Manifestations Of Gastroesophageal Reflux Disease Research Articles

Gastroesophageal reflux disease and risk factors in schoolchildren

Aim. To study the association between family predisposition to gastrointestinal diseases with gastroesophageal reflux disease (GERD) in schoolchildren in ethnic populations of Tuva. Material and methods. A total of one thousand seventy nine children (761 Mongoloid-Tuvinian and 318 Caucasian) aged of 7–17 years in the Republic of Tyva were examined. Anamnestic data and information on gastrointestinal complaints in schoolchildren were obtained. The diagnostic criterion for GERD was complaints of weekly heartburn. Statistical analysis was performed using the Pearson chi-square test. Results. GERD children more often had anamnestic data on gastritis (p = 0.025), gastric ulcer (p = 0.039) and oncological diseases of the gastrointestinal tract (p = 0.052) in parents. At the same time, schoolchildren of the indigenous population with GERD manifestations had greater unfavourable conditions for a number of diseases in parents: gastritis (p = 0.01), gastric ulcer (p = 0.012). Whereas in Caucasians, a similar association was not established. The association between GERD in schoolchildren and gastrointestinal pathology in grandparents (2nd degree of kinship) also concerned only Tuvans in the presence of gastritis (p = 0.023). Summary data on family history of gastrointestinal diseases (1st and 2nd generation relatives) in GERD children, as expected, prevailed in Tuvans (gastritis (p = 0.004), peptic ulcer (p = 0.033) and specifically gastric ulcer (p = 0.02)). A more negative association between GERD in Tuvan children and a family predisposition to gastrointestinal diseases, in contrast to Caucasians, may be due to a higher prevalence of a number of gastrointestinal diseases in adults and is related with the functional features of the system, formed under the influence of the features of traditional life and nutrition. Conclusion. In the Republic of Tyva, GERD in native schoolchildren is associated with a wide range of gastrointestinal diseases in relatives.

The role of P-CABs in GERD.

Potassium-competitive acid blockers (P-CABs) constitute a relatively new class of gastric acid-suppressing drugs. Among this class, vonoprazan is the first to have been approved in the United States. However, some P-CABs including vonoprazan, tegoprazan and fexuprazan have been available in other countries since at least 2014. The first aim of this article is to review pharmacological differences between P-CABs that are currently approved or in development with proton pump inhibitors (PPIs). The specific focus thereafter is on the likely role of P-CABs in the treatment of different manifestations of gastroesophageal reflux disease (GERD). Multiple clinical trials have compared P-CABs with PPIs in erosive esophagitis. Additional trials have compared P-CABs with placebo in non-erosive reflux disease. Relevant results are reviewed and inferences drawn for their use in the US. Lastly, consideration is given to additional, potential uses of P-CABs in the broader spectrum of GERD and some suggestions made for future research initiatives.

Clinical manifestations of gastroesophageal reflux disease in medical university students

Clinical manifestations of gastroesophageal reflux disease in medical university students

279. NOVEL REFLUX MICROASPIRATION SCINTIGRAPHY ALLOWS EFFECTIVE PATIENT SELECTION FOR ANTIREFLUX SURGERY IN PROXIMAL REFLUX EVENTS

Abstract Background and Aims There is currently no reference standard test for the detection of the extra-esophageal manifestations of gastroesophageal reflux disease (GORD). The current suite of diagnostic tests principally assess reflux events in the oesophagus have problematic accuracy issues in the pharynx. A new scintigraphic technique has been developed and validated against 24-hour oesophageal monitoring with pH, impedance. It allows direct visualization of refluxate in the laryngopharynx and lungs. This was utilised to evaluate patients having laparoscopic fundoplication for severe proximal reflux resistant to maximal medical therapy. Scanning may allow succesful patient selection for antireflux surgery. Methodology Following Institutional Ethics approval, 50 patients were assessed by scintigraphy before and after laparoscopic fundoplication (LF) at a single nuclear medicine facility. Standardised Reflux Symptom Indices (RSI) were obtained from each patient before and after surgery. Patients were scanned after oral 99m technetium Fyton administration with early dynamic images and delayed SPECT/CT images of the head, neck and lungs. Background corrected time-activity curves were generated for the pharynx and upper oesophagus from which frequency of reflux was estimated by counting events with activities greater than 2 standard deviations above fitted values. Frequencies, Spearman correlation and the student’s t test were utilised for analysis. Results The study population (35F, 15M) had a mean age of 63.9 years (Range 21-86). All patients underwent LF. Mean BMI was 26.8 with 67% being over-weight or obese. All patients had proximal reflux events in the early dynamic study. SPECT/ CT showed LPR events in 45/50 and pulmonary micro-aspiration (PMA) in 45/50 pre-operatively and in 36/50 and 20/50 post-operatively. The RSI, cough and throat clearing indices showed a significant fall post-operatively (p< 0.001). The frequency of scintigraphic pharyngeal reflux events was reduced from a mean of 4.5 in 30 minutes to 2.9 (t=9.1, p=0.004). Conclusion The novel scintigraphic test detects oesophageal and extra-oesophageal reflux events and permits direct visualization of refluxate in the head and neck structures and lungs. Scintigraphy correlates well with symptoms of reflux in the oesophagus and extra-esophageal structures such as the laryngopharynx (chronic cough and throat clearing) and the response to LF albeit partial. PMA was significantly reduced.

