Re-resection Rates and Disease Recurrence in Crohn's Disease - A Population-Based Study Using Individual-Level Patient Data.

BACKGROUND AND AIMS: Despite advances in the medical treatment of Crohn's disease (CD), many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection. METHODS: We conducted a retrospective, population-based, individual patient data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020. RESULTS: Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after one, five, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity (57%) and stoma reversal (40%). Disease activity-driven re-resection rates after one, five, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within one year (80%). The median time to recurrence was 11.0 months. Biologics started within one year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocecal resection reduced disease recurrence and re-resection risk (HR 0.58, 95% CI (0.34-0.99), p=0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behavior, smoking, and perianal disease. CONCLUSION: Re-resection rates, categorized by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localization. Biological therapy may be disease-modifying for certain subgroups when initiated within one year of resection.

Survival in patients initiating home parenteral support due to nonmalignant short bowel syndrome compared with background population.

BACKGROUND: Survival has frequently been studied and reported in patients with long term intestinal failure (IF). However, studies comparing the survival and mortality rates with the background population are rare. This study compares the survival in an adult IF, non-malignant, short bowel syndrome (SBS) cohort with a control group and with age- and sex-specific background mortality rates. DESIGN: Patients with SBS, defined by a small bowel length of 200 cm or less, due to non-malignant disease, were included and followed until death or censoring on 31 December 2017. Causes of deaths occurring during home parenteral support (HPS) were assessed by review of the charts. Each case was matched with ten controls from the background population according to year of HPS initiation, age, and sex, and their survival was compared. Furthermore, age- and sex-specific mortality rates of the background population were used to calculate the standardized mortality ratio (SMR) and excess mortality. RESULTS: After five years, patients who initiated HPS had a relative survival of 76%. The SMR was 5.0 and the excess mortality was 50 per 1000 years. HPS-related deaths were assessed to account for 11% of deaths during HPS and occurred with an incidence of 10 per 1000 years. The excess mortality was as low as 15 per 1000 years in cases aged less than 40 years. Patients weaning off HPS had a mortality rate closer to that expected in the background population. CONCLUSIONS: In adult patients with a non-malignant cause of SBS-IF, the excess mortality was 50 per 1000 years. However, HPS related deaths were rarely registered with an incidence of 10 HPS related deaths per 1000 HPS treatment years.

Renal function in patients with intestinal failure receiving home parenteral support.

BACKGROUND: Progressive renal impairment, given by an annual decline in estimated glomerular filtration rate (eGFR), has been described in patients with intestinal failure (IF) receiving home parenteral support (HPS). The objective of this study was to examine changes in eGFR over 5 years following initiation of HPS treatment and to identify potential risk factors for loss of renal function. METHOD: This retrospective database study investigates eGFR changes in nonmalignant IF patients discharged with HPS from Rigshospitalet, Copenhagen, in an 8-year period. RESULTS: One year after HPS initiation, mean eGFR decreased by 15.3 ml/min/1.73 m2 . Paired t-test showed a decline of 15.0 ml/min/1.73 m2 (95% CI, -18.3 to -11.6; P < .0001). Over the following years, eGFR continued to decrease but at insignificant lower rates. Decreased eGFR was associated with increasing age, female sex, increasing body weight, diabetes at HPS initiation, and a high requirement of HPS volume. CONCLUSION: In nonmalignant IF patients, the decrease of eGFR was mainly seen during the first year of HPS. This may be due to a higher risk of dehydration and possibly secondary hyperaldosteronism leading to renal damage following the onset of IF. However, the decrease in eGFR may also represent a higher production of creatinine due to a beneficial increase of muscle mass in the initial recovery phase. In general, once the patients were stabilized, the eGFR decline followed a physiological course resembling the background population. Patients with diabetes or high HPS volume needs seem to be more vulnerable and may require special attention.

Drug use in patients with short bowel syndrome and intestinal failure.

INTRODUCTION: In patients with short bowel syndrome (SBS), severe malabsorption may cause a need for parenteral support and, by definition, these patients suffer from SBS intestinal failure. Absorption of oral medications is likely diminished in patients with SBS intestinal failure and higher than normal doses may be required to achieve sufficient pharmacologic effect. We investigated the prescription patterns and oral dosages in a well-defined population of patients with non-malignant SBS intestinal failure. METHODS: This was a cross-sectional analysis based on a cohort of adult patients with SBS intestinal failure treated with home parenteral support and registered in 2016 at the Department of Gastroenterology at the Copenhagen University Hospital - Rigshospitalet. The patients' clinical data and prescription patterns were extracted from electronic medical and medications records. RESULTS: The patients in our cohort (n = 74) were primarily females (58%), the median age was 63 years (interquartile range (IQR): 52-72 years) and the median BMI was 22 kg/m2 (IQR: 19-26 kg/m2). Each patient was treated with a median of eight drugs (range: 1-20). Most (75%) of the medications were administered orally. Only codeine, levothyroxine and loperamide were prescribed in higher dosages than recommended in their product labelling. All medication-treated patients were prescribed between one and four different analgesics. CONCLUSION: In our single-centre cohort of patients with SBS intestinal failure, orally administered medications were generally prescribed in recommended dosages. FUNDING: none Trial registration. Approved by the Danish Data Protection Agency (BFH-2016-058, I-Suite no.: 04906) and the Danish Patient Safety Authority (3-3013-1884/1/).

