The comparison of total energy and protein intake relative to estimated requirements in chronic spinal cord injury.

In chronic spinal cord injury (SCI), individuals experience dietary inadequacies complicated by an understudied research area. Our objectives were to assess (1) the agreement between methods of estimating energy requirement (EER) and estimated energy intake (EEI) and (2) whether dietary protein intake met SCI-specific protein guidelines. Persons with chronic SCI (n = 43) completed 3-day food records to assess EEI and dietary protein intake. EER was determined with the Long and Institute of Medicine (IOM) methods and the SCI-specific Farkas method. Protein requirements were calculated as 0·8-1·0 g/kg of body weight (BW)/d. Reporting accuracy and bias were calculated and correlated to body composition. Compared with IOM and Long methods (P < 0·05), the SCI-specific method did not overestimate the EEI (P = 0·200). Reporting accuracy and bias were best for SCI-specific (98·9 %, -1·12 %) compared with Long (94·8 %, -5·24 %) and IOM (64·1 %, -35·4 %) methods. BW (r = -0·403), BMI (r = -0·323) and total fat mass (r = -0·346) correlated with the IOM reporting bias (all, P < 0·05). BW correlated with the SCI-specific and Long reporting bias (r = -0·313, P = 0·041). Seven (16 %) participants met BW-specific protein guidelines. The regression of dietary protein intake on BW demonstrated no association between the variables (ß = 0·067, P = 0·730). In contrast, for every 1 kg increase in BW, the delta between total and required protein intake decreased by 0·833 g (P = 0·0001). The SCI-specific method for EER had the best agreement with the EEI. Protein intake decreased with increasing BW, contrary to protein requirements for chronic SCI.

Reasons for meal termination, eating frequency, and typical meal context differ between persons with and without a spinal cord injury.

Overeating associated with neurogenic obesity after spinal cord injury (SCI) may be related to how persons with SCI experience satiation (processes leading to meal termination), their eating frequency, and the context in which they eat their meals. In an online, cross-sectional study, adults with (n = 688) and without (Controls; n = 420) SCI completed the Reasons Individuals Stop Eating Questionnaire-15 (RISE-Q-15), which measures individual differences in the experience of factors contributing to meal termination on five scales: Physical Satisfaction, Planned Amount, Decreased Food Appeal, Self-Consciousness, and Decreased Priority of Eating. Participants also reported weekly meal and snack frequency and who prepares, serves, and eats dinner with them at a typical dinner meal. Analysis revealed that while Physical Satisfaction, Planned Amount, and Decreased Food Appeal were reported as the most frequent drivers of meal termination in both groups, scores for the RISE-Q-15 scales differed across the groups. Compared to Controls, persons with SCI reported Physical Satisfaction and Planned Amount as drivers of meal termination less frequently, and Decreased Food Appeal and Decreased Priority of Eating more frequently (all p < 0.001). This suggests that persons with SCI rely less on physiological satiation cues for meal termination than Controls and instead rely more on hedonic cues. Compared to Controls, persons with SCI less frequently reported preparing and serving dinner meals and less frequently reported eating alone (all p < 0.001), indicating differences in meal contexts between groups. Individuals with SCI reported consuming fewer meals than Controls but reported a higher overall eating frequency due to increased snacking (p ≤ 0.015). A decrease in the experience of physical fullness, along with a dependence on a communal meal context and frequent snacking, likely contribute to overeating associated with neurogenic obesity after SCI.

Characteristics and Outcomes of Right- Versus Left-Sided Early-Onset Colorectal Cancer.

