Harmsen, William S.

Abstract Background Certolizumab pegol (CZP) has been successfully used for the treatment of Crohn disease (CD); however, real-world data regarding the utility of CZP trough levels (CTLs) are lacking. We aimed to correlate CTL with CD outcomes and to determine frequency of CZP antibodies. Methods Retrospective evaluation of all CD patients on maintenance CZP with CTL obtained between 2016 and 2019. Outcomes included: median CTL, presence of anti-CZP antibodies, biochemical response (BR), clinical response (CR), radiologic response (RR), radiologic healing (RH), and mucosal healing (MH). Results Seventy-seven CD patients were included. Median CTL was 18.9 µg/mL (interquartile range, 7.6–35.4). Twenty-three patients (27.3%) had positive antibody levels, with lower median CTL compared to patients with no antibodies (0.0 vs 29.8; P < 0.0001). Median CTL levels were higher in patients with vs without CR (30.4 vs 10.3 µg/mL; P = 0.0015) and RR (29.6 vs 5.8 µg/mL; P = 0.006). CZP dosing at least every 2 weeks was associated with higher odds of achieving MH (odds ratio, 3.2; 95% confidence interval, 1.03–9.97). CTL resulted in change in clinical management in 62.7% of cases and presence of CMZ antibodies was associated with an odds ratio of 5.83 (95% confidence interval, 1.57–21.73) of change in management. Receiver operating characteristic curve and quartile analysis suggested that CTL >19 µg/mL is associated with increased rates of CR and RR. Conclusions Higher CTL was significantly associated with CR and RR. The rate of CZP antibodies was 27.3%. Our data suggest maintenance CTL of ≥19 µg/mL should be achieved in order to optimize outcomes in clinical practice.

ABSTRACTObjectives:Excessive fecal bile acids in adults have been associated with diarrhea‐predominant irritable bowel syndrome (IBS‐D), but their role in pediatric IBS‐D is unknown. Serum markers including 7α‐hydroxy‐4‐cholesten‐3‐one (C4) and fibroblast growth factor‐19 (FGF‐19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48‐hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF–19 and 48FBA in a pediatric population, to compare measurements in IBS‐D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS‐D.Methods:Using a cross‐sectional design, 26 patients with IBS‐D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF‐19 and 48FBA were obtained. Participants completed a 7‐day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations.Results:Mean age was 14.7 ± 2.5 years (42.3% female) in IBS‐D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF‐19 (r = –0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF‐19 (P = 0.1), or 48FBA (P = 0.5) between IBS‐D and HC groups; however, 20% of IBS‐D patients had elevated C4 and 28% had low FGF‐19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002).Conclusions:Correlations of C4 with 48FBA and FGF‐19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS‐D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS‐D.

ABSTRACTThere is a high prevalence of blood-borne infections in West Africa. This study sought to determine the seroprevalence of blood-borne infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, and syphilis, in blood donors in Burkina Faso. Blood donors were recruited from 2009 to 2013 in four major cities in Burkina Faso of urban area (Ouagadougou) and rural area (Bobo Dioulasso, Fada N’Gourma, and Ouahigouya). Serology tests including hepatitis B surface antigen, anti-HCV, anti-HIV, and rapid plasma reagin test were used for screening and were confirmed with ELISA. Disease prevalence was calculated among first-time donors. Incidence and residual risk were calculated from repeat donors. There were 166,681 donors; 43,084 had ≥ 2 donations. The overall seroprevalence of HBV, HCV, HIV, and syphilis were 13.4%, 6.9%, 2.1%, and 2.4%, respectively. The incidence rates (IRs) of HBV, HCV, HIV, and syphilis infection were 2,433, 3,056, 1,121, and 1,287 per 100,000 person-years. There was lower seroprevalence of HBV and HCV in urban area than in rural area (12.9% versus 14.0%, P < 0.001; and 5.9% versus 8.0%, P < 0.001), and no difference in HIV (2.1% versus 2.1%, P = 0.25). The IRs of new HBV, HCV, HIV, and syphilis were 2.43, 3.06, 1.12, and 1.29 per 100,000 person-years, respectively. The residual risk was one per 268 donations for HBV, one per 181 donations for HCV, and one per 1,480 donations for HIV, respectively. In conclusion, this comprehensive study from four blood donation sites in Burkina Faso showed high HBV and HCV seroprevalence and incidence with high residual risk from blood donation.

