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Purpose of Review: Intestinal failure (IF), a rare organic dysfunction, is characterized by a reduction in intestinal function, necessitating intravenous supplementation to sustain health and/or growth due to inadequate absorption of macro and micronutrients, water, and electrolytes. This condition is distinct from "Intestinal Insufficiency," where intravenous replacement is not immediately necessary. The purpose of this review is to evaluate the literature published in the last 5 years on drug treatment in the management of patients with intestinal failure (IF) and short bowel syndrome (SBS) and to identify strategies to minimize fluid and electrolyte loss by increasing nutrient-enterocyte contact time, improving intestinal transit time, replenishing micronutrients, and enhancing nutrient absorption. Recent Findings: We describe current treatments for rehabilitation aimed at optimizing absorption of the intestinal mucosa. We also outline recommended pharmacological adjustments of some drugs used in the treatment of commonly found comorbidities in these patients. Recent articles have demonstrated that GLP-2 analogs have become an important tool in the treatment of SBS, improving intestinal secretory control, gastrointestinal transit time, nutrient absorption, and, most importantly, positively impacting quality of life. Summary: IF is a rare disease defined by need for intravenous hydration and nutrients delivery and associated with malnutrition and high mortality rate. Medical management and treatment of IF can increase survival time and quality of life. [ABSTRACT FROM AUTHOR]

Background: Intestinal failure-associated liver disease (IFALD) is a complication of long-term PN use, attributed to the use of ω-6 injectable lipid emulsions (ILE). Fish oil (FO) ILE have been successful in reversing liver injury in neonates. Evidence for pure FO ILE use in adult patients is limited. Methods: Case series of the use of FO lipid emulsions in adults with IFALD from the University of Chicago PN registry. Analysis of medical charts and PN formulations was performed. Results: Three cases of IFALD treated with FO ILE were identified. The first case was a 30-year-old man with short bowel syndrome (SBS), hyperbilirubinemia, and biopsy-proven IFALD. Following a change from a soy lipid emulsion to FO lipid emulsion, his liver tests rapidly improved and remained stable over 202 weeks of use. The second case was a 76-year-old woman with intestinal failure (IF) due to a frozen bowel. A change from a soy ILE to a composite lipid and later to a pure FO ILE did not result in improvement in her liver tests. The third case was a 28-year-old man with SBS and biopsy-proven IFALD. Change to a composite ILE and subsequently FO lipid emulsion resulted in a gradual improvement in liver tests. No clinical essential fatty acid (EFA) deficiencies were identified during treatment. Conclusion: FO ILE may be effective in the treatment of adult patients with cholestatic IFALD. Use is safe with no EFA deficiencies detected in up to 4 years of use. [ABSTRACT FROM AUTHOR]

To evaluate the influence of early nutritional intake on the growth pattern of very preterm infants. This was an observational study including 109 newborns (< 32 weeks gestational age). Perinatal morbidities, nutritional therapy (first four weeks of life), and weight, length, and head circumference (HC) growth at term-equivalent age were evaluated. Growth restriction was defined as a difference > 1.2 SD between the birth and term age measurements. Growth restriction at term-equivalent age: 52.3% (weight), 42.9% (length), and 22% (HC). Morbidities were positively correlated with nutrition therapy and negatively correlated with the total energy provision: protein ratio. The duration of parenteral nutrition, the time to reach full enteral feedings, and the total energy provision: protein ratio were significantly correlated. Nutrient intake influenced weight, length, and HC growth, and cumulative energy deficit was significantly associated with HC growth restriction. Conclusion: Perinatal morbidities interfere with nutritional therapy and early nutrient intake, leading to insufficient energy and energy provision: protein ratio for growth. What is Known: • The intake of macronutrients early in life, mainly protein, is important for the optimal growth of pretem infants. • The severity of morbidities and low gestational ages impact the nutritional management of preterm infants. What is New: • The number of morbidities, reflecting the severity of the neonatal clinical course, had a detrimental effect on the nutritional therapy and nutrients intake. • The inadequate energy provision per gram of protein ratio was significantly associated with growth restriction in all growth measures at the second week of life, persisting for head circumference up to the fourth week, highlighting the importance of its measurement, as it could be a precocious sign of development risk. [ABSTRACT FROM AUTHOR]

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5 years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3 months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4–4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12–40) cm. The median duration of teduglutide therapy was 19 (IQR 12–36) months, with 23 patients (74%) treated for > 1 year and 9 treated for > 3 years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5–22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028). Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate. What is Known: • Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS. • Data about long-term therapy with teduglutide in children in real life are still scarce. What is New: • Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional. • Starting treatment with the drug at a young age is associated with a greater response rate. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the impact of hepatocyte growth factor (HGF) on colonic morphology and gut microbiota in a rat model of short bowel syndrome (SBS). Methods: SD rats underwent jugular vein catheterization for total parenteral nutrition (TPN) and 90% small bowel resection [TPN + SBS (control group) or TPN + SBS + intravenous HGF (0.3 mg/kg/day, HGF group)]. Rats were harvested on day 7. Colonic morphology, gut microflora, tight junction, and Toll-like receptor-4 (TLR4) were evaluated. Results: No significant differences were observed in the colonic morphological assessment. No significant differences were observed in the expression of tight junction-related genes in the proximal colon. However, the claudin-1 expression tended to increase and the claudin-3 expression tended to decrease in the distal colon of the HGF group. The Verrucomicrobiota in the gut microflora of the colon tended to increase in the HGF group. The abundance of most LPS-producing microbiota was lower in the HGF group than in the control group. The gene expression of TLR4 was significantly downregulated in the distal colon of the HGF group. Conclusion: HGF may enhance the mucus barrier through the tight junctions or gut microbiome in the distal colon. [ABSTRACT FROM AUTHOR]

Background: Thromboembolic occlusion of the superior mesenteric artery (SMA) is a grave complication in individuals diagnosed with atrial fibrillation (AF). This condition often necessitates extensive bowel resection, culminating in short bowel syndrome, which presents challenges for anticoagulant administration and/or antiarrhythmic therapy. Case presentation: Presented here are findings of two patients, aged 78 and 72 years, respectively, who underwent comprehensive thoracoscopic AF surgery subsequent to extensive small bowel resection following SMA embolization. In each, onset of AF precipitated an embolic event, while the concurrent presence of short bowel syndrome complicated anticoagulation management. Total thoracoscopic AF surgery, comprised stapler-closure of the left atrial appendage (LAA) and bilateral epicardial clamp-isolation of the pulmonary veins, an operative modality aimed at addressing AF rhythm control and mitigating embolic events such as cerebral infarction, led to favorable outcomes in both cases. Additionally, computed tomography (CT) conducted one month post-surgery revealed the absence of residual tissue in the LAA, with the left atrium demonstrating a well-rounded, spherical shape. At the time of writing, the patients have remained asymptomatic following surgery regarding thromboembolic and arrhythmic manifestations for 29 and 10 months, respectively, notwithstanding the absence of anticoagulant or antiarrhythmic pharmacotherapy. Additionally, electrocardiographic surveillance has revealed persistent sinus rhythm. Conclusions: The present findings underscore the feasibility and efficacy of a total thoracoscopic AF surgery procedure for patients presented with short bowel syndrome complicating SMA embolization, thus warranting consideration for its broader clinical application. [ABSTRACT FROM AUTHOR]

