Tissue-resident immunity mediates host defense against pathogens and enables rapid adaptive memory responses. However, the study of tissue-resident immunity is hindered by a singular lack of experimental systems allowing pathogenic epithelial infection amidst the full spectrum of endogenous immune subsets. Particularly in lung, differing notions of transient versus sustained residency of tissue-resident memory T cells (TRM) have questioned the extent to which recall immunity to respiratory pathogens occurs locally or in concert with secondary lymphoid organs. We thus generated long-term adult human distal lung organoids from intact tissue fragments in 3D air-liquid interface (ALI) culture that co-preserved epithelial and stromal architecture alongside endogenous lung-resident immune cells (T, B, NK, myeloid). The organoid T cells exhibited persistent cytokine-assisted maintenance, expressed residency and memory markers, and preserved T cell receptor (TCR) repertoires of cognate fresh tissue. SARS-CoV-2 vigorously infected the organoid lung epithelium, stimulated inflammatory cytokine production, and crucially, induced widespread SARS-CoV-2-specific, tissue-resident T cell responses. Our studies introduce a robust adult human lung organoid experimental system containing a physiologic air interface and diverse resident immune subsets, demonstrate the organ-autonomous sufficiency of lung pathogen memory T cell responses, distinct from secondary lymphoid tissue, and provide a platform to investigate tissue-resident immunity in health and disease.

INTRODUCTION:Spring-mediated distraction enterogenesis aims to use mechanical stretch to generate new functional intestinal tissue in patients with short bowel syndrome. Because of the incremental nature of spring-mediated distraction enterogenesis, patients may require multiple spring insertions to produce enough tissue to wean off parenteral nutrition. We aim to demonstrate the feasibility of repeated lengthening within the same intestinal segment. METHODS:Juvenile Yucatan pigs underwent a laparotomy to introduce a gelatin-encapsulated nitinol spring into the jejunum. After 14-21 days, a second laparotomy was performed to remove the initial spring and insert a new compressed spring with a greater force constant into a portion of the previously lengthened jejunum. After 7 days, the pigs were killed, and samples were collected. RESULTS:Spring insertion produced a significant increase in jejunal length when compared to controls. Both the initial and the subsequent stronger springs produced an equivalent amount of lengthening. Crypt depth, mucosal thickness, muscularis thickness, and the outer serosal perimeter of the repeatedly lengthened jejunal segments all increased compared with control segments. CONCLUSION:Previously lengthened segments of jejunum were successfully relengthened using spring-mediated distraction enterogenesis in a porcine model. This suggests that patients with short bowel syndrome may be offered repeat distraction procedures to achieve a greater increase in bowel length than a single spring-mediated distraction enterogenesis procedure.

Abstract Epithelial regeneration and barrier integrity are impaired in inflammatory bowel diseases, including Crohn’s disease (CD), yet current therapies largely target immune inflammation without directly promoting mucosal repair. While regulatory T cells are classically immunomodulatory, their capacity to directly support human intestinal stem cells (ISCs) and barrier function remains unclear. In this study, we tested the hypothesis that FOXP3-expressing regulatory T cells—engineered CD4 LVFOXP3 and thymic-derived T reg (tT reg )—directly support human ISC maintenance and restore epithelial barrier function independent of their immunomodulatory function. Using CD patient ISCs-derived enteroids that display disease-associated damage, we established co-culture with FOXP3-engineered T reg cell-CD4 LVFOXP3 or thymic-derived T reg (tT reg ). The presence of either CD4 LVFOXP3 or tT reg cells enhanced enteroid growth, improved epithelial barrier function, and restored apical-basal polarity of ISCs, indicating reparative capacity. Conversely, activated conventional CD4 + T cells reduced barrier function and abrogated apical-basal polarity. Integrating secretome profiling with ligand add-back and receptor or ligand blockade, we identify the PDGF-AA–PDGFRα axis as a key regulator of T reg -mediated intestinal epithelial barrier integrity, but dispensable for T reg suppressive capacity. Collectively, our data delineate a direct, human tissue-intrinsic role of FOXP3-driven Treg in the interaction with ISCs via PDGF-AA-PDGFRα, enhancing epithelial barrier function and positioning CD4 LVFOXP3 as a treatment approach coupling immunoregulation with epithelial repair. One Sentence Summary Regulatory T cells improve the intestinal epithelial barrier function, primarily, through the PDGF-AA–PDGFRα axis

