D-lactic Acidosis Research Articles

Lactate dehydrogenase D is a general dehydrogenase for D-2-hydroxyacids and is associated with D-lactic acidosis

Mammalian lactate dehydrogenase D (LDHD) catalyzes the oxidation of D-lactate to pyruvate. LDHD mutations identified in patients with D-lactic acidosis lead to deficient LDHD activity. Here, we perform a systematic biochemical study of mouse LDHD (mLDHD) and determine the crystal structures of mLDHD in FAD-bound form and in complexes with FAD, Mn2+ and a series of substrates or products. We demonstrate that mLDHD is an Mn2+-dependent general dehydrogenase which exhibits catalytic activity for D-lactate and other D-2-hydroxyacids containing hydrophobic moieties, but no activity for their L-isomers or D-2-hydroxyacids containing hydrophilic moieties. The substrate-binding site contains a positively charged pocket to bind the common glycolate moiety and a hydrophobic pocket with some elasticity to bind the varied hydrophobic moieties of substrates. The structural and biochemical data together reveal the molecular basis for the substrate specificity and catalytic mechanism of LDHD, and the functional roles of mutations in the pathogenesis of D-lactic acidosis.

SAT136 Severe Lactic Acidosis Due To Metformin Use.

Abstract Disclosure: A. Khan: None. Lactic acidosis is an important cause of metabolic acidosis. Broadly, etiology can be divided into type A (impaired tissue oxygenation), type B (systemic hypoperfusion), and D-lactic acidosis. One such etiology which deserves mentioning is metformin associated lactic acidosis (MALA). The incidence of MALA is more notable in the setting of kidney dysfunction, hepatic failure, and alcohol use. Severe acidosis due to Metformin is an emergency and warrants timely management to avoid further hemodynamic compromise. 73-year-old female with a history of hypertension and type II diabetes mellitus (on metformin) presented to the hospital with acute onset of abdominal pain, nausea, and vomiting. She reported having intermittent vomiting and diarrhea for three days prior to admission, and describes the abdominal pain as 10/10, sharp with radiation to the lower back, and worsening 6 hours prior to arrival. She denies fever, melena, hematochezia, change in appetite. She was brought to the hospital via EMS and was given fentanyl for her pain. Vitals on arrival were stable. On exam, she appeared in distress due to pain, with diffuse tenderness in her abdomen, with normal cardiac and lung exam. Labs showed leukocytosis 15 K/mm3, hemoglobin 11.1 gm/dl, hyperkalemia 5.7 mEq/L, bicarb <5 mEq/L, creatinine 13.4 mg/dl, BUN 107 mg/dl, venous lactate 15.1 mmol/l, lipase 435 U/L, ammonia 229 umol/L, with normal AST, ALT and ALP, and troponin. Urinalysis was negative. Initial ABG showed an unreadable pH, which was then repeated, and pH was noted to be 6.72, pCO2 of 29.4 mm/hg, CTA angiography was negative for dissection, mesenteric or bowel ischemia. Soon she was noted to be hypotensive and went into shock requiring pressors, bicarbonate drip, and broad-spectrum antibiotics. She eventually was intubated for airway protection. Subsequently, she was admitted to the ICU for possibly combined hypovolemic and septic shock with multi-organ dysfunction, severe lactic acidosis, acute kidney failure, and respiratory failure. Nephrology was consulted and dialysis was initiated. It was postulated that the presentation was likely due to metformin associated lactic acidosis (MALA). She required dialysis daily for 4 days and ultimately her kidney function improved. On discharge, she was not dialysis dependent. The case above illustrates the severity of lactic acidosis that can occur due to Metformin use. It is important to bear in mind that such presentation, may not necessarily occur on initiation of Metformin, but rather at any point of use. More importantly, its of utmost importance to consider effective therapeutic options like dialysis once severe academia is noted to allow correction of metformin induced acid-base disorder. Mortality estimates of MALA have been around 25-50%, highlighting the significance of prompt treatment of this condition. Presentation: Saturday, June 17, 2023

Gut Microbial Changes Following Fecal Microbiota Transplantation for D-Lactic Acidosis in Two Children.

