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Short bowel syndrome is the most common reversible cause of intestinal failure. Most of the children are started on parenteral nutrition (PN) after surgery to enable growth and allow time for intestinal adaptation. This is a process whereby the shorter length of bowel is able to achieve complete function as if the entire length of bowel is present. With management advances, most children with short bowel syndrome can discontinue PN and establish full enteral feeds. This article mainly focuses on the complications of short bowel syndrome that need to be avoided for the child to achieve intestinal adaptation, establish on enteral feeds/oral diet and achieve enteral autonomy. [ABSTRACT FROM AUTHOR]

Loss of venous access is threatening for patients with intestinal failure (IF) under long-term parenteral nutrition (PN). We aimed to identify the incidence of central venous catheter (CVC) complications, compare different devices, and analyze interventional recanalizing procedures to restore the patency of occluded CVCs. For this retrospective cohort study, patient data from a prospective IF database spanning 16 years was analyzed at a tertiary referral center. Catheter dwell times (CDTs) were distinguished by Kaplan–Meier survival analysis and subgroup analyses were performed for different CVC types (tunneled/port catheters). Specific complications (occlusion, catheter-related infection (CRI), displacement, and material defect) were analyzed. Explantation rates and CDTs were compared. Overall, 193 CVCs in 77 patients with IF under PN could be enrolled (62.524 "CVC-days"). Broviac type "B" was found to be significantly superior to type "A" regarding occlusion, CRI, and material defects (log-rank test: p = 0.05; p = 0.026; p = 0.005 respectively). Port catheters were displaying the highest incidence of CRI (2.13 events/1000 catheter days). Interventional catheter recanalization was performed 91 times and significantly increased the CDT from a median of 131 days (IQR: 62; 258) to 389 days (IQR: 262; 731) (Mann-Whitney-U-test: p= <0.001) without increasing complications. Different complication rates and CDT were seen depending on CVC type. Tunneled catheters were significantly superior concerning CRI. Interventional catheter recanalization is a viable alternative to fibrinolytics to restore CVC patency, but long-term patency data is scarce. [ABSTRACT FROM AUTHOR]

Fecal microbiota was investigated in adult patients with chronic intestinal failure (CIF) due to short bowel syndrome (SBS) with jejunocolonic anastomosis (SBS-2). Few or no data are available on SBS with jejunostomy (SBS-1) and CIF due to intestinal dysmotility (DYS) or mucosal disease (MD). We profiled the fecal microbiota of various pathophysiological mechanisms of CIF. Cross-sectional study on 61 adults with CIF (SBS-1 30, SBS-2 17, DYS 8, MD 6). Fecal samples were collected and profiled by 16S rRNA amplicon sequencing. Healthy controls (HC) were selected from pre-existing cohorts, matched with patients by sex and age. Compared to HC, SBS-1, SBS-2 and MD patients showed lower alpha diversity; no difference was found for DYS. In beta diversity analysis, SBS-1, SBS-2 and DYS groups segregated from HC and from each other. Taxonomically, the CIF groups differed from HC even at the phylum level. In particular, CIF patients' microbiota was dominated by Lactobacillaceae and Enterobacteriaceae , while depleted in typical health-associated taxa belonging to Lachnospiraceae and Ruminococcaceae. Notably, compositional peculiarities of the CIF groups emerged. Furthermore, in the SBS groups, the microbiota profile differed according to the amount of parenteral nutrition required and the duration of CIF. CIF patients showed marked intestinal dysbiosis with microbial signatures specific to the pathophysiological mechanism of CIF as well as to the severity and duration of SBS. [ABSTRACT FROM AUTHOR]

• Cystic fibrosis (CF) features bile acids, fat, and cholesterol malabsorption. • Malabsorption is associated with decreased intestinal nuclear receptor signaling. • The laxative PEG increased bile acids, fat, and cholesterol absorption in CF mice. • Concomitantly, PEG improved intestinal nuclear receptor signaling in CF mice. • PEG decreased hepatic inflammation and cholesterol synthesis in CF mice. Cystic Fibrosis (CF) is a genetic disease affecting multiple organs, primarily the lungs and digestive system. Improved pulmonary management significantly improved life expectancy of CF patients. As a result, extrapulmonary manifestations, including gastrointestinal and liver-related symptoms, have become more relevant. We previously reported that the osmotic laxative polyethylene glycol (PEG), which hydrates the CF gut, decreased fecal bile acid loss in a CF knockout mouse model. In the current study we investigated the effect of PEG on intestinal fat and cholesterol absorption and on CF-related liver features in a CF mouse model with the most common CF-causing mutation. CftrΔF508/ΔF508 (n=13) and wild-type (WT) (n=12) mice were treated with PEG for 2 weeks. The intestinal and hepatic effects of PEG were assessed by analysis of intestinal bile acid, cholesterol, and fat fluxes, transcriptome analysis as well as histology. PEG improved intestinal malabsorption of bile acids, fat, and cholesterol in CftrΔF508/ΔF508 mice. Transcriptome analysis showed that PEG partially restored the intestinal signaling of nuclear receptors RXR, FXR, and CAR/PXR, which are involved in bile acid and xenobiotic metabolism. PEG also reduced liver inflammation in CF mice as assessed by transcriptome and histological analyses. PEG, a non-absorbable osmotic laxative, improved intestinal nutrient absorption, intestinal bile acid and xenobiotic signaling, as well as CF-related liver features. These findings highlight the potential for osmotic laxation to improve gastrointestinal complications of CF in humans. [Display omitted] [ABSTRACT FROM AUTHOR]

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions. [ABSTRACT FROM AUTHOR]

Schizophrenia is a mental health disorder that often includes psychomotor disturbances, impacting how individuals adjust their motor output based on the cause of motor errors. While previous motor adaptation studies on individuals with schizophrenia have largely focused on large and consistent perturbations induced by abrupt experimental manipulations, such as donning prism goggles, the adaptation process to random perturbations, either caused by intrinsic motor noise or external disturbances, has not been examined – despite its ecological relevance. Here, we used a unified behavioral task paradigm to examine motor adaptation to perturbations of three causal structures among individuals in the remission stage of schizophrenia, youth with ultra-high risk of psychosis, adults with active symptoms, and age-matched controls. Results showed that individuals with schizophrenia had reduced trial-by-trial adaptation and large error variance when adapting to their own motor noise. When adapting to random but salient perturbations, they showed intact adaptation and normal causal inference of errors. This contrasted with reduced adaptation to large yet consistent perturbations, which could reflect difficulties in forming cognitive strategies rather than the often-assumed impairments in procedural learning or sense of agency. Furthermore, the observed adaptation effects were correlated with the severity of positive symptoms across the diagnosis groups. Our findings suggest that individuals with schizophrenia face challenges in accommodating intrinsic perturbations when motor errors are ambiguous but adapt with intact causal attribution when errors are salient. [ABSTRACT FROM AUTHOR]

• Therapeutic management, benefit/risk balance and delivery planning of suspected IUGR is sometimes difficult. • This study introduces an innovative predictive model for adverse neonatal adaptation in fetuses with severe intrauterine growth restriction after 34 gestational weeks. • Demonstrating feasibility, the model offers a quantifiable risk assessment with satisfactory performance and acceptable uncertainty. • This model could potentially aid decision-making and couple information. To establish a predictive model for adverse immediate neonatal adaptation (INA) in fetuses with suspected severe fetal growth restriction (FGR) after 34 gestational weeks (GW). Methods. We conducted a retrospective observational study at the University Hospitals of Strasbourg between 2000 and 2020, including 1,220 women with a singleton pregnancy and suspicion of severe FGR who delivered from 34 GW. The primary outcome (composite) was INA defined as Apgar 5-minute score <7, arterial pH <7.10, immediate transfer to pediatrics, or the need for resuscitation at birth. We developed and tested a logistic regression predictive model. Results. Adverse INA occurred in 316 deliveries. The model included six features available before labor: parity, gestational age, diabetes, middle cerebral artery Doppler, cerebral-placental inversion, onset of labor. The model could predict individual risk of adverse INA with confidence interval at 95 %. Taking an optimal cutoff threshold of 32 %, performances were: sensitivity 66 %; specificity 83 %; positive and negative predictive values 60 % and 87 % respectively, and area under the curve 78 %. Discussion. The predictive model showed good performances and a proof of concept that INA could be predicted with pre-labor characteristics, and needs to be investigated further. [ABSTRACT FROM AUTHOR]