Purpose: By selectively perfusing the first three jejunal arteries (JA), we aim to assess the individual perfusion length of small bowel (SB) and its impact on nodal resection in stage III-up small-intestinal neuroendocrine tumors (SI-NET). Methods: Our anatomical research protocol implies a midline laparotomy and three measures of the SB length. We then perform a classical anterior approach of the superior mesenteric vessels. We carry on with the complete dissection and checking of the superior mesenteric artery (SMA) in order to identify the first three JA. Then we selectively perfuse each artery with colored latex solutions and measure the length of small bowel perfused respectively. Results: We conducted our protocol on six cadaveric subjects. Mean(SD) SB length was 413(5.7), 535(13.2), 485(15), 353(25.1), 730(17.3) and 525(16° cm respectively from subject one to six. Most JA originated from the left side of the SMA. The first JA originated from its posterior wall in two subjects. Mean(SD) distance of origin of the first three JA was 4.6(1.3)cm, 6(1.1)cm and 7.1(0.9)cm respectively. Mean(SD) diameter of SMA was 10.8(3.3)mm. Mean diameter of the three first JA was 4(1.4)mm, 4(1.5)mm and 5(1.2)mm respectively. Mean(SD) SB length perfused by first and second JA was 224(14.9)cm, 175(8.6)cm, 238.3(7.6)cm, 84.3(5.1)cm, 233.3(5.8)cm and 218.3(10.4)cm respectively from subject one to six. Conclusion: We observed a trend suggesting that the first and second JA may sustain a SB length beyond the viable 1.5 m limit, implying the feasibility of stage III-up SI-NET resection with just two JA. [ABSTRACT FROM AUTHOR]

The aging of populations is a global phenomenon that follows a possible increase in the incidence of neurodegenerative diseases. Alzheimer's, Parkinson's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Huntington's diseases are some neurodegenerative disorders that aging could initiate or aggravate. Recent research has indicated that intestinal microbiota dysbiosis can trigger metabolism and brain functioning, contributing to the etiopathogenesis of those neurodegenerative diseases. The intestinal microbiota and its metabolites show significant functions in various aspects, such as the immune system modulation (development and maturation), the maintenance of the intestinal barrier integrity, the modulation of neuromuscular functions in the intestine, and the facilitation of essential metabolic processes for both the microbiota and humans. The primary evidence supporting the connection between intestinal microbiota and its metabolites with neurodegenerative diseases are epidemiological observations and animal models experimentation. This paper reviews up-to-date evidence on the correlation between the microbiota-gut-brain axis and neurodegenerative diseases, with a specially focus on gut metabolites. Dysbiosis can increase inflammatory cytokines and bacterial metabolites, altering intestinal and blood-brain barrier permeability and causing neuroinflammation, thus facilitating the pathogenesis of neurodegenerative diseases. Clinical data supporting this evidence still needs to be improved. Most of the works found are descriptive and associated with the presence of phyla or species of bacteria with neurodegenerative diseases. Despite the limitations of recent research, the potential for elucidating clinical questions that have thus far eluded clarification within prevailing pathophysiological frameworks of health and disease is promising through investigation of the interplay between the host and microbiota. [ABSTRACT FROM AUTHOR]

Background & Aims: The intestinal rehabilitation program (IRP) is a specialized approach to managing patients with intestinal failure (IF). The goal of IRP is to reduce the patient's dependence on parenteral nutrition by optimizing nutrition intake while minimizing the risk of complications and providing individualized medical and surgical treatment. We aimed to provide a thorough overview of our extensive history in adult IRP. Methods: We reviewed the medical records of adults with IF treated at our center's IRP over the past two decades. We collected data on demographic and clinical results, such as the causes of IF, the current status of the remaining bowel, nutritional support, and complications or mortality related to IF or prolonged parenteral nutrition. Results: We analyzed a total of 47 adult patients with a median follow-up of 6.7 years. The most common cause of IF was massive bowel resection due to mesenteric vessel thrombosis (38.3%). Twenty-eight patients underwent rehabilitative surgery, including 12 intestinal transplants. The 5-year survival rate was 81.9% with 13 patients who expired due to sepsis, liver failure, or complication after transplantation. Of the remaining 34 patients, 18 were successfully weaned off from parenteral nutrition. Conclusion: Our results of IRP over two decades suggest that the individualized and multidisciplinary program for adult IF is a promising approach for improving patient outcomes and achieving nutritional autonomy. [ABSTRACT FROM AUTHOR]

Objectives: The standard treatment for short bowel syndrome is home parenteral nutrition. Patients' strict adherence to protocols is essential to decrease the risk of complications such as infection or catheter thrombosis. Patient training can even result in complete autonomy in daily care. However, some patients cannot or do not want too much responsibility. However, doctors often encourage them to acquire these skills. Based on qualitative investigations with patients, we wanted to document issues of importance concerning perceptions of autonomy in daily care. Methods: Semistructured interviews were conducted with 13 adult patients treated by home parenteral nutrition using a maximum variation sampling strategy. We proceeded to a thematic analysis following an inductive approach. Results: After achieving clinical management of symptoms, a good quality of life is within the realm of possibility for short bowel syndrome patients with home parenteral nutrition. In this context, achieving autonomy in home parenteral nutrition could be a lever to sustain patients' quality of life by providing better life control. However, counterintuitively, not all patients aim at reducing constraints by reaching autonomy in home parenteral nutrition. First, they appreciate the social contact with the nurses, which is particularly true among patients who live alone. Second, they can feel safer with the nurse's visits. Regaining freedom was the main motivation for patients in the training program and the main benefit for those who were already autonomous. Conclusions: Medical teams should consider patients' health locus of control (internal or external) for disease management to support them concerning the choice of autonomy in daily care for parenteral nutrition. [ABSTRACT FROM AUTHOR]

Background: Despite being a long-term therapy for patients with short bowel syndrome (SBS), subcutaneous injections of teduglutide promote the regeneration of the gastrointestinal tract. Such cases are particularly concerning for patients with residual small bowel. Methods: In this report, we present a case of an SBS patient with only 5 cm of remaining small bowel and a high-output duodenal stoma, who was treated with teduglutide. Results: The initiation of teduglutide injections in our patient resulted in a reduction of stoma output, improvement in the patient's nutritional status, regulation of fluid balance, and stabilization of their clinical condition. Conclusions: This case suggests that subcutaneous injections of teduglutide, when combined with appropriate nutritional care, can effectively treat high-output stomas, even in cases where the small bowel is nearly absent. [ABSTRACT FROM AUTHOR]

Introduction and hypotheses: The International Continence Society recommends the International Consultation on Incontinence Questionnaire-Bladder Diary (ICIQ-BD) for the assessment, management, and monitoring of lower urinary tract symptoms (LUTS). Translation, cross-cultural adaptation and validation will establish a valid and reliable tool for Brazilian women with LUTS. Methods: A cross-sectional study involving 101 women was carried out at the Urogynecology Outpatient Clinic in Belo Horizonte, Brazil, between August 2020 and April 2022. The process of cross-cultural adaptation and validation was executed following the ICIQ Group's protocol. Reviewed by an expert committee, the first pre-test was followed by subsequent adaptations, resulting in a second adapted version that underwent expert revisions. A second pretest was conducted, followed by cross-cultural adaptation and construct validation. Finally, the International Consultation on Incontinence Questionnaire-Bladder Diary-Brazilian Portuguese Version (ICIQ-BD-Br) underwent a validation process. Results: Construct validity (IVC >0.78) and internal consistency were satisfactory (α-Cronbach coefficient 0.87–0.94). The following adjustments were made: a specific field was created to document sleep and wake times, and a printed score ranging from 0 to 4 was included in the bladder sensation column. Test–retest reliability ranged from fair to excellent for all analyzed items (Spearman correlation: 0.64–0.95). Criterion validity analysis indicated slight agreement for one of the four symptoms analyzed (nocturia k=0.32). The final version was approved by the ICIQ Group. Conclusions: The ICIQ-BD-Br has been adapted for use in Brazilian Portuguese and has exhibited robust construct validity and reliability for Brazilian women with LUTS. [ABSTRACT FROM AUTHOR]