Piezo1 is a mechanosensitive cation channel expressed in intestinal muscularis cells (IMCs), including smooth muscle cells (SMCs), interstitial cells of Cajal, and Pdgfrα+ cells, which form the SIP syncytium, crucial for GI contractility. Here, we investigate the effects of SMC-specific Piezo1 deletion on small bowel function. Piezo1 depletion results in weight loss, delayed GI transit, muscularis thinning, and decreased SMCs. Ex vivo analyses demonstrated impaired contractile strength and tone, while in vitro studies using IMC co-cultures show dysrhythmic Ca 2+ flux with decreased frequency. Imaging reveal that Piezo1 localizes intracellularly, thereby likely impacting Ca 2+ signaling mechanisms modulated by Ca 2 + -handling channels located on the sarcoplasmic reticulum and plasma membrane. Our findings suggest that Piezo1 in small bowel SMCs contributes to contractility by maintaining intracellular Ca 2+ activity and subsequent signaling within the SIP syncytium. These findings provide new insights into the complex role of Piezo1 in small bowel SMCs and its implications for GI motility.

BACKGROUND:Colon displays structural and functional diversity. However, the region-specific motility effects of spinal nerves on the colon are unclear. We mapped the regional colonic motor response to thoracolumbar (T12-L1) (TLNS) and sacral (S1-S4) (SNS) roots nerve electrical stimulation (ES) in an anesthetized porcine model, with or without concomitant afferent (AB) or efferent (EB) transmission block. METHODS:Adult male Yucatan pigs (n = 16) underwent a laminectomy followed by unilateral (left root) SNS (S1-S4, 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) or with concomitant AB or EB (40 kHz, 0.1 ms, 2 mA). In a separate group (n = 7), TLNS (T12-L1, 10 Hz, 0.3 ms, 0.5 mA, continuous or 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) of the left root concomitant with or without EB was applied. Proximal (pC), transverse (tC), distal (dC) colon and anal canal (AC) luminal manometry were monitored before, during and after stimulation. Area under the curve of contraction (AUC), luminal pressure heat maps, and contraction spectral analysis were analyzed. KEY RESULTS:S2 ES increased the power of the contraction frequency spectrum in both dC and AC during stimulation and increased the AUC of contraction in dC and AC during and post-stimulation. AB and EB partially reduced dC, while EB abolished the increase in AC. In contrast, S1, S3, or S4 ES as well as TLNS had little effect on motility. CONCLUSIONS:In anesthetized male pigs, S2 ES induces a robust motility response in the distal colon via the central network while in the anal canal via efferent pathways.

Spring-mediated distraction enterogenesis has shown success in intestinal lengthening, with spring confinement achieved by external plication with sutures to reduce the lumen diameter at both ends of the intestinal segment. Endoscopic spring placement would minimize the morbidity associated with device insertion. This study investigates the use of submucosal injection of engineered hydrogel to temporarily confine a compressed spring within an intestinal segment. Engineered hydrogels were composed of hyaluronic acid (HA) alone or HA with elastin-like protein (HELP). To simulate endoscopic injection in six juvenile pigs, hydrogel was injected into the submucosa in everted jejunum, followed by the placement of a gelatin-encapsulated, compressed nitinol spring. The jejunum was then unfolded over the spring, and hydrogel was injected distally into the submucosa. Sutures were placed as fiducial markers. After 7 days on a liquid diet, the pigs were euthanized, and their intestinal segments were analyzed for lengthening and histological changes. The spring-containing jejunal segments expanded in all animals, lengthening to 132% in the HA group and 188% in the HELP group. HELP hydrogels exhibited slower biodegradation than HA-only hydrogels. Histological analysis showed increased crypt width and decreased crypt density in the spring-containing segments compared to controls. Hydrogel effectively provides temporary spring confinement within intestinal segments without adverse effects. The mechanical stimulation from the spring induces crypt fission, expanding the intestinal epithelium. These results support the feasibility of gel-enabled, spring-mediated distraction enterogenesis for intestinal lengthening.