BACKGROUND: Early-onset colorectal cancers are increasing in incidence. Studies reported more left-sided cancers in patients aged <50 years. Some advocate for screening via flexible sigmoidoscopy at age 40 years. OBJECTIVE: The purpose of this study was to investigate characteristics and outcomes in sporadic right- and left-sided early-onset colorectal cancers. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at a single, tertiary care institution. PATIENTS: This study included patients aged <50 years diagnosed with colorectal cancer between 2000 and 2018. MAIN OUTCOME MEASURES: We analyzed patient demographics, tumor characteristics, and survival. RESULTS: A total of 489 patients aged 20 to 49 years were identified from 2000 to 2018. The majority of patients were white (90%) and male (57%). The median age at diagnosis was 44 years, and 75% were diagnosed at age 40-49 years. There was a predominance of left-sided tumors (80%). The majority of patients presented with stage 3 (35%) and stage 4 (35%) disease. Right-sided tumors were more likely to have mucinous (24% vs 7.4%; p < 0.001) and signet-ring cell (4.4% vs 1.7%; p < 0.001) histology. There was no difference in age, sex, race, ethnicity, and stage at presentation. Right-sided tumors were associated with lower 5-year overall survival (44% vs 61%; p < 0.005) with the decrease in survival most prominent in right-sided stage 3 tumors (41% vs 72%; p < 0.0001) and in ages 40 to 49 years (43% vs 61%; p = 0.03). Sex, tumor location, increasing stage, and signet-ring cell histology were independent prognostic factors of overall survival. There was no difference in disease-free survival. LIMITATIONS: This study was a retrospective review at a single institution. CONCLUSIONS: The majority of early-onset colorectal cancers arise from age 40 to 49 years with a left-sided predominance but higher mortality in right-sided tumors. These findings provide further evidence in favor of recommending earlier initial screening colonoscopy for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B892 . CARACTERSTICAS Y RESULTADOS DEL CNCER COLORRECTAL DE INICIO TEMPRANO DEL LADO DERECHO FRENTE AL IZQUIERDO: ANTECEDENTES:Los cánceres colorrectales de aparición temprana están aumentando en incidencia. Los estudios han informado una preponderancia de cánceres en el lado izquierdo en pacientes <50 años, lo que ha llevado a algunos a abogar por la detección con sigmoidoscopia flexible a los 40 años.OBJETIVO:El propósito de nuestro estudio fue investigar las características del tumor y los resultados de los pacientes en cánceres colorrectales esporádicos del lado derecho e izquierdo de aparición temprana.DISEÑO:Este fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en una única institución de atención terciaria.PACIENTES:Pacientes <50 años diagnosticados de cáncer colorrectal entre 2000 y 2018.RESULTADO PRINCIPAL:Analizamos los datos demográficos de los pacientes, las características del tumor, la supervivencia general y la supervivencia libre de enfermedad.RESULTADOS:Se identificaron un total de 489 pacientes de entre 20 y 49 años entre 2000 y 2018. La mayoría de los pacientes eran blancos (90%) y varones (57%). La mediana de edad en el momento del diagnóstico fue de 44 años y el 75% se diagnosticó entre los 40 y los 49 años. Predominó los tumores del lado izquierdo (80%). La mayoría de los pacientes presentaban enfermedad en estadio 3 (35%) y estadio 4 (35%). Los tumores del lado derecho tenían más probabilidades de tener histología mucinosa (24% frente a 7,4%, p < 0,001) y de células en anillo de sello (4,4% frente a 1,7%, p < 0,001). No hubo diferencia en edad, sexo, raza, etnia, estadio AJCC en la presentación. Los tumores del lado derecho se asociaron con una menor supervivencia general a 5 años (44% frente al 61%, p < 0,005) con la disminución de la supervivencia más prominente en los tumores del lado derecho en estadio 3 (41% frente al 72%, p < 0,0001) y en edades 40-49 (43% vs 61%, p = 0.03). El sexo, la ubicación del tumor, el estadio AJCC en aumento y la histología de las células en anillo de sello fueron factores pronósticos independientes de la supervivencia general. No hubo diferencias significativas en la supervivencia libre de enfermedad.LIMITACIONES:Este estudio fue una revisión retrospectiva en una sola institución.CONCLUSIONES:La mayoría de los cánceres colorrectales de aparición temprana surgen entre los 40 y los 49 años con un predominio en el lado izquierdo pero una mayor mortalidad en los tumores del lado derecho. Estos hallazgos proporcionan evidencia adicional a favor de recomendar una colonoscopia de detección inicial más temprana para el cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B892 . (Traducción-Dr. Ingrid Melo ).

Clinical and Genetic Factors Impact Time to Surgical Recurrence After Ileocolectomy for Crohn's Disease.

OBJECTIVE: The aim of this study was to evaluate factors associated with time to surgical recurrence after Crohn's ileocolectomy. SUMMARY BACKGROUND DATA: The most common surgery performed for Crohn's disease is ileocolectomy. Identifying patients at high risk for surgical recurrence may assist with medical and surgical decision-making. METHODS: Data were obtained from 409 patients with Crohn's disease (CD) who had undergone ≥1 ileocolectomies at Penn State Hershey Medical Center. Six single-nucleotide polymorphisms (SNPs) associated with CD were evaluated in these patients: rs2076756, rs2066844, and rs2066845 in NOD2, rs4958847 and rs13361189 in IRGM, and rs2241880 in ATG16L1. Genotype and clinical factors were analyzed to determine associations with time to recurrent ileocolectomy. A subgroup analysis was performed on 241 patients naïve to biologics before initial ileocolectomy to assess the effect of biologic therapy on time to recurrent surgery. RESULTS: There were 286 patients who underwent a single ileocolectomy, whereas 123 required multiple ileocolectomies. Ileocolonic involvement [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.21-3.00, P = 0.006] and rs2066844 in NOD2 (HR 1.8, 95% CI 1.17-2.77, P = 0.007) were associated with decreased time to surgical recurrence by multivariate analysis. In patients naïve to preoperative biologics, the initiation of postoperative biologics was associated with a 40% decreased incidence of surgical recurrence (HR 0.60, CI 0.39-0.93, P = 0.02) over time. CONCLUSIONS: Ileocolonic distribution of disease and the rs2066844 SNP in NOD2 are associated with shorter time to recurrent ileocolectomy. The initiation of postoperative biologics in naïve patients was associated with a reduced incidence of recurrence over time.

