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Cureus May 2024Patients with 21trisomy often develop congenital or acquired gastrointestinal diseases, such as duodenal or anal atresia, celiac disease, intussusception, and...
Patients with 21trisomy often develop congenital or acquired gastrointestinal diseases, such as duodenal or anal atresia, celiac disease, intussusception, and constipation. In these patients, it is often challenging to diagnose gastrointestinal diseases because most patients have difficulty explaining their complaints in detail. Furthermore, these patients also possess immunological disorders, such as increased type I interferon activation, innate immune hypersensitivity, and polarization to autoimmune. Here, we present a girl with 21trisomy and constipation who developed severe anemia, occult blood and elevated levels of calprotectin in stool, and chronic ileum obstruction confirmed by computed tomography. The patient underwent surgical resection of the ileum and recovered without complications. Pathological examination demonstrated intussusception, ischemia, ulceration, inflammatory granulation, and massive IgG4-positive plasma cell infiltration. After the surgery, her fecal calprotectin levels were normalized. We assumed that the ileum inflammation caused by ileum dilation generated ulcers and granulation, which could be associated with immunological, gastrointestinal, and intellectual disorders in patients with 21trisomy.
PubMed: 38868234
DOI: 10.7759/cureus.60177 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Jun 2024To observe the effects of electroacupuncture (EA) on the expression of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the pancreatic nuclear...
OBJECTIVE
To observe the effects of electroacupuncture (EA) on the expression of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the pancreatic nuclear factor-κB (NF-κB) pathway in type 2 diabetes mellitus (T2DM) rats, and to explore the possible mechanism by which EA improving the dedifferentiation of pancreatic β-cells in the treatment of T2DM.
METHODS
Among 18 SPF-grade male Wistar rats, 6 rats were randomly selected as the control group, and the remaining 12 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of 2% streptozotocin solution (35 mg/kg) to establish T2DM model. After successful modeling, the 12 rats were randomly divided into a model group and an EA group, with 6 rats in each group. The EA group received EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20), with continuous wave, frequency of 15 Hz, current intensity of 2 mA, for 20 min each time, once a day, 6 times a week, for a total of 6 weeks. Fasting blood glucose (FBG) levels were measured before modeling and before and after intervention. After intervention, ELISA was used to detect the serum fasting insulin (FINS), IL-1β and TNF-α levels, and the β-cell function index (HOMA-β) and insulin resistance index (HOMA-IR) were calculated; HE staining was used to observe the morphology of the pancreatic islets; Western blot was used to detect the protein expression of pancreatic forkhead box protein O1 (FoxO1), pancreatic and duodenal homeobox 1 (PDX-1), neurogenin 3 (NGN3), and NF-κB p65.
RESULTS
After intervention, the FBG in the model group was higher than that in the control group (<0.01), and the FBG in the EA group was lower than that in the model group (<0.01). Compared with the control group, the model group had increased levels of serum FINS, IL-1β, TNF-α, and HOMA-IR (<0.01), and decreased HOMA-β (<0.01), reduced protein expression of pancreatic FoxO1 and PDX-1 (<0.01), and increased protein expression of pancreatic NGN3 and NF-κB p65 (<0.01, <0.05). Compared with the model group, the EA group had lower serum FINS, IL-1β, TNF-α levels, and HOMA-IR (<0.01), higher HOMA-β (<0.05), increased protein expression of pancreatic FoxO1 and PDX-1 (<0.01, <0.05), and decreased protein expression of pancreatic NGN3 and NF-κB p65 (<0.01, <0.05). The control group's pancreatic islets showed no obvious abnormalities; the model group's pancreatic islets were irregular in shape and had unclear boundaries with the surrounding area, with immune cell infiltration, reduced β-cell nuclei, disordered arrangement of islet cells, and increased intercellular spaces; the EA group showed improvements in islet morphology, immune cell infiltration, β-cell nuclei count, and the arrangement and spacing of islet cells approaching normal.