Scintigraphic Imaging of Extra-Esophageal Manifestation of Gastresophageal Reflux Disease.

There is currently no reference standard test for the detection of the extra-esophageal manifestations of gastroesophageal reflux disease (GERD). The current suite of diagnostic tests principally assesses reflux events in the esophagus. A new scintigraphic technique has been developed and validated against reference standards. It allows direct visualization of refluxate in the laryngopharynx and lungs. Fifty patients were assessed by scintigraphy before and after fundoplication at a single nuclear medicine facility. Standardized reflux symptomindices (RSIs) were obtained from each patient before and after surgery. Patients were scanned after oral 99 m technetium Fyton administration with early dynamic images and delayed SPECT/CT images of the head, neck, and lungs. ANOVA, Spearman correlation, and the Student's t-test were utilized for analysis. The study population (35F, 15 M) had a mean age of 63.9 years. Mean BMI was 26.8 with 67% being overweight or obese. All patients had significant reflux. SPECT/CT showed LPR events in 45/50 and pulmonary micro-aspiration (PMA) in 45/50 preoperatively and in 36/50 and 20/50 postoperatively, respectively. The RSI, cough, and throat clearing indices showed a significant fall postoperatively (p < 0.001). Frequency of scintigraphic reflux events was reduced from a mean of 4.5 in 30 min to 2.9 (t = 9.1, p = 0.004). The novel scintigraphic test detects esophageal and extra-esophageal reflux events and permits direct visualization of refluxate in the head and neck structures and lungs. It correlates well with symptoms of reflux in the esophagus and extra-esophageal structures and the response to therapy. Although prospective, the study did not randomize patients and in effect each patient became their own control following an intervention (fundoplication). Thus, the study is Level 3 evidence Laryngoscope, 2024.

Systematic review and meta-analysis: proton pump inhibitors slightly decrease the severity of chronic cough

The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI − 0.22; 0.88), 0.31 (CI − 1.74; 2.35), 0.32 (CI − 0.29; 0.93) and 0.34 (CI − 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI − 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.

Diagnostic value associated with the combination of saliva pepsin and microorganisms in functional heartburn and gastroesophageal reflux disease.

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.

Noninvasive diagnosis of laryngopharyngeal reflux as an extraesophageal manifestation of gastroesophageal reflux disease: A literature review

Тo date, gastroesophageal reflux disease (GERD) is considered as a condition that includes various subgroups: erosive esophagitis, non-erosive reflux disease, Barrett’s esophagus, hypersensitive esophagus and functional heartburn. A common extraesophageal manifestation of GERD is laryngopharyngeal reflux (LFR), in which, in addition to dyspeptic symptoms, patients note hoarseness, cough, tickling and a feeling of a foreign body in the throat. When LFR occurs, the direct effect of gastroduodenal reflux on the mucous membrane of the larynx and pharynx leads to morphological changes, the development of pachyderma and laryngeal granuloma; indirect activation of reflex mechanisms causes the manifestation of esophagobronchial reflux. The diagnosis of LFR includes an analysis of the patient’s life history, registration of complaints using questionnaires (Index of reflux symptoms), assessment of the clinical and functional state of the larynx using a visually analog scale of reflux signs and videolaryngostroboscopy, the use of instrumental methods and laboratory tests. The detected laryngoscopic signs are not always pathognomonic for GERD-associated LFR: extraesophageal manifestations of the disease can also be observed in the absence of the most typical esophageal symptoms, which is a serious diagnostic problem. Due to the fact that not all instrumental diagnostic methods are informative in various cases of reflux-associated diseases, non-invasive methods are more convenient at the outpatient stage of patient examination questioning patients using special scales and questionnaires. The article presents the most informative and rational methods of noninvasive screening of GERD-associated diseases available in the available literature, aimed at identifying the severity of reflux manifestations, the level of patient satisfaction with their condition and the effectiveness of therapy. In order to improve the screening diagnostic process of LFR, it is necessary to develop and implement a reliable and sensitive questionnaire with an interdisciplinary approach.