COLQ and ARHGAP15 are Associated with Diverticular Disease and are Expressed in the Colon.

BACKGROUND: Diverticular disease is a common but poorly understood disease of the gastrointestinal tract. Recent studies have identified several single nucleotide polymorphisms (SNPs) that are associated with diverticular disease. MATERIALS AND METHODS: The genotypes of three SNPs (rs4662344 in ARHGAP15, rs7609897 in COLQ, and rs67153654 in FAM155A) were identified by Taqman assay in 204 patients with diverticular disease. Clinical characteristics were obtained from the medical record to study association with genotype. To evaluate gene expression in colon tissue, qPCR was performed on 24 patients with diverticulitis, and COLQ was localized using immunohistochemistry. RESULTS: The ARHGAP15 and COLQ SNPs were significantly associated with both diverticular disease and specifically diverticulitis, while the FAM155A was not associated with either. No association was found with clinical disease characteristics. Heterozygous genotypes at the ARHGAP15 SNP was associated with lower ARHGAP15 expression in colon tissues. COLQ protein localized to the myenteric plexus in the colon. CONCLUSIONS: This study confirmed association of the ARHGAP15 and COLQ SNPs with diverticular disease in our patients but could not confirm FAM155A SNP association. Neither of these SNPs appeared to associate with more severe disease, but genotype at the ARHGAP15 SNP did impact expression of ARHGAP15 in the colon. Additionally, this study is the first to localize COLQ in the colon. Its presence in the myenteric nervous system suggests COLQ SNP variants may contribute to diverticular disease by altering motility.

Clinical and Genetic Factors Associated With Complications After Crohn's Ileocolectomy.

BACKGROUND: Ileocolectomy is the most common surgery performed for Crohn's disease, and postoperative complications occur frequently. There has been minimal evaluation of complications after ileocolectomy as a function of both clinical and genetic factors. OBJECTIVE: The purpose of this study was to evaluate both genetic and clinical factors associated with complications after Crohn's ileocolectomy. DESIGN: This was a retrospective clinical and genetic cohort study. SETTINGS: This study was conducted at a high-volume tertiary care center. PATIENTS: We identified 269 patients with Crohn's disease who had undergone 287 ileocolectomies at our institution between July 2008 and October 2018. MAIN OUTCOME MEASURES: We measured the association of complications with a combination of clinical factors and 6 Crohn's-associated single nucleotide polymorphisms in NOD2 (rs2076756, rs2066844, and rs2066845), IRGM (rs4958847 and rs13361189), and ATG16L1 (rs2241880). RESULTS: There were 86 ileocolectomies of 287 (30%) with complications requiring intervention. The single nucleotide polymorphism rs13361189 in the gene IRGM was significantly associated with complications on univariate and multivariate analysis. There were 61 patients with a variant at the rs13361189 single nucleotide polymorphism and 26 of them had complications, although only 55 of the 208 wild-type patients had complications (43% vs 26%; OR = 2.1; p = 0.02). Other significant factors associated with complication after ileocolectomy were open surgery, placement of a proximal ileostomy, and a greater perioperative decrease in hematocrit. LIMITATIONS: This study was limited by its retrospective design and inherent selection bias. CONCLUSIONS: In addition to clinical risk factors, the rs13361189 single nucleotide polymorphism in the IRGM gene was independently associated with complications after ileocolectomy for Crohn's disease. The use of such genetic determinants may identify patients at increased risk for surgical complications after ileocolectomy. See Video Abstract at http://links.lww.com/DCR/B124. FACTORES CLÍNICOS Y GENÉTICOS ASOCIADOS CON COMPLICACIONES DESPUÉS DE LA ILEOCOLECTOMÍA DE CROHN: La ileocolectomía es la cirugía más común realizada para la enfermedad de Crohn y con frecuencia ocurren complicaciones postoperatorias. Ha habido una evaluación mínima de complicaciones después de la ileocolectomía, en función de factores clínicos y genéticos.Evaluar factores genéticos y clínicos asociados con complicaciones, después de la ileocolectomía por Crohn.Estudio retrospectivo de cohorte clínico y genético.Este estudio se realizó en un centro de atención terciaria de alto volumen.Identificamos a 269 pacientes con enfermedad de Crohn, sometidos a 287 ileocolectomías en nuestra institución, entre julio de 2008 y octubre de 2018.La asociación de complicaciones con una combinación de factores clínicos y seis polimorfismos de un solo nucleótido asociados a Crohn en NOD2 (rs2076756, rs2066844 y rs2066845), IRGM (rs4958847 y rs13361189) y ATG16L1 (rs2241880).Hubieron 86 ileocolectomías en 287 (30%) pacientes con complicaciones que requirieron intervención. El polimorfismo de un solo nucleótido rs13361189 en el gen IRGM se asoció significativamente con complicaciones en el análisis univariado y multivariado. Hubieron 61 pacientes con una variante en el polimorfismo de un solo nucleótido rs13361189 y 26 de ellos tuvieron complicaciones, mientras que solo 55 de los 208 pacientes de tipo salvaje (WT) tuvieron complicaciones (43% vs 26%, OR 2.1, p = 0.02). Otros factores significativos asociados con las complicaciones después de la ileocolectomía fueron, la cirugía abierta, la colocación de una ileostomía proximal y una mayor disminución perioperatoria del hematocrito.Este estudio estuvo limitado por su diseño retrospectivo y sesgo de selección inherente.Además de los factores de riesgo clínicos, el polimorfismo de un solo nucleótido rs13361189 en el gen IRGM se asoció independientemente con complicaciones después de la ileocolectomía, para la enfermedad de Crohn. El uso de tales determinantes genéticos puede identificar a los pacientes con mayor riesgo de complicaciones quirúrgicas, después de la ileocolectomía. Consulte Video Resumen en http://links.lww.com/DCR/B124.