CONCLUSION
EA could lower the blood glucose levels in T2DM rats, alleviate chronic inflammatory responses in the islets, and improve the dedifferentiation of pancreatic β-cells, which may be related to the inhibition of pancreatic NF-κB pathway expression.
Topics: Animals; Electroacupuncture; Male; Rats; Diabetes Mellitus, Type 2; Insulin-Secreting Cells; NF-kappa B; Rats, Wistar; Humans; Interleukin-1beta; Tumor Necrosis Factor-alpha; Signal Transduction; Cell Dedifferentiation; Blood Glucose; Acupuncture Points; Insulin
PubMed: 38867629
DOI: 10.13703/j.0255-2930.20230821-k0002 -
Forensic Science, Medicine, and... Jun 2024Hypothermia can occur in patients with diabetic ketoacidosis (DKA), and these two conditions can exacerbate each other. Fatal hypothermia and DKA have overlapping...
Hypothermia can occur in patients with diabetic ketoacidosis (DKA), and these two conditions can exacerbate each other. Fatal hypothermia and DKA have overlapping features and findings such as Wischnewsky spots (WS), black esophagus, basal subnuclear vacuolization in the renal tubule, dehydration, and increased acetone levels. Therefore, it may be challenging to differentiate or clarify the context of these two conditions. Herein, we report a case of a 49-year-old man with type 1 diabetes who was found lying in his house in mid-winter. He experienced cardiopulmonary arrest 10 h after the initial discovery and died at the hospital. On autopsy, florid left cardiac blood was observed. Black discoloration of the distal part of the esophageal mucosa, widespread WS in the gastric mucosa, and black discoloration of the duodenal mucosa were observed. Histologically, neutrophil infiltration in the esophageal mucosa, neutrophil infiltration and bleeding in the gastric mucosa, basal subnuclear vacuolization and Armanni-Ebstein lesion in the renal tubule epithelium in the kidney, and hyalinization of the islets of Langerhans were observed in the pancreas. Blood acetone and β-hydroxybutyrate levels were 538 µg/mL and 8947 µmol/L, respectively. Glycated hemoglobin A1c and glucose levels were 16.2% and 883 mg/dL, respectively, while C-reactive protein level was 3.64 mg/dL. In conclusion, obnubilation due to DKA was assumed to be the underlying cause of hypothermia, and the combination of these two conditions led to the outcome of death. The concurrent presence of these conditions likely contributed to the conspicuous mucosal findings in the upper gastrointestinal tract.
PubMed: 38867122
DOI: 10.1007/s12024-024-00837-0 -
Clinical Gastroenterology and... Jun 2024In this Clinical Practice Update (CPU), we will Best Practice Advice (BPA) guidance on the appropriate management of iron deficiency anemia.
DESCRIPTION
In this Clinical Practice Update (CPU), we will Best Practice Advice (BPA) guidance on the appropriate management of iron deficiency anemia.