BACKGROUND: Surgical treatment for transverse colon cancer involves either extended colectomy or segmental resection, depending on the location of the tumor and surgeon perspective. However, the oncological safety of segmental resection has not yet been established in large cohort studies. OBJECTIVE: This study aims to compare segmental resection versus extended colectomy for transverse colon cancer in terms of oncological outcomes. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted using a nationwide cohort. PATIENTS: A total of 66,062 patients who underwent colectomy with curative intent for transverse stage I to III adenocarcinoma were identified in the National Cancer Database (2004–2015). MAIN OUTCOME MEASURES: Patients were divided in 2 groups based on the type of surgery received (extended versus segmental resection). The primary outcome was overall survival. Secondary outcomes were 30- and 90-day mortality, length of hospital stay, and readmission rate within 30 days of surgical discharge. RESULTS: Extended colectomy was performed in 44,417 (67.2%) patients, whereas 21,645 (32.8%) patients underwent segmental resection. Extended colectomy was associated with lower survival at multivariate analysis (HR, 1.07; 95% CI, 1.04–1.10; p < 0.001). The subgroup analysis showed that extended resection was independently associated with poorer survival in mid transverse colon cancers (HR, 1.08; 95% CI, 1.04–1.12; p < 0.001) and in stage III tumors (HR, 1.11; 95% CI, 1.04–1.18; p < 0.001). The number of at least 12 harvested lymph nodes was an independent predictor of improved survival in both overall and subgroup analyses. LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Extended colectomy was not associated with a survival advantage compared with segmental resection. On the contrary, extended colectomy was associated with slightly poorer survival in mid transverse cancers and locally advanced tumors. Segmental resection was found to be safe when appropriate margins and adequate lymph node harvest were achieved. See Video Abstract at http://links.lww.com/DCR/B454. ABORDAJE QUIRÚRGICO DEL CÁNCER DE COLON TRANSVERSO: ANÁLISIS DE LA PRÁCTICA ACTUAL Y LOS RESULTADOS ONCOLÓGICOS UTILIZANDO LA BASE DE DATOS NACIONAL DE CÁNCER ANTECEDENTES: El tratamiento quirúrgico para el cáncer de colon transverso implica colectomía extendida o resección segmentaria, según la ubicación del tumor y la perspectiva del cirujano. Sin embargo, la seguridad oncológica de la resección segmentaria aún no se ha establecido en estudios de cohortes grandes. OBJETIVO: Este estudio tiene como objetivo comparar la resección segmentaria versus la colectomía extendida para el cáncer de colon transverso en términos de resultados oncológicos. DISEÑO: Este fue un estudio de cohorte retrospectivo. ESCENARIO: Este estudio se realizó utilizando una cohorte a nivel nacional. PACIENTES: Un total de 66,062 pacientes que se sometieron a colectomía con intención curativa por adenocarcinoma de colon transverso en estadio I-III fueron identificados en la Base de Datos Nacional del Cáncer (2004-2015). PRINCIPALES MEDIDAS DE RESULTADO: Los pacientes se dividieron en dos grupos según el tipo de cirugía recibida (resección extendida versus resección segmentaria). El resultado primario fue la supervivencia global. Los resultados secundarios fueron la mortalidad a los 30 y 90 días, la duración de la estancia hospitalaria y la tasa de reingreso dentro de los 30 días posteriores al alta quirúrgica. RESULTADOS: Se realizó colectomía extendida en 44,417 (67.2%) casos, mientras que 21,645 (32.8%) pacientes fueron sometidos a resección segmentaria. La colectomía extendida se asoció con una menor supervivencia en el análisis multivariado (HR 1.07 IC 95% 1.04-1.10; p <0.001). El análisis de subgrupos mostró que la resección extendida se asoció de forma independiente con una menor supervivencia en los cánceres de colon transverso medio (HR 1.08 IC 95% 1.04-1.12; p <0.001) y en tumores en estadio III (HR 1.11 IC 95% 1.04-1.18; p <0.001). Un número de al menos 12 ganglios linfáticos cosechados fue un predictor independiente de una mejor supervivencia en los análisis general y de subgrupos. LIMITACIONES: Este estudio estuvo limitado por su diseño retrospectivo. CONCLUSIÓN: La colectomía extendida no se asoció con una ventaja de supervivencia en comparación con la resección segmentaria. Por el contrario, la colectomía extendida se asoció con una supervivencia levemente menor en cánceres de colon transverso medio y tumores localmente avanzados. Se encontró que la resección segmentaria es segura cuando se logran los márgenes apropiados y la cosecha adecuada de ganglios linfáticos. Consulte Video Resumen en http://links.lww.com/DCR/B454.