Nutritional status in chronic spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The objective was to investigate nutritional status in chronic spinal cord injury (SCI), and compare macronutrient and micronutrient intake to the recommended values by the United States Department of Agriculture (USDA) 2015-2020 Dietary Guidelines for Americans. SETTING: United States of America. METHODS: A MEDLINE/PubMed, Google Scholar, Scopus, and Web of Science search was performed, identifying 268 papers. All papers included were English-language papers examining adults with chronic SCI. A meta-analysis was performed to produce weighted averages and 95% confidence intervals (CI) when summary statistics were provided. RESULTS: The systematic review included 15 articles, while the meta-analysis included 12. Resting metabolic rate (1492 kcal/day; CI: 1414-1569) fell below the able-bodied average, and total energy (1876 kcal/day; CI: 1694-2059) and fiber (17 g/day; CI: 14-20) intake were below USDA guidelines. Protein (319 kcal/day; CI: 294-345) and carbohydrate (969 kcal/day; CI: 851-1087) intake were above guidelines. Fat intake (663 kcal/day; CI: 590-736) was within USDA guidelines. Vitamins A, B5, B7, B9, D, E, potassium, and calcium were deficient, while vitamins B1, B2, B3, B12, C, K, sodium, phosphorus, copper, and zinc were in excess according to USDA guidelines. Vitamin B6, iron, and magnesium were within USDA guidelines. CONCLUSION: Findings indicate greater energy intake relative to energy needs in those with chronic SCI, and an imbalance in fiber intake and micronutrients compared to the USDA guidelines. Future research examining nutritional health status is needed in order to establish evidence-based, SCI-specific dietary guidelines.

Correction: Nutritional status in chronic spinal cord injury: a systematic review and meta-analysis.

The authors noted that there were two typographical errors in Table 2. Under the 'Tetraplegia' group of 'Gorgey et al. [55]' the 'RMR' value was originally given as '14,101 ± 10'. This has now been corrected to '1411 ± 10'. Under the 'Tetra' group of 'Sabour et al. [22]' the 'Energy intake' was originally given as '20,123 ± 681'. This has now been corrected to '2013 ± 681'. This has been corrected in both the PDF and HTML versions of the Article.

The Effect of Elevated A1C on Immediate Postoperative Complications: A Prospective Observational Study.

IN BRIEF This study examined whether elevated A1C in patients with diabetes is associated with a higher incidence of postoperative infections and other complications. Researchers followed 50 noncardiac surgical patients for 7 postoperative days. Half of the patients had an A1C <7% and the other half had an A1C ≥7%. The two groups were otherwise comparable except that the higher-A1C group had significantly higher pre-induction and postoperative blood glucose levels, with wider variability in the first 24 hours after surgery. During the first postoperative week, 11 patients developed complications, of whom 10 were in the higher-A1C group. Elevated A1C, unlike a single preoperative blood glucose value, may predict difficult postoperative glucose control and postsurgical complications.

Diverticulitis and Crohn's disease have distinct but overlapping tumor necrosis superfamily 15 haplotypes.