Clinical manifestations of gastro esophageal reflux among patients with chronic laryngitis in Benghazi, 2018

Gastroesophageal reflux disease is a chronic, complex condition that may present with atypical symptoms, including laryngitis. The aim of study to demonstrates the relationship of sings of reflux laryngitis in patients with typical manifestations of Gastroesophageal reflux disease (GERD). The present study included a total of 60 patients suffering chronic laryngitis with a range of age of 23 to 88 years in descriptive study in Benghazi Medical Center in the year 2018. History was collected and indirect laryngoscopy done for cases and data were analyzed using SPSS 23.0. Results The most common symptoms were hoarseness of voice, throat clearing, dysphagia, throat discomfort and globus sensation. No significant association of symptoms with gender of the patients. Most common laryngeal findings were hyperemia, vocal cord changes and posterior commisure hypertrophy. Significant association included only posterior commissure hypertrophy and infra-glottal edema. Conclusions and recommendations, Many didn't seek medical advice and most had no diagnostic procedure. Stronger study designs using proper diagnostic technique and patient education with staff training are recommended.

The role of α-lipoic acid in the treatment of patients with gastroesophageal reflux disease against the background of type 2 diabetes mellitus

Objective — to study the role of α‑lipoic acid (ALA) in the treatment of patients with gastroesophageal reflux disease (GERD) in combination with type 2 diabetes mellitus (T2DM).&#x0D; Materials and methods. The study involved 120 subjects, who were divided into four groups: 1st group included 60 patients with GERD against the background of T2DM, 2nd group consisted of 20 patients with GERD and 3rd group included 20 patients with isolated T2DM. Additionally, the 1st group was divided into 2 subgroups: 25 patients receiving standard treatment and 29 patients receiving standard treatment + ALA supplementation. The control group consisted of 20 practically healthy age‑matching subjects. Ghrelin and leptin levels were determined by enzyme‑linked immunosorbent assay (ELISA) on the analyzer «Labline‑90» (Austria).&#x0D; Results. The comparison of the standard treatment regimen and proposed treatment demonstrated significantly lower frequency of such symptoms as epigastric pain, regurgitation and symptoms, specific for ischemic heart disease, in the subgroup with the proposed treatment regimen (p &lt;0.05). Investigation of carbohydrate and lipid metabolism in a subgroup of patients receiving standard treatment, showed improvements in all parameters, but significant (p &lt;0.05) improvement in patients on the standard therapy was recorded in glucose, insulin, glycosylated hemoglobin (HbA1C) levels, and insulin resistance index (HOMA‑IR). In the subgroup receiving ALA, improvement was gained in the indices of glucose, glycosylated hemoglobin, HOMA‑IR, triglycerides, cholesterol, high and very low‑density lipoproteins and atherogenicity coefficient. After the treatment in the subgroups of standard therapy and therapy with the ALA addition, an increase in ghrelin levels was registered from 0.99±0.41 to 1.09±0.45 ng/ml and from 0.93±0.52 to 1.22±0.59 ng/ml, respectively, and decrease in leptin levels from 19.04±9.48 to 16.66±7.14 ng/ml and from 20.75±9.09 to 16.39±6.88 ng/ml. However, in the first subgroup, the difference between the indicators before and after treatment did not reach the level of statistical significance (p=0.421 and p=0.320, respectively), while in the subgroup where ALA was used, the difference was significant (p &lt;0.05).&#x0D; Conclusions. It has been established that ALA positively influences on the state of carbohydrate and lipid metabolism, improving these parameters. The addition of ALA to the standard treatment for GERD against the background of type 2 diabetes showed significant improvement in the studied parameters. Since reference values for ghrelin and leptin levels have not been established yet, it can be assumed that increase in ghrelin and decrease in leptin levels against the background of decrease in well‑studied parameters of lipid and carbohydrate metabolism, have a positive impact on the clinical manifestation of GERD against T2DM background. This assumption may be used as a marker for effective treatment of GERD in combination with T2DM.&#x0D;

Tonghua Liyan granules in the treatment of Laryngopharyngeal reflux disease with stagnation of phlegm and qi syndrome: a randomized, double-blind, placebo-controlled study.