METHODS
This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: No single formulation of oral iron has any advantages over any other. Ferrous sulfate is preferred as the least expensive iron formulation. BEST PRACTICE ADVICE 2: Give oral iron once a day at most. Every-other-day iron dosing may be better tolerated for some patients with similar or equal rates of iron absorption as daily dosing. BEST PRACTICE ADVICE 3: Add vitamin C to oral iron supplementation to improve absorption. BEST PRACTICE ADVICE 4: Intravenous iron should be used if the patient does not tolerate oral iron, ferritin levels do not improve with a trial of oral iron, or the patient has a condition in which oral iron is not likely to be absorbed. BEST PRACTICE ADVICE 5: Intravenous iron formulations that can replace iron deficits with 1 or 2 infusions are preferred over those that require more than 2 infusions. BEST PRACTICE ADVICE 6: All intravenous iron formulations have similar risks; true anaphylaxis is very rare. The vast majority of reactions to intravenous iron are complement activation-related pseudo-allergy (infusion reactions) and should be treated as such. BEST PRACTICE ADVICE 7: Intravenous iron therapy should be used in individuals who have undergone bariatric procedures, particularly those that are likely to disrupt normal duodenal iron absorption, and have iron-deficiency anemia with no identifiable source of chronic gastrointestinal blood loss. BEST PRACTICE ADVICE 8: In individuals with inflammatory bowel disease and iron-deficiency anemia, clinicians first should determine whether iron-deficiency anemia is owing to inadequate intake or absorption, or loss of iron, typically from gastrointestinal bleeding. Active inflammation should be treated effectively to enhance iron absorption or reduce iron depletion. BEST PRACTICE ADVICE 9: Intravenous iron therapy should be given in individuals with inflammatory bowel disease, iron-deficiency anemia, and active inflammation with compromised absorption. BEST PRACTICE ADVICE 10: In individuals with portal hypertensive gastropathy and iron-deficiency anemia, oral iron supplements initially should be used to replenish iron stores. Intravenous iron therapy should be used in patients with ongoing bleeding who do not respond to oral iron therapy. BEST PRACTICE ADVICE 11: In individuals with portal hypertensive gastropathy and iron-deficiency anemia without another identified source of chronic blood loss, treatment of portal hypertension with nonselective β-blockers can be considered. BEST PRACTICE ADVICE 12: In individuals with iron-deficiency anemia secondary to gastric antral vascular ectasia who have an inadequate response to iron replacement, consider endoscopic therapy with endoscopic band ligation or thermal methods such as argon plasma coagulation. BEST PRACTICE ADVICE 13: In patients with iron-deficiency anemia and celiac disease, ensure adherence to a gluten-free diet to improve iron absorption. Consider oral iron supplementation based on the severity of iron deficiency and patient tolerance, followed by intravenous iron therapy if iron stores do not improve. BEST PRACTICE ADVICE 14: Deep enteroscopy performed in patients with iron-deficiency anemia suspected to have small-bowel bleeding angioectasias should be performed with a distal attachment to improve detection and facilitate treatment. Small-bowel angioectasias may be treated with ablative thermal therapies such as argon plasma coagulation or with mechanical methods such as hemostatic clips. BEST PRACTICE ADVICE 15: Endoscopic treatment of angioectasias should be accompanied with iron replacement. Medical therapy for small-bowel angioectasias should be reserved for compassionate treatment in refractory cases when iron replacement and endoscopic therapy are ineffective.
PubMed: 38864796
DOI: 10.1016/j.cgh.2024.03.046 -
Cureus May 2024We present a 45-year-old African American male with a medical history of advanced-stage HIV/AIDS (CD4 count: 1 cell/μL) and poor adherence to highly active...
We present a 45-year-old African American male with a medical history of advanced-stage HIV/AIDS (CD4 count: 1 cell/μL) and poor adherence to highly active antiretroviral therapy (HAART), who presented with symptoms of diarrhea, weakness, and respiratory distress. Upon admission, duodenal and colonic biopsies revealed a diffuse histiocytic infiltrate consistent with complex (MAC), and a cecal biopsy was positive for Kaposi sarcoma (KS). Further workup showed consolidation and a right pleural effusion on chest X-ray, suggesting a pneumonia infection. The patient's hypoglycemic state and lung consolidation raised concerns for sepsis, despite negative blood cultures for the first 24 hours. The patient was initiated on HAART and treated with azithromycin, rifabutin, and ethambutol for disseminated MAC. Despite the aggressive immunotherapy, the patient's condition did not improve, and he eventually expired. This case uniquely highlights the wide range of opportunistic infections and malignancies that can present in individuals with advanced-stage HIV/AIDS, underscoring the importance of early recognition and treatment. This susceptible demographic warrants further research due to the non-solidified prognosis of individuals with severe immunodeficiency.