There is an increasing demand for multimodal sensing and stimulation bioelectronic fibres for both research and clinical applications1,2. However, existing fibres suffer from high rigidity, low component layout precision, limited functionality and low density of active components. These limitations arise from the challenge of integrating many components into one-dimensional fibre devices, especially owing to the incompatibility of conventional microfabrication methods (for example, photolithography) with curved, thin and long fibre structures2. As a result, limited applications have been demonstrated so far. Here we use 'spiral transformation' to convert two-dimensional thin films containing microfabricated devices into one-dimensional soft fibres. This approach allows for the fabrication of high-density multimodal soft bioelectronic fibres, termed Spiral-NeuroString (S-NeuroString), while enabling precise control on the longitudinal, angular and radial positioning and distribution of the functional components. Taking advantage of the biocompatibility of our soft fibres with the dynamic and soft gastrointestinal system, we proceed to show the feasibility of our S-NeuroString for post-operative multimodal continuous motility mapping and tissue stimulation in awake pigs. We further demonstrate multi-channel single-unit electrical recording in mouse brain for up to 4 months, and a fabrication capability to produce 1,280 channels within a 230-μm-diameter soft fibre. Our soft bioelectronic fibres offer a powerful platform for minimally invasive implantable electronics, where diverse sensing and stimulation functionalities can be effectively integrated.

In 2017, our hospital transitioned to a standardized post-KPE high-dose steroid protocol. We sought to compare outcomes for biliary atresia (BA) for this protocol against historical treatment with no or low-dose steroids. Between 2006 and 2024, 50 children underwent KPE for BA. Patients were stratified into three groups: no steroids, low-dose steroids (defined by a starting dose of 2–4 mg/kg/day), and high-dose steroids (starting dose of 10 mg/kg/day). After the initial taper, patients in both steroid groups continued with 2 mg/kg/day for 4–6 weeks. 8 patients received no steroids, 21 received low-dose steroids, and 21 received high-dose steroids. Patients treated with high-dose steroids had significantly greater readmission rates compared to the no or low-dose steroid cohorts. There was an overall trend towards improved native liver survival for the high-dose steroid cohort at 1 and 5 years after KPE. There was no significant difference in rates of cholangitis, though the high-dose cohort tended to present with cholangitis within 30 days of discharge. We describe the 18-year experience of adjuvant steroid use in BA patients at a single institution. We show improved early postoperative biliary drainage with high-dose steroid use and identify a trend towards improved native liver survival with high-dose steroids.

OBJECTIVE:To quantify liver fibrosis in infants with biliary atresia (BA) through automated analysis of collagen extracellular matrix (ECM) ultrastructure in index liver biopsies and use a composite fibrosis architecture score to predict native liver survival. BACKGROUND:Despite early management with Kasai portoenterostomy, BA remains the leading indication for pediatric liver transplantation. There is no established method for quantitatively assessing liver fibrosis in patients with BA, and no factors to accurately predict which patients will ultimately require transplantation early versus late. METHODS:Index liver biopsies from 12 patients with BA who underwent Kasai portoenterostomy at our institution were retrieved from our pathology archives. Liver biopsies from control patients without BA and with minimal liver fibrosis on biopsy were used as "Low Fibrosis Controls". Biopsies from BA patients who underwent upfront liver transplantation were used as "High Fibrosis Controls". Masson's trichrome-stained biopsies were scanned, tiled, binarized, and quantified for 147 ECM features. These features were reduced by Uniform Manifold Approximation and Projection. Pseudotime analysis was applied to summarize global variations in architecture and assign BA-ECM scores to all biopsy images in an unsupervised manner. A retrospective chart review was then performed to correlate clinical characteristics with BA-ECM score. BA-ECM scores were compared between BA patients who had been actively listed for liver transplantation during the study period and those who had not. RESULTS:BA-ECM score, a multidimensional fibrosis architecture score, was significantly higher for biopsies from listed patients compared with non-listed patients (35.9 vs 22.9, * P < 0.0001). High BA-ECM score was characterized by thick, patchy, irregular ECM, whereas low BA-ECM score was associated with large-volume thin, porous collagen fibers. Survival analysis stratified by the third quartile BA-ECM score of all data points demonstrated a significant difference in native liver survival (* P = 0.02). CONCLUSIONS:We present the application of an automated ECM ultrastructure analysis tool designed to capture and quantify 147 aspects of fibrotic tissue heterogeneity. These manifold features are summarized using a multidimensional BA-ECM score that could be used to prognosticate disease course for patients with BA.