Objectives: Position- and posture-dependent deformation of the vascular system is a relatively unexplored field. The goal of this scoping review was to create an overview of existing vascular imaging modalities in different body positions and postures and address the subsequent changes in vascular anatomy. Methods: Scopus, Medline, and Cochrane were searched for literature published between January 1, 2000, and June 30, 2022, incorporating the following categories: image modality, anatomy, orientation, and outcomes. Results: Out of 2446 screened articles, we included 108. The majority of papers used ultrasound (US, n = 74) in different body positions and postures with diameter and cross-sectional area (CSA) as outcome measures. Magnetic resonance imaging (n = 22) and computed tomography (n = 8) were less frequently used but allowed for investigation of other geometrical measures such as vessel curvature and length. The venous system proved more sensitive to postural changes than the arterial system, which was seen as increasing diameters of veins below the level of the heart when going from supine to prone to standing positions, and vice versa. Conclusions: The influence of body positions and postures on vasculature was predominantly explored with US for vessel diameter and CSA. Posture-induced deformation and additional geometrical features that may be of interest for the (endovascular) treatment of vascular pathologies have been limitedly reported, such as length and curvature of an atherosclerotic popliteal artery during bending of the knee after stent placement. The most important clinical implications of positional changes are found in diagnosis, surgical planning, and follow-up after stent placement. Clinical relevance statement: This scoping review presents the current state and opportunities of position- and posture-dependent imaging of vascular structures using various imaging modalities that are relevant in the fields of clinical diagnosis, surgical planning, and follow-up after stent placement. Key Points: • The influence of body positions and postures on the vasculature was predominantly investigated with US for vessel diameter and cross-sectional area. • Research into geometrical deformation, such as vessel length and curvature adaptation, that may be of interest for the (endovascular) treatment of vascular pathologies is limited in different positions and postures. • The most important clinical implications of postural changes are found in diagnosis, surgical planning, and follow-up after stent placement. [ABSTRACT FROM AUTHOR]

Background: Intestinal Failure, parenteral nutrition (PN) dependence, and subsequent liver disease are the most challenging and life-threatening complications of short bowel syndrome experienced by patients with total intestinal aganglionosis. Skipped Aganglionic Lengthening Transposition (SALT) showed to be a promising procedure to overcome such problems. We herein report the results of two patients who underwent SALT at the Umberto Bosio Center for Digestive Diseases. Patients and methods: Between November 2019 and July 2022, 2 patients with total intestinal aganglionosis underwent SALT as autologous intestinal lengthening procedure. Perioperative data and long-term outcomes are reported. Patient #1—A 18 month-old male (PN dependant) with 30 cm of ganglionated bowel at birth experienced a 35% increase of intestinal length after SALT (from 43 to 58 cm) thanks to three 5 cm interposed aganglionic loops. Postoperative course was uneventful and he was totally weaned by PN after 28 months postoperatively. He is without PN only receiving enteric feeding 53 months after the procedure. Patient #2—A 11 year-old female (PN dependant) with 100 cm of ganglionated jejunum underwent SALT at 11 years and experienced a 19% increase of bowel length thanks to four 5 to 7 cm interposed aganglionic loops. Postoperatively she required excision of two out of the four loops due to severe strictures and inadequate perfusion with a subsequent overall 10% increase of length after SALT. Of note, she improved significantly with a progressive reduction of PN that has been stopped after 18 months. Conclusion: Skipped aganglionic lengthening transposition (SALT) seems to be very effective in improving nutrients absorption in patients with total intestinal aganglionosis by increasing absorptive bowel surface and decelerating intestinal flow for a longer and more effective contact of enteric material with ileal mucosa. Provided these impressive results are confirmed in the very long-term, SALT could become a valid alternative for the treatment of patients with total intestinal aganglionosis carrying at birth at least 20 to 30 cm of ganglionated jejunum. [ABSTRACT FROM AUTHOR]

Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD. [ABSTRACT FROM AUTHOR]

Background: Long tubular duplication is a rare congenital intestinal disease, that can lead to emergency situations marked by massive hemorrhage. However, preoperative diagnosis and surgical treatment are challenging. This report presents preoperative images and details a surgical procedure for long tubular intestinal duplications with massive hemorrhage. Case presentation: A 3-year-old boy presented to the emergency department with melena. Despite undergoing a Tc-99m pertechnetate scintigraphy one year prior, which revealed nonspecific findings with enhancement of some parts of the intestine, enhanced abdominal CT revealed an edematous small intestine with luminal extravasation. The patient received a transfusion of red blood cells; however, his hemoglobin level did not improve. Arterial angiography and double-balloon endoscopy revealed no remarkable findings. Exploratory laparotomy revealed a long tubular duplication in half of the small intestine. Utilizing the Wrenn procedure, we successfully removed all duplicate mucosa. Pathological findings showed that almost all duplications contained gastric mucosa and revealed an ulcer with a ruptured arterial vessel. His symptoms were resolved, and the hemoglobin level stabilized. At 2 months postoperatively, no surgical complications were present. Conclusions: Effective management of long tubular duplications with massive hemorrhage involves timely application of the Wrenn procedure. Recognition of specific imaging findings is crucial to prompt exploratory laparotomy, ensuring optimal outcomes and preventing delays in treatment. [ABSTRACT FROM AUTHOR]

Background: Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder characterized by multiple hyperproliferative polyps of the gastrointestinal tract, particularly of the colon, rectum, and stomach. SMAD4 mutations are frequently associated with multiple polyposis of the stomach; the condition causes severe bleeding and hypoproteinemia, which may progress to severe dysplasia and adenocarcinoma formation. We report our experience with the first case of total gastrectomy with pancreaticoduodenectomy following two partial jejunectomies for JPS, who presented with refractory anemia and protein-losing gastroenteropathy due to polyposis of the stomach and duodenum. Case presentation: A 33-year-old Japanese man presented with the chief complaint of shortness of breath on exertion. His family history included gastric polyposis (mother, aunt, and cousin) and cerebral infarction (grandmother). Blood testing at the initial visit indicated iron-deficiency anemia, whereas endoscopy revealed multiple polyps in the duodenum and jejunum. Genetic testing revealed a 4 bp deletion (TGAA) in exon 5 of the SMAD4 gene; two partial small bowel resections were performed, but polyps grew in the remaining stomach, duodenum, and small intestine. The patient developed hypoalbuminemia and anemia, and required central venous nutrition and blood transfusion. However, because the hyponutrition and anemia remained poorly controlled, a total gastrectomy with concomitant pancreaticoduodenectomy was performed. Malnutrition and anemia improved, and there was no polyp recurrence in the remaining intestinal tract at 18 months after the surgery. Conclusions: We report a case of JPS with refractory anemia and protein-losing gastroenteropathy that was treated with total gastrectomy with concomitant pancreaticoduodenectomy. Although the surgery was highly invasive, the patient's nutritional status and anemia improved postoperatively, and the treatment was successful. However, to determine the appropriate surgical procedure, a detailed examination of the gastrointestinal lesions and the effects of the surgical invasion on nutritional status must be undertaken. [ABSTRACT FROM AUTHOR]

Background: Intestinal Behçet's disease (BD) is often associated with ulceration that requires surgery, including perforation and abscess formation. However, no consensus has been reached on the optimal extent of resection or treatment strategy. This study reviewed four cases of intestinal or suspected intestinal BD. Case presentations: In Case 1, a 74-year-old woman diagnosed with BD 2 years earlier was treated with anti-tumor necrosis factor α antibody (Infliximab) and steroids. She had oral and pubic ulcers. After close investigation of abdominal pain, perforation of the gastrointestinal tract was suspected and surgery was performed. Multiple perforating ulcers and abscesses were found in the distal ileum, and the small intestine was resected. Postoperatively, the patient was treated with an increased steroid dose and symptoms have remained stable. Case 2 involved a 69-year-old woman with oral and pubic ulcers, ocular ulcer, and skin lesions. She experienced sudden onset of abdominal pain during treatment for lymphoma. She showed multiple perforating ulcers throughout the ileum and underwent resection of the small intestine and ileostomy. Upper abdominal pain appeared during postoperative treatment for high-output syndrome. The patient underwent omentoplasty after perforation of the upper gastrointestinal tract was diagnosed. Postoperatively, anti-interleukin-1 beta antibodies (canakinumab) was administered to control the disease. Case 3 involved an 81-year-old, previously healthy woman. She presented to her previous physician with complaints of pubic ulcer, hemorrhage and abdominal pain. Colonoscopy showed multiple ulcers throughout the entire colon. Steroid therapy was started, but bleeding proved difficult to control and total proctocolectomy was performed. Histopathology revealed multiple perforating ulcers and BD was diagnosed. Postoperatively, the patient remains under steroid control. Case 4 involved a 43-year-old man with abdominal pain who showed abscess formation in the ileocecal region. After excision of the ileocecal area, multiple ulcers were diagnosed. Two years later, abdominal pain recurred and free air was found in the abdomen on close imaging. Emergency anastomotic resection was performed due to ulceration and perforation of the anastomosis. Conclusions: Intestinal BD may flare up after surgical treatment and require multiple surgeries. Introducing pharmacotherapy as soon as possible after surgical treatment is important to control the disease. [ABSTRACT FROM AUTHOR]

