Citations

BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting >30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. RESULTS: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17–26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression ( P < .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44–8.30; P < .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P < .0001) identified using continuous oximetry and capnography monitoring. CONCLUSIONS: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor.

Statins can decrease hepatocellular carcinoma (HCC) occurrence, but the magnitude and the predictors of these effects remain unclear. This meta-analysis provides a pooled estimate of the impact of statin use on HCC occurrence. Pooled effects were calculated using a random-effects model by means of the DerSimonian and Laird test. Primary endpoint was the time-dependent correlation between statin use and HCC incidence expressed as hazard ratio (HR), both crude and adjusted. The crude and adjusted odds ratios (OR) for HCC occurrence between statin users and non-users were analyzed. Twenty-five studies with 1,925,964 patients were included. Crude OR for HCC incidence was 0.59 (95% CI: 0.47–0.74), confirmed in adjusted analysis (OR: 0.74, 95% CI: 0.70–0.78). Adjusted HR was 0.73 (95% CI: 0.69–0.76). This effect was more pronounced in HBV patients (HR: 0.46, 95% CI: 0.36–0.60) and with a cumulative daily dose beyond 365 (HR: 0.27, 95% CI: 0.11–0.67). Lipophilic statins were associated with reduced HCC incidence (HR: 0.49, 95% CI: 0.39–0.62). Atorvastatin determined the greater magnitude of effect (HR: 0.43, 95% CI: 0.28–0.65). This meta-analysis demonstrates the beneficial chemopreventive effect of statins against HCC occurrence. This effect is dose-dependent and more pronounced with lipophilic statins.

BACKGROUND: Risk factors for pouch survival may or may not have a linear relationship with pouch loss over time. Conditional survival is a method to describe these nonlinear time-to-event relationships by reporting the expected survival at various time points. OBJECTIVE: The aim of this study was to calculate conditional pouch survival based on occurrence of risk factors for pouch loss. DESIGN: This was a retrospective study from an institutional database. SETTINGS: The study was conducted at the Cleveland Clinic Foundation. PATIENTS: Patients with ulcerative or indeterminate colitis who underwent index IPAA construction between 1986 and 2016 were included. MAIN OUTCOME MEASURES: Patients were stratified based on postoperative anastomotic leak, abscess, or fistula occurrence. The Kaplan–Meier method with conditional survival was used to estimate overall and cause-specific survival at 10 years. RESULTS: A total of 3468 patients underwent IPAA during the study period. The overall 10-year pouch survival rate was 0.94 (95% CI, 0.93–0.95), and after 1 year the conditional pouch survival increased to 0.95 (95% CI, 0.94–0.96), after 3 years to 0.97 (95% CI, 0.96–0.98), and after 5 years to 0.98 (95% CI, 0.98–0.99). A total of 122 patients (3.5%) developed anastomotic leak, and the 10-year IPAA survival in patients with leak was 0.85 (95% CI, 0.77–0.93). In this group, after 1 year of pouch survival, the conditional pouch survival increased to 0.89 (95% CI, 0.82–0.96) and after 3 years to 0.98 (95% CI, 0.94–1.00). A similar pattern was seen for IPAA with postoperative abscess. The conditional survival curve was stable over time for patients with a fistula. LIMITATIONS: This was a retrospective, single-institution study. CONCLUSIONS: Overall conditional pouch survival improved over time for patients with postoperative anastomotic leak and abscess. These novel findings can be useful to counsel patients regarding expectations for long-term pouch survival even if they develop leaks and abscesses. See Video Abstract at