Severe Gastrointestinal Disorders Research Articles

Surgical treatment of diaphragmatic hernia in a 3-year-old child

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a serious condition associated with abnormal development of the diaphragm. Its occurrence among newborns ranges from 1 per 2000 to 1 per 4000. Depending on location, CDH can be divided into four types: diaphragmatic-pleural, parasternal, diaphragmatic-pericardial, and hernias at the esophageal opening of the diaphragm. Hernias can be classified as true or false depending on the presence or absence of the hernia sac. In case of diaphragmatic-pleural hernias, when the intestine, spleen, and stomach almost completely protrude into the pleural cavity, symptoms manifest early in the form of severe cardiorespiratory and gastrointestinal disorders. CLINICAL CASE DESCRIPTION: The article discusses a case of a three-year-old child with a congenital diaphragmatic pleural hernia. From birth, the child experienced difficulty breathing at feeding, coughing; he also had recurrent pneumonia. X-ray examination and computed tomography of the chest revealed a left-sided hernia. Surgery was done via a left-sided thoracotomy, no complications. In four months after the surgery, X-ray examination showed straightened lungs and normal mediastinum; left diaphragm cupula was also normal. The child is considered to be completely healthy due to the absence of symptoms and normal chest X-ray findings. The authors' main goal was to raise awareness among doctors about rare congenital diseases such as CDH. Also, they would like to draw attention to the fact that congenital malformations of the lungs, intestines, and other organs can be unexpectedly manifested at any age. Children with frequent respiratory problems or cardiorespiratory conditions have to be X-rayed as soon as possible to detect congenital malformations of the diaphragm or other chest organs for timely surgical intervention. CONCLUSION: As the authors have noted, in recent years X-ray examination of children often reveals undiagnosed at an early age "findings" related to diaphragm pathology, such as false and true diaphragmatic hernias and dome relaxation. CDH is rare in children older than 3 years and has no specific symptoms. It often leads to delayed diagnostics, often visits to pediatricians because of respiratory infections, retardation in physical development and, as a result, to late surgical treatment.

Study on Effects of Probiotics on Severity of Allergic Rhinitis

Introduction: Allergic rhinitis, a common and often debilitating condition affecting millions globally, remains a challenge for clinicians and patients alike. As we venture into the realm of probiotics and allergic rhinitis, it becomes imperative to unravel the multifaceted ways in which these microorganisms may influence immune modulation, inflammation, and the overall balance of the microbiome. In this exploration, we navigate the microbial frontier, seeking to unravel the intricate connections between probiotics and the management of allergic rhinitis. Methods: This study employed a randomized controlled trial (RCT) design to investigate the effects of probiotics on allergic rhinitis symptoms. The trial adhered to CONSORT guidelines, ensuring robust methodological standards. Participants were recruited from allergy clinics and community health centres. Inclusion criteria encompassed individuals aged 18-65 years, diagnosed with allergic rhinitis, and not currently undergoing immunotherapy. Exclusion criteria included severe gastrointestinal disorders, antibiotic use within the past three months, and concurrent participation in other clinical trials. A total of 80 participants were enrolled. Results: The probiotic group demonstrated a significantly higher improvement rate, with 32 participants (80%) showing improved allergic rhinitis symptoms compared to 8 participants (20%) in the placebo group (p < 0.001). Conclusion: In conclusion, this RCT contributes compelling evidence supporting the use of probiotics in alleviating allergic rhinitis symptoms. The significant improvement observed, coupled with the favourable safety profile, positions probiotics as a promising complementary strategy.

Cross-sectional study using the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) for gastrointestinal disorders of systemic sclerosis.