PubMed: 38864070
DOI: 10.7759/cureus.60129 -
Frontiers in Microbiology 2024Bariatric and metabolic surgery often leads to significant changes in gut microbiota composition, indicating that changes in gut microbiota after bariatric and metabolic...
BACKGROUND
Bariatric and metabolic surgery often leads to significant changes in gut microbiota composition, indicating that changes in gut microbiota after bariatric and metabolic surgery might play a role in ameliorating type 2 diabetes (T2D). However, the effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) on gut microbiota in T2D remain unclear.
OBJECTIVES
To investigate the effects of SADI-S on gut microbiota and glucose metabolism in T2D rats.
METHODS
Nineteen T2D rats were randomly divided into the SADI-S group ( = 10) and the sham operation with pair-feeding group (sham-PF, = 9). Fecal samples were collected to analyze the gut microbiota composition with 16S ribosomal DNA gene sequencing. The fasting blood glucose and glycated hemoglobin were measured to evaluate the effects of SADI-S on glucose metabolism.
RESULTS
The Chao and ACE index results indicated the richness of the gut microbial community. The ACE and Chao index values were significantly lower in the SADI-S group than in the sham-PF group, indicating that indicating that species richness was significantly lower in the SADI-S group than in the sham-PF group ( < 0.05). Shannon and Simpson indices were used to estimate the species diversity of the gut microbiota. Compared with the sham-PF group, the SADI-S group showed significantly lower Shannon index and higher Simpson index values, indicating that the species diversity was significantly lower in the SADI-S group than in the sham-PF group ( < 0.05). At the genus level, SADI-S significantly changed the abundances of 33 bacteria, including the increased anti-inflammatory bacteria ( and ) and decreased pro-inflammatory bacteria (). SADI-S significantly decreased the fasting blood glucose and glycated hemoglobin levels. The blood glucose level of rats was positively correlated with the relative abundances of 12 bacteria, including , and negatively correlated with the relative abundances of seven bacteria, including .
CONCLUSION
SADI-S significantly altered the gut microbiota composition of T2D rats, including the increased anti-inflammatory bacteria ( and ) and decreased pro-inflammatory bacteria (Bacteroides). The blood glucose level of rats was positively correlated with the abundances of 12 bacteria, including , but negatively correlated with the relative abundance of 7 bacteria, including . These alternations in gut microbiota may be the mechanism through which SADI-S improved T2D. More studies should be performed in the future to validate these effects.
PubMed: 38863754
DOI: 10.3389/fmicb.2024.1357749 -
Frontiers in Oncology 2024Robot-assisted surgery has shown remarkable progress as a minimally invasive procedure for gastric cancer. This study aimed to compare the pre-emptive suprapancreatic...
BACKGROUND
Robot-assisted surgery has shown remarkable progress as a minimally invasive procedure for gastric cancer. This study aimed to compare the pre-emptive suprapancreatic approach without duodenal transection and the conventional approach in terms of perioperative feasibility and short-term surgical outcomes.
METHODS
We retrospectively analyzed all patients who underwent robotic distal gastrectomy with D2 lymph node dissection using the da Vinci Xi robotic system between December 2021 and April 2023 and categorized them into two groups for comparison. Patients treated using the pre-emptive suprapancreatic approach (observation group) were compared with those who received the conventional approach (control group). Employing one-to-one propensity score matching, we evaluated the postoperative morbidity and short-term outcomes in these two distinct groups to assess the efficacy and safety of the novel surgical technique.
RESULTS
This study enrolled 131 patients: 70 in the observation group and 61 in the control group. After propensity score matching, the operative times were significantly longer in the control group than in the observation group (229.10 ± 33.96 vs. 174.84 ± 18.37, p <0.001). The mean blood loss was lower in the observation group than in the control group (25.20 ± 11.18 vs. 85.00 ± 38.78, p <0.001). Additionally, the observation group exhibited a higher number of retrieved lymph nodes, including suprapyloric, perigastric, and superior pancreatic lymph nodes (28.69 ± 5.48 vs. 19.21 ± 2.89, p <0.001; 4.98 ± 1.27 vs. 4.29 ± 1.21, p = 0.012; 10.52 ± 2.39 vs. 5.50 ± 1.62, p <0.001; 6.26 ± 2.64 vs. 5.00 ± 1.72, p = 0.029). Drain amylase levels in the observation group were significantly lower than those in the control group (30.08 ± 33.74 vs. 69.14 ± 66.81, p <0.001).