Introduction:Management of intestinal failure involves supplemental nutrition and complication minimization to achieve enteral autonomy. Previous research to identify prognostic factors in IF focused on the small bowel, yet little work has been done to associate the colon with IF outcomes. We hypothesize that like small bowel dilation, colonic dilation is associated with intestinal failure morbidity. We also investigate whether a standardized colonic diameter ratio differs from the maximal colonic width in predicting outcomes in children with intestinal failure. Material and methods:We conducted a retrospective cohort study of all children with gastrointestinal contrast imaging and intestinal failure in our intestinal rehabilitation program between 2013 and 2023. Medical records were reviewed for patient information and imaging review. A colonic diameter ratio was calculated by dividing the maximal colonic diameter by the height of the fifth lumbar vertebra. Results:Thirty-two patients were assessed based on colonic width and colonic diameter ratio. The median age of patients was 7.0 years (IQR 3 - 11 years). Maximum colonic width correlated positively with age, catheter-associated bloodstream infection, and parenteral nutrition duration. Colonic diameter ratio, on the other hand, did not show a significant correlation with age or parenteral nutrition duration, but had significant positive correlations with catheter-associated bloodstream infection. Conclusion:Maximum colonic width was significantly associated with increased morbidity in patients with intestinal failure. Increased colonic dilation after normalization by the size of the patient is associated with increased central line associated bloodstream infections.

Background and Aim Loss of functional small intestine in short bowel syndrome results in profound nutrient malabsorption and diarrhea. We previously developed an expandable spring device that triggers intestinal lengthening. The aim of this study was to assess the functional ion transport capabilities of spring-lengthened jejunum. Method Mini-Yucatan pigs underwent laparotomy and spring placement in the jejunum. After 7 days, pigs were euthanized to retrieve spring-lengthened and distal control jejunum. Tissues were mounted in Ussing chambers to measure transepithelial resistance and short-circuit current (Isc). Forskolin and carbachol were used to measure cAMP- and calcium-mediated anion secretory capacities, and glucose was used for absorptive capacity. Tissue samples were then preserved for histopathology and immunochemistry. Results Intestinal segments exposed to springs became longer at euthanasia. Baseline transepithelial resistance and Isc were similar between spring-lengthened and control jejunum. Forskolin, carbachol, and glucose increased Isc above baseline in both lengthened and control jejunum. While glucose-stimulated Isc was similar between lengthened and control jejunum, forskolin- and carbachol-stimulated Isc were reduced. Spring-lengthened jejunum had greater mucosal area with deeper crypts and taller villi, but similar crypt: villus ratios as control jejunum. Spring-lengthened jejunum had thicker muscularis propria compared to controls. Conclusion Spring-lengthening of small bowel does not disrupt mucosal barrier function, based on histological and functional assessments. While spring-lengthened jejunum showed reduced transepithelial secretory function, its absorptive function appears intact. This change may be related to early tissue remodeling during distraction enterogenesis and further investigation into the cellular changes induced by distraction enterogenesis are ongoing.

Abstract The intestinal epithelium is a dynamic barrier that allows the selective exchange of ions, hormones, proteins, and nutrients. To accomplish this, the intestinal epithelium adopts a highly columnar morphology which is partially lost in submerged culturing systems. To achieve this, small intestinal tissue samples were utilized to obtain human intestinal crypts to form enteroids. The Transwell system was subsequently employed to form a monolayer of cells that was cultured in either the submerged condition or the air–liquid Interface (ALI) condition. We found that the human intestinal monolayer under the ALI condition exhibited morphology more similar to the normal intestinal epithelium. F‐actin localization and brush border formation were observed apically, and the integrity of the tight junctions was preserved in the ALI condition. Fewer apoptotic cells were observed in the ALI conditions as compared to the submerged conditions. The monolayer of cells expressed a higher level of secretory cell lineage genes in the ALI condition. The ALI condition positively contributes toward a more differentiated phenotype of epithelial cells. It serves as an amplifier that enhances the existing differentiation cue. The ALI system provides a more differentiated platform to study intestinal function compared to submerged conditions.