This study aimed to identify severe gastrointestinal ailments in patients with systemic sclerosis (SSc), investigate the role of antibodies in gastrointestinal disorders, and explore the relationship between limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) in terms of gastrointestinal involvement and its association with skin stiffness. We used the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) questionnaire to assess gastrointestinal disturbances in 100 patients with SSc. Gastrointestinal impairment was categorized into three levels: absence of or minor symptoms, moderate symptoms, and severe symptoms, as indicated by the total gastrointestinal tract (GIT) score. Comparing 27 patients with dcSSc and 73 patients with lcSSc, severe gastrointestinal disturbances were found in 7.4% of patients with dcSSc and 4.1% of patients with lcSSc. A total of 18.0% of anticentromere antibody (ACA)-positive patients exhibited moderate to severe symptoms, while 9.1% of antitopoisomerase 1 antibody-positive patients displayed similar symptoms. The average disease duration in patients with severe symptoms was 15.0 years, in those with moderate symptoms was 10.3 years, and in those who were symptom-free or mildly affected was 8.5 years. Among 16 patients with moderate to severe gastrointestinal disorders, a positive correlation was observed between the modified Rodnan skin thickness score (mRSS) and total GIT score. In addition, a positive correlation was identified between fecal incontinence and mRSS, with weaker correlations for reflux and bloating symptoms. Patients with gastrointestinal disorders showed a tendency to worsen over time, particularly in ACA-positive patients with dcSSc. Furthermore, a correlation was observed between mRSS and fecal incontinence, reflux, and abdominal bloating in patients with moderate to severe gastrointestinal disturbances.

Probiotic formulations and gastro-intestinal diseases in the paediatric population: a narrative review.

Probiotics are live microbial supplements that improve the microbial balance in the host animal when administered in adequate amounts. They play an important role in relieving symptoms of many diseases associated with gastrointestinal tract, for example, in necrotizing enterocolitis (NEC), antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, Helicobacter pylori infections, and inflammatory bowel disease (IBD). In this narrative review, the authors aim to evaluate the role of different probiotic formulations in treating gastrointestinal diseases in pediatric population aged 18 years or younger and highlight the main considerations for selecting probiotic formulations for use in this population. The authors searched PubMed and Clinicaltrials.gov from inception to 24th July 2022, without any restrictions. Using an iterative process, the authors subsequently added papers through hand-searching citations contained within retrieved articles and relevant systematic reviews and meta-analyses. The effectiveness of single-organism and composite probiotics in treating gastrointestinal disorders in pediatric patients aged 18 or under were analyzed and compared in this study. A total of 39 studies were reviewed and categorized based on positive and negative outcomes, and compared with a placebo, resulting in 25 studies for single-organism and 14 studies for composite probiotics. Gastrointestinal disorders studied included NEC, acute gastroenteritis (AGE), Acute Diarrhea, Ulcerative Colitis (UC), and others. The results show that probiotics are effective in treating various gastrointestinal disorders in children under 18, with single-organism probiotics demonstrating significant positive outcomes in most studies, and composite probiotics showing positive outcomes in all studies analyzed, with a low incidence of negative outcomes for both types. This study concludes that single-organism and composite probiotics are effective complementary therapies for treating gastrointestinal disorders in the pediatric population. Hence, healthcare professionals should consider using probiotics in standard treatment regimens, and educating guardians can enhance the benefits of probiotic therapy. Further research is recommended to identify the optimal strains and dosages for specific conditions and demographics. The integration of probiotics in clinical practice and ongoing research can contribute to reducing the incidence and severity of gastrointestinal disorders in pediatric patients.

Gastrointestinal dysmotility in rodent models of Parkinson's disease.

Multiple studies describe prodromal, nonmotor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal dysfunctions comprise a wide array of autonomic issues, including severe gastrointestinal (GI) motility disorders such as dysphagia, delayed gastric emptying, and chronic constipation. Indeed, strong evidence from studies in humans and animal models suggests that the GI tract and its neural, mainly vagal, connection to the central nervous system (CNS) could have a major role in the etiology of PD. In fact, misfolded α-synuclein aggregates that form Lewy bodies and neurites, i.e., the histological hallmarks of PD, are detected in the enteric nervous system (ENS) before clinical diagnosis of PD. The aim of the present review is to provide novel insights into the pathogenesis of GI dysmotility in PD, focusing our attention on functional, neurochemical, and molecular alterations in animal models.

