Autoimmune comorbidity in achalasia patients Romero-Hernández, Fernanda; Furuzawa-Carballeda, Janette; Hernández-Molina, Gabriela ...
Journal of gastroenterology and hepatology
33, Številka:
1
Journal Article
Recenzirano
Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies ...participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD).
It was a cross-sectional and included 114 patients with idiopathic achalasia and 114 age-matched and sex-matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records.
Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47-9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00-9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65-6.20).
The non-negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component.
Objective
To determine the differences between clinical, manometric, and neuroimmunological profile of esophagogastric junction outflow obstruction (EGJOO) and achalasia patients.
Methods
Seven EGJOO ...and 27 achalasia patients were enrolled in a blind cross‐sectional study. Peripheral blood (PB) of 10 healthy donors and 10 lower esophageal sphincter (LES) muscle biopsies from organ transplant donors were included as controls. The presence of ganglion cells, cells of Cajal, Th22/Th7/Th2/Th1/Tregs/Bregs/pDCregs in tissue, and PB was assessed by immunohistochemistry and flow cytometry. Serum concentration of IL‐22/IL‐17A/IL‐17F/IL‐4/IFN‐γ/IL‐1β/IL‐6/IL‐23/IL‐33/TNF‐α/IL‐10 was determined using bioplex plates. ANAs and antineuronal antibodies were evaluated by immunofluorescence and Western blot.
Key Results
EGJOO and achalasia patients had lower ganglion cells and cells of Cajal percentage vs. controls, while fibrosis was present only in achalasia patients. EGJOO and controls had lower cell percentage of Th22/Th17/Th2 vs. achalasia. EGJOO tissue had lower Th1/Treg cell number vs. achalasia, but higher levels vs. control group. Bregs and pDCregs percentage was higher in EGJOO vs. control group. Percentage of PB subpopulations in EGJOO was not significantly different from control group. Serum cytokine levels were higher for IL‐1β/IL‐6/TNF‐α, while IL‐17A levels were lower in EGJOO vs. achalasia and control group. EGJOO group was negative for ANAs, while in achalasia group, 54% were positive. GAD65 and PNMa/Ta2 antibodies were present in achalasia, whereas Yo and recoverin were positive in EGJOO group.
Conclusions and Inferences
Although EGJOO shares some clinical characteristics with achalasia, the neuroimmunological profile is completely different, suggesting that EGJOO might be a different entity.
Hypothetical model of EGJOO neuroimmunological pathophysiology.
Idiopathic achalasia is a relatively infrequent esophageal motor disorder for which major histocompatibility complex (MHC) genes are well-identified risk factors. However, no information about ...HLA-achalasia susceptibility in Mexicans has previously been reported. We studied a group of 91 patients diagnosed with achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and conserved extended haplotypes were analyzed using high-resolution HLA typing based on Sanger and next-generation sequencing technologies. Admixture estimates were determined using HLA-B and short tandem repeats. Results were analyzed by non-parametric statistical analysis and Bonferroni correction. P-values < 0.05 were considered significant. Patients with achalasia had 56.7% Native American genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was comparable with the estimates in the controls. Significant increases in the frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction (pC<0.05), were found in the achalasia group compared to those in the controls. Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the extended haplotype are risk factors for achalasia in mixed-ancestry Mexican individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03 haplotype was introduced by admixture with European and/or Asian populations.
Abstract
Objective
This study aims to describe the behavior of chromosomopathy screenings in euploid fetuses.
Methods
This is a prospective descriptive study with 566 patients at 11 to 14 weeks of ...gestation. The associations between ultrasound scans and serological variables were studied. For the quantitative variables we used the Spearman test; for the qualitative with quantitative variables the of Mann-Whitney U-test; and for qualitative variables, the X
2
test was applied. Significance was set at
p
≤ 0.05.
Results
We have found that gestational age has correlation with ductus venosus, nuchal translucency, free fraction of β subunit of human chorionic gonadotropin, pregnancy-associated plasma protein-A and placental growth factor; there is also a correlation between history of miscarriages and nasal bone. Furthermore, we correlated body mass index with nuchal translucency, free fraction of β subunit of human chorionic gonadotropin, and pregnancy-associated plasma protein-A. Maternal age was associated with free fraction of β subunit of human chorionic gonadotropin and pregnancy-associated plasma protein-A.
Conclusion
Our study demonstrates for the first time the behavior of the biochemical and ultrasonographic markers of chromosomopathy screenings during the first trimester in euploid fetuses in Colombia. Our information is consistent with international reference values. Moreover, we have shown the correlation of different variables with maternal characteristics to determine the variables that could help with development of a screening process during the first trimester with high detection rates.