http://links.lww.com/DCR/B217. SUPERVIVENCIA CONDICIONAL DESPUÉS DE ANASTOMOSIS CON BOLSA ÍLEO ANAL, PARA COLITIS ULCERATIVA E INDETERMINADA: ¿LA SOBREVIDA DE LA BOLSA A LARGO PLAZO, MEJORA O EMPEORA CON EL TIEMPO? ANTECEDENTES: Los factores de riesgo para la sobrevida de la bolsa, pueden o no tener una relación lineal con la pérdida de la bolsa y con el tiempo. La supervivencia condicional es un método para describir estas relaciones no lineales de tiempo, hasta el evento informando la supervivencia esperada en varios puntos de tiempo. OBJETIVO: El objetivo de este estudio fue calcular la supervivencia condicional de la bolsa, en función de aparición de factores de riesgo para la pérdida de bolsa. DISEÑO: Estudio retrospectivo de una base de datos institucional. AJUSTES: Cleveland Clinic Foundation. PACIENTES: Pacientes con colitis ulcerativa o indeterminada, sometidos a una anastomosis de bolsa íleo anal, de 1986 a 2016. PRINCIPALES MEDIDAS DE RESULTADO: Los pacientes fueron estratificados en función de la fuga anastomótica postoperatoria, absceso o aparición de fístula. El método de Kaplan Meier con supervivencia condicional, se utilizó para estimar la supervivencia general y la causa específica a los 10 años. RESULTADOS: Un total de 3.468 pacientes fueron sometidos a anastomosis ileal con bolsa anal durante el período de estudio. La tasa de supervivencia global de la bolsa a 10 años, fue de 0,94 (0,93 a 0,95), y después de 1 año, la supervivencia condicional de la bolsa aumentó a 0,95 (0,94 a 0,96), después de 3 años a 0,97 (0,96 a 0,98) y después de 5 años a 0.98 (0.98 - 0.99). Un total de 122 (3,5%) pacientes desarrollaron fuga anastomótica, y la supervivencia de la anastomosis de bolsa íleo anal a 10 años en pacientes con fuga fue de 0,85 (IC del 95%: 0,77 a 0,93). En este grupo, después de 1 año de supervivencia de la bolsa, la supervivencia condicional de la bolsa aumentó a 0,89 (IC del 95%: 0,82 a 0,96), y después de 3 años a 0,98 (IC del 95%: 0,94 a 1). Se observó un patrón similar para la anastomosis de bolsa íleo anal con absceso postoperatorio. La curva de supervivencia condicional fue estable en el tiempo para los pacientes con una fístula. LIMITACIONES: Estudio retrospectivo, de una sola institución. CONCLUSIONES: La supervivencia condicional global de la bolsa, mejoró con el tiempo para pacientes con fuga anastomótica postoperatoria y absceso. Estos nuevos hallazgos pueden ser útiles para aconsejar a los pacientes con respecto a las expectativas de supervivencia de la bolsa a largo plazo, incluso si desarrollan fugas y abscesos. Consulte Video Resumen http://links.lww.com/DCR/B217. (Traducción—Dr Fidel Ruiz Healy)

Abstract The extracellular matrix is a highly reactive scaffold formed by a wide array of multifunctional molecules, encompassing collagens and noncollagenous glycoproteins, proteoglycans, glycosaminoglycans, and polysaccharides. Besides outlining the tissue borders, the extracellular matrix profoundly regulates the behavior of resident cells by transducing mechanical signals, and by integrating multiple cues derived from the microenvironment. Evidence is mounting that changes in the biostructure of the extracellular matrix are instrumental for biliary repair. Following biliary damage and eventually, malignant transformation, the extracellular matrix undergoes several quantitative and qualitative modifications, which direct interactions among hepatic progenitor cells, reactive ductular cells, activated myofibroblasts and macrophages, to generate the ductular reaction. Herein, we will give an overview of the main molecular factors contributing to extracellular matrix remodeling in cholangiopathies. Then, we will discuss the structural alterations in terms of biochemical composition and physical stiffness featuring the “desmoplastic matrix” of cholangiocarcinoma along with their pro-oncogenic effects.