Background: Chronic myelomonocytic leukemia (CMML) is a rare chronic myeloid malignancy with a poor prognosis. There are few epidemiologic studies on CMML. We studied population-based outcomes in CMML using the Surveillance, Epidemiology, and End Results (SEER) and the National Cancer Database (NCDB). Methods: The SEER 18 registries and NCDB Participant User File were used to identify patients with ICD-O-3 diagnosis code 9945/3 from 2004-2015. Incidence was identified using SEER and age-adjusted to the U.S. 2000 standard population. Causes of death were obtained and CMML-related death was defined as death from any myeloid disorder (CMML, acute monocytic leukemia, acute myeloid leukemia [AML], chronic myeloid leukemia, other myeloid/monocytic leukemia, and aleukemic, subleukemic, and NOS) to avoid misattribution. Relative survival (RS) was defined as the ratio of the proportion of observed survivors in a cohort of CMML patients to the proportion of expected survivors in a comparable set of individuals that did not have CMML, adjusting for the general survival of the US population for race, sex, age, and time when the diagnosis was established. Time to AML was calculated using the left-truncated life tables session and a 3 month latency period was used to prevent misattribution. Per the NCDB's system on classifying treatment, hydroxyurea, decitabine, and azacitidine are considered chemotherapy. The Kaplan-Meier method was used to calculate overall survival (OS), and Cox regression model was used to identify predictors of survival. Variables significant in univariate analysis (age, Charlson Deyo score [CDS], insurance type, and treatment facility type) were included in a multivariate analysis. Statistical analyses were performed using SAS version 9.0. Results: In the SEER database (n=4437), the median age at diagnosis was 76 years (interquartile range [IQR] 68-83) and 2,783 patients (63%) were male. Incidence rates (1 case/1,000,000 individuals) were as follows: overall 4.4, male 6.6, female 2.9, Non-Hispanic White 4.9, and Non-Hispanic Black 3.3. The incidence did not significantly change from 2004 to 2015. With a median follow up of 5.8 years (95% CI: 5.5-6.3), the median OS was 1.3 years (95% CI: 1.3-1.4). 3635 patients (82%) died. Among those who died, 2016 patients (55%) deaths were CMML-related. When comparing CMML patients to the US general population, 3,156 patients were matched to the expected survival tables. In the general U.S. population, the expected survival for 12, 24, 36, 48 and 60 months was 95.6%, 91.3%, 87.1%, 83.1%, and 79.2%, respectively. In contrast, the RS for patients with CMML at the same time points was 63.6%, 46.2%, 35.2%, 28.8%, and 23.1% (Figure 1). 229 patients (5.2%) progressed to AML. The median time to AML was 1.2 years (IQR 0.6-2.3). In NCDB (n=6403), the median age at diagnosis was 74 years (IQR 66-82). With the median follow up of 6 years (95% CI 3.5-9), the median OS was 1.3 years (95% CI 0.4-3.3). The distribution of CDS score 0, 1, and &gt;1 was 4518 (71%), 1193 (18%), and 692 (11%) respectively. 4687 (77%) had government insurance, while 1399 (23%) had private insurance. 3750 (60%) were treated at a non-academic center. The year of diagnosis was associated with improved OS (HR 0.99, 95% CI: 0.98-0.99). Patients who were diagnosed in 2012-2015 had improved OS compared to patients diagnosed in 2004-2007 (HR 0.89, 95% CI 0.83-0.95) with OS at 1- and 5- years being 60% and 16% (2012-2015) vs. 56% and 17% (2008-2011) vs. 53% and 15% (2004-2007) respectively. 3029 (48%) patients received chemotherapy, while 270 (4%) patients received stem cell transplant as the first-line therapy. The median time to chemotherapy from diagnosis was 19 days (IQR 6-43). OS at 1-, 5-, and 10-years was 57%, 18%, and 4% (no chemotherapy), 56%, 14%, and 7% (received chemotherapy), 79%, 44%, and 38% (received stem cell transplant), and 56%, 15%, 5% (no stem cell transplant). OS curves are shown in Figure 2. Factors independently predicting inferior OS were age ≥ 65 years at the time of diagnosis (p&lt;0.001), CDS ≥ 1 (p&lt;0.001), government insurance (p&lt;0.001), and treatment at a non-academic center (p&lt;0.001) (Table). Conclusion: Despite an improvement in survival over the years, CMML continues to be a cause of significant morbidity and mortality. Older age, CDS ≥ 1, government insurance, and treatment at non-academic facilities were predictive of inferior survival. Disclosures Shah: Dren Bio: Consultancy.