To evaluate the effectiveness of an evaporation reduction method in which the greater part of the water surface was covered with PET-type plastic bottles. The capacity of this method to diminish ...natural evaporation was compared to water aeration, water recirculation, and the control (without intervention). With evolutionary computation, including genetic algorithms and genetic programming, equations for calculating evaporation were developed based on meteorological factors.
Four containers of water were placed on a flat roof in Mexico City (thus exposed to the factors of weather), and evaporation was measured daily with an evaporimeter. Each container was assigned to one of the evaporation reduction methods (PET bottles, water aeration, or water recirculation) or to the control (without intervention). Evaporation-related variables were selected according to previous reports and principal component analysis, and their values were acquired from a nearby meteorological station. The study was conducted from April of 2020 to February of 2021.
Covering the water surface with PET bottles avoided 38.61% (a total of 139 mm) of natural evaporation, which is represented by the control. The water aeration and water recirculation methods diminished evaporation by 7.22% (26 mm) and 2.22% (8 mm), respectively. The best equations for estimating evaporation were obtained with genetic programming for the control container and a genetic algorithm for the container with PET bottles.
The PET bottle method of evaporation reduction was 7 and 17 times more effective than water aeration and water recirculation, respectively. The 38.61% decrease in evaporation achieved by covering the water surface with PET bottles constitutes a substantial savings in water. Hence, the implementation of such a method should be considered to contribute to water conservation in reservoirs. The use of PET bottles is a practical and inexpensive method requiring only a few cleaning maneuvers to prevent the proliferation of unwanted aquatic fauna.
Spinal cord injury (SCI) causes a dysfunction of sympathetic nervous system innervation that affects the immune system, leading to immunosuppression syndrome (ISS) and contributing to patient ...degeneration and increased risk of several infections. A possible therapeutic strategy that could avoid further patient deterioration is the supplementation with Vitamin E or trace elements, such as Zinc, Selenium, and Copper, which individually promotes T-cell differentiation and proliferative responses. For this reason, the aim of the present study was to evaluate whether Vitamin E, Zinc, Selenium, and Copper supplementation preserves the number of T-lymphocytes and improves their proliferative function after traumatic SCI. Sprague–Dawley female rats were subjected to moderate SCI and then randomly allocated into three groups: (1) SCI + supplements; (2) SCI + vehicle (olive oil and phosphate-buffered saline); and (3) sham-operated rats. In all rats, the intervention was initiated 15 min after SCI and then administered daily until the end of study. Locomotor recovery was assessed at 7 and 15 days after SCI. At 15 days after supplementation, the quantification of the number of T-cells and its proliferation function were examined. Our results showed that the SCI + supplements group presented a significant improvement in motor recovery at 7 and 15 days after SCI. In addition, this group showed a better T-cell number and proliferation rate than that observed in the group with SCI + vehicle. Our findings suggest that Vitamin E, Zinc, Selenium, and Copper supplementation could be part of a therapy for patients suffering from acute SCI, helping to preserve T-cell function, avoiding complications, and promoting a better motor recovery. All procedures were approved by the Animal Bioethics and Welfare Committee (Approval No. 201870; CSNBTBIBAJ 090812960).
Introduction
Peritoneal carcinomatosis is considered a late‐stage manifestation of neoplastic diseases. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC) can be an ...effective treatment for these patients. However, the procedure is associated with significant morbidity. Our aim was to develop a machine learning model to predict the probability of achieving textbook outcome (TO) after CRS‐HIPEC using only preoperatively known variables.
Methods
Adult patients with peritoneal carcinomatosis and who underwent CRS‐HIPEC were included from a large, single‐center, prospectively maintained dataset (2001–2020). TO was defined as a hospital length of stay ≤14 days and no postoperative adverse events including any complications, reoperation, readmission, and mortality within 90 days. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated, and a user‐friendly risk calculator was then developed.
Results
A total of 1954 CRS‐HIPEC procedures for peritoneal carcinomatosis were included. Overall, 13% (n = 258) achieved TO following CRS‐HIPEC procedure. XGBoost and logistic regression had the highest area under the curve (AUC) (0.76) after model optimization, followed by random forest (AUC 0.75) and neural network (AUC 0.74). The top preoperative variables associated with achieving a TO were lower peritoneal cancer index scores, not undergoing proctectomy, splenectomy, or partial colectomy and being asymptomatic from peritoneal metastases prior to surgery.
Conclusion
This is a data‐driven study to predict the probability of achieving TO after CRS‐HIPEC. The proposed pipeline has the potential to not only identify patients for whom surgery is not associated with prohibitive risk, but also aid surgeons in communicating this risk to patients.
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