BACKGROUND: Diverticulitis (DD) and Crohn's disease (CD) have overlapping features including bowel structuring, inflammation, and infection. Tumor necrosis superfamily 15 (TNFSF15) is an immunoregulatory, anti-angiogenic gene. CD has been previously associated with a haplotype of five TNFSF15 single-nucleotide polymorphism alleles: rs3810936 (G allele), rs6478108 (A), rs6478109 (G), rs7848647 (G), and rs7869487 (A). We aimed to determine the TNFSF15 risk haplotype for DD versus controls with a subgroup analysis of youthful DD patients (aged ≤55 y) versus older controls (aged ≥55 y). METHODS: A total of 148 diverticulitis patients (90 aged ≤55 y) and 200 controls (87 aged ≥55 y) were genotyped using our custom-designed Illumina Veracode microarray chip. Genotypes from rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 and two additional TNFSF15 single nucleotide polymorphisms, rs3810936 and rs11554257, were analyzed. PHASE version 2.1, R with HaploStats and the Broad Institute's Haploview program were used for statistics and imputed haplotype frequency. Permutation corrected for multiple comparisons. RESULTS: The CD GAGGA haplotype was significantly associated with diverticulitis (P = 0.03) in the all DD versus all controls comparison. A second haplotype, rs6478108 (A), rs6478109 (G), rs7869487 (A), and rs4263839 (G), was also associated with DD in this cohort (P = 0.025). A third haplotype rs6478108 (A), rs6478109 (G), rs7848647 (G) and rs7869487 (A), rs4263839 (G) was demonstrated in the DD < 55 versus controls >55 comparison (P = 0.045). CONCLUSIONS: Distinct but overlapping TNFSF15 haplotypes were demonstrated in diverticulitis patients versus healthy controls when compared with the known Crohn's risk haplotype suggesting similar but distinct genetic predispositions. This study strengthens the role for a genetic predisposition to diverticulitis that involves the TNFSF15 gene.

Single-Site Laparoscopic Colorectal Surgery Provides Similar Clinical Outcomes Compared With Standard Laparoscopic Surgery: An Analysis of 626 Patients.

BACKGROUND: Compared with standard laparoscopy, single-site laparoscopic colorectal surgery may potentially offer advantages by creating fewer surgical incisions and providing a multifunctional trocar. Previous comparisons, however, have been limited by small sample sizes and selection bias. OBJECTIVE: The purpose of this study was to compare 60-day outcomes between standard laparoscopic and single-site laparoscopic colorectal surgery patients undergoing elective and urgent surgeries. DESIGN: This was an unselected, retrospective cohort study comparing patients who underwent elective and unplanned standard laparoscopic or single-site laparoscopic colorectal resections for benign and malignant disease between 2008 and 2014. Outcomes were compared using univariate analyses. SETTINGS: This study was conducted at a single institution. PATIENTS: A total of 626 consecutive patients undergoing laparoscopic colorectal surgery were included. MAIN OUTCOME MEASURES: Morbidity and mortality rates within 60 postoperative days were measured. RESULTS: A total of 318 (51%) and 308 patients (49%) underwent standard laparoscopic and single-site laparoscopic procedures. No significant differences were noted in mean operative time (standard laparoscopy, 182.1 ± 81.3 vs single-site laparoscopy, 177.0 ± 86.5; p = 0.30) or postoperative length of stay (standard laparoscopy, 4.8 ± 3.4 vs single-site laparoscopy, 5.5 ± 6.9; p = 0.14). Conversions to laparotomy and 60-day readmissions were also similar for both cohorts across all of the procedures performed. A significant difference was identified in the number of patients who developed postoperative complications (standard laparoscopy, 19.2% vs single-site laparoscopy, 10.7%; p = 0.004), especially with respect to surgical-site infections (standard laparoscopy, 11.3% vs single-site laparoscopy, 5.8%; p = 0.02). LIMITATIONS: This was a retrospective, single institution study. CONCLUSIONS: Single-site laparoscopic colorectal surgery demonstrates similar results to standard laparoscopic colorectal surgery with regard to operative time, length of stay, and readmissions. Single-site laparoscopic colorectal surgery may provide advantages in limiting the development of certain complications, such as superficial surgical-site infections.

Genetic determinants associated with early age of diagnosis of IBD.

BACKGROUND: Inflammatory bowel disease (IBD) is typically diagnosed at 20 to 40 years of age. However, very young versus elderly patients with IBD may have different mechanisms of disease that may affect prognosis and care. OBJECTIVES: The purpose of this work was to identify single nucleotide polymorphisms associated with age of onset of Crohn's disease and ulcerative colitis. DESIGN: Patients were genotyped using a custom microarray chip containing 332 IBD-associated single nucleotide polymorphisms. Age at diagnosis as a continuous variable was assessed using linear regression. Patients were then subgrouped by age at diagnosis and compared by the Fisher exact test. Bonferroni correction was used in all of the analyses. SETTINGS: This study was conducted at a tertiary academic hospital. PATIENTS: Sixty patients with Crohn's disease and 26 with ulcerative colitis were ≤ 16 years old, 259 patients with Crohn's disease and 248 with ulcerative colitis were 17-60 years old, and 10 patients with Crohn's disease and 20 with ulcerative colitis were >60 years old at diagnosis and included in this study. MAIN OUTCOME MEASURES: Age at diagnosis and single nucleotide polymorphism correlations were measured in this study. RESULTS: The NOD2 single nucleotide polymorphism rs2076756 was associated with younger age at Crohn's disease diagnosis (p = 0.0002). Patients with the AA/wild-type genotype were diagnosed at 31.9 ± 1.23 years, AG heterozygotes at 25.6 ± 0.99 years, and GG/at-risk allele homozygotes at 22.6 ± 1.32 years. Depending on age categories compared, single nucleotide polymorphisms in POU5F1, TNFSF15, and HLA DRB1*501 were associated with age of Crohn's disease diagnosis. No genetic associations were seen between ulcerative colitis and linear age at diagnosis; however, the G allele of the LAMB1 single nucleotide polymorphism rs886774 was found to be associated with ulcerative colitis diagnosed at ≤ 16 versus >17 years old (p = 0.008). LIMITATIONS: This study was limited to known IBD single nucleotide polymorphisms. CONCLUSIONS: This analysis reaffirms the association between NOD2, a molecule of innate immunity, and early Crohn's disease onset. This is the first report of a possible association between early Crohn's disease and the POU5F1, TNFSF15, and HLA DRB1*501 genes. The LAMB1 gene, associated with mucosal basement membrane integrity, was associated with early onset ulcerative colitis and, thus, suggests a fundamentally different mechanism of early disease pathogenesis in ulcerative colitis versus Crohn's disease.