Differences in methodology impact estimates of survival and dependence on home parenteral support of patients with nonmalignant short bowel syndrome.

BACKGROUND: In patients with intestinal failure (IF), who are receiving home parenteral support (HPS), variations between centers in estimates of survival and HPS dependency often reflect differences in population characteristics. However, variations in methodology and adherence to model assumptions may further contribute. OBJECTIVES: We investigated how differences in methodology affect estimates of outcomes in IF patients. METHODS: We applied different model assumptions and statistical methods to real-life outcome data from a well-characterized cohort of nonmalignant short bowel syndrome (SBS) patients. This retrospective study was based on extracts from the Copenhagen IF database and from the Danish death registry. RESULTS: Estimates of mortality varied substantially, depending on the study design and statistical method. The 5-y mortality rate obtained with the Kaplan-Meier (KM) method was estimated to be 10.1% higher if patients were only followed during HPS treatment, compared with follow-up regardless of HPS treatment. The 5-y cumulative incidence of weaning off HPS was overestimated by 4.4% when inappropriately using the KM method, instead of the cumulative incidence function. The 5-y survival rates in nonmalignant SBS-IF patients who initiated HPS were 89.1% for those aged younger than 40 y, 74.8% for patients aged 40-60 y, and 52.1% for those older than 60 y. A Cox regression analysis identified age and diagnoses other than inflammatory bowel disease as significant risk factors for mortality. For HPS dependency, bowel anatomy was significantly associated with the ability to wean off, and no patients without a colon and less than 100 cm remnant of the small bowel remained continuously weaned off and alive for one year. CONCLUSIONS: The large variations in outcomes illustrated in this study emphasize the importance of the appropriate selection of statistical methods. A comparison between studies is problematic, due to differences in the methods employed.

Hospitalizations in Patients With Nonmalignant Short-Bowel Syndrome Receiving Home Parenteral Support.

BACKGROUND: The objective of this retrospective cohort study was to assess the frequency, duration, and causes of hospitalizations in patients receiving home parenteral support (HPS) due to short-bowel syndrome (SBS) of nonmalignant causes. Furthermore, we aimed to investigate potential risk factors and hypothesized that patients with the shortest remnant, functional, small bowel-hence, the highest need for HPS-would have the highest incidence of hospitalizations. METHODS: Patients with nonmalignant SBS who initiated HPS in the period from 1970 to 2016 from the Department of Gastroenterology, Rigshospitalet, Copenhagen, Denmark, were included. Information about demography, hospitalizations at the department, and duration of HPS was obtained from the Copenhagen intestinal failure database. RESULTS: Patients (n = 331) received HPS for a total of 1409.9 years in the period. Hospitalizations accounted for 6.6% of the time registered as HPS-dependent. The average patient was hospitalized for 5.7% (range 0%-82%) of the registered HPS days. The incidence of admissions was 2.5 per HPS year. The median length of stay was 7 days (range; 0-387). Catheter-related complications were the most frequently registered causes of admissions (35.2%), subsequently accounting for 31.3% of the total admission time. A Cox regression of admissions showed no significant influence of the remnant-bowel anatomy but identified the ability to administer HPS unaided as associated with a significantly reduced hazard. CONCLUSIONS: This retrospective study illustrated that 6.6% of the provided HPS days were, in fact, spent hospitalized. Since admissions elsewhere were not accounted for, this may be an underestimation.

A case report of polymicrobial bacteremia with Weissella confusa and comparison of previous treatment for successful recovery with a review of the literature.

Weissella confusa is a Gram-positive coccus and a commensal bacterium of the human gastrointestinal tract with a potential to cause invasive infections. We report the presence of W. confusa in the blood of a 25-year-old male patient with Crohn's disease, short bowel syndrome treated with home parenteral nutrition, and a history of recurrent bloodstream infections, admitted to our hospital with fever and malaise. A polymicrobial culture of W. confusa and Aeromonas hydrophila was identified from blood, for which treatment with meropenem and metronidazole was initiated. The literature was searched for previous cases of infection with W. confusa . In total, 14 reports describing infection of 28 patients were found, most cases presenting with bacteremia. The previous reports have described variable susceptibility to antibiotics; however, all were reported to be vancomycin resistant. Because of its similarities to other vancomycin-resistant cocci, isolates of W. confusa might be difficult to identify with traditional methods. Infection may be facilitated by its natural vancomycin resistance, leading to severe infection in hosts with underlying diseases. We describe the treatment of previous cases of infection and suggest treatment methods shown effective in other cases. Vancomycin is often used as treatment of infection with Gram-positive organisms, but this may need to be reevaluated, as several pathogenic bacteria are intrinsically vancomycin resistant. A review on reported treatments of bacteremia by W. confusa suggests the use of daptomycin, amoxicillin-clavulanate or piperacillin/tazobactam as recommendable antibiotic regimens.

Nutritional Therapy in Adult Short Bowel Syndrome Patients with Chronic Intestinal Failure.

Intestinal failure (IF) is the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that parenteral support (PS) is required to maintain health and/or growth. This article critically revises the gaps in and evidence for providing general nutritional therapy recommendations in the Short Bowel Syndrome-IF population. It addresses the need for an individualized approach, aiming to reduce or even eliminate the need for PS, and emphasizes a need to focus on effects of dietary interventions on the quality of life of these patients.