR 5.9) and higher temperature (OR 1.51) and CRP ≥200 (OR 4.1). CONCLUSION: SIRS, high pain score and CRP, first episode and regular steroid/immunomodulator use were identified as predictors of worse outcome in uncomplicated AD. These findings have the potential to inform prospective treatment decisions in this patient group.