Acid-base disturbances are common in short bowel (SB) patients due to increased intestinal bicarbonate loss. However, the resulting systemic acid load has not been quantified. Base excess is used to monitor metabolic acid-base disturbances but inadequately reflects the acid load. Our aim was to investigate the systemic acid/base load in SB-patients to obtain quantitative estimates to guide the composition of parenteral support. We calculated total acid load in SB patients by summing 24-h urinary net acid excretion (NAE) and the provision of base equivalents in parenteral support. We then compared differences among anatomical SB-types: jejunostomy (SB-J), jejunocolostomy (SB-JC), and jejunoileostomy (SB-JIC). 47 urine samples from 34 SB patients were analyzed for bicarbonate (HCO 3 -), ammonium (NH 4 +), and titratable acid (TA) concentrations. NAE was calculated as (TA + NH 4 +) - HCO 3 -. Mixed-effects repeated-measures models were used to statistically examine differences between SB-types and associations with parenteral nutrition and NAE. A healthy cohort served as control. In comparison to SB-J, SB-JC patients had a 4.1 mmoL/l lower base excess (95% CI: −6.3 to −1.8) and an 84.5 mmol/day higher total acid load (CI: 41.3 to 127.7). There were no significant differences between SB-JIC and SB-J regarding base excess, NAE, or total acid load. Higher amounts of infused acetate, sodium, and chloride, but not the acetate/chloride ratio, were associated with lower NAE and higher base excess. Due to increased colonic bicarbonate loss, patients with SB-JC have a ∼4.4-fold higher acid load than healthy controls. The ion transport mechanisms mediating this bicarbonate loss from the remaining colon need further experimental investigation. NAE could be a useful tool to adjust base infusion in SB. [ABSTRACT FROM AUTHOR]

Spiritual pain and financial distress are two important dimensions of cancer care that are often overlooked. Both dimensions can have a significant impact on the quality of life of patients with cancer and their families. This study conducted a cross-cultural adaptation, feasibility study, and psychometric properties of the Edmonton Symptom Assessment System-Financial and Spiritual (ESAS-FS) in a Spanish-speaking population with advanced cancer. The ESAS-FS is a patient-reported outcome measure that assesses 12 symptoms, including spiritual pain and financial distress. In the cross-cultural adaptation process, the terms "spiritual pain" and "financial distress" were refined to "sufrimiento espiritual" and "preocupación por asuntos económicos" respectively, with strong professional consensus and high patients' acceptancy (relevant questions 80%, appropriate terms 91%). A cohort of 100 onco-hematologic patients revealed that 70% experienced spiritual pain (mean 2.9/10), while 49% reported financial distress (mean 2.2/10). Symptomatic analyses illustrated significant associations of spiritual pain with various symptoms like fatigue, drowsiness, and depression. Similarly, financial distress correlated notably with drowsiness, depression, and anxiety. Moreover, a distinct correlation was observed between spiritual pain and financial distress. The findings of this study suggest that the ESAS-FS is a valuable tool for assessing spiritual pain and financial distress in Spanish-speaking patients with advanced cancer. The tool can be used to identify patients who are experiencing these dimensions of distress and to provide them with appropriate care. [ABSTRACT FROM AUTHOR]

To clinically and radiographically evaluate patient-specific titanium meshes via a trans -antral approach for correction of enophthalmos and orbital volume in patients with recent unilateral orbital floor fracture. Seven patients with unilateral orbital floor fractures received patient-specific titanium meshes that were designed based on a mirror-image of the contralateral intact orbit. The patient-specific implants (PSIs) were inserted via a trans -antral approach without endoscopic assistance. The patients were evaluated clinically for signs of diplopia and restricted gaze as well as radiographically for enophthalmos and orbital volume correction. Diplopia was totally resolved in two of the three patients who reported diplopia in the upward gaze. Whereas enophthalmos significantly improved in all but two patients, with a mean value of 0.2229 mm postoperatively compared to 0.9914 mm preoperatively. CT scans showed excellent adaptation of the PSIs to the orbital floor with a mean reduction of the orbital volume from 29.59 cc to 27.21 cc, a mean of 0.6% smaller than the intact orbit. It can be concluded that the proposed PSI can offer good reconstruction of the orbital floor through an isolated intraoral transantral approach with minimal complications. It could of special benefit in extensive orbital floor fractures. [ABSTRACT FROM AUTHOR]

This study evaluated the quality of life (QoL) in patients who have recovered from surgical necrotizing enterocolitis (NEC). This is a cross-sectional study conducted in a tertiary centre and patients who have received surgery for NEC between 2000 and 2014 were invited to participate. The Pediatric Quality of Life Inventory Generic (PedsQL™) Core Scale Version 4.0 was used as the assessment tool. Values were reported as median (interquartile rage) and compared with age-matched controls. During the study period, 90 patients were eligible for the study and 29 patients have completed the survey. There was no gender difference and the median age was 10 years (9–13 years). Nine patients have suffered from short bowel syndrome (SBS) as a result of the surgery. For the QoL assessment, 17 participants have completed both parent proxy and child-rated survey; 11 completed the parent-rated survey and 1 completed child-rated survey only. The scores for parent-rated survey were - overall: 86.4 (70.7–92.7); physical: 95.3 (83.6–100) and psychosocial: 82.5 (66.3–90.4). The scores for child-rated survey were – overall: 82.1 (73.4–96.2); physical: 96.9 (90.6–99.2) and psychosocial: 81.7 (64.2–95.8). Regarding the impact of previous SBS on the QoL, there were no significant difference in the overall score for both parent proxy and child-rated survey (SBS-ve vs + ve) (parent-rated: 87.5 vs 85.3, p = 0.849; child-rated: 81.0 vs 88.0, p = 0.503). There were also no differences in physical and psychosocial assessments (parent-rated: [physical] 95.3 vs 95.3, p = 0.267; [psychosocial] 84.2 vs 80.0, p = 0.274; child-rated: [physical] 95.3 vs 96.9, p = 0.395; [psychosocial] 79.2 vs 87.5, p = 0.611). The QoL in long-term survivors of surgical NEC without major medical illnesses is comparable to normal population. However, they may have a lower psychosocial well-being that should be addressed. Previous history of SBS does not have a significant impact on the future QoL. III. [ABSTRACT FROM AUTHOR]

The PEARL study is a phase 2 multi-centre trial for good prognosis HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, currently open in the UK. PEARL is investigating the dosimetric impact of re-planning a radical radiotherapy plan midway through a course of treatment, based upon the biological response of the primary GTV on 18 FDG PET-CT. With the wider availability of proton beam therapy in the form of Intensity Modulated Proton Therapy (IMPT) as a potential option for radiotherapy in the management of OPSCC, in addition to substantial cost implications, improving methods to determine the patients who will benefit most from IMPT is required. The organ sparing benefits of IMPT are well documented. This modelling planning study investigated whether the benefits of proton therapy can be improved by applying biological response-based adaptation as per the PEARL study planning method. Objectives: 1. Investigate the dosimetric impact of IMPT by comparing mean dose received by swallowing OARs (SWOARs) between non-adaptive VMAT and non-adapted IMPT plans 2. Investigate the dosimetric impact of adaptation by comparing dose received by SWOARs between non-adaptive IMPT and adapted IMPT plans 3. Investigate the relative dosimetric impact of adaptation by comparing dose received by SWOARs between adaptive VMAT and IMPT plans 4. Identify whether adaptation as per the PEARL Study protocol would influence the delta normal tissue complication probability (ΔNTCP) threshold for proton beam therapy funding in The Netherlands Anonymized patient datasets were used to model VMAT and IMPT plans using RayStation and optimised for SWOARs. The following plans were generated: 1. 'NON-ADAPTIVE': Manually planned non-adapted VMAT 2. 'ADAPTIVE': Manually planned adapted VMAT 3. 'NON-ADAPTIVE_PROTON': Manually planned non-adapted IMPT 4. 'ADAPTIVE_PROTON': Manually planned adapted IMPT NTCP calculations for dysphagia risk we performed using the validated dysphagia model described by Christianen et al (1). Individual calculations were performed on each case comparing adapted and non-adapted VMAT plans to non-adapted IMPT plans to explore whether they reached the threshold for proton beam treatment funding as per The Netherlands scheme. Mean dose to the superior pharyngeal constrictor muscle and the supraglottis was entered into the following calculation: 1/NTCP = (1+ e)– s where s = -6.09 + (mean dose to the superior pharyngeal constrictor muscle x 0.057) + (mean dose to the supraglottis × 0.037) All cases had a reduction in their total mean dose to SWOARs, adapted as per PEARL, and planned with IMPT. The magnitude of impact was ranked in the same order for all cases, with optimisation reducing the total mean dose the least, and adapted IMPT the most. Cases 1 and 2, and Cases 3 and 4, demonstrated similar total mean dose reductions despite having different degrees of biological GTV reduction on the iPET-CT. Adaptation had the greatest impact on Cases 2 and 3 for both VMAT and IMPT plans. [Display omitted] The NTCP differences between non-adaptive VMAT plans and non-adaptive IMPT plans were >10% suggesting these cases would be candidates for IMPT funding as as per the National Indication Protocol Proton therapy (NIPP) - head and neck cancer criteria in The Netherlands. Whilst primarily limited by the small number of cases, we have demonstrated that IMPT markedly reduces doses to SWOARs compared to VMAT planning in line with widely published studies. We have also demonstrated that adaptation based on the biological response to the tumour after 2 weeks of chemoradiotherapy can further improve the tissue sparing already achieved with IMPT. This is the first study to demonstrate that SWOAR sparing by IMPT can be improved with biological response guided adaptive radiotherapy. Our results are in line with published data that IMPT can spare many head and neck SWOARs to a greater extent than VMAT in the treatment of oropharyngeal cancers. In the cases studied here, the impact of IMPT on the mean dose to SWOARs was greater than the impact of adaptation, when compared to standard VMAT planning. However, there may be additional dosimetric benefit when IMPT is adapted to tumour response during a course of radiotherapy treatment, particularly dose to more caudal SWOARs. In this small cohort, adaptation on VMAT plans was unlikely to have affected a decision for IMPT treatment as per the Netherlands NTCP-based algorithm. Further work with a larger cohort of patients, as well as real-time studies to collect prospective clinical data on xerostomia and dysphagia rates, is required to properly investigate the clinical advantages of adaptive IMPT. [ABSTRACT FROM AUTHOR]