Intussusception in a Nigerian Indigenous Dog: A Case Report and Probable Associated Pathologic Mechanisms

Intussusception, a serious gastrointestinal disorder characterized by invading one segment of the intestine into another, poses significant health risks in veterinary medicine. This case report presents the clinical and pathological findings of intussusception in a 10-month-old brown male Nigerian indigenous dog (NID). The dog, which had no history of vaccination, underwent abdominal surgical procedures including gastrotomy and intestinal resection with anastomosis seven days prior to death. Postoperatively, the dog exhibited clinical signs of vomiting and weakness despite treatment with penicillin-streptomycin antibiotics and a bland diet. Necropsy revealed severe pathological changes, including congested liver, gastric haemorrhage, peritoneal adhesions, leakage of intestinal contents into the peritoneum, peritonitis, intestinal congestion with intussusception, and infarction at anastomosed intestinal sites. These findings highlight the multifaceted nature of intussusception, involving mechanical obstruction, compromised blood supply, and systemic infection. The case emphasizes the challenges in managing post-surgical complications and the importance of early diagnosis and intervention in severe gastrointestinal disorders in dogs. This manuscript, therefore, contributes to the veterinary literature by providing a detailed description of the clinical course, pathological findings, and potential complications associated with intussusception in Nigerian indigenous dogs. The insights gained from this case report are crucial for improving diagnostic accuracy, optimizing treatment strategies, and enhancing clinical outcomes in similar clinical scenarios.

Citrus tangerine pith extract alleviates hypoxia-induced ileum damage in mice by modulating intestinal microbiota.

Visitors to high altitude are susceptible to hypoxia-induced acute intestinal mucosal barrier injury and severe gastrointestinal disorders, which are life-threatening. Citrus tangerine pith extract (CTPE) is rich in pectin and flavonoids and has been proved to enhance intestinal health and improve gut dysbiosis. In this study, we aim to explore the protective effect of CTPE on ileum injury induced by intermittent hypobaric hypoxia in a mouse model. Balb/c mice were divided into blank normoxia (BN), blank hypobaric hypoxia (BH), hypobaric hypoxia plus CTPE (TH), and hypobaric hypoxia plus Rhodiola extract (RH) groups. From the 6th day of gavage, mice in BH, TH, and RH groups were transferred into a hypobaric chamber at a simulated elevation of 6000 m for 8 hours per day for 10 days. Then half the mice were tested for small intestine movement, and others were used to evaluate intestinal physical barrier function, inflammation, and gut microbiota. Results showed that CTPE reversed the increase of intestinal peristalsis, effectively attenuated impaired structural integrity of ileum, improved the mRNA and protein expression levels of tight junction proteins, and reduced serum D-LA content in mice to alleviate hypoxia-induced mucosal barrier damage. Moreover, CTPE supplementation ameliorated hypoxia-induced intestinal inflammation response by significantly downregulating the proinflammatory cytokines IL-6, TNF-α and IFN-γ. By 16S rDNA gene sequencing of gut microbiota, CTPE significantly increased the abundance of probiotic Lactobacillus, suggesting that CTPE may be used as a prebiotic to regulate ecology of intestinal microorganisms. In addition, Spearman rank correlation analysis revealed that changed gut microbiota were significantly correlated with alteration of intestinal barrier function indexes. Taken together, these results indicate that CTPE effectively alleviates hypoxia-induced intestinal injury in mice and enhances intestinal integrity and barrier function by altering intestinal microbiota composition.

