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Neuroscience Letters Aug 2023Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and...
Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and disease. Enteric glia react to intestinal inflammation by converting to a 'reactive glial phenotype' and enteric gliosis, contributing to neuroinflammation, enteric neuropathy, bowel motor dysfunction and dysmotility, diarrhea or constipation, 'leaky gut', and visceral pain. The focus of the minireview is on the impact of inflammation on enteric glia reactivity in response to diverse insults such as intestinal surgery, ischemia, infections (C. difficile infection, HIV-Tat-induced diarrhea, endotoxemia and paralytic ileus), GI diseases (inflammatory bowel diseases, diverticular disease, necrotizing enterocolitis, colorectal cancer) and functional GI disorders (postoperative ileus, chronic intestinal pseudo-obstruction, constipation, irritable bowel syndrome). Significant progress has been made in recent years on molecular pathogenic mechanisms of glial reactivity and enteric gliosis, resulting in enteric neuropathy, disruption of motility, diarrhea, visceral hypersensitivity and abdominal pain. There is a growing number of glial molecular targets with therapeutic implications that includes receptors for interleukin-1 (IL-1R), purines (P2X2R, A2BR), PPARα, lysophosphatidic acid (LPAR1), Toll-like receptor 4 (TLR4R), estrogen-β receptor (ERβ) adrenergic α- (α-R) and endothelin B (ETBR), connexin-43 / Colony-stimulating factor 1 signaling (Cx43/CSF1) and the S100β/RAGE signaling pathway. These exciting new developments are the subject of the minireview. Some of the findings in pre-clinical models may be translatable to humans, raising the possibility of designing future clinical trials to test therapeutic application(s). Overall, research on enteric glia has resulted in significant advances in our understanding of GI pathophysiology.
Topics: Humans; Infant, Newborn; Gliosis; Clostridioides difficile; Enteric Nervous System; Gastrointestinal Diseases; Neuroglia; Inflammation; Abdominal Pain; Gastrointestinal Motility; Diarrhea; Constipation; Intestinal Pseudo-Obstruction
PubMed: 37451357
DOI: 10.1016/j.neulet.2023.137395 -
Revista Espanola de Enfermedades... Jul 2023Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a relatively new therapeutic approach for patients with several cancer types including...
Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a relatively new therapeutic approach for patients with several cancer types including non-small cell lung cancer1. Targeted monoclonal antibodies based drugs can activate anti-tumor immunity by blocking immune checkpoint receptors (CTLA-4, PD-1 receptor and its ligand PD-L1), in order to restore T-cell effector function2,3. However, the use of immune checkpoint inhibitors can lead to a unique side effect profile termed as immune-related adverse events (irAEs). Loss of T-cell inhibition results in an enhanced immune response driven by T-cell activation and is capable of inducing an autoimmune-related inflammation in normal tissue as a consequence of impaired self tolerance4. These irAEs can potentially involve every organ system including gastrointestinal, dermatologic, hepatic, and endocrine toxicities. For example, Fernandez-Gordon Sanchez et al reported a patient with immune-mediated colitis and nonimmune-mediated cholestasic injury induced by pembrolizumab that was successfully treated with Ustekinumab5. We report a steroid-refractory case of lung adenocarcinoma patient with an unusual irAE (intestinal pseudo-obstruction) during the treatment with immune checkpoint inhibitors that could be successfully managed by the administration of infliximab.
PubMed: 37449519
DOI: 10.17235/reed.2023.9796/2023 -
Journal of Medical Case Reports Jul 2023Sclerosing encapsulating peritonitis is a rare condition with a typical macroscopic appearance, with fibrocollagenous membrane enclosing loops of the small intestine,...
BACKGROUND
Sclerosing encapsulating peritonitis is a rare condition with a typical macroscopic appearance, with fibrocollagenous membrane enclosing loops of the small intestine, causing intestinal obstruction. Unexplained recurrent abdominal pain, obstruction, and a large array of other possible clinical signs and symptoms make sclerosing encapsulating peritonitis a diagnostic challenge.