Surgical diverticulitis is not associated with defects in the expression of wound healing genes.

PURPOSE: The development of diverticuli may represent defects in collagen vascular tissue integrity possibly from a genetic predisposition. We evaluated the tissue expression of wound healing genes in sigmoid tissue from youthful patients undergoing surgery for diverticulitis and thus would more likely suffer from a genetic predisposition (SD mean age 39 ± 0.9) versus controls in the form of patients over the age of 50 (mean age 52.9 ± 10.5 years) without evidence of diverticular disease. METHODS: The mRNA expression of 84 genes associated with the extracellular matrix, cellular adhesion, growth factors, inflammatory cytokines, and signal transduction was evaluated in 16 SD and 15 control tissues using a Qiagen Wound Healing Array. Vitronectin, the gene protein with the highest potential significance on raw analysis, was further investigated using a Taqman assay with an additional 11 SD (total n = 27) and four control (total n = 19) samples. Statistics were by Student's t and Mann-Whitney tests with Bonferroni correction. RESULTS: No significant differences in mRNA expression between the SD and control tissue in the 84 measured genes were demonstrated after correction. Vitronectin mRNA expression was downregulated 2.7-fold in SD tissue vs. tissue from non-neoplastic control patients (p = 0.001 raw/0.08 corrected). However, on vitronectin TaqMan analysis, no difference in expression was seen in SD vs. all controls or in all subset comparisons. CONCLUSIONS: The lack of significant alteration in mRNA expression of traditionally associated wound healing genes/proteins in young SD patients suggests that such genes play a minor role in the genetic predisposition to youthful diverticulitis.

Single nucleotide polymorphisms of the tcdC gene and presence of the binary toxin gene predict recurrent episodes of Clostridium difficile infection.

OBJECTIVE: To identify Clostridium difficile genotypes, which are associated with recurrent C difficile infection (RCDI). BACKGROUND: Reliable bacterial genetic factors predicting RCDI are currently lacking. METHODS: Inpatients and outpatients 18 years or older treated at our institution for C difficile infection (CDI) of any severity were consecutively enrolled. CDI was defined as symptoms of colitis with a positive PCR stool test. Each bacterial isolate was studied for virulence factors: tcdC mutations, including single nucleotide polymorphisms (SNPs) via PCR, the presence of genes for toxins A, B and binary toxin using restriction fragment length polymorphism, and identification of ribotype by PCR. χ tests, t tests, and logistic and linear regression were used to determine which virulence factors predicted RCDI and the need for hospital admission, with corrections made for multiple statistical comparisons. RESULTS: Seventy-three patients (male: 52%; mean age: 66 ± 15 years) were studied. Binary toxin gene (P = 0.03) was associated with at least 1 episode of RCDI, as was the presence of SNPs C184T (P = 0.006) and A117T (P = 0.003). The presence of the binary toxin gene with either of these tcdC SNPs increased RCDI by 80% (P = 0.0002) but did not predict the need for hospital admission. None of the other virulence factors, including ribotype 027, were predictive of RCDI. CONCLUSIONS: The presence of the binary toxin gene and tcdC SNPs C184T and A117T strongly predict RCDI. The presence of both tcdC SNPs and the binary toxin gene significantly increased the risk of RCDI, which might warrant longer antibiotic courses to eradicate the infection.

The TNFSF15 gene single nucleotide polymorphism rs7848647 is associated with surgical diverticulitis.