AbstractBackground and ObjectivesDescribe patient‐reported functional outcomes for hand and foot sarcoma survivors treated with limb‐sparing surgery and radiation therapy (LSS + RT).MethodsFifty‐four patients with hand/wrist and foot/ankle sarcomas treated with LSS + RT from 1991 to 2015 were identified. Survivors ≥18 years old without subsequent amputation completed self‐assessed functional surveys: Toronto upper extremity salvage score (TESS‐UE) and Michigan hand outcomes (MHQ) surveys for hand; TESS lower extremity (TESS‐LE) and Foot and Ankle Outcomes (FAOS) surveys for foot. Scoring scales: 0–100, MHQ and TESS; ‐26 to 56 and 25‐59, FAOS core and shoe comfort, respectively. Higher scores denote superior function.ResultsFive‐year local tumor control was 88%. Fourteen of 24 hand (58%) and 14/18 foot (78%) survivors completed surveys. Mean TESS‐UE and MHQ scores were 89.4 and 72.8, respectively. Mean TESS‐LE, core FAOS, and shoe comfort scores were 92.4, 46.19, and 53.1, respectively. No factors correlated with outcomes. TESS‐UE and MHQ scores strongly correlated (r = .87). TESS‐LE and FAOS scores were associated with a poor correlation (r = .02 and r = .69).ConclusionsThe largest patient‐reported functional outcomes analysis for hand and foot sarcoma survivors treated with LSS + RT demonstrates excellent local tumor control and acceptable functional outcomes. Further exploration of optimal functional assessment tools is needed given the potential scope differences.

Abstract Background We sought to estimate the incidence of home parenteral nutrition (HPN) use in a population-based cohort of patients with Crohn disease (CD), and to assess clinical outcomes and complications associated with HPN. Methods We used the Rochester Epidemiology Project (REP) to identify residents of Olmsted County, who were diagnosed with CD between 1970 and 2011, and required HPN. Results Fourteen out of 429 patients (3.3%) with CD received HPN (86% female). Eleven patients (79%) had moderate–severe CD and 12 patients (86%) had fistulizing disease. Thirteen patients (93%) underwent surgery, primarily due to obstruction. Among CD incidence cases, the cumulative incidence of HPN from the date of CD diagnosis was 0% at 1 year, 0.5% at 5 years, 0.8% at 10 years, and 2.4% at 20 years. Indications for HPN included short bowel syndrome in 64%, malnutrition in 29%, and bowel rest in 21%. The median duration of HPN was 2.5 years. There was an average weight gain of 1.2 kg at 6 months, an average weight loss of 1.4 kg at 1 year, and a further weight loss of 2.2 kg at 2 years from the start of HPN. Patients were hospitalized a mean of 5 times after the start of HPN, mainly due to catheter-related bloodstream infections and thrombosis. Conclusions Less than 4% of patients with CD need HPN. Most have moderate to severe disease with short bowel syndrome or malnutrition. Possible reasons for the patients’ weight loss could be noncompliance, and increased metabolic needs because of active disease.

Goals: We aimed to describe the diagnostic and prognostic performance of transient elastography (TE) and magnetic resonance elastography (MRE) in patients with primary biliary cholangitis (PBC). Background: The diagnostic performance of TE and MRE in detecting advanced fibrosis in PBC and in predicting outcomes independent of existing serologic prognostic markers is incompletely understood. Materials and Methods: Five hundred thirty-eight consecutive patients with PBC at 3 centers with liver stiffness (LS) measurements by TE (n=286) or MRE (n=332) were reviewed. LS cutoffs for predicting fibrosis stages were determined by receiver operating characteristic curves among those with a liver biopsy (TE, n=63; MRE, n=98). Cox proportional hazard regression modeling was used to identify associations between covariates and hepatic decompensation. Results: The optimal LS thresholds for predicting histologic stage F4 were 14.40 kPa (area under the curve=0.94) for TE and 4.60 kPa (area under the curve=0.82) for MRE. Both TE and MRE outperformed biochemical markers for the prediction of histologic advanced fibrosis. Optimal LS thresholds to predict hepatic decompensation were 10.20 kPa on TE and 4.30 kPa on MRE. LS by TE and MRE (respectively) remained predictors of hepatic decompensation after adjusting for ursodeoxycholic acid responsiveness [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.24 and HR, 1.68; 95% CI, 1.28-2.19] and the GLOBE score (HR, 1.13; 95% CI, 1.07-1.19 and HR, 2.09; 95% CI, 1.57-2.78). Conclusion: LS measurement with either TE or MRE can accurately detect advanced fibrosis and offers additional prognostic value beyond existing serologic predictive tools.