Background: Laryngopharyngeal reflux disease (LPRD) is an extraesophageal syndromic manifestation of gastroesophageal reflux disease (GERD). Despite the increasing incidence of and concern about LPRD, treatment with proton pump inhibitors (PPIs) is unsatisfactory. Here, LPRD was treated with Tonghua Liyan (THLY) granules in combination with PPIs to evaluate treatment efficacy and possible adverse reactions. Methods: Seventy-six LPRD patients with stagnation of phlegm and qi syndrome (SPQS) were randomly divided into an experimental group and a control group. The experimental group received THLY granules combined with rabeprazole capsules. The control group received THLY granule placebo combined with rabeprazole capsules. A parallel, randomized, double-blind, placebo-controlled clinical trial was conducted with these two groups. The treatment cycle was 8weeks. The reflux symptom index (RSI), clinical symptom score, salivary pepsin content, reflux finding score (RFS) and gastroesophageal reflux disease questionnaire (GerdQ) were used to evaluate clinical efficacy. The final efficacy rate was evaluated according to the RSI and clinical symptom score. Results: Compared with those at baseline, all the indicators in the experimental group and control group significantly improved (p < 0.01). In terms of the RSI, clinical symptom score, and RFS, the experimental group had a higher degree of improvement (p < 0.05), and the overall efficacy rate was higher (p < 0.05). In terms of the salivary pepsin concentration and GerdQ, there was no significant difference between the test group and the control group (p > 0.05). Both groups of safety indicators showed no abnormalities and did not cause any allergic reactions in the body. Conclusion: Compared with PPIs alone, THLY granules combined with PPIs are more effective in the treatment of LPRD patients with SPQS in terms of symptoms and signs. This combination treatment, because of its higher clinical efficacy and lack of obvious adverse reactions, is worthy of clinical promotion and further in-depth study. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046614.

Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis.

Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making. A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score. Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety. Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

Community Awareness for GERD Extra Gastrointestinal Manifestations

Objective: This study aimed to explore the population&amp;apos;s knowledge of extraintestinal manifestations of gastroesophageal reflux disease (GERD). Methods: A cross-sectional study was implemented through an online survey aimed at adults from five different regions across the country, containing demographical data and questions relating to GERD extraintestinal manifestations, and questions relating to the knowledge of extra systemic symptoms in general. Results: A total of 1,045 submissions were included. Demographical data showed predominantly male and local participants. Most participants (54%) claimed to have a &amp;quot;medium&amp;quot; level of knowledge regarding GERD extraintestinal manifestations. As for the medical and family history of GERD, 20.1% and 28.9% of participants had positive medical history and family history, respectively. Significant differences were also detected among different participants&amp;apos; genders, educational levels, and age groups. Conclusions: Significant deficits were found amongst several demographic variables indicating non-satisfactory results. Most of the population acknowledged limitations to their awareness shown by their submissions.

Clinical characteristics of patients with gastroesophageal reflux disease against type 2 diabetes mellitus, depending on the presence of obesity