D-lactic acidosis (D-LA) is an uncommon complication of short bowel syndrome characterized by elevated plasma D-lactate and encephalopathy. Treatments include rehydration, dietary carbohydrate restriction, and antibiotics to alter the gut microbiota. Fecal microbiota transplantation (FMT) has recently been used in children to successfully treat D-LA. We compared the clinical course and then utilized metagenomic shotgun sequencing to describe changes in the composition and function of the intestinal microbiome following FMT in 2 patients with recurrent D-LA. FMT altered the composition of the fecal microbiota in these 2 patients with recurrent D-LA, though not necessarily in a consistent manner. Importantly, microbial metabolic pathways were also impacted by FMT, which may be critical for achieving desired clinical outcomes. While sample size limits the generalizability of our results, these findings set the stage for further understanding of the role of microbes in the pathogenesis of recurrent D-LA.

D-Lactate: Implications for Gastrointestinal Diseases.

D-lactate is produced in very low amounts in human tissues. However, certain bacteria in the human intestine produce D-lactate. In some gastrointestinal diseases, increased bacterial D-lactate production and uptake from the gut into the bloodstream take place. In its extreme, excessive accumulation of D-lactate in humans can lead to potentially life-threatening D-lactic acidosis. This metabolic phenomenon is well described in pediatric patients with short bowel syndrome. Less is known about a subclinical rise in D-lactate. We discuss in this review the pathophysiology of D-lactate in the human body. We cover D-lactic acidosis in patients with short bowel syndrome as well as subclinical elevations of D-lactate in other diseases affecting the gastrointestinal tract. Furthermore, we argue for the potential of D-lactate as a marker of intestinal barrier integrity in the context of dysbiosis. Subsequently, we conclude that there is a research need to establish D-lactate as a minimally invasive biomarker in gastrointestinal diseases.

Short bowel syndrome: Complications and management.

Short bowel syndrome (SBS) occurs when a patient loses bowel length or function significantly enough to cause malabsorption, oftentimes requiring lifelong parenteral support. In adults, this occurs most commonly in the setting of massive intestinal resection, whereas congenital anomalies and necrotizing enterocolitis predominate in children. Many patients with SBS develop long-term clinical complications over time related to their altered intestinal anatomy and physiology or to various treatment interventions such as parenteral nutrition and the central venous catheter through which it is administered. Identifying, preventing, and treating these complications can be challenging. This review will focus on the diagnosis, treatment, and prevention of several complications that can occur in this patient population, including diarrhea, fluid and electrolyte imbalance, vitamin and trace element derangements, metabolic bone disease, biliary disorders, small intestinal bacterial overgrowth, d-lactic acidosis, and complications of central venous catheters.

Taste Responses and Ingestive Behaviors to Ingredients of Fermented Milk in Mice.

Fermented milk is consumed worldwide because of its nutritious and healthful qualities. Although it is somewhat sour, causing some to dislike it, few studies have examined taste aspects of its ingredients. Wild-type mice and T1R3-GFP-KO mice lacking sweet/umami receptors were tested with various taste components (sucrose, galactose, lactose, galacto-oligosaccharides, fructo-oligosaccharides, l- and d-lactic acid) using 48 h two-bottle tests and short-term lick tests. d-lactic acid levels were measured after the ingestion of d- or; l-lactic acid or water to evaluate d-lactic acidosis. In wild-type mice, for the sweet ingredients the number of licks increased in a concentration-dependent manner, but avoidance was observed at higher concentrations in 48 h two-bottle tests; the sour ingredients d- and l-lactic acid showed concentration-dependent decreases in preference in both short- and long-term tests. In 48 h two-bottle tests comparing d- and l-lactic acid, wild-type but not T1R3-GFP-KO mice showed higher drinking rates for l-lactic acid. d-lactic acidosis did not occur and thus did not contribute to this preference. These results suggest that intake in short-term lick tests varied by preference for each ingredient, whereas intake variation in long-term lick tests reflects postingestive effects. l-lactic acid may have some palatable taste in addition to sour taste.

Low Serum Bicarbonate in a Patient With Diabetes Mellitus:: A Quiz

Low Serum Bicarbonate in a Patient With Diabetes Mellitus:: A Quiz

Probiotic treatment vs empiric oral antibiotics for managing dysbiosis in short bowel syndrome: Impact on the mucosal and stool microbiota, short-chain fatty acids, and adaptation.