Impact of COVID-19 on the digestive system: A descriptive cross-sectional study

Background: Various digestive symptoms caused by COVID-19 are frequently reported. This study aims to describe the most frequent digestive signs in patients with COVID-19, the relationship between the severity of digestive symptoms and some serological markers associated with liver manifestation, the detection of SARS-CoV-2 in a stool sample, and the mortality rate of those patients. Materials and Methods: A descriptive cross-sectional study on 100 confirmed COVID-19 cases with digestive and hepatic manifestation in one center (Fallujah Teaching Hospital), Anbar governorate, Iraq, during a period of study. Questioner’s data were formed for all patients regarding age, sex, and comorbidities such as diabetes and hypertension. Liver function enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, total bilirubin (TBIL), and direct bilirubin and haematological parameters such as ferritin D-dimer, C-reactive protein (CRP), albumin, amylase, leukocyte count, and prothrombin time were used. SARS-CoV-2 prevalence in stool is determined using reverse transcription polymerase chain reaction according to manufacturer’s instructions. The mortality rate of patients with COVID-19 was also determined. Data were followed up until April 22, 2022. Results: Patients with digestive symptoms who had COVID-19 had an average age of 45.03 (SD 20.078), 52 (52%) were men, and 48 (48%) were women. No statistically significant variances were observed in the severity of digestive symptoms among age groups. The three digestive symptoms that patients with COVID-19 experienced most frequently were fatigue, fever, and abdominal colic. SARS-CoV-2 was detected in the stool of 11% of the patients with COVID-19 with digestive signs. The COVID-19 mortality rate was 9%. Statistically, significant variance was observed in ALT (P value 0.01) and TBIL (P value 0.0027) levels between mild, moderate, and severe gastrointestinal (GI) diseases. The levels of CRP varied considerably among those with mild, moderate, and severe GI conditions (P value 0.0182, according to the findings). In mild, moderate, and severe GI disorders, ferritin levels differed considerably (P value 0.05). Conclusions: The faecal sample with a nasopharyngeal swab is needed to confirm COVID-19 diagnosis; hepatic manifestations are connected with increased COVID-19 mortality in individuals with digestive symptoms.

50 Years Ago in TheJournalofPediatrics: Zinc Deficiency—Both a Rare and Common Problem!

Freier S, Faber J, Goldstein R, Mayer M. Treatment of acrodermatitis enteropathica by intravenous amino acid hydrolysate. J Pediatr 1973;82:109-12. Freier et al described an infant who developed failure to thrive, a severe rash, and alopecia, as well as profound diarrhea. A sibling had died following a similar course. The diagnosis of congenital acrodermatitis enteropathica was made. She was treated initially with diiodohydroxyquinoline. She was then treated with intravenous amino acids and eventually a protein hydrolysate. Her skin and diarrhea improved with the treatment. These were considered standard treatment at the time. In retrospect, there must have been trace amounts of zinc in the hydrolysate. The infant described likely had the congenital form of acrodermatitis enteropathica, an autosomal-recessive trait involving a mutation in the zinc transporter gene. This has been localized to the SLC39A4 gene on chromosome 8. It is a rare condition, with an estimated prevalence of 1-9 per million. Acrodermatitis enteropathica was first described in 1936, but the role of zinc in treating acrodermatitis enteropathica was not recognized at the time of this article’s publication. It was an often-fatal condition. Human zinc deficiency was first described in the 1970 by Prasad—he described short patients with hypogonadism. Around the same time, parenteral nutrition increasingly was being used to support infants with severe gastrointestinal disorders. The initial solutions were often free of trace metals. There were soon increasing reports of severe rashes in infants receiving zinc-free total parenteral nutrition. It also was noted that zinc losses paralleled intestinal losses. Today, we are much more likely to see acquired acrodermatitis enteropathica. The advent of total parenteral nutrition heralded an increase in previously unrecognized nutrient deficiencies. The 2 most common were zinc and essential fatty acid deficiency; however, reports of copper, chromium, iodine, and biotin deficiency followed. There was increased recognition of the importance of trace nutrients in human health. Zinc deficiency may occur because of decreased intake, increased needs, malabsorption, increased losses, or impaired use. It may be primary or secondary, usually due to poor intake or chronic diarrhea. Recent pharmaceutical shortages have aggravated the possibility of deficiencies. Infants on prolonged exclusive breastfeeding may suffer deficiencies, and patients with prolonged diarrhea and/or severely restricted diets are also at risk.1Prasad A.S. Impact of the discovery of human zinc deficiency on health.J Am Coll Nutr. 2009; 28: 257-265Crossref Scopus (209) Google Scholar

Prevalence, antimicrobial resistance, virulence gene profile and molecular typing of Campylobacter species isolated from poultry meat samples.