• Recurrence of underlying disease after intestinal transplantation (IT) for short bowel syndrome should be taken into consideration when symptoms flare. • Magnifying endoscopy with narrow-band imaging with "VENCH scoring system" can differentiate between cute cellular rejection (ACR) and disease recurrence in patients with Crohn's disease after IT. • Early detection of ACR or disease recurrence by the VENCH score allows prompt treatment accordingly and results in favorable outcomes Crohn disease (CD) is one of the most common causes of short bowel syndrome and intestinal failure. Intestinal transplantation (IT) is sometimes needed for patients with CD who develop intestinal failure after multiple intestinal resections resulting from CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been few case reports concerning the endoscopic surveillance of patients with CD after IT. In this article, we present 2 patients with CD who underwent IT because of short bowel syndrome with intestinal failure. We administered posttransplantation immunosuppressants and conducted regular follow-up magnifying endoscopy with narrow-band imaging (ME-NBI). Both cases demonstrated favorable outcomes after surveillance with ME-NBI. In this report, we outline our post-IT follow-up strategies applying the VENCH scoring system, which is based on endoscopic features using ME-NBI to predict graft rejection. Our approach could effectively distinguish between acute cellular rejection and non-rejection, particularly disease recurrence of underlying CD. This study was approved by the institutional review board of Far Eastern Memorial Hospital (FEMH-105023-F). The patients provided written informed consent for publication. [ABSTRACT FROM AUTHOR]

A growing proportion of children with short bowel syndrome (SBS) remain dependent on long-term parenteral nutrition (PN). Teduglutide offers the potential for more children to decrease PN support and achieve enteral autonomy (EA), but at a significant expense. This study aims to assess the incremental costs of teduglutide plus standard of care compared to standard of care alone in weaning PN support per quality-adjusted life year (QALY) gained in children with SBS. This is a cost-utility analysis comparing teduglutide with standard of care alone in children with SBS. A microsimulation model of children with SBS on PN aged 1–17 years was constructed over a time horizon of six years, with a cycle length of one month. The study adopted the healthcare system and societal payer perspectives in Ontario, Canada. The health outcome measure was QALYs, with results expressed in terms of incremental costs and QALYs. Scenario analyses were performed to examine the effects of different time horizons, timing of teduglutide initiation, and modeling cost of teduglutide based on pediatric weight-dosing. Incremental healthcare system costs for teduglutide compared to standard of care were CAD$441,314 (95% CI, 414,006 to 441,314) and incremental QALYs were 1.80 (95% CI, 1.70 to 1.89) resulting in an incremental cost-effectiveness ratio (ICER) of CAD$285,334 (95% CI, 178,209 to 392,459) per QALY gained. Incremental societal costs were CAD$418,504 (95% CI, 409,487 to 427,522) and incremental societal QALYs were 1.91 (95% CI, 1.85 to 1.98) resulting in an ICER of CAD$261,880 (95% CI, 136,887 to 386,874) per QALY gained. Scenario analysis showed that teduglutide was cost-effective when it was started two years after intestinal resection (ICER CAD$48,741, 95% CI, 17,317 to 80,165) and when its monthly cost was adjusted using weight-based dosing, avoiding wastage of the remaining 5 mg dose vial (Teduglutide dominated over SOC as the less costly and most effective strategy). Although teduglutide was not cost-effective in weaning PN support in children with SBS, starting teduglutide once natural intestinal adaptation is reduced and adjusting its monthly cost to reflect cost by volume as dictated by weight-based dosing rendered the intervention cost-effective relative to standard of care. These results indicate the potential for clinicians to re-assess optimal time for initiation of teduglutide after intestinal resection, drug manufacturers to consider the use of multi-dose or paediatric-dose vials, and the opportunity for decision-makers to re-evaluate teduglutide funding. [ABSTRACT FROM AUTHOR]

• Gastrointestinal involvement is common in Duchenne Muscular Dystrophy. • Bowel dysmotility can manifest as life-threatening pseudo-obstruction or volvulus. • Cardiorespiratory co-morbidities can make surgical interventions high-risk. • Parenteral nutritional has a role in the management of this bowel dysmotility. Duchenne muscular dystrophy is a progressive muscle wasting disease caused by pathogenic variants in DMD. Gastrointestinal involvement is increasingly recognised in older patients and can manifest as life-threatening bowel dysmotility. We describe a series of adults with Duchenne muscular dystrophy who developed either severe colonic pseudo-obstruction or sigmoid volvulus requiring urgent assessment and intervention. The presentations varied in their clinical picture and outcomes, but together highlight the complexity of managing gastrointestinal complications in this cohort of patients. Key considerations include pre-existing cardiorespiratory compromise and the increased risk associated with surgery and general anaesthesia. We also outline a role for home parenteral nutrition in the long-term management of associated bowel dysmotility. [ABSTRACT FROM AUTHOR]

Short Bowel Syndrome (SBS) is the major cause of chronic intestinal failure (IF) and requires parenteral nutrition (PN). After bowel resection, some patients develop spontaneous intestinal adaptations and hyperphagia. Since promoting oral energy intake contributes to PN weaning, this study aims to characterize hyperphagia in patients with SBS and identify its determinants. This observational retrospective study included adult patients with SBS who were followed at an expert PN center between 2006 and 2019, with at least 2 separate nutritional assessments. Exclusion criteria were: active neoplasia, alternative treatment for IF or appetite-affecting medication. Resting energy expenditure (REE) was calculated for each patient using the Harris–Benedict equation. Food Intake Ratio (FIR) was calculated by dividing the highest caloric oral intake by REE and hyperphagia was defined as FIR >1.5. Among the 59 patients with SBS included in this study, 82.6% had a FIR >1.5, including 15.5% with a FIR >3. Protein supplied approximately 16% of total energy intake while fat and carbohydrates provided 36% and 48%, respectively. The FIR was independent of gender and whether patients received oral nutrition alone (n = 28) or combined with PN (n = 31). The FIR was also not associated with residual small bowel length, nor the proportion of preserved colon. However, it was negatively correlated with the body mass index (BMI) of these patients (r = −0.533, p < 0.001), whether they had PN support or not. Patients with either a jejuno-colonic (n = 31) or a jejuno-ileal anastomosis (n = 9), had a significantly higher FIR compared to those with an end-jejunostomy (n = 18) (p < 0.05). However, no difference was found in the proportion of calories provided by protein, fat and carbohydrate between the 3 patients groups divided according to the SBS anatomical type. A large majority of patients with SBS exhibited a hyperphagia regardless of PN dependence or bowel length, which was inversely correlated with BMI. The presence of the colon in continuity, thus in contact with the nutritional flow, seems to favor a higher oral intake which is beneficial for the nutritional autonomy of patients. This raises the question of a role of colonic microbiota and hormones in this behavior. Finally, this study also revealed an unexpected discrepancy between recommended energy intakes from protein, fat and carbohydrate and the actual intake of patients with SBS. [ABSTRACT FROM AUTHOR]