BACKGROUND: In selected patients with ulcerative colitis and pelvic pouch failure, redo pouch is an option. However, it is unknown whether selected patients with Crohn’s disease should be offered a chance to avoid permanent diversion after failure of IPAA. OBJECTIVE: The objective was to compare the outcomes of redo pouch for ulcerative colitis and Crohn’s disease. DESIGN: This was a retrospective analysis of a prospectively maintained pouch database (1983–2017). SETTINGS: The setting was the Cleveland Clinic. PATIENTS: This study included patients who underwent redo pouch with a primary surgical specimen diagnosis of ulcerative or Crohn’s colitis at the time of initial pouch. MAIN OUTCOME MEASURES: Pouch failure was defined as either pouch excision or indefinite pouch diversion. Patient characteristics, perioperative and functional outcomes, pouch survival, and quality of life were compared according to the diagnosis. RESULTS: Of 422 patients, 392 had ulcerative colitis and 30 had Crohn’s disease. Age and sex were comparable. The most common indications for redo pouch included anastomotic separation and fistulas (220 (56.1%) in ulcerative colitis and 21 (70%) in Crohn’s disease). The majority of redo pouches required mucosectomy with handsewn anastomosis (310 (79%) in ulcerative colitis and 30 (100%) in Crohn’s disease; p = 0.23). A new pouch was constructed in 160 patients (41%) with ulcerative colitis and repair of old pouch in 231 patients (59%) compared with 25 (83%) in Crohn’s disease, who had creation of new pouch; only in 5 (17%) was the old pouch re-anastomosed. Stool frequency, seepage, and fecal urgency were comparable between groups. Cumulative 5-year pouch survival was longer in ulcerative colitis versus Crohn’s disease (88% vs 55%; p = 0.008). Major causes of redo failure in Crohn’s disease were pouch fistulas and/or strictures occurring after ileostomy closure. These were more common in Crohn’s disease than in ulcerative colitis (p < 0.001). LIMITATIONS: This was a retrospective design. CONCLUSIONS: Redo pouch can be offered to selected patients with colonic Crohn’s disease diagnosed at the time of their primary pouch. See Video Abstract at http://links.lww.com/DCR/B206. Rehacer la Anastomosis Ileoanal con Reservorio Después de un Reservorio Ileal Fallido en Pacientes con Enfermedad de Crohn: ¿Vale la Pena Intentarlo? ANTECEDENTES: En pacientes seleccionados con colitis ulcerativa y falla del reservorio pélvico, rehacer el reservorio es una opción. Sin embargo, se desconoce si en los pacientes seleccionados con enfermedad de Crohn se debería ofrecer la oportunidad de evitar la derivación permanente después de la falla de la anastomosis ileoanal con reservorio ileal. OBJETIVO: El objetivo fue comparar los resultados de reservorios re-hechos en colitis ulcerosa y la enfermedad de Crohn. ESCENARIO: El escenario fue la Cleveland Clinic. DISEÑO: Análisis retrospectivo de una base de datos de reservorios ileales mantenida prospectivamente (1983-2017). PACIENTES: Este estudio incluyó a pacientes que se sometieron a cirugía para rehacer el reservorio ileal con un diagnóstico en el espécimen quirúrgico primario de colitis ulcerosa o de Crohn en el momento del reservorio inicial. PRINCIPALES MEDIDAS DE RESULTADO: La falla del reservorio se definió como la escisión del reservorio o la derivación indefinida del reservorio. Las características del paciente, los resultados perioperatorios y funcionales, la supervivencia del reservorio y la calidad de vida se compararon de acuerdo con el diagnóstico. RESULTADOS: De 422 pacientes, 392 tenían colitis ulcerativa y 30 tenían enfermedad de Crohn. La edad y el género fueron comparables. Las indicaciones más comunes para rehacer el reservorio incluyeron dehiscencia anastomótica y fístulas [220 (56,1%) en colitis ulcerosa y 21 (70%) en la enfermedad de Crohn]. La mayoría de los reservorios rehechos requirieron mucosectomía con anastomosis manual [310 (79%) en colitis ulcerosa y 30 (100%) en la enfermedad de Crohn, p = 0.23]. Se construyó un nuevo reservorio en 160 (41%) pacientes con colitis ulcerativa y se reparó el reservorio antiguo en 231 (59%) pacientes, en comparación con 25 (83%) en la enfermedad de Crohn, que requirieron creación de un nuevo reservorio, y solo 5 (17%) donde el reservorio antiguo se volvió a anastomosar. La frecuencia de las evacuaciones, el manchado fecal y la urgencia fecal fueron comparables entre grupos. La supervivencia acumulada del reservorio a 5 años fue mayor en la colitis ulcerativa frente a la enfermedad de Crohn (88% frente a 55%, p = 0.008). Las principales causas de falla del reservorio rehecho en la enfermedad de Crohn fueron las fístulas del reservorio y / o las estenosis que ocurrieron después del cierre de ileostomía. Estas fueron más comunes en la enfermedad de Crohn que en la colitis ulcerativa (p <0.001). LIMITACIONES: Este fue un diseño retrospectivo. CONCLUSIÓN: Rehacer el reservorio ileal se puede ofrecer a pacientes seleccionados con enfermedad de Crohn colónica diagnosticada en el momento de su reservorio primario. Consulte Video Resumen en http://links.lww.com/DCR/B206. (Traducción—Dr Jorge Silva Velazco)

Lyme disease (LD) is an increasing public health problem. Current laboratory testing is insensitive in early infection, the stage at which appropriate treatment is most effective in preventing disease sequelae. The Lyme Disease Biobank (LDB) collects samples from individuals with symptoms consistent with early LD presenting with or without erythema migrans (EM) or an annular, expanding skin lesion and uninfected individuals from areas of endemicity. Samples were collected from 550 participants (298 cases and 252 controls) according to institutional review board-approved protocols and shipped to a centralized biorepository.

Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have suggested that alloHSCT after PD-1 mAbs may be associated with severe immune-related complications including acute graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytokine release/febrile non-infectious syndrome (CRS). Prior studies of alloHSCT after PD-1 blockade in cHL have been limited by the small number of pts and short follow-up, preventing an accurate assessment of long-term outcomes and complications, risk factors for early toxicity, and the impact of transplant strategies such as choice of GVHD prophylaxis. We therefore assembled a large retrospective international cohort of cHL pts who underwent alloHSCT after PD-(L)1 blockade to better answer these questions, including an assessment of the impact of post-transplant cyclophosphamide (PTCy) on efficacy and toxicity. Methods: Medical records and databases were reviewed at 26 European and United States transplant centers to identify pts with cHL who underwent an alloHSCT any time after receiving a PD-1 or PD-L1 mAb. Response assessment was performed by local investigators according to Lugano 2014 criteria. Overall survival (OS), progression-free survival (PFS), cumulative incidence (CumInc) of relapse (CIR), non-relapse mortality (NRM), acute (a) and chronic (c) GVHD were estimated, as was the association between baseline variables and these outcomes. Results: Between 2014 and 2019, 150 pts were identified who underwent alloHSCT after a median of 10 (range, 1-74) doses of nivolumab (n=118), pembrolizumab (n=31), or avelumab (n=1). The median age was 31 (range 17-68) and pts had received a median of 4 (range, 2-11) lines of therapy prior to PD-(L)1 blockade. 138 pts (92%) had failed BV and 111 (74%) autologous HSCT. The best overall response to PD-(L)1 mAbs was CR for 62 pts (41%), PR for 55 (37%), SD for 17 (11%), PD for 15 (10%) and unknown for 1 (1%). Median time from last dose of PD-(L)1 mAb to alloHSCT was 80 days (range, 17-756) with 70 pts (47%) receiving intervening systemic therapy. At alloHSCT, 90 pts were in CR (60%), 45 in PR (30%), 5 in SD (3%), and 10 in PD (7%). Donors were haploidentical (n=71, 47%), matched sibling (n=29, 19%), matched unrelated (n=39, 26%), mismatched unrelated (n=7, 5%), cord blood (n=2, 1%), or unknown (n=2, 1%). Stem cell source was bone marrow (n=38, 25%), peripheral blood (n=110, 73%), or cord blood (n=2, 1%). GVHD prophylaxis included PTCy in 88 pts (59%) (69/71 (97%) with haploidentical donors; 19/79 (24%) with other donors). With a median post-alloHSCT follow-up for survivors of 23.8 months (range, 1-67), the 2y OS and PFS were 79% (95CI 71-86%) and 65% (95CI 55-73%), respectively, while the 2y CumIncs of relapse and NRM were 21% (95CI 13-29%) and 14%, (95CI, 8-22%), respectively (Fig. 1A-B). 27 pts have died, 3 due to disease and 24 to NRM, including aGVHD (n=7) and VOD (n=2). Veno-occlusive disease (VOD) occurred in 5 pts (day 100 CumInc 4%) and 29 pts (19%) developed CRS (grade 1 n=16; grade 2 n=7; grade 3 n=4; grade 4 n=2). The 6-month CumIncs of grade 2-4, grade 3-4 and grade 4 aGVHD were 39%, 16% and 8%, respectively. Hyperacute GVHD (onset ≤ 14 days after alloHSCT) occurred in 4% of pts and was fatal in 2 pts. The 2y CumInc of cGVHD was 45%. Neither receipt of &gt; 10 doses (median) of