Infants and children with short bowel syndrome (SBS) are presumed to be at risk of gut microbial dysbiosis with potential sequelae of bacterial overgrowth that include sepsis, d-lactic acidosis, mucosal inflammation, and malabsorption. In neonatal piglets with SBS, we compared intestinal microbial composition, short-chain fatty acids (SCFAs), and adaptation given probiotic (PRO) treatment (Lactobacillus and Bifidobacterium spp) vs oral metronidazole (MET). Following 75% distal small intestinal resection, piglets were allocated to PRO (500 mg twice a day, n = 7), MET (15 mg/kg twice a day, n = 8), and placebo (PLA) (500 mg twice a day, n = 8). After 10 days of parenteral and enteral nutrition, 16S ribosomal RNA gene amplicon sequencing (colon tissue and stool) was undertaken and SCFA analysis (stool and colon effluent) was performed using gas chromatography. In colon, Shannon diversity was higher for PRO compared with MET and PLA (P = 0.002). PRO and PLA increased abundance of Bacteroidetes species (eg, Bacteroides fragilis) compared with MET (P < 0.001). PRO, compared with PLA, increased abundance of Firmicutes species (eg, Lactobacillus fermentum) (P < 0.001). MET increased abundance of Proteobacteria members, predominately Enterobacteriaceae, compared with PRO (P = 0.004). In stool, microbial findings were similar and SCFA (butyrate) concentrations were highest for PRO (P = 0.003) compared with MET. In pediatric SBS, the empiric use of oral antibiotics, such as MET, is common for presumed clinical consequences of microbial dysbiosis. In this study of SBS piglets, that approach was associated with decreased microbial diversity and increased abundance of potentially inflammatory Proteobacteria. In contrast, a PRO treatment using Lactobacillus and Bifidobacterium spp increased both diversity and SCFAs.

Comparing bowel lengthening procedures: which, when, and why?

Purpose of reviewIntestinal failure secondary to short bowel syndrome is still a very serious condition. Treatment consists of parenteral nutrition to provide nutrients and maintain body weight. During the last decades, intestinal lengthening procedures have become more available. The goal of this review is to discuss the results of the literature on the most commonly performed intestinal lengthening procedures.Recent findingsLongitudinal Intestinal Lengthening, Serial Transverse Enteroplasty (STEP), and Spiral Intestinal Lengthening and Tailoring (SILT) are currently the most frequently reported intestinal lengthening procedures. The most recent literature of these procedures is described with respect to indication, technical details, complications, short and long-term outcome, and PN independence.SummaryOn the basis of indication, surgical complexity, complications, and clinical success, we conclude that the STEP procedure is probably the best choice for most centers.

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

An unusual cause of acute encephalopathy: D-lactic acidosis secondary to short bowel syndrome

Background: Blood D-lactate levels increase in short bowel syndrome (SBS) and may lead to neurological manifestations. Clinical Description: A 5-year-old boy, postoperative case of SBS, presented with loose stools, generalized weakness, and lethargy for 2 days. The child had undergone significant intestinal resection in the past. On examination, he had some dehydration, and was drowsy, but arousable. Remaining examination was normal. Metabolic abnormalities detected included metabolic acidosis (pH of 7.1, HCO3 7 mmol/L), high anion gap (20 mmol/l), and normal lactate levels (2 mmol/L). Other baseline investigations were normal. He was treated as a case of acute gastroenteritis with some dehydration and metabolic acidosis and improved. He was discharged after 5 days. After 2 months, he was readmitted with drowsiness and unsteady gait. This time there was no diarrhea or dehydration. Investigations again revealed severe metabolic acidosis, high anion gap, and normal lactate levels. Management: We considered SBS induced D-lactate encephalopathy but were unable to prove it by assay due to unavailability of tests. The child was kept nil per orally and given bicarbonate infusion, on which he showed dramatic improvement. He was also given a low carbohydrate diet and oral metronidazole. The family was counseled at discharge 5 days later regarding dietary modifications and microsupplementation. The patient had 6 admissions for D-lactic encephalopathy over 4 years that coincided with dietary lapse. Conclusion: D-lactate acidosis is an underrecognized condition and its diagnosis and management is challenging. A high index of suspicion should be kept in patients with history of intestinal resection presenting with acute encephalopathy and unexplained metabolic acidosis.