OBJECTIVE: To determine if single nuclear polymorphisms (SNPs) in the TFNSF15 gene play a role in patients requiring surgery for diverticulitis. BACKGROUND: A role for a genetic predisposition in diverticulitis is suggested by its association with hereditary connective tissue disorders, youthful onset in some patients, and the observation of families with multiple affected individuals. The TNFSF15 gene has been associated with other inflammatory diseases affecting the colon such as medically refractory ulcerative colitis (UC), aggressive Crohn's disease (CD), and pouchitis after restorative proctocolectomy. METHODS: In the discovery phase of this study, 21 sporadic surgical diverticulitis (SD) patients (9 female, mean age = 52 ± 5) and 5 individuals from a single family with surgically managed diverticulitis [familial diverticulitis (FD), 4 female, mean age = 51.1 ± 7] were studied. SD patients were age and sex matched with 3 separate groups of healthy, CD and UC control patients. All patients were genotyped for 5 known TNFSF15-associated SNPs. The SNP discovered to be associated with diverticulitis (rs7848647) was then confirmed in a separate test group composed of 34 additional patients (20 female, mean age 57.7 ± 2) who also underwent surgical treatment for diverticulitis. These patients were age matched to a new control cohort of patients having no history of diverticulitis (26 female). Patients were genotyped using a TaqMan assay. In the discovery phase, logistical regression on matched subjects was performed to determine an association of TNFSF SNP with diverticulitis versus the control groups. In the test phase, significance for the rs7848647 SNP was assessed by the Fischer's exact test. RESULTS: In the discovery phase, the TNFSF15 SNP rs7848647 was significantly associated with SD (p = 0.0003) versus all control groups studied. The risk allele for this SNP (G substituted for A) was found in all SD patients. The homozygous GG allele was found in 62% (13/21) of SD patients versus only 5% (1/21) of healthy controls (p = 0.001) and 24% (10/42) of all UC + CD controls (p = 0.002). All 5 members of the FD cohort were homozygous for the at-risk "G" allele. In the test group, the homozygous GG genotype was found in 56% of SD patients compared with 17% of healthy controls (p = 0.006). Risk of SD seemed to increase with number of the G alleles with 8% of SD patients having AA homozygosity, 35% of SD patients having AG heterozygosity, and 56% of SD patients having GG homozygosity. CONCLUSIONS: The SNP rs7848647 associated with the TNFSF15 gene is associated with surgical diverticulitis. This finding suggests a fundamental role for TNFSF15, a T-cell receptor gene involved in T-cell maturation, in the pathophysiology of diverticulitis requiring surgery. This SNP may be a marker of diverticular disease severity that might assist in surgical decision making.

T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease.

BACKGROUND: The T-cell activation Rho GTPase-activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location. MATERIALS AND METHODS: Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann-Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results. RESULTS: Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049). CONCLUSIONS: Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.

Association of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal cancer in a population-based case-control study.

Previous research has shown that greater intakes of dietary folate are associated with reduced risk for colorectal cancer (CRC) and that single nucleotide polymorphisms (SNPs) in genes involved in folate-mediated one-carbon metabolism (FOCM) also may be involved in altering CRC risk. The objective of this study was to evaluate the role of folate intake (and intakes of related dietary components such as methionine), 35 SNPs in three FOCM pathway genes (MTHFD1, MTHFR, and TYMS), and their interactions on CRC risk in a population-based case-control study in Pennsylvania (686 cases, 740 controls). Diet and supplement use was assessed for the year before diagnosis or interview for cases and controls, respectively, with a modified Diet History Questionnaire from the National Cancer Institute. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Using a dominant model for the variant allele, several SNPs were significantly associated with CRC including MTHFD1 rs8003379 (OR = 1.65; 95% CI = 1.00-2.73) and rs17824591 (OR = 1.98; 95% CI = 1.14-3.41) and the TYMS rs2853533 SNP (OR = 1.38; 95% CI = 1.05-1.80). Using a nondominant model, the AA genotype for MTHFR rs1476413 exhibited a marginally significant (OR = 1.56; 95% CI = 1.00-2.44) association with CRC. Two TYMS SNPs (rs16948305 and rs495139) exhibited significant (P = 0.024 and P = 0.040, respectively) gene-diet interactions with folate intake. One MTHFD1 (P = 0.019) and one MTHFR (P = 0.042) SNP exhibited gene-diet interactions with methionine intake. These findings suggest that allelic variants in genes involved in FOCM interact with dietary factors including folate and methionine to modify risk for CRC.

A single nucleotide polymorphism in the STAT5 gene favors colonic as opposed to small-bowel inflammation in Crohn's disease.