Objective — to reveal the features of the clinical course in patients with gastroesophageal reflux disease (GERD) depending on anthropometric indicators against the background of type 2 diabetes mellitus (DM2).&#x0D; Materials and methods. The study involved 100 patients, who were divided into 3 groups: group 1 consisted of 60 patients with DM2 in combination with GERD, group 2 included 20 patients with isolated GERD, and group 3 included DM2 patients. The patients of group 1 were additionally divided into 2 subgroups: 27 subjects with normal weight and 33 subjects with excessive body weight (EBW) or obesity of various degrees. The control group consisted of 20 practically healthy people. The distribution of patients by gender and age was carried out in accordance with the standards of the international classification of age periods of the World Health Organization, revised in 2015. From the total number of patients, 44 (44%) were men and 56 (56%) were women. Body mass index (BMI) was calculated according to the Quetelet formula. Endoscopic examination of the upper part of the gastrointestinal tract with targeted biopsy was performed with an esophagogastroduodenoscope with end optics «Olympus GIF Q 150­03» (manufacturer Olympus Europa SE &amp; CO. KG, Japan). To increase the diagnostic value of esophagogastroduodenoscopy, methods of chromoscopy and pinch biopsy of the esophageal mucosa were used.&#x0D; Results. Comparison of GERD manifestations with account of anthropometric data revealed significant differences in the subgroups with normal weight and obesity (p &lt;0.05). Gastroenterological complaints were not registered in 6 (26.1%) patients of the obesity subgroup (DM2 + GERD + obesity) and 8 (21.6%) patients of the non‑obese subgroup (DM2 + GERD). In the subgroup with obesity (DM2 + GERD + obesity), the significant differences (p &lt;0.001) were detected in heartburn depending on the obesity stage. Heartburn in this subgroup occurred 7.4 times more often than in patients with normal weight compared to the subgroup without obesity (odds ratio 89.13% (95%CI 12.83—137.77) χ2=35.06; р &lt;0.0001). Cardiac symptoms in patients with increased body weight were revealed 12.3 times more often vs. subjects with BMI less than 25 kg/m2 (odds ratio 5.0 (95% CI 1.58 ‑14.10); χ2=6.95; р=0.008).&#x0D; The presence of heartburn complaints at the 2nd stage of obesity (39±5 kg/m2) and its absence at normal body mass (28±2 kg/m2), p &lt;0.001) have been established. Analysis of the dependence of the Helicobacter pylori contamination degree on the BMI value showed no statistically significant differences between the subgroups with normal body weight and subgroup with EBW and obesity. The highest contamination degree was found in group 1 (DM2 + GERD) with the same number of positive results in both subgroups, with and without obesity.&#x0D; Conclusions. It has been established that excessive body weight and obesity significantly affect the development and progression of gastroenterological complaints in patients with DM2 combined with GERD. The heartburn was more often registered in patients with DM2 with obesity, than in those with normal weight. Comparison of GERD findings with anthropometric data revealed significant differences between the subgroups with normal body weight and obesity (р &lt;0.05). Heartburn in the obesity subgroup occurred 7.4 times more often.&#x0D;

Biallelic PI4KA mutations Disrupt B Cell Mitochondrial Metabolism and Cause Hypogammaglobulinemia

Introduction Biallelic mutations in the PI4KA gene cause PI4KA-related disorder, a novel condition with neurological (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus), gastrointestinal (GI; inflammatory bowel disease [IBD] and multiple intestinal atresia [MIA]) and immunological manifestations. PI4KA encodes phosphatidylinositol (PI) 4-kinase alpha, which catalyzes the first step of phosphoinositide metabolism, phosphorylating PI to PI4P (phosphatidylinositol 4-phosphate). Phosphoinositides collectively have fundamental signalling roles in the plasma membrane and other organelles. We collected comprehensive clinical and laboratory data on 13 patients and performed a multiomic strategy, combining transcriptome, proteome, lipidome and metabolome analyses of three patients' EBV-transformed cell lines to unravel the burden of B cell deficiency in PI4KA-related disorder and define the role of PI4KA in B cells. Results Recurrent or severe infections (8/13) and GI (either gastroesophageal reflux disease, MIA or IBD; 6/13) manifestations were frequent. Thyroid disease (either hypo- or hyperthyroidism; 2/13), juvenile idiopathic arthritis (JIA; 1/13) and non-Hodgkin lymphoma (1/13) were reported. At last follow up 11 patients were alive. Ten had either hypogammaglobulinemia, decreased absolute numbers of B cells or decreased B cell subsets. B cell subsets showed increased transitional (4/7), decreased naive (2/7) and decreased switched memory (4/7) B cells. B cell proliferation to T independent mitogens, specifically IgM + CpG or pokeweed, was impaired in 2/2. T-cell (either CD3+, CD4+ or CD8+) lymphopenia was detected in 4/13. T-cell proliferation was maintained in 5/5. NK cells were decreased in 6/13. Ig replacement therapy (4/13) and immunosuppressive treatment (due to JIA [1/13] or IBD [2/13]) were given. Lipidome analysis showed that different glycerophospholipids profile (i.e., phosphatidylcholine [PC], phosphatidylethanolamines [PE] and phosphatidylserine [PS]) was altered. Metabolome analysis and pathway enrichment analysis confirmed impaired phosphatidylethanolamine biosynthesis and additionally showed altered PIP metabolism and mitochondrial dysfunction (i.e., beta-oxidation of short and long fatty acids). Although the total number of mitochondria was not affected, the mitochondrial activity was significantly reduced. Integration analyses of proteomics, metabolomic and lipidomic data reveals biochemical mechanisms underlying biallelic PI4KA mutation. In particular, dysregulation of metabolic enzymes and pathways involved in glutathione metabolism and tricarboxylic acid cycle was found (Fig. 1). These metabolic impairments ultimately impacted on oxidative phosphorylation, thus disrupting mitochondrial integrity. Gene set enrichment analysis of differentially expressed genes suggested a skewing towards naive B cell gene sets. Pathways enrichment analysis of transcriptome and proteome showed enrichment in B cell receptor (BCR) pathway and complex, PI3K/mTOR pathway and phospholipids metabolism. PI4P and its metabolite PI(4,5)P2 are determinants of PM identity, specifically controlling cytoskeletal dynamics. Deranged basal actin organization was reverted after anti-IgM stimulation. Hyperactivation of PI3K targets (pAKT473, p4EBP1 and pS6) was observed. Dysregulation of RABGAP1, RAB8B and LAMP3 mRNA prompted us to investigate autophagy. Indeed, LC3 was increased either in the presence or absence of chloroquine, showing that PI4KA mutations enhanced autophagosome formation and inhibited its degradation. Conclusion Overall, by altering the production of several key lipids, biallelic PI4KA mutations disrupt B cell metabolism causing mitochondrial dysfunction, mTOR hyperactivation, increased autophagy and deranged cytoskeleton organization. PI4KA-related disorder is a novel syndromic inborn error of immunity causing B cell deficiency and hypogammaglobulinemia. Figure 1. Integration of proteomics, metabolomics and lipidomics reveals biochemical mechanisms underlying biallelic PI4KA mutations.