Campylobacter jejuni and Campylobacter coli are the most significant Campylobacter species responsible for severe gastrointestinal disorders. Raw poultry meat is considered a source of Campylobacter transmission to the human population. The present study was aimed to assess the prevalence rate, antibiotic resistance properties, virulence characters and molecular typing of C. jejuni and C. coli strains isolated from raw poultry meat samples. Three hundred and eighty raw poultry meat samples were collected and analysed for the presence of Campylobacter spp. using the microbial culture. Species identification was done using the Polymerase Chain Reaction. Disk diffusion was developed to assess the antimicrobial resistance pattern of isolates. The distribution of virulence and antimicrobial resistance genes was determined by PCR. Enterobacterial Repetitive Intergenic Consensus-PCR was used for molecular typing. Campylobacter species were isolated from 6.25% of examined samples. C. jejuni and C. coli contamination rates were found to be 57.44% and 48.14%, respectively. C. jejuni strains harboured the highest resistance rate against serythromycin (42.59%), ampicillin (38.88%), ciprofloxacin (33.33%), chloramphenicol (31.48%) and tetracycline (31.48%). C. coli isolates harboured the highest resistance rate against ampicillin (73.07%), ciprofloxacin (73.07%), erythromycin (65.38%) and chloramphenicol (50%). AadE1 (44.44%), blaOXA-61 (42.59%) and tet(O) (35.18%) were the most commonly detected resistance genes in C. jejuni and cmeB (34.61%) and blaOXA-61 (34.61%) were the most commonly detected among C. coli strains. The most frequent virulence factors among the C. jejuni isolates were flaA (100%), ciaB (100%), racR (83.33%), dnaJ (81.48%), cdtB (81.48%), cdtC (79.62%) and cadF (74.07%). The most frequent virulence factors among the C. coli isolates were flaA (100%), ciaB (100%), pldA (65.38%) and cadF (61.53%). The majority of C. jejuni and C. coli strains had more than 80% similarities in their ERIC-PCR pattern, which may show their common source of transmission. The role of goose and quebec meat samples as reservoirs of virulent and antimicrobial resistant Campylobacter spp. was determined.

Functional gastrointestinal disorders are associated with capsaicin cough sensitivity in severe asthma

BackgroundAlthough sensory nerve dysfunction is related to the pathology of severe uncontrolled asthma and functional gastrointestinal disorders (FGIDs), the impact of comorbid FGIDs on the pathophysiology of severe uncontrolled asthma remains poorly understood. The aim was to clarify the physiological relationships between severe uncontrolled asthma and FGIDs. MethodsFifty-two patients with severe uncontrolled asthma who visited our hospital between September 2016 and August 2019 were retrospectively analyzed. Clinical characteristics, other comorbidities including gastroesophageal reflux disease (GERD), and biomarkers such as fractional nitric oxide (FeNO) and capsaicin cough sensitivity (C-CS) before the beginning of biologics or bronchial thermoplasty, were compared between patients with and without comorbid FGIDs. C-CS was evaluated by C5 (concentration of inhaled capsaicin that induced five or more coughs), and C5 ≤2.44 μM was defined as heightened C-CS. ResultsSeventeen patients had comorbid FGIDs. These patients had a lower FeNO level (21.9 ± 1.7 ppb vs. 33.9 ± 2.8 ppb, P = 0.04), a lower C5 threshold (2.24 ± 2.88 μM vs. 8.91 ± 5.5 μM, P < 0.001), a higher prevalence of comorbid GERD (64.7% vs. 31.7%, P = 0.03), and a higher prevalence of heightened C-CS (70.6% vs. 28.6%, P = 0.007) than those without FGIDs. Analysis of covariance showed a significant effect of FGIDs on C-CS in severe uncontrolled asthma without being affected by GERD. ConclusionsComorbid FGIDs are associated with heightened C-CS in patients with severe uncontrolled asthma, and they may be an important extra-respiratory manifestation of the airway neuronal dysfunction phenotype of severe uncontrolled asthma.

Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives.

Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.