Background Distraction enterogenesis lengthens the intestine through applied mechanical stress. The Hedgehog pathway (Hh) is responsible for intestinal tract development and directing the multi-layer patterning of the intestinal lumen. This study investigates the alteration in the principal components of this pathway in spring-mediated colonic lengthening. Methods Samples from the murine cecal lengthening model were used to study Hh alteration during the cecal lengthening process. Primary components of this pathway were analyzed using RT-qPCR and immunostaining after 7 and 14 days of force application. The spring-mediated lengthened segments were compared to untreated control segments within each animal. Results The spring-treated segments showed a 50% increase in length. There was a significant increase in the expression of the Desert Hedgehog ligand as opposed to the Sonic Hedgehog and Indian Hedgehog ligands. Additionally, the downstream targets of the pathway, Gli1, Gli2, and Gli3, were significantly overexpressed. The highest alterations in these components occurred at the earlier time point, after 7 days. Conclusions These findings highlight the contribution of the conserved Hedgehog developmental pathway during mechanical force-induced cecal lengthening, primarily through the Desert Hedgehog ligand. These data suggest that the Desert Hedgehog pathway may serve as therapeutic targets for intestinal regeneration.

In vitro models of autoimmunity are constrained by an inability to culture affected epithelium alongside the complex tissue-resident immune microenvironment. Coeliac disease (CeD) is an autoimmune disease in which dietary gluten-derived peptides bind to the major histocompatibility complex (MHC) class II human leukocyte antigen molecules (HLA)-DQ2 or HLA-DQ8 to initiate immune-mediated duodenal mucosal injury1-4. Here, we generated air-liquid interface (ALI) duodenal organoids from intact fragments of endoscopic biopsies that preserve epithelium alongside native mesenchyme and tissue-resident immune cells as a unit without requiring reconstitution. The immune diversity of ALI organoids spanned T cells, B and plasma cells, natural killer (NK) cells and myeloid cells, with extensive T-cell and B-cell receptor repertoires. HLA-DQ2.5-restricted gluten peptides selectively instigated epithelial destruction in HLA-DQ2.5-expressing organoids derived from CeD patients, and this was antagonized by blocking MHC-II or NKG2C/D. Gluten epitopes stimulated a CeD organoid immune network response in lymphoid and myeloid subsets alongside anti-transglutaminase 2 (TG2) autoantibody production. Functional studies in CeD organoids revealed that interleukin-7 (IL-7) is a gluten-inducible pathogenic modulator that regulates CD8+ T-cell NKG2C/D expression and is necessary and sufficient for epithelial destruction. Furthermore, endogenous IL-7 was markedly upregulated in patient biopsies from active CeD compared with remission disease from gluten-free diets, predominantly in lamina propria mesenchyme. By preserving the epithelium alongside diverse immune populations, this human in vitro CeD model recapitulates gluten-dependent pathology, enables mechanistic investigation and establishes a proof of principle for the organoid modelling of autoimmunity.

Background: Pilonidal disease begins in puberty when males and females have different sex hormone expression. We hypothesize that sex differences can lead to clinical differences in pilonidal disease. Methods: Patient demographics, Fitzpatrick skin type, hair characteristic, presentation, pain score, recurrence were recorded 2019–2022. All patients underwent regular epilation+/-pit excision. Excised pits were stained for estrogen receptor, progesterone receptor, and androgen receptor. Results: 237 patients (110F, 127 M) were followed 351±327days. Females present younger than males (17.5 ± 3.9 vs.18.4 ± 3.6years). While no sex-related differences noted in recurrence rate (4.5% vs.7.9 %) or skin type, there were significant sex-related differences in hair amount, thickness, density, and color. More males had granuloma than females (34% vs.12 %): 63 % granuloma were located left of midline, 30 % right, 7 % center. More males than females presented with drainage (67% vs.35 %). Significant differences were noted in patient-reported pain: Females’ mean initial pain score was higher than that of males’ (5.6 ± 2.5 vs.4.7 ± 2.2). 35 % females had menstruation-related gluteal cleft pain (MRGCP), not associated with recurrence or pads/tampons use. Females on contraceptives (15.5 %females) had lower pain score than those who were not (3.9 ± 2.7 vs.5.8 ± 2.4) and none of these females reported MRGCP. Patients with drainage had lower pain score than those without (4.5 ± 2.4 vs.5.8 ± 2.2). Excised pits from females with MRGCP had higher proportion of fibroblasts stain positive for estrogen receptor and androgen receptor compared to those without MRGCP (28.4 %±9.0 %vs.14.4 %±6.5 %, 18.0 %±11.7 %vs.6.9 %±9.0 %, respectively). Conclusions: Male and female pilonidal patients differ in pain intensity, drainage, and granuloma formation. More fibroblasts with estrogen receptor and androgen receptor expression is a potential mechanism for MRGCP that is ameliorated by contraceptive use.