In 2016, ESPEN published the guideline for Chronic Intestinal Failure (CIF) in adults. An updated version of ESPEN guidelines on CIF due to benign disease in adults was devised in order to incorporate new evidence since the publication of the previous ESPEN guidelines. The grading system of the Scottish Intercollegiate Guidelines Network (SIGN) was used to grade the literature. Recommendations were graded according to the levels of evidence available as A (strong), B (conditional), 0 (weak) and Good practice points (GPP). The recommendations of the 2016 guideline (graded using the GRADE system) which were still valid, because no studies supporting an update were retrieved, were reworded and re-graded accordingly. The recommendations of the 2016 guideline were reviewed, particularly focusing on definitions, and new chapters were included to devise recommendations on IF centers, chronic enterocutaneous fistulas, costs of IF, caring for CIF patients during pregnancy, transition of patients from pediatric to adult centers. The new guideline consist of 149 recommendations and 16 statements which were voted for consensus by ESPEN members, online in July 2022 and at conference during the annual Congress in September 2022. The Grade of recommendation is GPP for 96 (64.4%) of the recommendations, 0 for 29 (19.5%), B for 19 (12.7%), and A for only five (3.4%). The grade of consensus is "strong consensus" for 148 (99.3%) and "consensus" for one (0.7%) recommendation. The grade of consensus for the statements is "strong consensus" for 14 (87.5%) and "consensus" for two (12.5%). It is confirmed that CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for the underlying gastrointestinal disease and to provide HPN support. Most of the recommendations were graded as GPP, but almost all received a strong consensus. [ABSTRACT FROM AUTHOR]

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases. The transepithelial transport-related proteins up-regulated within two disease-specific intestinal PC (IPC), which improved the transcytosis by exploiting the secretory pathways. Consequently, the disease-specific IPC endowed nanoparticles (NPs) with enhanced oral absorption. [Display omitted] [ABSTRACT FROM AUTHOR]

In short bowel syndrome, insufficient absorptive capacity of the remnant bowel may lead to metabolic and nutritional consequences including electrolyte disturbances, severe diarrhea and malnutrition. While intestinal failure requires parenteral nutrition, short bowel patients with intestinal insufficiency (SB/II) have achieved oral autonomy. The aim of this exploratory study was to assess the nutritional, muscular and functional status of orally compensated SB/II patients. 28 orally compensated SB/II patients with a mean of 46 months after termination of parenteral nutrition and 56 age- and sex-matched healthy controls (HC) were compared regarding anthropometric parameters, body composition using bioelectrical impedance analysis, handgrip strength and gait speed, blood parameters as well as nutritional intake and physical activity using validated questionnaires. Malnutrition and sarcopenia were diagnosed according to the criteria of the GLIM or EWGSOP2. SB/II patients had lower body mass index (BMI) and anthropometric parameters than HC but were within the normal weight range. The GLIM algorithm operationally diagnosed malnutrition in 39% (n = 11) of SB/II patients. Reduced skeletal muscle mass index and phase angle were rarely accompanied by a reduction of handgrip strength below cut-off values and the subsequent diagnosis of sarcopenia in SB/II patients (15%, n = 4). Compared to 11% of HC, 37% of SB/II patients had low physical activity level. Female SB/II patients had higher caloric and macronutrient intake. Caloric intake negatively correlated with body weight indicating compensatory hyperphagia in patients with lower body weight. Some of the SB/II patients showed signs of dehydration. Orally compensated SB/II patients are thinner than HC but have mostly normal BMI. Malnutrition is frequently diagnosed but may be overestimated due to the underlying malabsorption and its interplay with hyperphagia. Muscle mass is often reduced but is rarely accompanied by functional impairment leading to sarcopenia diagnosis. Thus, SB/II patients long term after termination of parenteral support may be malnourished but usually do not develop sarcopenia. [ABSTRACT FROM AUTHOR]

• ICG-FA is used to determine anastomotic perfusion rates, thereby reducing surgical complications and aiding in intraoperative decision-making in adults, but not yet extensively described in pediatric surgery. • This systematic review analyzes the current knowledge on usefulness of ICG for intestinal perfusion assessment in pediatric gastrointestinal surgery and its safety in neonates. • ICG might be useful for intraoperative intestinal perfusion assessment, perhaps even more than conventional clinical assessment. • The safety profile of ICG looks promising in neonates. Larger prospective studies are necessary to confirm these assumptions and seem warranted given the safety profile. Although ICG-FA may be valuable in assessing anastomotic perfusion, reliable data on its use in pediatric gastrointestinal surgery is lacking. This systematic review analyzes whether ICG is useful for intestinal perfusion assessment in pediatric gastrointestinal surgery and safe to use in neonates. Systematic searches of PubMed, EMBASE & MEDLINE and CENTRAL were performed (last conducted December 6, 2021). The main inclusion criteria were (1) use of ICG for intestinal perfusion assessment and (2) use of ICG in young infants. Exclusion criteria were lack of an English or Dutch full-text and MINORS quality score <60%. Data was presented in overview tables. The usefulness in pediatric gastrointestinal surgery was assessed by surgical outcome. Safety of ICG in neonates was assessed by complication or adverse event occurrence. Regarding intestinal perfusion assessment, four studies were included, reporting 45 patients (median age 1.5 years). ICG was considered useful for anastomotic blood flow evaluation and intraoperative determination of resection length. Regarding ICG safety in neonates, eight studies were included, reporting 46 infants (median age 24.9 days), of which 18 neonates. All but one studies reported the absence of complications or adverse events. Two studies reported subcutaneous dye retention, which fully disappeared within two weeks. Although the number of available studies is small, ICG might be useful for intraoperative intestinal perfusion assessment, perhaps even more than conventional clinical assessment. Furthermore, its safety profile looks promising in neonates. Larger prospective studies are necessary to confirm these assumptions and seem warranted given the safety profile. Since this is a systematic review, a Level of Evidence for clinical studies cannot be determined for this manuscript. [ABSTRACT FROM AUTHOR]

Intestinal transplantation (IT) and multivisceral transplantation (MVT) are curative therapies for patients with intestinal failure and severe complications associated with total parenteral nutrition. High levels of immunosuppression are required to prevent acute cellular rejection (ACR) from the bowel. Studies regarding pre-treatment, induction, and post-transplant therapy have improved graft acceptance, reducing immunosuppression doses and infectious complications. However, the low rate of IT and MVT and the small number of specialized centers have resulted in a limited number of evidence-based immunosuppression protocols. We reviewed immunosuppression in IT and MVT to draw useful conclusions regarding the best protocol strategies for the induction, maintenance, and management of ACR. A review was performed using the PubMed database. Articles on immunosuppression protocols in IT and MVT that addressed graft rejection, infection, or survival, published between 2006 and 2022, were selected. A total of 690 articles were selected. Two researchers applied the inclusion and exclusion criteria and selected 14 articles independently. For induction, thymoglobulin, alemtuzumab, and basiliximab are the most frequently used immunosuppressants for induction. Classic maintenance therapy consists of a combination of corticosteroids and tacrolimus. Methylprednisolone with an increased tacrolimus dose is used most frequently to manage ACR. Depending on the receptor response, such as thymoglobulin, infliximab, adalimumab, or bortezomib, other immunosuppressants should be considered. There have been great advances in IT and TMV immunosuppression. We conclude that the gold standard immunosuppressive protocol is triple therapy, comprising induction with thymoglobulin, maintenance with steroids for a few months, and tacrolimus and mycophenolate therapy. Innovative approaches for treating intestinal rejection episodes with more appropriate drugs, such as infliximab, adalimumab, or bortezomib, are necessary. [ABSTRACT FROM AUTHOR]

It is well known that small bowel length is a dominant prognostic indicator in patients 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. 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. 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. 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. IV. [ABSTRACT FROM AUTHOR]