Background and purpose: The prognostic nutrition index (PNI) has been associated with the prognosis of various medical disorders. This study aimed to explore the correlation between PNI and the long-term outcomes of adult patients afflicted with moyamoya disease (MMD). Methods: This prospective study initially employed 138 adult patients diagnosed with MMD. After excluding 15 patients who did not meet the criteria, a total of 123 patients were included. Participants were divided into three groups based on the tertile of change in the PNI score. Statistical analysis compared clinical information and lab tests among the groups. The study was conducted between July 1 and December 31, 2019. Results: After adjusting for multiple variables, patients in the upper two tertiles (tertiles 2–3) exhibited a significantly lower risk of adverse long-term outcomes compared to those in the lowest tertile (tertile 1) (OR, 0.089; 95% CI, 0.009–0.895; P = 0.040). Furthermore, adding PNI tertile to traditional risk factors substantially improved predicting adverse long-term outcomes (net reclassification improvement: 98.03%, P = 0.000; integrated discrimination improvement: 4.65%, P = 0.030). However, there was no statistically significant difference between the first PNI tertile (tertile 1) and the upper two tertiles (tertiles 2–3) in the Kaplan–Meier curve of stroke incidence (log-rank test, P = 0.244). Conclusions: A higher PNI level was significantly associated with a reduced risk of unfavorable long-term outcomes. Nevertheless, the PNI score did not predict stroke recurrence during extended follow-up. This study provides insights into a potential predictor of adverse long-term outcomes after revascularization in MMD patients. Registration number: ChiCTR2000031412 [ABSTRACT FROM AUTHOR]

Purpose: High output is a common complication after stoma formation. Although the management of high output is described in the literature, there is a lack of consensus on definitions and treatment. Our aim was to review and summarise the current best evidence. Methods: MEDLINE, Cochrane Library, BNI, CINAHL, EMBASE, EMCARE, and ClinicalTrials.gov were searched from 1 Jan 2000 to 31 Dec 2021 for relevant articles on adult patients with a high-output stoma. Patients with enteroatmospheric fistulas and case series/reports were excluded. Risk of bias was assessed using RoB2 and MINORS. The review was registered in PROSPERO (CRD42021226621). Results: The search strategy identified 1095 articles, of which 32 studies with 768 patients met the inclusion criteria. These studies comprised 15 randomised controlled trials, 13 non-randomised prospective trials, and 4 retrospective cohort studies. Eighteen different interventions were assessed. In the meta-analysis, there was no difference in stoma output between controls and somatostatin analogues (g − 1.72, 95% CI − 4.09 to 0.65, p = 0.11, I2 = 88%, t2 = 3.09), loperamide (g − 0.34, 95% CI − 0.69 to 0.01, p = 0.05, I2 = 0%, t2 = 0) and omeprazole (g − 0.31, 95% CI − 2.46 to 1.84, p = 0.32, I2 = 0%, t2 = 0). Thirteen randomised trials showed high concern of bias, one some concern, and one low concern. The non-randomised/retrospective trials had a median MINORS score of 12 out of 24 (range 7–17). Conclusion: There is limited high-quality evidence favouring any specific widely used drug over the others in the management of high-output stoma. Evidence, however, is weak due to inconsistent definitions, risk of bias and poor methodology in the existing studies. We recommend the development of validated core descriptor and outcomes sets, as well as patient-reported outcome measures. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the autophagy associated with apoptosis in hepatic damage in the short bowel syndrome rat model. Methods: SD rats underwent jugular vein catheterization for continuous total parenteral nutrition (TPN) and 90% small bowel resection. Animals were divided into two groups: TPN plus SBS (Control group) or TPN plus SBS plus intravenous administration of HGF (HGF group). On day 7, the rats were harvested, and hepatocellular injury was evaluated. Results: In an SBS rat model, hepatic steatosis and lobular inflammation were histologically suppressed in the HGF group (p < 0.01). The expression of tumor necrosis factor-α in the HGF group tend to be higher than that in the control group (p = 0.13). The gene expression of transforming Growth Factor-β in the HGF group was suppressed compared to the control group (p < 0.01). HGF treatment may have an antiapoptotic effect via the intrinsic pathway by caspase 9. Protein expressions of Rubicon (p = 0.03) and p62 (p < 0.01) in the HGF group were found to have increased compared to those in the control group. Conclusion: The inhibitory effect of HGF on hepatic steatosis remains unclear, and further studies focusing on the mechanisms of fat accumulation are needed. [ABSTRACT FROM AUTHOR]

Introduction: After extensive small and colon resections, quality of life can be affected. We propose the antiperistaltic transverse coloplasty as a solution that allows for preservation of the transverse colon after both right and left colectomies while achieving a tension-free colorectal anastomosis slowing the transit and increasing the absorption time, resulting in better stool consistency and quality of life compared with an ileorectal anastomosis. Methods: This technique was performed in a 41-year-old woman with Goblet cell adenocarcinoma of the appendix with peritoneal metastasis. The transverse colon is rotated anticlockwise over the axis of the middle colic vessels toward the left parietocolic flank and relocated to the usual position of the descending colon. Results: After 1 year of follow-up, the patient led a normal life without parenteral nutrition with five bowel movements per day and a weight gain of 15%. Conclusions: The use of an antiperistaltic transverse coloplasty may be worthwhile to perform in cases of extensive bowel resections during cytoreductive surgery leading to short-bowel syndrome to avoid a permanent stoma or intestinal failure and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) is a severe, life-threatening condition and one of the leading causes of intestinal failure in children. Here we were interested in changes in muscle layers and especially in the myenteric plexus of the enteric nervous system (ENS) of the small bowel in the context of intestinal adaptation. Twelve rats underwent a massive resection of the small intestine to induce SBS. Sham laparotomy without small bowel transection was performed in 10 rats. Two weeks after surgery, the remaining jejunum and ileum were harvested and studied. Samples of human small bowel were obtained from patients who underwent resection of small bowel segments due to a medical indication. Morphological changes in the muscle layers and the expression of nestin, a marker for neuronal plasticity, were studied. Following SBS, muscle tissue increases significantly in both parts of the small bowel, i.e., jejunum and ileum. The leading pathophysiological mechanism of these changes is hypertrophy. Additionally, we observed an increased nestin expression in the myenteric plexus in the remaining bowel with SBS. Our human data also showed that in patients with SBS, the proportion of stem cells in the myenteric plexus had risen by more than twofold. Our findings suggest that the ENS is tightly connected to changes in intestinal muscle layers and is critically involved in the process of intestinal adaptation to SBS. [ABSTRACT FROM AUTHOR]