anti-PD-(L)1 mAb nor undergoing alloHSCT ≤80 days (median) after last dose of PD-(L)1 mAb were associated with PFS or OS. However, pts with a shorter time to transplant (≤80 days) appeared to have a higher risk of severe (grade 3-4) aGVHD (6m CumInc 24% vs 9%, p=0.006). Recipients of PTCy in this cohort had lower 2y CumIncs of cGVHD (34% vs 58%, p=0.01) and relapse (12% vs 31%, p=0.02), superior 2y PFS (76% vs 54%, p=0.015), and similar rates of severe aGVHD (15% vs 18%, p=0.5), 2y NRM (12% vs 16%, p=0.5), and 2y OS (82% vs 78%, p=0.6). Conclusions: With extended follow-up of a large international cohort, our results argue that alloSCT performed after PD-(L)1 mAbs is a feasible strategy associated with an excellent PFS and a very low CIR for this disease. The use of PT-Cy appears to be associated with improved outcomes and may at present represent the optimal transplant strategy in this pt population. Figure Disclosures Corradini: kite: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Unum Therapeutics Inc.: Research Funding. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria. Hamadani:Pharmacyclics: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy. Ansell:LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Feldman:Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Takeda: Honoraria, Speakers Bureau. McGuirk:ArticulateScience LLC: Other: Assistance with manuscript preparation; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria. Manson:Bristol Myers Squibb: Honoraria. Orvain:Incyte: Honoraria; Novartis: Honoraria; Jazz Pharmaceuticals: Other: Travel & accommodations; Pfizer: Other: Travel & accommodations. Bouabdallah:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frigault:Novartis: Consultancy; Kite/Gilead: Honoraria; Nkarta: Consultancy; Incyte: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy. Chen:Takeda: Consultancy; Kiadis: Consultancy; Magenta: Consultancy; Abbvie: Consultancy; Incyte: Consultancy. Lynch:T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; Takeda Pharmaceuticals: Research Funding; Juno Therapeutics: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Smith:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Denovo Biopharma: Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Incyte Corporation: Research Funding; Ayala (spouse): Research Funding; Seattle Genetics: Research Funding. Byrne:Karyopharm: Research Funding. Cohen:Hutchison: Research Funding; Astra Zeneca: Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Genentech, Inc.: Consultancy, Research Funding; UNUM: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau. Armand:Sigma Tau: Research Funding; Otsuka: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Genentech: Research Funding. Zinzani:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Carlo-Stella:Servier: Consultancy, Honoraria, Other: Travel, accommodations; Genenta Science srl: Consultancy; Boehringer Ingelheim: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations.

PURPOSETo compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation.PATIENTS AND METHODSWe retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide.RESULTSCompared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively).CONCLUSIONWhen considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.