Massive small bowel resection (SBR) is associated with liver injury and fibrosis. Efforts to elucidate the driving force behind hepatic injury have identified multiple factors, including the generation of toxic bile acid metabolites. Sham, 50% proximal, and 50% distal SBR were carried out in C57BL/6 mice to determine the effect of jejunal (proximal SBR) versus ileocecal resection (distal SBR) on bile acid metabolism and liver injury. Tissues were harvested at 2 and 10-week postoperative timepoints. When compared with 50% proximal SBR, mice that underwent distal SBR exhibited less hepatic oxidative stress as verified by decreased mRNA expression of tumor necrosis factor-α (TNFα , p ≤ 0.0001), nicotinamide adenine dinucleotide phosphate oxidase (NOX , p ≤ 0.0001), and glutathione synthetase (GSS , p ≤ 0.05). Distal SBR mice also exhibited a more hydrophilic bile acid profile with reduced abundance of insoluble bile acids (cholic acid (CA), taurodeoxycholic acid (TCA), and taurolithocholic acid (TLCA)), and increased abundance of soluble bile acids (tauroursodeoxycholic acid (TUDCA)). In contrast with proximal SBR, ileocecal resection alters enterohepatic circulation leading to reduced oxidative stress and promotes physiological bile acid metabolism. These findings challenge the notion that preservation of the ileocecal region is beneficial in patients with short bowel syndrome. Administration of selected bile acids may present potential therapy to mitigate resection-associated liver injury. III—Case-Control Study. • DDistal SBR and TUDCA supplementation decreases oxidative stress and SBR-associated hepatic injury. • Distal SBR and TUDCA supplementation have healthier bile acid profiles compared to proximal SBR. • Enterohepatic circulation has critical involvement in liver injury prevention, but distal SBR and TUDCA supplementation likely differ in the mechanism utilized to confer hepatoprotection. [ABSTRACT FROM AUTHOR]

Resection-associated liver steatosis, injury, and fibrosis is a devastating complication associated with massive small bowel resection (SBR). Peroxisome proliferator-activated receptor-alpha (PPARα) is a key regulator of intestinal lipid transport and metabolism whose expression is selectively increased after SBR. Here we asked if attenuating intestinal PPARα signaling would prevent steatosis and liver injury after SBR. Pparα was deleted selectively in adult mouse intestine using a tamoxifen-inducible Cre-LoxP breeding schema. Mice underwent 50% SBR. At 10 weeks post-operatively, metabolic phenotyping, body composition analysis, in vivo assessment of lipid absorption and intestinal permeability, and assessment of adaptation and liver injury was completed. Pparα intestinal knockout and littermate control mice were phenotypically similar in terms of weight trends and body composition after SBR. All mice demonstrated intestinal adaptation with increased villus height and crypt depth; however, Pparα intestinal knockout mice exhibited decreased villus growth at 10 weeks compared to littermate controls. Liver injury and fibrosis were similar between groups as assessed by serum AST and ALT levels, Sirius Red staining, and hepatic expression of Col1a1 and Acta2. Inducible intestinal deletion of Pparα influences structural adaptation but does not mitigate liver injury after SBR. These findings suggest that enterocyte PPARα signaling in adult mice is dispensable for resection-induced liver injury. The results are critical for understanding the contribution of intestinal lipid metabolic signaling pathways to the pathogenesis of hepatic injury associated with short bowel syndrome. • What is known? Resection-associated liver steatosis, injury, and fibrosis is a devastating complication associated with massive small bowel resection. Peroxisome proliferator-activated receptor-alpha is a key regulator of lipid transport and metabolism whose expression is selectively increased in the intestine after SBR. • What is new? Inducible intestinal deletion of PPARα, a major regulator of intestinal lipid metabolism, influences structural adaptation but does not mitigate liver injury after SBR. These findings suggest that enterocyte PPARα signaling in adult mice is dispensable for liver injury following SBR. [ABSTRACT FROM AUTHOR]

Infection due to multidrug-resistant Klebsiella pneumoniae is a common cause of graft resection after small bowel transplantation. We report a failed case in which the intestinal graft was resected 18 days after the operation due to postoperative infection with multidrug-resistant K pneumoniae and a literature review of other common causes of small bowel transplantation failure have been reported. A female, 29 years of age, underwent partial living small bowel transplantation for short bowel syndrome. After the operation, the patient was infected with multidrug-resistant K pneumoniae, even though various anti-infective regimens were employed. It further developed into sepsis and disseminated into intravascular coagulation, leading to exfoliation and necrosis of the intestinal mucosa. Finally, the intestinal graft had to be resected to save the patient's life. Multidrug-resistant K pneumoniae infection often affects the biological function of intestinal grafts and can even lead to necrosis. Other common causes of failure, including postoperative infection, rejection, post-transplantation lymphoproliferative disorder, graft-vs-host disease, surgical complications, and other related diseases, were also discussed throughout the literature review. Pathogenesis due to diverse and interrelated factors makes the survival of intestinal allografts a great challenge. Therefore, only by fully understanding and mastering the common causes of surgical failure can the success rate of small bowel transplantation be effectively improved. [ABSTRACT FROM AUTHOR]

The short-term effects of teduglutide (TED) for short bowel syndrome with chronic intestinal failure (SBS–IF) in patients with Crohn's disease (CD) remain unknown. The aim of this study was to investigate the effects of TED in patients with CD on home parenteral support (PS) for SBS–IF. We retrospectively investigated the medical records of patients with CD associated with SBS–IF who initiated TED between 2020 and 2021. The primary outcomes were the change in PS volume and proportion of patients with a reduction of PS volume by ≥ 20% at week 8. Secondary outcomes were the change in PS volume in patients with CD without/with colon in continuity and adverse events during the observation period. Eighteen patients with CD who underwent home PS for SBS–IF were included in this study. Two patients were excluded owing to intolerable abdominal pain or vomiting within 8 weeks (11%). Sixteen patients continued TED throughout the observation period. The median PS duration was 10.5 years. The median observation period was 22 weeks after starting TED. TED significantly reduced the PS volume from 15,825.0 mL/week to 10,700.0 mL/week (p = 0.0038), and the PS volume decreased by ≥ 20% in 7 patients (43.8%) at week 8. The PS volume was significantly reduced at week 4 (p = 0.0078) in 11 patients without colon in continuity but not in 5 patients with colon in continuity. Two patients successfully stopped home PS. No serious adverse events occurred. TED administration significantly reduced PS volume at week 8 in patients with CD associated with SBS–IF, and at week 4 in patients without colon in continuity. [ABSTRACT FROM AUTHOR]

Prior to the late 1960s, pediatric short bowel syndrome was a frequently fatal disease. Currently, pediatric interdisciplinary bowel rehabilitation centers report very high survival rates. The mortality trends, up-to-date definitions, incidence, causes, and clinical manifestations of short bowel syndrome are reviewed. Emphasis is placed upon the nutritional, medical, and surgical advances that have contributed to the dramatic improvement in outcomes for pediatric short bowel syndrome patients. Recent findings and remaining challenges are highlighted. [ABSTRACT FROM AUTHOR]

[Display omitted] Teduglutide (Revestive®) is a glucagon-like peptide-2 analogue used for the treatment of short bowel syndrome, a rare life-threatening condition in which the amount of functional gut is too short to enable proper absorption of nutrients and fluids. During handling prior to administration to the patient in hospital, it is possible that peptide-based medicines may be exposed to environmental stress conditions that could affect their quality. It is therefore essential to carry out stress testing studies to evaluate how such medicines respond to these stresses. For this reason, in this paper we present a strategy for a comprehensive analytical characterization of a peptide and a stress testing study in which it was subjected to various stress conditions: heating at 40 °C and 60 °C, light exposure and shaking. Several complementary analytical techniques were used throughout this study: Far UV circular dichroism, intrinsic protein fluorescence spectroscopy, dynamic light scattering, size-exclusion chromatography and intact and peptide mapping reverse-phase chromatography coupled to mass spectrometry. To the best of our knowledge, this is the first study to offer an in-depth description of the chemical structure of teduglutide peptide and its physicochemical characteristics after stress stimuli were applied to the reconstituted medicine Revestive®. [ABSTRACT FROM AUTHOR]

• Meconium ileus may be the first clinical presentation in patients with D1152H. • Sweat testing alone in patients with D1152H is insufficient to suggest against CF. • Patients with D1152H may remain pancreatic sufficient impacting quality of life. • CFTR gene sequencing is important in patients with meconium ileus for this reason. Meconium ileus (MI) is one presenting manifestation of Cystic Fibrosis (CF), classically associated with class I-III CF transmembrane conductance regulator (CFTR) mutations and pancreatic insufficiency (PI). D1152H is a class IV mutation that corresponds with a milder CF phenotype and pancreatic sufficiency (PS). We present the case of an infant with G542X/D1152H mutations and MI who required surgical intervention with small bowel resection. The sweat testing was normal, and this child presently remains PS, however at age 5 continues to experience short gut syndrome and failure to thrive. Eight cases were identified in the CF Registry and seven cases in the literature describing patients with D1152H and echogenic bowel (EB) or MI. Our case highlights the importance of CFTR gene sequencing in infants with EB or MI and sweat testing not suggestive of CF. It is our practice to perform full CFTR gene sequencing for infants who present with MI, recognizing protocols for newborn screening across the United States vary. Increased awareness of D1152H association with PS may also well inform both prenatal and postnatal genetic counseling. [ABSTRACT FROM AUTHOR]