Background: Small bowel cancer is very rare, accounting for less than 5% of all gastrointestinal cancers, and small bowel adenocarcinoma accounts for approximately 40% of all small bowel cancers. Small bowel adenocarcinoma is often found in advanced stages, with only 40–65% of cases being curatively resectable. The prognosis is poor, with a 5-year survival rate of 14–33% for all patients and 40–60% for those who are curatively resectable. In Japan, practice guidelines for duodenal cancer were instituted in 2021. However, evidence-based standard treatments have not been established for jejunal and ileal cancers. In particular, chemotherapeutic options are limited, and there are only a few reports on multidisciplinary treatments, including adjuvant chemotherapy. Case presentation: We report five cases of jejunal or ileal lesions that were treated with adjuvant chemotherapy after radical resection. Three patients were male and two were female, with a median age of 67 years. Tumor localization was observed in the jejunum in all cases. Clinical staging was as follows: stage IIIA in two cases and stage IIIB in three cases. Laparotomy was then performed in all cases, employing partial resection with lymph node dissection. Pathological staging in all cases was as follows: stage IIB in two cases, stage IIIA in one case, and stage IIIB in two cases. In all cases, the regimen for adjuvant chemotherapy was selected based on the colorectal cancer guidelines. No serious complications arose from adjuvant therapy; however, adverse events occurred in patients receiving multi-agent chemotherapy. No recurrence was observed in any of the cases, and all the patients survived, with a median survival time of 32 months. As a representative case, we present a case of adjuvant chemotherapy for jejunal adenocarcinoma staged as pT3N2M0, pStage IIIB, with no recurrence at 32 months postoperatively. Conclusions: In general, favorable outcomes were achieved with adjuvant therapy applied in accordance with the criteria for colorectal cancer. These favorable outcomes suggest that it is necessary to identify the risk factors and indications for adjuvant therapy, specifically for small bowel adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: The incidence and risk factors of catheter-related bloodstream infections (CRBSI) in patients with intestinal failure (IF) have not been established, partly because catheter management methods vary from different facilities. This study aimed to identify the risk factors and incidence rate of CRBSIs in patients with IF who were given prophylactic treatment. Methods: Sixteen patients with IF who required home parenteral nutrition were enrolled in this study. Prophylactic management of CRBSI included monthly ethanol lock therapy and standardized infection prevention education. The outcomes included the incidence and risk factors of CRBSI. Results: The median incidence rate of CRBSI was 1.2 per 1000 catheter days. Univariate analysis showed that the risk of developing CRBSI was significantly associated with short bowel syndrome (< 30 cm) (p = 0.016). Other relevant findings included a significant negative correlation between serum albumin and CRBSI rate (r = − 0.505, p = 0.046), and past history of mixed bacterial infections was significantly associated with increased CRBSI rate (p = 0.013). Conclusion: CRBSIs can still develop despite undergoing prophylactic management. Risk factors for CRBSI include the residual intestinal length, nutritional status, and susceptibility to certain microorganisms. [ABSTRACT FROM AUTHOR]

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype–phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first 'European Forum on Visceral Myopathy'. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy. [ABSTRACT FROM AUTHOR]

Background: Acute superior mesenteric artery (SMA) occlusion is an uncommon condition associated with high mortality. If extensive bowel resection is performed for patients with acute SMA occlusion and the patient survives, long-term total parenteral nutrition (TPN) may be needed due to short bowel syndrome. This study examined factors associated with the need for long-term TPN after the treatment of acute SMA occlusion. Methods: We retrospectively analyzed 78 patients with acute SMA occlusion. Patients were abstracted from a Japanese database from institutions with at least 10 patients with acute SMA occlusive disease from January 2015 through December 2020 Results: Among the initial cohort there were 41/78 survivors. Of these, 14/41 (34%) required permanent TPN who were compared with those who did not require long-term TPN (27/41, 66%). Compared to patients in the non-TPN group, those in the TPN group had significantly shorter remaining small intestine (90.7 cm vs. 218 cm, P<0.01), more patients with time from onset to intervention >6 hours (P=0.02), pneumatosis intestinalis on enhanced computed tomography scan (P=0.04), ascites (Odds Ratio 11.6, P<0.01), and a positive smaller superior mesenteric vein sign (P= 0.03). These were considered significant risk factors for needing long-term TPN. Age, gender, underlying disease, presence of peritoneal sign, presence of shock requiring vasopressors, site of obstruction (proximal vs. distal), and initial treatment (surgery vs. interventional radiology vs. thrombolytic therapy) were not significantly different between the two groups. Long-term TPN was significantly associated with longer hospital stay (52 vs. 35 days, P=0.04). Multivariate analysis identified the presence of ascites as an independent risk factor for needing long-term TPN. Conclusion: The need for permanent TPN after treatment of acute SMA occlusion is significantly associated with longer hospital stay, longer time to intervention, and characteristic imaging findings (pneumatosis intestinalis, ascites, Smaller SMV sign). Ascites is an independent risk factor. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal transplantation (ITx) is the ultimate treatment for intestinal failure (IF). In Japan, most cases of IF are a result of pediatric disease, including secondary or congenital intestinal disease or allied disorders of Hirschsprung's disease. Here, we report the results of the Japanese ITx registry. Methods: A web-based survey form was completed. We investigated the number, age, sex, indication, surgical procedure, immunosuppressants, postoperative course, and the effects of transplantation in patients who underwent cadaveric or living-donor ITx. Results: By the end of 2022, 42 cases of ITx have been performed in 38 patients in Japan. The donor sources included cadavers (29 cases) and living donors (13 cases). The surgical method was isolated ITx (N = 40) and combined liver and ITx (n = 2). Survival rates were 92%, 73%, and 59% at 1 year, 5 years, and 10 years, respectively. Ninety percent of patients completely discontinued parenteral nutrition. Approximately 80% of the patients had a performance status of 1 or less, indicating that the QOL of patients after ITx was extremely good. Conclusion: The results of ITx are acceptable to treat IF patients and the QOL after transplantation is also good. [ABSTRACT FROM AUTHOR]

Hirschsprung disease (HSCR) is a congenital disorder caused by the failure of enteric neural crest cells (ENCCs) to colonize the distal bowel, resulting in absence of enteric nervous system. While a range of molecules and signaling pathways have been found to contribute to HSCR development, the risk factors and pathogenesis of this disease in many patients remain unknown. We previously demonstrated that increased activity of the prostaglandin E2 (PGE2)/PGE2 receptor subtype EP2 pathway can be a risk factor for HSCR. In this study, an Ednrb-deficient mouse model of HSCR was generated and used to investigate if PGE2/EP2 pathway could be a potential therapeutic target for HSCR. We found that downregulation of PGE2/EP2 signaling by siRNA-mediated ablation of a PGE2 synthase or pharmacologic blockage of EP2 enhanced ENCC colonization in the distal bowel of Ednrb−/− mice and alleviated their HSCR-like symptoms. Furthermore, blockage of EP2 was shown to promote ENCC migration through upregulating p38 mitogen-activated protein kinase activity, which was downregulated in the colon of Ednrb−/− mice and in the distal aganglionic bowel of HSCR patients. These data provide evidence that maternal exposure during embryonic development to an environment with dysregulated activation of the PGE2/EP2 pathway may predispose genetically susceptible offspring to HSCR, and avoidance or early disruption of maternal events (e.g. inflammation) that possibly enhance PGE2/EP2 signaling during pregnancy would reduce the occurrence and severity of this disease. Key messages: Knockdown of PTGES alleviates HSCR severity in Ednrb−/− mice. Blockage of EP2-mediated PGE2 signaling alleviates HSCR severity in Ednrb−/− mice. Blockage of EP2-mediated PGE2 signaling promotes ENCC migration via enhancing p38 activity. [ABSTRACT FROM AUTHOR]

To date, teduglutide, a peptide analog to the endogenous Glucagon-Like Peptide-2 (GLP-2), represents the most effective pharmacologic treatment to improve the absorption of nutrients in short bowel syndrome (SBS) patients. Currently, this peptide drug cannot be administered orally due to its negligible permeability and rapid degradation in the gastrointestinal tract; and thus, requires patients to take daily sub-cutaneous injections. In SBS patients, oral drug delivery has additional challenges because the site of absorption, the intestine, is short and less functional. Results of the reported herein study in rats, indicate that a novel, SNAC-based oral drug delivery platform designed to enable gastro-mucosal absorption of therapeutic peptides and proteins, may be utilized for the delivery of intestinotrophic peptides in the unique population of SBS patients, as a convenient alternative to daily injections. [ABSTRACT FROM AUTHOR]

Purpose of Review: Anastomotic ulceration following intestinal resection is an under- recognized problem in pediatrics. We discuss the relevant literature regarding this condition. Recent Findings: Anastomotic Ulceration following intestinal resection is a potentially life threatening cause of refractory anemia. Evaluation should include correction of micronutrient deficiencies and endoscopic evaluation by upper and lower endoscopy and small intestinal endoscopy if necessary. Initial treatment by medical therapy may consist of anti-inflammatory agents as well as antibiotics to treat small intestinal bacterial overgrowth. Surgical resection should be considered if refractory to treatment. Summary: Anastomotic ulcers in pediatric patients with small bowel resection should be considered as a cause of refractory iron deficiency anemia. Endoscopic evaluation should be undertaken to look for evidence of anastomotic ulcers. Surgical resection should be considered if medical therapy fails. [ABSTRACT FROM AUTHOR]