CASE PRESENTATION
A 48-year-old man of Persian ethnicity was admitted multiple times to the emergency surgery department due to recurrent sudden abdominal pain and chronic obstruction without significant findings in medical history or clinical evaluation. Computed tomography was positive for proximal jejunal dilatation and duodenojejunal flexure stenosis due to internal mesenteric hernia. Exploratory laparoscopy, followed by laparotomy, confirmed thick membrane-like fibrous tissue with complete small intestinal loop envelopment. Extensive membrane excision and adhesiolysis was performed, but no mesenteric herniation was found. Early postoperative paralytic ileus with introduction of low-dose steroid therapy, based on histopathological and immunological results, confirming type III sclerosing encapsulating peritonitis, was completely resolved.
CONCLUSION
Sclerosing encapsulating peritonitis is a rare and difficult-to-diagnose condition, further divided into primary and secondary sclerosing encapsulating peritonitis, on the basis of underlying etiology, dictating treatment modality and prognosis. Intraoperative diagnosis and surgical treatment are mandatory, besides a wide variety of abdominal computed tomography scans, inconclusive results, and clinical presentations. There are so far no known specific markers for the diagnosis of sclerosing encapsulating peritonitis.
Topics: Humans; Middle Aged; Peritonitis; Intestinal Obstruction; Prognosis; Laparotomy; Abdominal Pain
PubMed: 37443141
DOI: 10.1186/s13256-023-04020-x -
Journal of Neurogastroenterology and... Jul 2023Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study...
BACKGROUND/AIMS
Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study evaluates the clinical course of CIPO and palliative care needs of patients.
METHODS
From October 2010 to September 2021, 74 patients who underwent cine MRI and had a definitive diagnosis of CIPO were prospectively included. We investigated disease etiology and outcomes, age at onset, nutritional status at consultation (body mass index and serum albumin), hydrogen breath test results, and total parenteral nutrition (TPN) during the disease course.
RESULTS
Forty-seven patients (64%) were women, with a mean age of 44 years at onset and 49 years at diagnosis. Primary CIPO was observed in 48 patients (65%). Secondary CIPO was observed in 26 cases (35%), of whom 18 (69%) had scleroderma. The mean body mass index, serum albumin level, and hydrogen breath test positivity rate were 17 kg/m, 3.8 mg/dL, and 60%, respectively. TPN and invasive decompression therapy were required by 23 (31%) and 18 (24%) patients, respectively. Intestinal sterilization was performed in 51 (69%) patients and was effective in 33 (65%); of these, 28 (85%) were taking metronidazole. Seven (9%) patients used opioids. There were 9 deaths (12%), including 5 (56%) from infection and 2 (22%) from suicide. Of the deaths, 6 (67%) and 4 (44%) underwent TPN management and decompression therapy, respectively. Fifty-one patients (69%) wanted palliative care.
CONCLUSION
CIPO is a rare, severe, and under-recognized disease. Standardization of treatment strategies, including palliative care and psychiatric interventions, is desired.
PubMed: 37417265
DOI: 10.5056/jnm22152 -
European Journal of Medical Genetics Aug 2023The sodium-dependent multivitamin transporter (hSMVT) encoded by the SLC5A6 gene is required for the intestinal absorption of biotin, pantothenic acid and lipoate, three...
The sodium-dependent multivitamin transporter (hSMVT) encoded by the SLC5A6 gene is required for the intestinal absorption of biotin, pantothenic acid and lipoate, three micronutrients essential for normal growth and development. Systemic deficiency of these elements, either occurring from nutritional causes or genetic defects, is associated with neurological disorders, growth delay, skin and hair changes, metabolic and immunological abnormalities. A few patients with biallelic variants of SLC5A6 have been reported, exhibiting a spectrum of neurological and systemic clinical features with variable severity. We describe three patients from a single family carrying a homozygous p.(Leu566Valfs*33) variant of SLC5A6 disrupting the frame of the C-terminal portion of the hSMVT. In these patients, we documented a severe disorder featuring developmental delay, sensory polyneuropathy, optic atrophy, recurrent infections, and repeated episodes of intestinal pseudo-obstruction. Two patients who did not receive multivitamin supplementation therapy died in early infancy. In a third patient, early supplementation of biotin and pantothenic acid stabilized the clinical picture changing the course of the disease. These findings extend genotype-phenotype correlations and show how a timely and lifelong multivitamin treatment may be crucial to reduce the risk of life-threatening events in patients with pathogenic variants of the SLC5A6 gene.