Pathomorphological changes of the stomach and intestinum crassum in the intestinal form of parvoviral enteritis in dogs

Based on the analysis of literature sources, monitoring results and our own research, it has been established that viral enteritis occupies a leading place in the infectious pathology of dogs and causes significant damage to animal owners. Viral enteritis, most commonly caused by parvovirus, causes severe gastrointestinal disorders and is one of the most common causes of infectious diarrhea in dogs under 6 months of age. Therefore, given the relevance of this issue, the result of our study is to clarify, supplement and summarize data on the pathomorphological features of the intestinal form of parvovirus infection in dogs. Diagnostic studies to confirm parvovirus enteritis were performed using VetExpert CPV Ag or CPV/CCV Ag rapid tests, as well as by ELISA and PCR. Dissection of dead animals was performed in the conventional sequence. For pathomorphological examination, samples were taken from the gastrointestinal tract, fixed in 10 % neutral formalin solution, followed by dehydration in alcohols of increasing concentration and the procedure of organ compaction according to the generally accepted method. Histological sections 6–10 μm thick were obtained using a microtome. The article presents the results of pathological changes in dogs with parvovirus enteritis, namely macroscopically under the serous membrane of the stomach revealed striped hemorrhages, duodeno-gastric reflux, manifested by gray-green color of the mucous membrane (bile accumulation). Histological methods have shown that the blood vessels of the submucosal base of the mucous membrane are clearly dilated, filled with blood. The mucous membrane is swollen, unevenly colored in all parts of the stomach. In the muscular membrane of the stomach wall, the vast majority of cells were in a state of granular dystrophy, and in some animals, necrotic changes in smooth muscle tissue were recorded. Histochemical studies revealed the development of microscopic changes that indicated hypersecretion of mucus (acidic proteins) in the stomach of sick dogs. No specific macroscopic changes in the colon were recorded. Microscopically, a small amount of cellular detritus with mucus fragments, goblet cell hyperplasia, and a reaction of epithelial cells that were in a state of granular, less often, hydropic dystrophy were recorded on the lumen of the colon on the mucosal surface.

Megaduodenum in children in the outcom of correction of duadenal atreesia: literature review and own experience

Introduction. Despite the good long-term results of duodenal atresia correction in the long term, about 10% of patients have severe upper gastrointestinal motility disorders: GERD, gastroduodenitis, and megaduodenum, which requires re-reconstruction of the duodenal anastomosis. Materials and methods. For the period from 2010 to 2021 in the clinic of the FGBUZ DGKB them. N. F. Filatov DZM Moscow 7 patients was treated with megaduodenum, operated on for duodenal atresia. The average age of the patients was 5.4 ± 3.9, boys predominated (6/7). All children underwent a standardized examination: ultrasound, barium fluoroscopy, FGEDS and laboratory research methods. MRCP and abdominal CT were performed as indicated (3/7). All patients were operated on, depending on the cause of obstruction and the degree of its compensation. Reconstruction of the previously applied anastomosis (4/7) or resection of the duodenum (3/7) was performed. Results. Main patient complaints: abdominal pain 7/7 (100%), vomiting 7/7 (100%), abdominal distention 4/7 (57.1%), poor weight loss 3/7 (42.8%), constipation 3/7 (42.8%). 5 out of 7 had multiple congenital malformations (MCDs). Mechanical causes of chronic renal failure were detected in 4 out of 7 children: stenosis of the duodeno-duodenoanastomosis (2), “blind loop” syndrome (infringement of the Roux loop in the form of a “double-barrel” in the window of the mesentery of the transverse colon) (1), stenosis of the duodeno-duodenoanastomosis in in combination with fibrosis of the head of the pancreas (1). In the remaining 3 cases a secondary megaduodenum was detected with good obstruction of the previously imposed anastomosis. Hiowever, it was noted that the diameter of the anastomosis was definitely less than the diameter of the duodenum above its level. In 6 out of 7 patients chronic renal failure was complicated by secondary gastroesophageal reflux disease (GERD), which required surgical correction in only one patient after 6 months. In other cases, the dynamics of reflux spontaneously decreased to 1 degree and was intermittent, the patients had no complaints. All children were examined in follow-up after 1, 3, 6 and 12 months. All of them showed positive dynamics in the form of weight gain, absence of complaints and signs of protein-energy insufficiency. Conclusion. Children operated on for duodenal atresia need long-term careful dispensary observation. Since in the presence of pronounced motor-evacuation disorders of the duodenum, repeated interventions are necessary. Surgical tactics should be strictly differentiated. Resection of the duodenum improves passage through the upper gastrointestinal tract and is well tolerated by patients.