Purpose of Review: Intestinal adaptation is the main treatment goal in short bowel syndrome to control symptoms and improve health-related quality of life. This can be achieved in part through the use of medical therapies as well as parenteral and enteral nutrition, including oral dietary choices. This review will focus on dietary and medical management of short bowel syndrome and offer insights into novel nutritional and pharmacological approaches that may benefit patients. Recent Findings: A balanced oral diet inclusive of whole plant-based foods may be beneficial in short bowel syndrome for reasons including alleviating symptoms, preventing disease-related complications, and optimizing the intestinal microbiome. Adjunctive medical therapies are often needed to improve symptoms, treat comorbid conditions, and reduce reliance on parenteral nutrition. Summary: Though treatment must be tailored to individual anatomy and symptoms, newer dietary and pharmacologic approaches may be promising for short bowel patients. Future prospective studies are needed to further understand their efficacy. [ABSTRACT FROM AUTHOR]

Background: Glepaglutide is a novel, ready-to-use, long-acting, glucagon-like peptide-2 (GLP-2) analog intended for the treatment of patients with short bowel syndrome (SBS). This study investigated the impact of renal function on the pharmacokinetics and safety of glepaglutide. Methods: In this 3-site, non-randomized, open-label study, 16 subjects were enrolled: 4 with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m2), 4 with end stage renal disease (ESRD) not on dialysis (eGFR < 15 mL/min/1.73 m2), and 8 matching controls with normal renal function (eGFR ≥ 90 mL/min/1.73 m2). Blood samples were collected over a 14-day period following a single subcutaneous (SC) dose of glepaglutide 10 mg. Safety and tolerability were assessed throughout the study. The primary pharmacokinetic parameters were area under the curve between dosing and 168 h (AUC0–168 h) and the maximum plasma concentration (Cmax). Results: There was no clinically relevant difference between subjects with severe renal impairment/ESRD and normal renal function with respect to total exposure (AUC0–168 h) and peak plasma concentrations (Cmax) of glepaglutide following a single SC dose. A single SC dose of glepaglutide 10 mg appeared safe and well tolerated in subjects with normal renal function and subjects with severe renal impairment or ESRD. No serious adverse events were reported, and no safety issues were identified. Conclusions: No difference in glepaglutide pharmacokinetics was seen between renal impaired and normal subjects. Based on this trial, dose adjustment appears not to be warranted in SBS patients with renal impairment. Trial Registration: The trial is registered at http://www.clinicaltrials.gov (NCT04178447) and has the EudraCT number: 2019-001466-15. [ABSTRACT FROM AUTHOR]

Purpose: The short- and long-term efficacy, safety, and pharmacokinetics of teduglutide were analyzed in adult Japanese patients with short bowel syndrome and intestinal failure (SBS-IF). Methods: Patients received teduglutide 0.05 mg/kg/day in clinical trials (TED-C14-004, SHP633-306, and extension SHP633-307). Data were analyzed at 24 weeks and an interim data cut-off of 4.5 years. Results: The parenteral support (PS) volume decreased by ≥ 20% for 9/18 patients at 24 weeks and in all 11 patients by data cut-off in SHP633-307. The mean (standard deviation) PS volume decreased from baseline at 24 weeks in TED-C14-004 (−30.1 ± 25.9%) and SHP633-306 (−25.6 ± 25.5%), and at data cut-off in SHP633-307 (−57.08 ± 28.49%). Teduglutide was absorbed quickly. The adverse events were consistent with the underlying disease and known adverse drug reactions. Anti-teduglutide antibody titers declined with long-term treatment. Conclusions: In Japanese adults with SBS-IF, teduglutide treatment was associated with clinically meaningful reductions in PS requirements, similar to findings in prior international studies. No new safety concerns specific to the Japanese SBS-IF patient population were identified with short- or long-term teduglutide treatment. Anti-teduglutide antibody titers disappeared in most Japanese adults with long-term treatment. These results constitute the longest evaluation of teduglutide treatment within clinical trials reported to date. [ABSTRACT FROM AUTHOR]

Nearly all patients with systemic sclerosis (SSc) are negatively affected by dysfunction in the gastrointestinal tract, and the severity of gastrointestinal disease in SSc correlates with high mortality. The clinical complications of this dysfunction are heterogeneous and include gastro-oesophageal reflux disease, gastroparesis, small intestinal bacterial overgrowth, intestinal pseudo-obstruction, malabsorption and the requirement for total parenteral nutrition. The abnormal gastrointestinal physiology that promotes the clinical manifestations of SSc gastrointestinal disease throughout the gastrointestinal tract are diverse and present a range of therapeutic targets. Furthermore, the armamentarium of medications and non-pharmacological interventions that can benefit affected patients has substantially expanded in the past 10 years, and research is increasingly focused in this area. Here, we review the details of the gastrointestinal complications in SSc, tie physiological abnormalities to clinical manifestations, detail the roles of standard and novel therapies and lay a foundation for future investigative work. Gastrointestinal dysmotility is a major complication of systemic sclerosis but remains poorly understood. In this Review, the authors discuss the current understanding of systemic sclerosis gastrointestinal disease, existing and emerging therapies, and promising directions for future research Key points: Gastrointestinal disease in systemic sclerosis (SSc) is complex in its clinical presentation, physiology and mechanisms. Data suggest that the neuromuscular pathways that control gastrointestinal motility are dysfunctional in SSc and are a target of the autoimmune response in some patients. Identifying the part or parts of the gut affected and the type of gastrointestinal abnormality that is present can help to guide therapy. The microbiome is probably an important contributor to gastrointestinal symptoms in SSc, although the extent of its involvement and the role of dysbiosis in diagnosis and guiding therapy are unclear. Research is underway to better understand the mechanisms of gastrointestinal disease in SSc, and to optimize the approach to management. [ABSTRACT FROM AUTHOR]

To the Editor, We report the case of a 26-year-old male bone marrow transplant (BMT) recipient who presented 150 days post-transplantation with a painful nodular rash, preceded by weeks of intermittent confusion, with radiographic imaging findings of a frontal lobe lesion. One patient out of the reported cohort of 14 BMT patients had sinus involvement only without additional organ system involvement and was the longest surviving reported case following I Acanthamoeba i infection [[4]]. A repeat brain MRI with contrast 4 weeks after treatment initiation demonstrated slight interval decrease in the frontal lobe lesions. [Extracted from the article]

Short bowel syndrome (SBS) is a chronic disease whose natural history requires a changing array of management strategies over time. Chief amongst these is the chronic use of parenteral nutrition (PN) to ensure adequate nutritional intake. With time and appropriate management, approximately half of all SBS patients will successfully regain a functional, baseline level of intrinsic bowel function that will allow for them to achieve PN independence. However, the other half of SBS patients will progress into chronic intestinal failure which warrants a change in therapy to include more aggressive medical and potentially surgical measures. This review examines the evolving treatment strategies involved in the management of SBS as well as intestinal failure. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to analyze the evidence regarding the appropriateness of PEG placement in the following clinical situations: short bowel syndrome, head and neck cancer, dementia and palliative use in malignant bowel obstruction. Recent Findings: Percutaneous endoscopic gastrostomy (PEG) tubes are placed for a variety of clinical indications by numerous different specialties. First described in 1980, PEG tubes are now the dominant method of enteral access. Typically, PEG tubes are technically feasible procedures that can come with significant risk for both minor and major complications. Therefore, it is important to perform an in-depth, patient specific risk-benefit analysis when considering insertion. Summary: By analyzing the current evidence regarding benefits in these situations, superimposed by the lens of biomedical ethics, we make recommendations that are accessible to any provider who may be a consultant or proceduralist, helping to provide informed care that is in the patient's best interest. [ABSTRACT FROM AUTHOR]