Background Stomach, small intestine, and colon have distinct patterns of contraction related to their function to mix and propel enteric contents. In this study, we aim to measure gut myoelectric activity in the perioperative course using external patches in an animal model. Methods Four external patches were placed on the abdominal skin of female Yucatan pigs to record gastrointestinal myoelectric signals for 3 to 5 d. Pigs subsequently underwent anesthesia and placement of internal electrodes on stomach, small intestine, and colon. Signals were collected by a wireless transmitter. Frequencies associated with peristalsis were analyzed for both systems for 6 d postoperatively. Results In awake pigs, we found frequency peaks in several ranges, from 4 to 6.5 cycles per minute (CPM), 8 to 11 CPM, and 14 to 18 CPM, which were comparable between subjects and concordant between internal and external recordings. The possible effect of anesthesia during the 1 or 2 h before surgical manipulation was observed as a 59% (±36%) decrease in overall myoelectric activity compared to the immediate time before anesthesia. The myoelectrical activity recovered quickly postoperatively. Comparing the absolute postsurgery activity levels to the baseline for each pig revealed higher overall activity after surgery by a factor of 1.69 ± 0.3. Conclusions External patch measurements correlated with internal electrode recordings. Anesthesia and surgery impacted gastrointestinal myoelectric activity. Recordings demonstrated a rebound phenomenon in myoelectric activity in the postoperative period. The ability to monitor gastrointestinal tract myoelectric activity noninvasively over multiple days could be a useful tool in diagnosing gastrointestinal motility disorders.

The intestinal muscle layers execute various gut wall movements to achieve controlled propulsion and mixing of intestinal content. Engineering intestinal muscle layers with complex contractile function is critical for developing bioartificial intestinal tissue to treat patients with short bowel syndrome. Here, the first demonstration of a living intestinal muscle patch capable of generating three distinct motility patterns and displaying multiple digesta manipulations is reported. Assessment of contractility, cellular morphology, and transcriptome profile reveals that successful generation of the contracting muscle patch relies on both biological factors in a serum-free medium and environmental cues from an elastic electrospun gelatin scaffold. By comparing gene-expression patterns among samples, it is shown that biological factors from the medium strongly affect ion-transport activities, while the scaffold unexpectedly regulates cell-cell communication. Analysis of ligandreceptor interactome identifies scaffold-driven changes in intercellular communication, and 78% of the upregulated ligand-receptor interactions are involved in the development and function of enteric neurons. The discoveries highlight the importance of combining biomolecular and biomaterial approaches for tissue engineering. The living intestinal muscle patch represents a pivotal advancement for building functional replacement intestinal tissue. It offers a more physiological model for studying GI motility and for preclinical drug discovery.

Background: It is well known that small bowel length is a dominant prognostic indicator inpatients with short bowel syndrome (SBS). The relative importance of jejunum, ileum, and colon is less well defined in children with SBS. Here we review the outcome of children with SBS with respect to the type of remnant intestine.Methods: A retrospective review of 51 children with SBS was conducted at a single institution. The duration of parenteral nutrition use was the main outcome variable. The length of the remaining intestine as well as the type of intestine were recorded for each patient. Kaplan-Meier analyses were conducted to compare the subgroups.Results: Children with greater than 10% expected small bowel length or more than 30 cm of small bowel achieved enteral autonomy faster than those with less. The presence of ileocecal valve enhanced the ability to wean from parenteral nutrition. The presence of ileum significantly enhanced the ability to wean from parenteral nutrition. Patients with the entire colon also achieved enteral autonomy sooner than those with partial colon.Conclusions: The preservation of ileum and colon is important in patients with SBS. Approaches to preserve or lengthen ileum and colon may be beneficial for these patients. Level of evidence: IV.