Dietary Fat Effect on the Gut Microbiome, and Its Role in the Modulation of Gastrointestinal Disorders in Children with Autism Spectrum Disorder

Children with autism spectrum disorder (ASD) report a higher frequency and severity of gastrointestinal disorders (GID) than typically developing (TD) children. GID-associated discomfort increases feelings of anxiety and frustration, contributing to the severity of ASD. Emerging evidence supports the biological intersection of neurodevelopment and microbiome, indicating the integral contribution of GM in the development and function of the nervous system, and mental health, and disease balance. Dysbiotic GM could be a contributing factor in the pathogenesis of GID in children with ASD. High-fat diets may modulate GM through accelerated growth of bile-tolerant bacteria, altered bacterial ratios, and reduced bacterial diversity, which may increase the risk of GID. Notably, saturated fatty acids are considered to have a pronounced effect on the increase of bile-tolerant bacteria and reduction in microbial diversity. Additionally, omega-3 exerts a favorable impact on GM and gut health due to its anti-inflammatory properties. Despite inconsistencies in the data elaborated in the review, the dietary fat composition, as part of an overall dietary intervention, plays a role in modulating GID, specifically in ASD, due to the altered microbiome profile. This review emphasizes the need to conduct future experimental studies investigating the effect of diets with varying fatty acid compositions on GID-specific microbiome profiles in children with ASD.

Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma in Japan: An All-case Post-marketing Surveillance.

Objective To evaluate the safety profile of ixazomib combined with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) in clinical practice in Japan through an all-case post-marketing surveillance. Methods This was a nationwide non-interventional observational study conducted in Japan. The study included all patients who received ixazomib from May 24 to September 24, 2017. Ixazomib was administered to RRMM patients according to the Japanese package insert. All enrolled patients were observed until the completion of the sixth treatment cycle or until ixazomib discontinuation. The patient treatment course, including adverse events (AEs), was reported. Results The safety analysis set included 741 patients; the median age was 71 (range 35-92) years old, and the median number of prior treatment lines was 3 (range 1-30). Adverse drug reactions (ADRs) occurred in 572 (77.2%) patients, most commonly being thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Serious ADRs occurred in 193 (26.0%) patients, most commonly being thrombocytopenia (9.9%) and diarrhea (5.9%). Thrombocytopenia, severe gastrointestinal disorders, infections, skin disorders, and peripheral neuropathy were prespecified as ADRs of clinical importance; the frequency of these ADRs (grade ≥3) were 28.5%, 9.4%, 7.4%, 2.2%, and 1.3%, respectively. Treatment discontinuation was most common with thrombocytopenia and severe gastrointestinal disorders (49 and 43 patients, respectively). Eleven patients died due to ADRs (16 events). Conclusion These results suggest that ixazomib has a tolerable safety profile in clinical practice in Japan. However, close AE management for thrombocytopenia and gastrointestinal disorders should be considered.

Simultaneous determination of 12 lipophilic shellfish toxins in plasma and urine by ultra-high performance liquid chromatography-tandem mass spectrometry