BACKGROUND: Restorative total proctocolectomy with IPAA may not be feasible in some patients because of technical intraoperative limitations. OBJECTIVE: This study aimed to assess preoperative predictors for intraoperative IPAA and review management. DESIGN: This is a retrospective review. SETTING: This study was conducted at Cleveland Clinic between January 2010 and May 2018. PATIENTS: Patients ≥18 years of age who underwent ileoanal pouch surgery were included. Patients with successful pouch creation as planned were grouped as “successful IPAA creation.” Operative reports of patients who underwent alternative procedures were reviewed to identify cases when the pouch was preoperatively planned but intraoperatively abandoned (IPAA-abandoned group). Multivariate logistic regression models were developed to determine predictors of intraoperative pouch abandonment. We also reviewed the management of patients in whom the initial pouch creation failed. MAIN OUTCOME MEASURES: The primary outcomes measured were preoperative predictors for intraoperative ileoanal pouch abandonment. RESULTS: A total of 1438 patients were offered an ileoanal pouch; 21 (1.5%) experienced pouch abandonment due to inadequate reach (n = 17) and other technical reasons (n = 4). These patients underwent alternative procedures such as end or loop ileostomy with/without proctectomy. Multivariate logistic regression analysis indicated male sex (OR, 6.021; 95% CI, 1.540–23.534), BMI (OR, 1.217; 95% CI, 1.114–1.329), and a 2-stage procedure (OR, 14.510; 95% CI, 4.123–51.064) as independent factors associated with intraoperative abandonment of pouch creation. Alternative procedures were total proctocolectomy with end ileostomy (n = 14) and total abdominal colectomy with end ileostomy without proctectomy (n = 7). Ultimately, pouch creation was achieved in 6 of 21 patients after a median interval of 8.8 (range, 4.1–34.8) months. All patients had intentional weight loss before a reattempt and total abdominal colectomy with end ileostomy without proctectomy as their initial procedure. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Ileoanal pouch abandonment is rare and can be mitigated by initial total abdominal colectomy and weight loss. Male, obese patients are at a higher risk of failure. Intraoperative assessment of ileoanal pouch feasibility should occur before rectal dissection. See Video Abstract at http://links.lww.com/DCR/B156. PREDICCIÓN MULTIVARIANTE DEL ABANDONO INTRAOPERATORIO DE LA ANASTOMOSIS ANAL CON BOLSA ILEAL ANTECEDENTES: La proctocolectomía total restaurativa con anastomosis de bolsa ileoanal puede no ser posible en algunos pacientes debido a limitaciones técnicas intraoperatorias. OBJETIVO: Evaluar los predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal y revisar el manejo. DISEÑO: Revisión retrospectiva. MARCO: Cleveland Clinic entre Enero de 2010 y mayo de 2018. PACIENTES: Pacientes > 18 años que se sometieron a cirugía de bolsa ileoanal. Los pacientes con una creación exitosa de la bolsa según lo planeado se agruparon como “creación exitosa de anastomosis de bolsa ileoanal”. Se revisaron los informes operativos de los pacientes que se sometieron a procedimientos alternativos para identificar los casos en que la bolsa se planificó preoperatoriamente pero se abandonó intraoperatoriamente (grupo de “anastomosis anal de bolsa ileoanal abandonada”). Se desarrollaron modelos de regresión logística multivariante para determinar los predictores del abandono intraoperatorio de la bolsa. También revisamos el manejo de pacientes que fallaron en la creación inicial de la bolsa. MEDIDAS DE RESULTADOS PRINCIPALES: Predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal. RESULTADOS: A un total de 1438 pacientes se les ofreció una bolsa ileoanal; 21 (1.5%) experimentaron abandono de la bolsa debido a un alcance inadecuado (n = 17) y otras razones técnicas (n = 4). Estos pacientes se sometieron a procedimientos alternativos como ileostomía final o de asa con / sin proctectomía. El análisis de regresión logística multivariante indicó género masculino (OR, 6.021; IC 95%, 1.540–23.534), índice de masa corporal (OR, 1.217; IC 95%, 1.114–1.329) y procedimiento en 2 etapas (OR, 14.510; IC 95%, 4.123–51.064) como factores independientes asociados con el abandono intraoperatorio de la creación de la bolsa. Los procedimientos alternativos fueron la proctocolectomía total con ileostomía final (n = 14) y la colectomía abdominal total con ileostomía final sin proctectomía (n = 7). Finalmente, la creación de la bolsa se logró en 6/21 pacientes después de un intervalo medio de 8.8 (rango, 4.1–34.8) meses. Todos los pacientes tuvieron pérdida de peso intencional antes de la reintenta y colectomía abdominal total con ileostomía final sin proctectomía como procedimiento inicial. LIMITACIONES: Naturaleza retrospectiva. CONCLUSIONES: El abandono de la bolsa ileoanal es raro y puede mitigarse mediante la colectomía abdominal total inicial y la pérdida de peso. Los pacientes masculinos y obesos tienen un mayor riesgo de fracaso. La evaluación intraoperatoria de la viabilidad de la bolsa ileoanal debe ocurrir antes de la disección rectal. Consulte Video Resumen en http://links.lww.com/DCR/B156. (Traducción—Dr. Yesenia Rojas-Kahlil)