D-laktátová acidóza - zriedkavá komplikácia syndrómu krátkeho čreva

D-laktátová acidóza reprezentuje zriedkavú formu metabolickej acidózy, ktorá sa vyskytuje najčastejšie u&#8239;pacientov so syn­drómom krátkeho čreva. Ide o&#8239;závažnú, niekedy až život ohrozujúcu komplikáciu. Príčinou je akumulácia D-laktátu v&#8239;organizme, ktorý vzniká v&#8239;nadmernom množstve fermentáciou nevstrebaných sacharidov mikrobiotou hrubého čreva. Predominantne býva postihnutý nervový systém, z&#8239;čoho vyplýva aj klinická manifestácia. V&#8239;klinickom obraze dominuje široká škála nešpecifických neurologických príznakov. Ochorenie sa môže niekedy manifestovať somnolenciou až kómou. Z&#8239;aspektu laboratórnej diagnostiky ochorenie charakterizuje ťažká metabolická acidóza so zvýšenou aniónovou medzerou. V&#8239;tejto kazuistike prezentujeme ojedinelý prípad 54-ročnej ženy s&#8239;Crohnovou chorobou a&#8239;syndrómom krátkeho čreva, ktorá bola v&#8239;krátkom čase opakovane hospitalizovaná pre recidívu ťažkej metabolickej acidózy so závažnou poruchou vedomia. Na základe zhodnotenia anamnestických údajov, klinického obrazu a&#8239;laboratórnych vyšetrení bola pacientke diagnostikovaná D-laktátová acidóza. V&#8239;diskusii rozoberáme jednotlivé kroky, ktoré viedli k&#8239;tejto diagnóze a&#8239;porovnávame našu skúsenosť s&#8239;údajmi vo svetovej literatúre.

S2782 D-Lactic Acidosis in Short Bowel Syndrome

INTRODUCTION: Lactic acidosis (LA) in a patient presenting with abdominal pain raises concern for bowel ischemia. The physician is prompted to administer intravenous fluids, locate the ischemic area, and consider invasive procedures. However, different isomers of lactic acid exist. Elevation of D-lactic acid reveals an alternate diagnosis. Understanding D-lactic acidosis (D-LA) can guide physicians towards effective treatment and prevent harm from unnecessary imaging and invasive intervention. CASE DESCRIPTION/METHODS: 43 year old male with Crohn's Disease (CD) and bowel resection presents with 2 weeks of diffuse abdominal pain. On examination he was hypertensive and somnolent with slurred speech. His abdomen was soft but tender, with scarring from abdominal surgeries. Blood work revealed leukocytosis and anion-gap metabolic acidosis (AGMA) with LA. Testing for ketoacidosis and toxic ingestion was negative. Gastrointestinal pathogen panel was negative. Computed tomography (CT) was negative for bowel thickening or enhancement, and CT angiography was negative for mesenteric thrombosis. Endoscopy did not reveal active CD. Lactic acid remained elevated despite intravenous fluids. The patient was noted consuming juice and several packets of sugar with tea, raising concern for D-LA. After restricting carbohydrates, lactic acid and AGMA rapidly normalized. A blood sample sent out from time of admission showed elevated D-lactic acid. DISCUSSION: This patient's neurologic symptoms, AGMA and LA, simple carbohydrate intake and prior bowel resection raised concern for D-LA, a rare condition observed in patients with short bowel syndrome (SBS). Decreased intestinal absorption in SBS results in delivery of carbohydrates to the colon, where fermentation by colonic flora form L- and D-Lactic acid and other organic acids. Systemic absorption can cause AGMA, LA and neurologic symptoms, such as encephalopathy, dysarthria and ataxia. Diagnosis involves clinical suspicion, AGMA that resolves with carbohydrate restriction, and neurologic symptoms. D-lactate dehydrogenase assay confirms diagnosis. Treatment involves correction of acidosis and oral carbohydrate restriction. Enteric antibiotic use has been proposed to reduce acid-forming bacteria. Physicians should suspect D-LA in patients with CD post-bowel resection and otherwise unexplained AGMA, as this could prevent harm through inappropriate treatment including intravenous antibiotics and corticosteroids, radiation exposure, and invasive endoscopic evaluation.