• This is the first case report of needle disruption of the retroperitoneal lymph nodes for the chylothorax after double lung transplantation. • Chylothorax can be managed with medical, surgical, or interventional radiological management; however, chylothorax can increase morbidity and mortality after double lung transplantation. • Needle disruption of the retroperitoneal lymph nodes is a safe and effective percutaneous procedure to manage chylothorax. This procedure is as effective as thoracic duct embolization. Chylothorax is a rare complication after double lung transplantation. We report a case of a 55-year-old man with idiopathic pulmonary fibrosis. He underwent a double lung transplantation with venoarterial extracorporeal membrane support. The surgery was uncomplicated; however, his postoperative course was complicated with a refractory chylothorax that started postoperative day 4. Medical management could not control the chylothorax, including nil per os, total parenteral nutrition, and octreotide administration. After failed percutaneous embolization via lymphangiography and surgical ligation of the thoracic duct and pleurodesis via video-assisted thoracoscopic surgery, percutaneous needle disruption of the retroperitoneal lymph nodes was performed. After this procedure, the chylothorax resolved quickly. Percutaneous needle disruption of the retroperitoneal lymph node is safe and effective for refractory chylothorax. This technique can be one of the main modalities to manage chylothorax after lung transplantation. [ABSTRACT FROM AUTHOR]

Objective: To quantify the rate of venous thromboembolism (VTE) in patients with pediatric intestinal failure and identify associated risk factors.Study Design: We performed a retrospective cohort study in pediatric patients (<21 years old) with severe pediatric intestinal failure (≥90 consecutive days of parenteral nutrition) secondary to short bowel syndrome who were treated from 2014 to 2021 at an interdisciplinary intestinal rehabilitation program. The primary outcome was the incidence of VTE. Multivariable regression was performed to identify independent clinical predictors of VTE.Results: A total of 263 patients (59.7% male) met the criteria for inclusion. The cumulative incidence of VTE was 28.1%, with a rate of 0.32 VTEs per 1000 catheter-days. On univariate analysis, the number of catheter days, number of catheters, and history of central line-associated blood stream infection were associated with VTE. On multivariable logistic regression, a higher number of catheters was an independent risk factor for VTE (aOR, 1.17; 95% CI, 1.06-1.29). Additionally, earlier gestational age was a risk factor for VTE such that every week decrease in gestational age conferred a 9% increased risk of VTE (aOR, 1.09; 95% CI, 1.02-1.16).Conclusions: In this retrospective study, 28.1% of patients with severe pediatric intestinal failure developed VTE; the number of catheters and early gestational age were noted to be independent risk factors for VTE. This high incidence of VTE highlights the need to investigate VTE in pediatric intestinal failure prospectively, including the potential benefit of prophylactic anticoagulation. [ABSTRACT FROM AUTHOR]

• 44% of patients achieved enteral autonomy (EA) following autologous gastrointestinal reconstructive (AGIR) surgery. • Percentage of expected of small bowel length (≥15%) before AGIR is a strong predictor of achievement of EA. • The AGIR technique employed did not influence weaning from parenteral nutrition. • Aetiology of short bowel syndrome (gastroschisis) can affect outcomes and a tailored, multi-disciplinary approach is recommended. The implementation of multidisciplinary care and improvements in parenteral nutrition (PN) in patients with short bowel syndrome (SBS) have led to better outcomes and higher survivability. Autologous gastrointestinal reconstructive (AGIR) surgery can reduce the duration on PN and lead to earlier enteral autonomy (EA). Our aim was to investigate the effect of SBS aetiology and other predictors on the achievement of enteral autonomy following AGIR surgery. Retrospective review of all patients undergoing AGIR surgery in two tertiary paediatric surgical units, between 2010 and 2021. Continuous data is presented as median (range). Twenty-seven patients underwent 29 AGIR procedures (20 serial transverse enteroplasties (STEP), 9 longitudinal intestinal lengthening and tailoring (LILT)) at an age of 6.6 months (1.5 – 104.5). EA rate was 44% at 13.6 months after surgery (1 – 32.8). AGIR procedures achieved an increase in small bowel length of 70% (pre-operative 46.5 vs 77 cm, p = 0.003). No difference was found between STEP and LILT (p = 0.84). Percentage of expected small bowel length (based on the child's weight) was a strong predictor of EA (bowel length >15% – EA 80% vs bowel length ≤15% – EA 17%, p = 0.008). A diagnosis of gastroschisis showed a negative non-significant correlation with the ability to achieve EA (25% vs 60%, p = 0.12). Overall survival rate was 96%. AGIR surgery is an important tool in the multidisciplinary management of children with SBS. Percentage of expected small length and aetiology of SBS are likely predictors of achievement of EA in patients undergoing AGIR surgery. Retrospective Case-Series [ABSTRACT FROM AUTHOR]

The purpose of the study is to examine the long-term safety of an endoluminal bowel lengthening device prior to its use in the first human trial. In addition, device performance and natural passage will be evaluated. Endoluminal lengthening springs were surgically placed into the jejunum of Yucatan minipigs using the Eclipse XL1 device. A matching internal control segment of jejunum was marked at the time of operation. Weekly weights and fluoroscopic studies were obtained to evaluate spring deployment and position until devices passed. Animals were euthanized at 28, 60, 90, and 180 days. At necropsy, length measurements were recorded, and histopathologic analysis was performed. There were no bowel obstructions or overt perforations attributable to the device. All surviving animals gained weight and were clinically thriving. All devices passed out of the rectum by 180 days. Bowel lengthening was seen in all experimental segments, and minimal fibrosis was observed by 180 days. Jejunal lengthening persisted after device had passed through the intestinal tract after 180 days. Early histopathologic changes of the jejunum during distraction enterogenesis normalized over time. [ABSTRACT FROM AUTHOR]

Twenty percent of intestinal transplant recipients will require a surgical alternative to conventional primary abdominal wall closure. Abdominal wall transplant is a developing technique that is increasingly performed for this purpose in isolated intestinal or multivisceral recipients; however, adequate closure of the donor is paramount while simultaneously obtaining a large enough graft. The aim of this study is to describe alternative surgical techniques for closure of the donor in cases in which abdominal wall graft extraction hinders subsequent donor abdominal closure. We describe the cases of 2 young donors in whom intestinal extraction was not carried out and in whom wall closure was not feasible, following standard techniques after abdominal wall graft extraction. We performed 2 different procedures to obtain adequate closure. 1. Hemifascia and hemiabdominal wall graft extraction: It is an option when the recipients require an extension of the abdominal aponeurosis yet have enough skin to guarantee skin closure. The perfusion of both epigastric arteries is needed. The remaining cutaneous half is used for closing the donor's abdomen.2. Hemiabdominal wall graft extraction: Full-thickness abdominal wall is harvested from the donor, selecting the most vascularized half. It is an alternative for recipients who need a skin implant in addition to an aponeurosis extension. This option should be used for recipients who do not require a large fascial graft but do require a significant cutaneous graft. The nontransplanted half of full-thickness abdominal wall is used for donor closure. Abdominal wall transplant allows for expansion of the abdominal cavity in organ recipients and reduces the risk of compartmental syndrome and subsequent ischemia. However, the donor wall defect must be considered. The choice of donation technique was based on the magnitude of the defect in the donor as well as the size of defect to be covered in the recipient while ensuring a tight and complete closure of the donor's abdomen. Abdominal wall graft extraction can be performed using nonconventional techniques that account for the extension and type of coverage needed by the recipient while guaranteeing proper closure of the donor. [ABSTRACT FROM AUTHOR]