Topics: Humans; Biotin; Follow-Up Studies; Pantothenic Acid; Phenotype; Symporters
PubMed: 37391029
DOI: 10.1016/j.ejmg.2023.104808 -
Environmental Science & Technology Jul 2023The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based... (Review)
Review
The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based herbicides (GBHs) traditionally used in agriculture over the past decades. Commercialized in 1974, GBHs have now reached 350 million hectares of crops in over 140 countries with an annual turnover of 11 billion USD worldwide. However, rolling exploitation of GLP and GBHs in the last decades has led to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide of farm and companies' workers. Intoxication with these herbicides dysregulates the microbiome-gut-brain axis, cholinergic neurotransmission, and endocrine system, causing paralytic ileus, hyperkalemia, oliguria, pulmonary edema, and cardiogenic shock. Precision agriculture, i.e., an (information technology)-enhanced approach to crop management, including a site-specific determination of agrochemicals, derives from the benefits of smart materials (SMs), data science, and nanosensors. Those typically feature fluorescent molecularly imprinted polymers or immunochemical aptamer artificial receptors integrated with electrochemical transducers. Fabricated as portable or wearable lab-on-chips, smartphones, and soft robotics and connected with SM-based devices that provide machine learning algorithms and online databases, they integrate, process, analyze, and interpret massive amounts of spatiotemporal data in a user-friendly and decision-making manner. Exploited for the ultrasensitive determination of toxins, including GLP, they will become practical tools in farmlands and point-of-care testing. Expectedly, smart sensors can be used for personalized diagnostics, real-time water, food, soil, and air quality monitoring, site-specific herbicide management, and crop control.
Topics: Animals; Conservation of Natural Resources; Smart Materials; Plants, Genetically Modified; Agriculture; Herbicides; Glyphosate
PubMed: 37384557
DOI: 10.1021/acs.est.3c01269 -
European Journal of Pediatrics Sep 2023Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to...
UNLABELLED
Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case-control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13-65] vs. 30 h [IQR 9-66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99-1.03], 1.16 [0.86-1.55] and 0.97 [0.72-1.31], resp.).
CONCLUSION
In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC.
WHAT IS KNOWN
• Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment. • Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease.
WHAT IS NEW
• Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.
PubMed: 37349579
DOI: 10.1007/s00431-023-05035-8 -
Journal of Minimal Access Surgery 2023Hysterectomy is the most common gynaecological surgery and there are different techniques of performing hysterectomy. With the advent of laparoscopic technology,...
UNLABELLED
Hysterectomy is the most common gynaecological surgery and there are different techniques of performing hysterectomy. With the advent of laparoscopic technology, laparoscopic hysterectomy (LH) is rapidly gaining its ground. However, every surgery has its complications which are specific but also depends on various factors such as surgical sk[ills and experience of surgeons, levels of operative laparoscopy and patient populations.
AIMS AND OBJECTIVE
In this study, we evaluated the complications of total laparoscopic hysterectomy (TLH) and analysed the trend of complications, intraoperative and post-operative, over a period of time.
METHODS
It was a retrospective study conducted in the private care setting. All women who underwent hysterectomy for benign conditions from a 1 January 2003 to 31 December 2017, (15 years) were included in this study. A total of 3272 patients were operated during this period. All surgeries were performed by a single surgeon.
RESULTS
Intraoperative complications that occurred during surgery during the study period were 3 cases (0.09%) had bladder injury, 3 cases (0.09%) had bowel injury, 1 case (0.03%) had internal iliac vessel bleeding and 1 case(0.03%) needed conversion to vaginal hysterectomy due to cautery failure and post operative complications were 90 cases (2.75%) had vault bleeding, 2 cases (0.06%) had intestinal obstruction, 5 cases (0.15%) had paralytic ileus, 1 case (0.03%) had vesicovaginal fistula, 1 case(0.03%) had ureterovaginal fistula and 1 case (0.03%) had peritonitis.
CONCLUSIONS
TLH is a very effective, patient-friendly and safe technique in the hands of experienced surgeons giving good quality of life to patients postoperatively.
PubMed: 37282419
DOI: 10.4103/jmas.jmas_148_22 -
Archives of Gynecology and Obstetrics Feb 2024
Topics: Humans; Female; Pregnancy; Colonic Pseudo-Obstruction; Cesarean Section; Postoperative Complications
PubMed: 37156907
DOI: 10.1007/s00404-023-07052-2