Quantitative Evaluation of D-Lactate Pathophysiology: New Insights into the Mechanisms Involved and the Many Areas in Need of Further Investigation.

In contrast to L-lactate, D-lactate is produced in minimal quantities by human cells, and the plasma D-lactate concentration normally is maintained at a concentration of only about 0.01 mM. However, in short bowel syndrome, colonic bacterial production of D-lactate may lead to plasma concentrations >3mM with accompanying acidosis and neurological symptoms – a syndrome known as D-lactic acidosis. Minor increases in plasma D-lactate have been observed in various gastrointestinal conditions such as ischemia, appendicitis and Crohn’s disease, a finding touted to have diagnostic utility. The novel aspect of this review paper is the application of numerical values to the processes involved in D-lactate homeostasis that previously have been described only in qualitative terms. This approach provides a number of new insights into normal and disordered production, catabolism and excretion of D-lactate, and identifies multiple gaps in our understanding of D-lactate physiology that should be amenable to relatively simple investigative study.

Reccurent Reversible Encephalopathy with Ataxia and D-Lactic acidosis in Short bowel Syndrome

The short gut syndrome can lead to multiple metabolic disorders along with chronic malnutrition. Such patients can develop changes in mental status due to metabolic alterations. We present a case of eleven years old male who presented to the hospital with an altered mental state. There were repeated admissions to the hospital with a similar complain with non-conclusive cerebrospinal fluid analysis and normal neuroimaging findings. The patient suffered from chronic malnutrition and multiple hospitalizations with altered mental status, encephalopathy. However, he responded well to bicarbonate therapy and prophylactic metronidazole treatment.

Effect of Electroacupuncture at Zusanli (ST36) on Sepsis Induced by Cecal Ligation Puncture and Its Relevance to Spleen.

Background Acupuncture at Zusanli (ST36), Quchi (LI11), and Tianshu (ST25) is commonly used in septic patients by traditional Chinese physicians. The protective effect of acupuncture at ST36 on the intestinal barrier is associated with Cholinergic Anti-Inflammatory Pathway (CAIP). However, its detailed mechanism and whether acupuncture at LI11 and ST25 have similar effects to ST36 remain unclear. Aim To explore the effects of electroacupuncture (EA) at ST36, LI11, and ST25 on septic rats and investigate the role of the spleen in the treatment of EA at ST36. Methods A septic rat model caused by cecal ligation and puncture (CLP) and a postsplenectomy (SPX) CLP rat model were established. Rats were divided into nine groups depending on different treatments. Serum levels of TNF-α, IL-10, D-lactic acidosis (D-LA), double amine oxidase (DAO), and T-lymphocyte subgroup level in intestinal lymph nodes were compared. Results EA could not improve the 2-day survival of CLP rats. For CLP rats, EA at ST36 and LI11 significantly decreased the levels of TNF-α, IL-10, DAO, and D-LA in serum and normalized intestinal T-cell immunity. For SPX CLP rats, EA at ST36 failed to reduce serum concentrations of TNF-α, IL-10, and D-LA but increased the values of CD3+CD4+/CD3+CD8+ cells and Treg/Th17 cells. Conclusions EA at ST36 and LI11, respectively, could alleviate inflammation reaction, protect the intestinal barrier, and maintain intestinal T-cell function in septic rats. Spleen participated in the protective effect of EA at ST36 in sepsis.