• In the field of pediatric intestinal failure, there are limited data on the health-related quality of life (HRQOL) from the perspective of the child. • In this prospective study, children reported better HRQOL scores compared to parent-proxy data. Child-reported HRQOL scores increased with patient age. • Child-reported HRQOL scores in intestinal failure were lower than scores from reference populations of healthy children and children with chronic illness. Recent studies have focused on parent-reported health-related quality of life (HRQOL) in children with intestinal failure (IF). However, there is a paucity of data on HRQOL from the perspective of the child with IF. A prospective study of child self-reported HRQOL was performed in a regional intestinal rehabilitation program from 2015 to 2019. The PedsQL 4.0 Generic Core Scales were administered annually to children with IF ages five years and older along with their parents. Survey data was stratified by age and compared with parent-proxy scores and reference populations of healthy and chronically ill children. Linear mixed-effect models were constructed to identify associations with child self-reported HRQOL. A total of 140 surveys were administered to 69 children and their parents. Median child age at survey was 8 (IQR 6–10) years. Child self-reported HRQOL scores increased with each increasing age range. Children reported higher HRQOL scores compared to parent-proxy data in all age groups. Children with IF had lower HRQOL scores compared to healthy children in all survey dimensions (p < 0.001) and to children with chronic illness in the school and social functioning dimensions (p < 0.05). In adjusted analysis, longer remnant bowel length was independently associated with decreased HRQOL scores in children (p < 0.05). Children with IF reported better HRQOL compared to parent-proxy data. While these HRQOL scores improved with age, they remain significantly lower than healthy and chronically ill peers. The association between bowel length and child-reported HRQOL deserves further investigation. Level II [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) patients require total parenteral nutrition (TPN) following massive small bowel resection (SBR), which may cause intestinal failure-associated liver disease (IFALD), a life-threatening complication. Hepatocyte growth factor (HGF) acts as a potent hepatocyte mitogen with anti inflammatory and antioxidant actions. The present study evaluated the effect of recombinant human HGF (rh-HGF) on SBR and subsequent IFALD using a parentally fed rat model of SBS. Rats underwent jugular vein catheterization for continuous TPN and 90% SBR. They were divided into 2 groups: TPN alone (SBS/TPN group: n = 7) or TPN plus the intravenous administration of rh-HGF (0.3 mg/kg/day) (SBS/TPN+HGF group: n = 7). On day 7, their tissues and stool were harvested to evaluate the effects of HGF. Regarding the histological findings, based on the nonalcoholic fatty liver disease (NAFLD) activity score, the SBS/TPN+HGF group showed significantly less hepatic steatosis and inflammatory cell infiltration than the SBS/TPN group (NAFLD activity score, 4.00 ± 1.83 vs. 1.00 ± 0.82; p < 0.01). The SBS/TPN+HGF group showed a higher expression of Farnesoid X receptor in the liver and lower expression of Toll-like receptor 4 in the ileum than the SBS/TPN group. Regarding the composition of the bacterial gut microbiota, Actinobacteria, Bacteroidetes and Proteobacteria were decreased in the SBS/TPN+HGF group compared with the SBS/TPN group. In our SBS with TPN rat model, rh-HGF administration had a preventive effect against hepatic steatosis and dysbiosis. rh-HGF may therefore be a potentially effective therapeutic agent for SBS and subsequent IFALD. Experimental research. [ABSTRACT FROM AUTHOR]

Pediatric intestinal failure (PIF) affects nutrition, metabolism, and endocrine development, but its downstream impact on puberty is unknown. A retrospective review was performed of patients age >8 years with PIF managed at an intestinal rehabilitation program. Outcomes of interest were peak height velocity (PHV), age at PHV, and age at pubertal onset (Tanner stage 2). Outcomes were stratified by sex and compared to established norms. Of 110 patients with PIF, 54.5% were male. Compared to the CDC 50th percentile, PHV in PIF patients was similar for females (8.09±2.36 vs. 7.37 cm/yr; p = 0.23) but significantly higher for males (9.27±2.56 vs. 7.91 cm/yr; p = 0.038). Age at PHV in PIF patients was significantly younger for both males (12.31±2.14 vs. 13.38 years; p = 0.049) and females (10.70±1.06 vs. 11.71 years; p = 0.001). PIF patients reached pubertal onset earlier than published norms; this was significant for males (12.41±1.80 vs. 13.44 years; p = 0.014), but not for females (10.45±1.81 vs. -11.15 years; p = 0.13). The mean height-for-age Z-score was -1.2, with 20% of patients having a Z-score less than -2. Pubertal onset and growth are neither delayed nor diminished in patients with PIF. The high incidence of short stature, however, highlights the importance of optimizing prepubertal linear growth to attain full height potential. Type of Study: Prognosis study (Retrospective cohort study) [ABSTRACT FROM AUTHOR]

Congenital Treves' field hernia is the herniation of a visceral segment through a defect in the terminal ileal mesentery, poses a high risk of strangulation and bowel gangrene. Its preoperative diagnosis is challenging due to its rarity, nonspecific presentation, and often inconclusive imaging. A previously healthy 7-month-old female infant presented with an 18-h history of intense diffuse abdominal pain, nausea, and bilious vomiting. On examination, she appeared ill and dehydrated, with tachycardia and tachypnea. Her abdomen was grossly distended, tense, and tender, with no visible scars or hernias. Blood tests, including a complete blood count, urea, and electrolytes, were normal except for an elevated white blood cell count. Abdominal X-rays and ultrasound revealed features consistent with distal small bowel obstruction, with no evidence of intussusception. Following resuscitation, an emergency laparotomy was performed for suspected acute abdomen due to distal small bowel obstruction. Intraoperatively, the jejunum and proximal ileum were dilated, and a portion of the ilium was found herniated through a 6 × 4 cm mesenteric defect. After reduction, approximately 25 cm of necrotic small bowel was resected, followed by an end-to-end anastomosis. The postoperative recovery was smooth, and she was discharged on day seven with no signs of short bowel syndrome on follow-up. Congenital Treves' field transmesenteric hernia is a rare cause of intestinal obstruction in children that should be considered in cases of mechanical small bowel obstruction. [ABSTRACT FROM AUTHOR]

Congenital mesenteric defect is a rare cause of neonatal small bowel obstruction. We present a case of a newborn with cystic fibrosis experiencing small bowel herniation through a congenital mesenteric defect leading to bowel ischemia. A 0-day-old term, 3.2 kg female with a family history of cystic fibrosis carrier was evaluated for abdominal distension. Prenatal ultrasound showed bowel dilation with increased wall thickness, and post-delivery abdominal X-ray showed a cystic dilation of the bowel. Contrast fluoroscopy of the lower gastrointestinal tract showed small intestinal filling defects and microcolon. She was treated for suspected meconium ileus. Bowel dilation progressed necessitating exploratory laparotomy on day of life 4, with findings of jejunal perforation and ischemic ileal dilatation secondary to herniation through a congenital mesenteric defect. Ileal resection and ileal-ileal anastomosis with jejunostomy creation were performed. The postoperative course of ostomy takedown was complicated by anastomotic breakdown, requiring ileostomy creation. Genetic testing revealed cystic fibrosis. Because of high ileostomy output and meconium impaction in the distal bowel, Bishop-Koop ostomy construction and ileocolic anastomosis were performed. The residual small intestine was 61 cm with an ileocecal valve. At age 2, she remained dependent on total parental nutrition and gastrostomy tube feeding, with intestinal failure and chronic liver failure. Herniation through a congenital mesenteric defect is an extremely rare differential diagnosis for neonatal bowel obstruction. Concomitant cystic fibrosis can compromise postoperative management and cause complications resulting in short gut syndrome due to multiple surgical interventions. level 5. [ABSTRACT FROM AUTHOR]

With the increasing prevalence of metabolic disorders, hyperglycemia has become a common risk factor that endangers people's lives and the need for new drug solutions is burgeoning. Trans-2, 4-dimethoxystilbene (TDMS), a synthetic stilbene, has been found as a novel hypoglycemic small molecule from glucose consumption test. Normal C57BL/6 J mice, mouse models of type 1 diabetes mellitus and diet-induced obesity subjected to TDMS gavage were found with lower glycemic levels and better glycemic control. TDMS significantly improved the symptoms of polydipsia and wasting in type 1 diabetic mice, and could rise their body temperature at the same time. It was found that TDMS could promote the expression of key genes of glucose metabolism in HepG2, as do in TDMS-treated liver, while it could improve the intestinal flora and relieve intestinal metabolic dysbiosis in hyperglycemic models, which in turn affected its function in the liver, forming the gut-liver axis. We further fished PPARγ by virtual screening that could be promoted by TDMS both in-vitro and in-vivo, which was regulated by upstream signaling of AMPKα phosphorylation. As a novel hypoglycemic small molecule, TDMS was proven to be promising with its glycemic improvements and amelioration of diabetes symptoms. It promoted glucose absorption and utilization by the liver and improved the intestinal flora of diabetic mice. Therefore, TDMS is expected to become a new hypoglycemic drug that acts through gut-liver axis via AMPKα-PPARγ signaling pathway in improving glycemic metabolism, bringing new hope to patients with diabetes and glucose metabolism disorders. [Display omitted] • Trans-2, 4-dimethoxystilbene (TDMS) is identified as a novel hypoglycemic small molecule. • PPARγ is the hypoglycemic target of TDMS with AMPKα-PPARγ pathway being activated in the liver. • Trans-2, 4-dimethoxystilbene improved intestinal flora and acted through the gut-liver axis. [ABSTRACT FROM AUTHOR]