生物样品中脂溶性贝类毒素的检测,可为食物中毒等突发公共卫生事件的流行病学调查以及中毒者的临床救治提供技术支持。目前的研究存在目标化合物少,以及方法前处理复杂、灵敏度低等问题。该研究通过优化前处理和色谱分离技术,建立了超高效液相色谱-串联质谱法测定血浆、尿液中12种脂溶性贝类毒素的方法。实验对提取试剂以及流动相的选择进行了优化,采用乙腈对尿液和血浆样品进行提取。采用Phenomenex Kinetex C18色谱柱(50 mm×3 mm, 2.6 μm)进行分离,以0.05%(v/v)氨水水溶液、90%(v/v)乙腈水溶液为流动相,以流速0.40 mL/min梯度洗脱时,12种目标化合物分离效果最好。串联质谱的离子源为电喷雾离子(ESI)源,采用多反应监测(MRM)模式检测。12种目标物的基质效应均在0.8~1.1之间,表明该前处理方法的基质干扰低,采用外标法可对化合物进行准确定量。12种贝类毒素的线性范围为0.03~36.25 μg/L,相关系数均大于0.995。尿液检测的方法定量限为0.23~0.63 μg/L,血浆检测的方法定量限为0.31~0.84 μg/L。3个加标水平的回收率为72.7%~124.1%,日内精密度为2.1%~20.0%,日间精密度为2.1%~15.3%。利用该方法检测健康人尿液和血浆样本,以及经腹腔注射12种贝类毒素的小鼠尿液和血液样本。20份健康人样本中未检出目标物,20份小鼠样本中12种贝类毒素均有检出。该方法操作简便,样品取样量少,方法灵敏高,适用于血浆和尿液中脂溶性贝类毒素的快速检测。

The anthelmintic potentials of medicinal plant extracts and an isolated compound (rutin, C27H30O16) from Terminalia catappa L. against Gastrothylax crumenifer

Paramphistomosis is a pathogenic disease that occurs frequently in tropical and subtropical countries including Thailand. This disease is affected in the parasites causing severe gastrointestinal disorders and death in infected animals. In the present study, we examined the anthelmintic efficacy of albendazole (ABZ) and crude plant extracts from barks of Bombax ceiba L., Diospyros rhodocalyx Kurz. and Vitex glabrata R.Br., and leaves of Terminalia catappa L. and Cassia alata L. against Gastrothylax crumenifer. The hightest anthelmintic activity on the parasites after 24 h incubation was observed in the n-butanol extract of T. catappa leaf. In this study, fractionation bioassay of n-butanol extract of T. catappa leaf was conducted to both separation and discrimination of rutin served as a new efficient compound (LC50 = 28.96; LC90 = 88.75 μg/mL) against G. crumenifer. This compound was confirmed by 1H nuclear magnetic resonance (1H NMR), 13C NMR, infrared (IR) and ultraviolet (UV) spectra as well as mass spectra data. The rutin-treated parasites with all dosages showed swift decrease of the motility and the relative motility (RM) and survival index (SI) were decreased obviously from 3 h until flukes were killed after 12 h of incubation. When observed with light microscopy, the parasites showed the earliest change in a limited region of the tegument. When observed by scanning electron microscopy, the parasites’ tegument exhibited similar sequences of surface changes after treatments with rutin and ABZ, but less severity in ABZ treatment. The sequences of changes comprised swelling of folds and ridges, formation of blebbing, rupturing of blebs, erosions, lesions and the tegument demolition. Hence, rutin could be considered as the potential anthelmintic agent for treatment of paramphistomosis.

Curcumin for parkinson´s disease: potential therapeutic effects, molecular mechanisms, and nanoformulations to enhance its efficacy.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders worldwide. It is caused by the degeneration of dopaminergic neurons from the substantia nigra pars compacta. This neuronal loss causes the dopamine deficiency that leads to a series of functional changes within the basal ganglia, producing motor control abnormalities. L-DOPA is considered the gold standard for PD treatment, and it may alleviate its clinical manifestations for some time. However, its prolonged administration produces tolerance and several severe side effects, including dyskinesias and gastrointestinal disorders. Thus, there is an urgent need to find effective medications, and current trends have proposed some natural products as emerging options for this purpose. Concerning this, curcumin represents a promising bioactive compound with high therapeutic potential. Diverse studies in cellular and animal models have suggested that curcumin could be employed for the treatment of PD. Therefore, the objective of this narrative mini-review is to present an overview of the possible therapeutic effects of curcumin and the subjacent molecular mechanisms. Moreover, we describe several possible nanocarrier-based approaches to improve the bioavailability of curcumin and enhance its biological activity.

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID‐19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent‐to‐treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30‐day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30‐day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50‐4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID‐19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID‐19.