BACKGROUND: Crohn's disease is a chronic inflammatory ailment that can affect the colon and/or small intestine. A genetic basis for disease distribution is being sought, although the available data are seminal. The STAT5 gene is known to influence colonic permeability, mucosal regeneration, and interleukin 2 production, although its role in the distribution of Crohn's disease is unclear. OBJECTIVE: The aim of this study was identification of single nucleotide polymorphisms associated with Crohn's distribution, with the goal of distinguishing disease subcategories and differing pathophysiologies. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted in a single tertiary referral center. PATIENTS: A total of 173 patients with Crohn's disease who were identified from our biobank were segregated by disease distribution (colitis, n = 28; ileocolic disease, n = 116; enteritis, n = 29) and were genotyped for 258 Crohn's-associated single nucleotide polymorphisms. Patients with ulcerative colitis (n = 119) were also genotyped to confirm the association of identified single nucleotide polymorphisms with small-bowel sparing, colonic pathology. MAIN OUTCOME MEASURES: We investigated an association between single nucleotide polymorphisms and Crohn's disease distribution. RESULTS: Single nucleotide polymorphism rs16967637 in the STAT5 gene was associated with small-bowel sparing Crohn's disease when the enteritis group was compared with either a combined colitis/ileocolic group (p = 0.025) or those with only ileocolic disease (p = 0.04). Homozygosity for the at-risk allele (C) was present in 59% of patients with sparing of the small bowel. The association of this single nucleotide polymorphism with small-bowel sparing disease persisted when patients with ulcerative colitis were compared with the group with Crohn's enteritis (p = 0.036), as well as after combining patients with ulcerative colitis with both the Crohn's colitis group (p = 0.009) and the Crohn's ileocolitis/colitis group (p = 0.00008). LIMITATIONS: This study was limited by the small numbers of study subjects with isolated enteritis or colitis. CONCLUSIONS: Single nucleotide polymorphism rs16967637 in the STAT5 gene was the only single nucleotide polymorphism associated with Crohn's disease without enteritis. Homozygosity for the at-risk allele demonstrated the strongest association with this phenotype. These results suggest a role for this single nucleotide polymorphism in the development of inflammatory bowel disease of the large intestine.

Survival outcomes of anal adenocarcinoma versus rectal adenocarcinoma: A retrospective cohort study.

BACKGROUND: Anal adenocarcinoma (AA) is a rare malignancy with decreased survival compared to rectal adenocarcinoma (RA). However, AA continues to be treated with similar algorithms compared to rectal cancer with minimal data regarding the efficacy of these treatment algorithms. METHODS: A retrospective chart review of patients with non-metastatic AA at a single tertiary-care institution from 1995 to 2020. This cohort was matched 2:1 to a group of RA patients for comparison. The primary outcome of interest was overall survival rates. RESULTS: Sixteen patients with stages I-III AA were matched to a cohort of RA. There were no significant differences between the cohorts with regard to patient demographics, comorbidities, disease stage or histologic features. There were also no significant differences in treatment modalities between the two cohorts with a majority undergoing multimodal therapy with chemoradiation and surgery. All patients with AA demonstrated significantly worse survival than all patients with rectal adenocarcinoma (five-year survival 47.7% vs. 82.3%, respectively. p < 0.05). When looking at a sub-group of patients who underwent combination chemoradiation and surgery from each cohort, anal adenocarcinoma continued to exhibit lower overall survival (five-year survival 41.6% and 86.4%, respectively. p < 0.05). In a multi-variable model that adjusted for location, American Joint Committee on Cancer (AJCC) stage and treatment pathway, tumor location in the anal canal was an independent predictor of overall survival (Hazard ratio [HR] 2.7, p < 0.05). CONCLUSION: AA has worse survival as compared to RA despite similar treatment. This study highlights the need to evaluate the current classification and treatment pathways to improve outcomes.

The impacts of total body irradiation on umbilical cord blood hematopoietic stem cell transplantation.

Background: Umbilical cord blood hematopoietic stem cells are commonly used for hematopoietic system reconstitution in recipients after umbilical cord blood transplantation (UCBT). However, the optimal conditioning regimen for UCBT remains a topic of debate. The exact impact of total body irradiation (TBI) as a part of conditioning regimens remains unknown. Objectives: The aim of this study was to evaluate the impacts of TBI on UCBT outcomes. Design: This was a multi-institution retrospective study. Methods: A retrospective analysis was conducted on the outcomes of 136 patients receiving UCBT. Sixty-nine patients received myeloablative conditioning (MAC), in which 33 underwent TBI and 36 did not, and 67 patients received reduced-intensity conditioning (RIC), in which 43 underwent TBI and 24 did not. Univariate and multivariate analyses were conducted to compare the outcomes and the post-transplant complications between patients who did and did not undergo TBI in the MAC subgroup and RIC subgroup, respectively. Results: In the RIC subgroup, patients who underwent TBI had superior overall survival (adjusted hazard ratio [aHR] = 0.25, 95% confidence interval [CI]: 0.09-0.66, p = 0.005) and progression-free survival (aHR = 0.26, 95% CI: 0.10-0.66, p = 0.005). However, in the MAC subgroup, there were no statistically significant differences between those receiving and not receiving TBI. Conclusion: In the setting of RIC in UCBT, TBI utilization can improve overall survival and progression-free survival. However, TBI does not show superiority in the MAC setting.