Tolerance is the Holy Grail of solid organ transplantation (SOT) and remains its primary challenge since its inception. In this topic, the seminal contributions of Thomas Starzl at Pittsburgh University outlined foundational principles of graft acceptance and tolerance, with chimerism emerging as a pivotal factor. Immunologically, intestinal transplantation (ITx) poses a unique hurdle due to the inherent characteristics and functions of the small bowel, resulting in increased immunogenicity. This necessitates heavy immunosuppression (IS) while IS drugs side effects cause significant morbidity. In addition, current IS therapies fall short of inducing clinical tolerance and their discontinuation has been proven unattainable in most cases. This underscores the unfulfilled need for immunological modulation to safely reduce IS-related burdens. To address this challenge, the Leuven Immunomodulatory Protocol (LIP), introduced in 2000, incorporates various pro-tolerogenic interventions in both the donor to the recipient, with the aim of facilitating graft acceptance and improving outcome. This review seeks to provide an overview of the current understanding of tolerance in ITx and outline recent advances in this domain. [ABSTRACT FROM AUTHOR]

Intestinal transplantation is the standard treatment for patients with intestinal failure with severe complications due to parenteral nutrition; however, rejection leads to graft failure in approximately half of both adult and pediatric recipients within 5 years of transplantation. Although intensive immunosuppressive therapy is used in an attempt to reduce this risk, commonly used treatment strategies are generally practice- and/or expert-based, as head-to-head comparisons are lacking. In this ever-developing field, biologicals designed to prevent or treat rejection are used increasingly, with both infliximab and vedolizumab showing potential in the treatment of acute cellular rejection in individual cases and in relatively small patient cohorts. To help advance progress in clinical care, we review the current use of biologicals in intestinal transplantation, and we provide future perspectives to guide this progress. [ABSTRACT FROM AUTHOR]

Drosophila melanogaster , or the fruit fly, is widely used for modeling numerous human diseases, such as neurodegeneration, tumor development, cachexia, and intestinal dysfunction. It is a suitable model organism for research targeting the physiology and pathophysiology of the intestinal epithelial barrier and has also been used as a model organism for preliminary drug and bioactive nutrient screening. However, the application of D. melanogaster in research on drug bioavailability and pharmacokinetic properties has not yet been well explored. In this study, we applied D. melanogaster to investigate the absorption and excretion of the orally administered phytoestrogens daidzein, glycitein, genistein, and their glycosides. Therefore, we established a quick, noninvasive method to quantify compound retention in D. melanogaster , suitable for the investigation of a broad variety of potentially bioactive substances. We showed that fruit fly sex plays a key role in the metabolization, transportation, and excretion of phytoestrogenic isoflavones. In particular, female fruit flies retained significantly more isoflavones than male fruit flies, which was reflected in the greater metabolic impact of isoflavones on females. Male fruit flies excreted more isoflavones than females did, which was linked to the upregulation of the xenobiotic transporter gene Mdr50. We also demonstrated that micellized isoflavones were more bioavailable than powdered isoflavones, independent of sex, age or the addition of dietary fibers. [Display omitted] • Novel method for pharmacokinetic studies in Drosophila melanogaster. • Absorption and excretion of soy isoflavones was linked to sex of the fruit fly. • Mdr50 was significantly upregulated in males but not females fed with isoflavones. • Intestinal microbiota impacted bioconversion and absorption of isoflavones in fly. [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation. The FXR agonist, OCA, attenuates the intestinal barrier disruption in a rat model of short bowel syndrome. [Display omitted] • OCA upregulates the repressed FXR expression in SBS rats and Caco-2 cells. • OCA ameliorates the intestinal barrier disruption in SBS rats and LPS-pretreated Caco-2 cells. • OCA, as a selective activator of FXR, might realize its protective function through FXR activation. • Targeting FXR might offer new promises in SBS-induced intestinal barrier disruption. [ABSTRACT FROM AUTHOR]

The etiology of psychiatric disorders is multifactorial including genomic and environmental risk factors. Psychiatric genetic counseling is an emerging field that may promote processes of adaptation to, and the management of, psychiatric disorders. Many countries lack dedicated services leading to a gap in care. This scoping review will inform the development of psychiatric genetics-based educational resources. To explore individuals with a psychiatric disorder and their relatives' attitudes and beliefs toward psychiatric genetics, genetic counseling, and genetics-based education. To evaluate how best to convey education to consumers. Database literature searches occurred on May 2nd, 2023, using PubMed, Medline, and PsycINFO. Reviews, letters to the editor, case reports, and publications before 2003 were excluded. Twenty-four papers met the inclusion criteria. Results suggest individuals with a psychiatric disorder and their relatives tended to overestimate risk, and express concern about reproductive decision- making. Genetic counseling and educational resources were perceived to be useful and empowering. Affected individuals and relatives are interested in gaining greater insight into their own and/or their relative's psychiatric disorder, management strategies, and understanding familial risks. The evidence from this review may inform the development of genetics-based educational resources or guide future research. [ABSTRACT FROM AUTHOR]

Background: Short bowel syndrome (SBS) refers to a malabsorptive state caused by extensive resection of the intestinal tract that leads to chronic diarrhea, electrolyte disturbances, and malnutrition. Although relatively uncommon, patients with SBS can present to the emergency department with more serious complications that are potentially life-threatening. Among these complications, coagulopathy secondary to SBS is an underrecognized condition.Case Report: We present a case of severe coagulopathy secondary to vitamin K deficiency in SBS. The patient presented with unexplained coagulopathy and spontaneous bleeding in multiple organs. With a review of surgical history and detailed clinical evaluation, SBS complicated with vitamin K deficiency was diagnosed, and the patient was treated successfully. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When a patient with a history of repeated intestinal surgery presents with diarrhea, malnutrition, or electrolyte abnormalities, emergency physicians should suspect SBS. Among complications of SBS, vitamin K deficiency is a rare but serious cause of unexplained coagulopathy presenting to the emergency department. Understanding the pathophysiology of SBS facilitates early identification of complications and improves patient outcomes. [ABSTRACT FROM AUTHOR]

Le tractus gastro-intestinal produit une très grande diversité de peptides et peut être considéré comme la plus grande et la plus complexe des glandes endocrines. Depuis la découverte de la sécrétine, plus de 30 gènes codant pour des pro-hormones ont été identifiés et, du fait d'épissages alternatifs et/ou de maturations post-traductionnelles, ils permettent la production et la sécrétion de plus de 100 peptides actifs différents. Ces hormones intestinales, appelées également entérohormones, exercent de nombreux effets sur le tractus gastro-intestinal lui-même mais également à distance (cerveau, pancréas, foie...) participant au contrôle de l'entrée des nutriments dans l'organisme, de la prise alimentaire, de l'homéostasie glucidique. Les entérohormones sont produites par les cellules entéroendocrines dispersées le long du tractus gastro-intestinal et sécrétées en réponse à des signaux luminaux mais également endocrines, paracrines, et neuronaux. La fonction entéroendocrine est altérée au cours de la dénutrition ou de l'obésité. La chirurgie bariatrique, principal traitement des obésités sévères, et la résection étendue de l'intestin grêle menant au syndrome de grêle court, principale cause d'insuffisance intestinale, induisent des modifications importantes des secrétions de plusieurs entérohormones. Cette revue résume les dernières connaissances en physiologie de la fonction endocrine intestinale (les cellules entéroendocrines, les signaux les stimulant, les principaux rôles des entérohormones) mais aussi lors de pathologies nutritionnelles (obésité, dénutrition) et les possibles approches pour cibler cette fonction à des fins thérapeutiques. The gastrointestinal tract produces a very wide variety of peptides and is considered as the largest and most complex endocrine glands. Since the discovery of secretin, more than 30 genes encoding pro-hormones have been identified and, due to alternative splicing and/or regulated post-translational maturation, these genes allow the production and secretion of more than 100 different peptides. These intestinal hormones, also called enterohormones, exert numerous effects on the gastrointestinal tract itself but also at distance (brain, pancreas, liver...) participating in the control of the entry of nutrients into the body, the food intake, carbohydrate homeostasis. Enterohormones are produced by enteroendocrine cells scattered along the gastrointestinal tract and secreted in response to luminal, but also endocrine, paracrine, and neuronal signals. Enteroendocrine function is impaired during undernutrition or obesity. Bariatric surgery, the main treatment for severe obesity, and extensive resection of the small intestine leading to short bowel syndrome (the main cause of intestinal failure) induce significant changes in the secretions of several enterohormones. This review summarizes the latest knowledge in the physiology of intestinal endocrine function (enteroendocrine cells, the signals stimulating them, the main roles of enterohormones) but also during nutritional pathologies (obesity, undernutrition) and the possible approaches to target this function for specific therapeutic purposes. [ABSTRACT FROM AUTHOR]