Background: Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed. Aims: We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development. Methods: HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8–9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR performed. Morphology was evaluated and epithelial architecture graded on a scale of 1 (absence of crypts/villi) to 4 (elongated crypt-villus axis). RT-qPCR and immunofluorescence microscopy were performed for epithelial and mesenchymal differentiation markers. Results: Host survival and tHIO engraftment were equivalent in male and female hosts. tHIO weight and length were also equivalent between groups. The number of lumens per tHIOs from male and female hosts was similar, but the mean lumen circumference was larger for tHIOs from male hosts. tHIOs from male hosts were more likely to demonstrate higher grades of epithelial development. However, both groups showed similar differentiation into secretory and absorptive epithelial lineages. Markers for intestinal identity, mesenchymal development, and brush border enzymes were also expressed similarly between groups. Conclusions: While male host sex was associated with larger tHIO lumen size and mucosal maturation, tHIOs from both groups had similar engraftment, growth, and epithelial and mesenchymal cytodifferentiation. [ABSTRACT FROM AUTHOR]

Purpose: Each year, between 100 and 200 cases with shaken baby syndrome (SBS) are hospitalized in Germany. The reported incidence is 14 in 100,000 children. About 10 to 30% of the affected children do not survive. A high number of unreported cases are assumed. The rate of lifelong disability is high. The current situation in respect of abusive head injuries in infants has been investigated. Material and methods: A case-based overview on the management of SBS in a German reference center for pediatric neurosurgery is presented and discussed against the background of forensic data and child protection network institutions and guidelines. Results: The presented case is an example of a typical SBS presentation. All necessary diagnostic and therapeutic steps are explained and evaluated according to the existing guidelines in Germany. The authors state that hospital SOP can help to detect suspected cases of SBS and define the role of the pediatric neurosurgeon. Although the abusive mechanism of a head trauma is clear in most cases, forensic methods lack the precision to identify a perpetrator in all of them. According to an analysis of a multi-center study on criminal proceedings in Germany, 50% of the proceedings were closed without judgment due to lack of suspicion. Out of the remaining half with judgment, in 17%, the court decided on acquittal since the perpetration could not be assigned to a specific individual. Conclusion: Prevention is the most important factor to protect children from death and disability caused by inflicted brain injury. Pediatric healthcare professionals must be aware of typical signs of suspected child abuse, SBS in particular, and institutional SOP can help to improve management and outcome in these children. Forensic methods lack the precision to identify a perpetrator in every case. [ABSTRACT FROM AUTHOR]

Introduction: Abusive head injuries is a major cause of severe morbidity and the main cause of mortality by head trauma in infants. Material and methods: Based on published data and their own clinical and medicolegal practice, the authors review briefly the historical roots and emergence of the concept of abusive head injuries (AHI), until the present scientific understanding of shaken baby syndrome (SBS) and Silverman syndrome. They then discuss the present epidemic of denialism and how this challenge to science should be seen as a stimulus to increase research and improve the accuracy of diagnosis and medical practice. Results: The denial of SBS is especially damaging because it undermines the possibilities of prevention and reparation for victims. The authors expand on AHI being part of a wider context of domestic violence and the prevention of child abuse being part of a broad and long-term endeavor to defend civilization values. Conclusions: Prevention of AHI is a major challenge for the future. In the fields of science and prevention of child abuse, the input of pediatric neurosurgeons should not be underestimated. [ABSTRACT FROM AUTHOR]

Purpose: The number of accessible central veins (CVs) affects the prognosis of patients with intestinal failure (IF). The loss of residual CVs should be avoided. We, therefore, evaluated the efficacy of a new CV catheter-exchange technique using a subcutaneous fibrous sheath (FS) in pediatric IF patients. Methods: We retrospectively collected the CV catheter (CVC) data of pediatric IF patients managed from January 2009 to December 2019. The data were divided into two groups; Groups 1 (CVCs placed with the FS method) and Group 2 (CVCs placed by the primary or another insertion). The main outcome was the CVC indwelling time. Results: Eighty-five CVCs were analyzed. The FS method was attempted in 47 cases and succeeded in 40 (85%). No significant difference was observed between the groups regarding characteristics. A log-rank test revealed an equivalent CVC indwelling time between the two groups (Group 1: 268 [126–588] days vs. Group 2: 229 [126–387] days, p = 0.256). Conclusions: The FS method is highly recommended for pediatric IF patients, as its attempt showed a high success rate with an indwelling time equivalent to primary insertion. The FS method leads to the prolonged use of a single CV and thereby contributes to improving the outcomes of pediatric IF patients. [ABSTRACT FROM AUTHOR]

Purpose: Intestinal dysmotility (ID) problems are common in patients with pediatric-onset intestinal failure (IF) and short bowel syndrome (SBS), leading to significant morbidity and delays in the advancement of enteral nutrition (EN). We aimed to investigate the clinical features and complications of ID in children with IF and SBS. Methods: Retrospective chart review of all children with IF and/or SBS who required parenteral nutrition (PN) > 6 weeks or small-intestinal resection ≥ 50%. Patients were divided into SBS and non-SBS groups. SBS group was divided into two subgroups: with and without ID. Patients with ID were identified (clinically, radiologically and functionally) and analyzed with regard to demographics, intestinal anatomy, complications and outcomes (short and long term). Results: A total of 42 children with IF were treated in our institution during 2003–2022. In non-SBS group (n = 10), ID was the most common cause of IF (80%). SBS-group included 32 children; 18 children (56%) developed ID. The clinical profile of SBS-ID patients (vs SBS) was: female gender (56%), remaining small bowel length ≤ 55 cm, estimated residual small bowel ≤ 28% (p = 0.045) and absence of ICV (56%). Common symptoms of the SBS-ID group were: food intolerance (61%), abdominal distension (50%), vomiting (44%), malabsorption and severe constipation. Complications included FTT (67%) (p = 0.003), bacterial overgrowth with subsequent bloodstream infection (33%) (p = 0.75), and lactic acidosis (11%). Lengthening procedure (STEP) was performed in 11 SBS-ID patients (61%) (p = 0.002). In all patients, STEP operation "rescued" their dysfunctional intestine. Eight of these patients (73%) were weaned from TPN. Survival rate was 100%; however, one SBS-ID patient is a candidate for combined intestinal and liver transplantation. Conclusions: ID is the most common complication of SBS and is the most common cause of IF in non-SBS patients. ID has a high morbidity rate and various clinical manifestations. Successful treatment of these infants may be achieved with the use of tapering enteroplasty. [ABSTRACT FROM AUTHOR]

Purpose: The gut microbiota, via the gut-liver axis, plays an important role in the development of intestinal failure-associated liver disease. Here, we investigated whether partially hydrolyzed guar gum (PHGG), a dietary fiber could alleviate liver damage and modulate the gut microbiota in a murine liver injury (LI) model. Methods: Liver injury was induced in 6-week-old male C57BL/6 mice using an enteral liquid diet composed of parenteral nutrition (LI group) and treated with 5% PHGG (LI/PHGG group). Liver histopathology was examined using oil red O and a tumor necrosis factor-α (TNF-α) labeling. The gut microbiota was examined using 16S rRNA gene sequencing. Results: Lipid accumulation was significantly decreased in the LI /PHGG group when compared with that of the LI group. The area of TNF-α-positive cells was significantly higher in the LI group when compared with that of the control. The principal coordinate analysis (PCoA) revealed pronounced changes in the gut microbiota after PHGG treatment. Linear discriminant analysis of effect size showed that PHGG treatment significantly increased cecal abundance of Parabacteroides. Conclusions: PHGG alleviated hepatic steatosis following liver injury in mice. The protective effect of PHGG treatment could be associated with increased abundance of Parabacteroides in the cecum. [ABSTRACT FROM AUTHOR]