CONCLUSION
This study revealed that using the pre-emptive suprapancreatic approach without duodenal transection in the dissection of D2 lymph nodes for gastric cancer is a safe and feasible procedure in terms of surgical outcomes.
PubMed: 38863643
DOI: 10.3389/fonc.2024.1388626 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia...
BACKGROUND & AIMS
Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO).
METHODS
The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO.
RESULTS
In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/mvs 9.0 kg/m, p = 0.004; ASMMI: 6.2 kg/mvs 7.2 kg/m, p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3.
CONCLUSIONS
MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO.
Topics: Humans; Myostatin; Male; Female; Neoplasms; Muscle, Skeletal; Middle Aged; Obesity; Cachexia; Biomarkers; Sarcopenia; Hand Strength; Body Composition; Aged; Muscle Strength; Adult; Electric Impedance
PubMed: 38861892
DOI: 10.1016/j.clnu.2024.05.046 -
Blood Jun 2024Ferroportin (Fpn) is the only iron exporter, playing a crucial role in systemic iron homeostasis. Fpn is negatively regulated by its ligand hepcidin, but other potential...
Ferroportin (Fpn) is the only iron exporter, playing a crucial role in systemic iron homeostasis. Fpn is negatively regulated by its ligand hepcidin, but other potential regulators in physiological and disease conditions remain poorly understood. Diabetes is a metabolic disorder that develops body iron loading with unknown mechanisms. By utilizing diabetic mouse models and human duodenal specimens, we demonstrated that intestinal Fpn expression was increased in diabetes in a hepcidin-independent manner. Protein kinase C (PKC) is hyperactivated in diabetes. We showed that PKC was required to sustain baseline Fpn expression and diabetes induced Fpn upregulation in the enterocytes and macrophages. Knockout of PKC abolished diabetes associated iron overload. Mechanistically, activation of PKC increased the exocytotic while decreased the endocytic trafficking of Fpn in the resting state. Hyperactive PKC also suppressed hepcidin-induced ubiquitination, internalization, and degradation of Fpn. We further observed that iron loading in the enterocytes and macrophages activated PKC, acting as a novel mechanism to enhance Fpn-dependent iron efflux. Finally, we demonstrated that the loss-of-function of PKC and pharmacological inhibition of PKC significantly alleviated hereditary hemochromatosis associated iron overload. Our study has highlighted, for the first time, that PKC is an important positive regulator of Fpn and a new target in the control of iron homeostasis.
PubMed: 38861671
DOI: 10.1182/blood.2024023829 -
BioRxiv : the Preprint Server For... May 2024Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection....
Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2'-fucosyllactose (2'FL) in the same pocket as HBGAs for some HuNoV strains. We evaluated the effect of 2'FL on the replication of a globally dominant GII.4 Sydney [P16] HuNoV strain using human intestinal enteroids (HIEs) from adults and children. A significant reduction in GII.4 Sydney [P16] replication was seen in duodenal and jejunal HIEs from multiple adult donors, all segments of the small intestine from an adult organ donor and in two pediatric duodenal HIEs. However, 2'FL did not inhibit HuNoV replication in two infant jejunal HIEs that had significantly lower expression of α1-2-fucosylated glycans. 2'FL can be synthesized in large scale, and safety and tolerance have been assessed previously. Our data suggest that 2'FL has the potential to be developed as a therapeutic for HuNoV gastroenteritis.
PubMed: 38853945
DOI: 10.1101/2024.05.30.596597