P3B.16: The Overload Gut Syndrome

Introduction: Short bowel syndrome (SBS) is the main cause for intestinal failure in children. Parenteral nutrition allows survival and growth while physiological intestinal adaptation occurs. Most patients can be weaned off PN after two to three years. In some cases, although adaptation was successful and PN was weaned without difficulty, intestinal symptoms such as abdominal pain, discomfort, abdominal distension and diarrhea occur, along with a decrease in growth rate requiring the resumption of PN - defining the overload gut syndrome (OGS). The aim of this study was to describe the natural history, the clinical and biological characteristics and the management of OGS. Methods: this retrospective study included all children referred to our center with a history of SBS weaned off PN who needed to return to PN between 2013 and 2018. All children were evaluated in our ward before resuming PN. Clinical history, examination and biological testings, including plasma citrulline levels were collected. A stool balance analysis was performed using the duplicate meal technique and bomb calorimetry. Results: Nine children were included in the study. Mean age at PN resumption was 10 years and 10 months. PN discontinuation lasted six and a half years (mean). All patients presented with stunting which was more important on height than on weight (loss of 1.5 SD and 1.3 SD respectively). All patients were hyperphagic, five of them received tube feeding on top of oral feeding, with mean ingested calories of 2336 kcalories/day, with a ratio of ingested calories over resting energy expenditure of 205%. Mean number of stools was 4.4 per day, with a mean stool weight of 1400g/day (52g/kg/d). One patient presented with recurrent episodes of D-lactic acidosis. Four patients had bicarbonates concentration under 21mmol/l. Mean total absorption rate was 69%. After PN start, the intestinal symptoms resolved, weight increased by 1.4 SD and height by 0.8 SD at 12 months follow-up. Biological parameters all improved. Mean citrulline plasma levels remained stable (26mmol/l at PN re-start - 24mmol/l at 12 months follow-up). Conclusion: Overload gut syndrome is a rare complication of SBS in children. It occurs in children with high enteral intake and low absorption rate: the remnant intestine cannot face the calorie load and becomes overwhelmed. Symptoms should be recognized early in order to resume PN in time to avoid consequences on final stature.

Mo1610 – Characterizing Symptoms of Brain Fogginess and Its Association with D-Lactic Acidosis and Sibo

Mo1610 – Characterizing Symptoms of Brain Fogginess and Its Association with D-Lactic Acidosis and Sibo

Identification of human D lactate dehydrogenase deficiency

Phenotypic and biochemical categorization of humans with detrimental variants can provide valuable information on gene function. We illustrate this with the identification of two different homozygous variants resulting in enzymatic loss-of-function in LDHD, encoding lactate dehydrogenase D, in two unrelated patients with elevated D-lactate urinary excretion and plasma concentrations. We establish the role of LDHD by demonstrating that LDHD loss-of-function in zebrafish results in increased concentrations of D-lactate. D-lactate levels are rescued by wildtype LDHD but not by patients’ variant LDHD, confirming these variants’ loss-of-function effect. This work provides the first in vivo evidence that LDHD is responsible for human D-lactate metabolism. This broadens the differential diagnosis of D-lactic acidosis, an increasingly recognized complication of short bowel syndrome with unpredictable onset and severity. With the expanding incidence of intestinal resection for disease or obesity, the elucidation of this metabolic pathway may have relevance for those patients with D-lactic acidosis.

Long-term outcomes of ultrashort bowel syndrome due to malrotation with midgut volvulus managed at an interdisciplinary pediatric intestinal rehabilitation center

PurposeThe purpose of this study was to describe long-term outcomes of pediatric-onset ultrashort bowel syndrome owing to midgut volvulus managed at an interdisciplinary intestinal rehabilitation center. MethodsPatients with a history of malrotation and pediatric-onset midgut volvulus causing extensive bowel loss (<20% residual small bowel length expected for postconception age) and treated between 2010 and 2017 were reviewed. Data are expressed as median (IQR). ResultsTwenty-three patients had midgut volvulus at age 1 (0–21) day leading to 9 (8–12) percent predicted residual bowel length. Eight (35%) had gastroschisis. Follow-up was 8.5 (6.6–12.2) years from volvulus. Five (22%) patients underwent intestinal/multivisceral transplantation, and all achieved enteral autonomy. Eighteen (78%) patients remained transplant-free, 7 of whom achieved enteral autonomy after 718 (682–1030) days of parenteral nutrition. Transplant-free enteral autonomy was achieved by 0/6 patients with gastroschisis, compared to 7/12 without gastroschisis (p = 0.04). For the overall group, 18 (78%) patients had small bowel bacterial overgrowth, and 7 manifested symptomatic D-lactic acidosis. We observed 2 mortalities, one awaiting transplant and one 4 years following transplantation. ConclusionMidgut volvulus owing to malrotation with extensive bowel loss is associated with favorable long-term survival. Transplant-free enteral autonomy may be feasible, particularly in the absence of gastroschisis. Type of studyPrognosis study. Level of evidenceIIb, retrospective cohort study.