Background and Objective: Glepaglutide is a novel, long-acting, glucagon-like peptide-2 analogue in a stable aqueous formulation for subcutaneous dosing to treat patients with short bowel syndrome. This study was conducted primarily to characterise the pharmacokinetics of glepaglutide in healthy subjects. Methods: In this open-label, partially randomised, parallel-group study, healthy subjects were evenly randomised to glepaglutide 5 or 10 mg dosed subcutaneously once weekly for 6 weeks or to a single intravenous infusion of glepaglutide 1 mg. Each group comprised 15 subjects. Blood samples were drawn to determine plasma concentrations of the parent drug and its two main metabolites. Concentrations of glepaglutide were calculated as the sum of these three analytes. Citrulline was included as a pharmacodynamic biomarker. Safety was assessed throughout the study. Results: From a comparison of pharmacokinetic parameters following subcutaneous versus intravenous dosing, it is concluded that the pharmacokinetics of glepaglutide following subcutaneous dosing are primarily determined by slow release of the two main glepaglutide metabolites from a subcutaneous depot. For subcutaneous dosing once weekly, the two main metabolites accounted for >98% of the overall glepaglutide exposure at steady state, with the parent drug contributing to less than 1% of exposure. The estimated mean (95% confidence interval) effective half-life for glepaglutide 5 and 10 mg was 124 (73–185) h and 88 (31–146) h, respectively. There was an increase in the citrulline concentration for both glepaglutide subcutaneous dose levels. No safety issues were identified. Conclusions: Slow release of active metabolites following subcutaneous dosing leads to a significantly protracted pharmacokinetic profile for glepaglutide. These results support that once- or twice-weekly subcutaneous dosing of glepaglutide could be an efficacious therapy for intestinal rehabilitation. Clinicaltrials.gov Identifier: NCT03279302. [ABSTRACT FROM AUTHOR]

Children with short bowel syndrome (SBS) are at high risk for intestinal failure associated liver disease (IFALD). The aim of this retrospective follow-up study was to compare weaning off parenteral nutrition (PN) and IFALD between necrotizing enterocolitis (NEC) and non-NEC induced SBS. Altogether, 77 patients with neonatal SBS treated by our multidisciplinary intestinal failure unit (NEC n = 38, non-NEC SBS n = 39) were included and followed-up at least for 2 years until median age of 10 years (interquartile range, 6.0–16). Occurrence and characteristics of IFALD was assessed with liver biopsies obtained at median age of 3.2 (1.0–6.7) years (n = 62) and serum liver biochemistry. Overall, NEC patients had less end-jejunostomies and autologous intestinal reconstruction surgeries performed compared to non-NEC patients (< 0.05), while remaining small bowel anatomy was comparable between groups. Cumulative weaning off PN was more frequent and duration of PN shorter among NEC patients (P < 0.05). Overall cumulative probability of histological IFALD was lower among NEC patients during whole follow-up period (P = 0.052) and at 10 years (P = 0.024). NEC patients had lower ALT and GGT levels at last follow-up (P < 0.05 for all). In univariate Cox regression analysis, absence of end-jejunostomy, NEC diagnosis, longer remaining small bowel length, multidisciplinary treatment and prematurity were predictive for weaning off PN, while NEC diagnosis and lower birth weight in addition to multidisciplinary care protected from histological IFALD. Neonates with NEC induced SBS reached enteral autonomy earlier than those with non-NEC SBS, which associated with more efficient resolution of histological IFALD among long-term survivors. [ABSTRACT FROM AUTHOR]

Infants with congenital heart disease (CHD) often require supplemental nutrition via tube feeding, even after corrective surgical repair. The need for tube feeding can persist months after discharge home, and outpatient weaning from the tube can be a slow and difficult process. Lack of consensus exists in the literature as to the best approach to this challenge. We describe a single institution's initiative to decrease tube dependency after discharge through an intensive, telehealth-centric program for children with CHD. Of 16 children aged 1–26 months, 94% were able to be successfully tube weaned at home, with median time to tube-free of 12 days. No significant weight loss was noted during or after the wean process. Longer tube wean time was associated with older age at onset and comorbid genetic syndrome. Our telehealth-based intensive tube weaning program was successful but required a multidisciplinary team, targeted pre-participation patient evaluation, and frequent communication. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve replacement (TAVR) offers a solution, especially for high-risk aortic stenosis (AS) patients. However, patient outcomes post-TAVR show variability, highlighting the need for reliable prognostic indicators. Brachial–ankle pulse wave velocity (baPWV), a measure of arterial stiffness, may predict outcomes post-TAVR. This study aims to explore baPWV’s prognostic value in relation to all-cause mortality post-TAVR. This study prospectively enrolled 212 severe AS patients undergoing TAVR between September 2015 and December 2021, focusing on pre- and post-TAVR baPWV measurements to explore associations with all-cause mortality. Of the 212 patients (119 females, 93 males, mean age 85 years), post-TAVR baPWV increased significantly from 1589 ± 376 to 2010 ± 521 cm/s (p < 0.001). Aortic valve (AV) peak velocity and mean pressure gradient decreased, while AV area increased, indicating procedural success. Despite this, 88% of patients experienced an increase in baPWV, with higher pre-procedure AV peak velocity and mean pressure gradient identified as predictors of increased baPWV post-TAVR. Over 23 months, 29 patients (14%) reached the primary endpoint of all-cause mortality. Notably, changes in baPWV, rather than baseline values, were significantly associated with event-free survival (HR: 0.64 per 1SD increase, p = 0.009). The study highlights the prognostic value of baPWV changes post-TAVR in predicting patient outcomes. Elevated baPWV post-TAVR may reflect a beneficial adaptation to altered hemodynamics, suggesting the need for individualized patient evaluation and the integration of baPWV measurements into clinical practice for improved post-TAVR management. [ABSTRACT FROM AUTHOR]

Background: Short bowel syndrome (SBS) is a rare yet costly disease with an incidence rate of 3 per million people. Herein, we report a rare case of eosinophilic gastrointestinal disorders (EGIDs) with SBS after strangulated bowel obstruction. Case presentation: A 5-year-old male had a necrotic intestine of 340 cm resected due to strangulated bowel obstruction caused by an intestinal mesenteric hiatal hernia. The length of the residual intestine was 51 cm. Bloody stools appeared 19 days postoperatively. Colonoscopy showed diffuse redness of the colonic mucosa, and pathological findings showed moderate chronic inflammatory cellular infiltration. On blood examination, the eosinophil count was > 30%. EGIDs with short bowel syndrome (SBS) were suspected. Because his symptoms did not improve with initial nutrition therapy, he was transferred to our hospital 5 months after the operation. Prednisolone was administrated at an initial dose of 1.4 mg/kg/day, 6 days after his transfer. Bloody stools disappeared after prednisolone administration. Seven months after discharge, he had no bloody stool recurrence. Conclusion: The risk of developing secondary EGIDs in children with SBS should be considered, and postoperative management should include attention to abdominal symptoms and elevated eosinophil counts on blood examination. [ABSTRACT FROM AUTHOR]

Purpose: Short bowel syndrome (SBS) with intestinal failure (SBS-IF) requires long-term parenteral nutrition (PN). This study investigated the real-world etiologies of SBS, treatment patterns, and PN-related outcomes among adult patients with SBS-IF in Japan. Methods: This retrospective, observational cohort study was based on data from April, 2008 to January, 2020 from one of the largest hospital-based claim databases in Japan. Analyzed patients were aged ≥ 16 years, had received continuous PN for ≥ 6 months, and had SBS or undergone SBS-related surgery with a diagnosis of a causative disease. The primary endpoint was PN weaning. Results: We analyzed data for 393 patients. The most frequent causes of SBS-IF were ileus (31.8%), Crohn's disease (20.1%), and mesenteric ischemia (16.0%). Of 144/393 (36.6%) patients who were weaned off their PN, 48 (33.3%) were subsequently restarted on PN. Of 276/393 (70.2%) patients whose PN was initiated in hospital, 156 (56.5%) transitioned to home management. The mean duration of initial PN was 450.4 and 675.5 days for patients who were able or unable to be weaned off PN, respectively. Sepsis (67.4%), catheter-related bloodstream infections (49.1%), and liver disorders (45.0%) were the most reported PN-related complications. Conclusions: Most patients with SBS-IF in Japan could not be weaned off PN and suffered life-threatening complications. [ABSTRACT FROM AUTHOR]