Surgical treatment of gastroesophageal reflux-related cough

Gastroesophageal reflux-related cough (GERC) is an extra-esophageal manifestation of gastroesophageal reflux disease (GERD) and a common cause of chronic cough. GERC is the most difficult of the chronic cough to diagnose and treat because of its lack of specificity and its multidisciplinary nature. In recent years, research into GERC has led to a consensus on many key issues. The 2021 edition of the Guidelines for the Diagnosis and Treatment of Cough (Cough guidelines) provides important guidance on the diagnosis and treatment of GERC. However, the surgical treatment of GERC is not well covered in the Cough guidelines. This article summarizes the surgical treatment of GERC in terms of surgical methods, current situation, indications for operation and curative effects.

Заболевания верхних дыхательных путей как внепищеводные проявления гастроэзофагеальной рефлюксной болезни: современное состояние проблемы

Bronchial asthma, chronic cough, laryngitis, erosion of tooth enamel are attributed to extra esophageal manifestations of gastroesophageal reflux disease (GERD). This form of GERD is characterized by the difficulty of establishing the diagnosis and high frequency of ineffective therapy. The article describes the main endoscopic signs of damage to the esophagus and larynx, presents normal pH-impedance reflux monitoring and criteria for pathological reflux into the esophagus and the lower third of the pharynx, as well as the possibilities of additional diagnostic methods – esophageal manometry and pepsin test. Treatment of patients with extra esophageal manifestations of GERD is a difficult task; the results of randomized placebo-controlled studies are contradictory. At the same time, empirical therapy is most effective in patients whose extra esophageal symptoms are combined with typical ones

A perspective on the clinical relevance of weak or nonacid reflux.

Advances in ambulatory esophageal reflux monitoring that incorporated impedance electrodes to pH catheters have resulted in better characterization of retrograde bolus flow in the esophagus. With pH-impedance monitoring, in addition to acid reflux episodes identified by pH drops below 4.0, weakly acid reflux (WAR, pH 4-7) and nonacid reflux (NAR, pH >7.0) are also recognized, although both may be included under the umbrella term NAR. However, despite identification of ambulatory pH-impedance monitoring, data on clinical relevance and prognostic value of NAR are limited. The Lyon Consensus, an international expert review that defines conclusive metrics for gastroesophageal reflux disease (GERD), identifies NAR as "supportive" but not conclusive for GERD. This review provides perspectives on whether NAR fulfills three criteria for clinical relevance: whether NAR sufficiently explains pathogenesis of symptoms, whether it is associated with meaningful manifestations of GERD, and whether it can predict treatment efficacy.

Dental evaluation is helpful in the differentiation of functional heartburn and gastroesophageal reflux disease.

Heartburn is identically the key symptom of both, gastroesophageal reflux disease (GERD) and functional heartburn (FHB), making the differential diagnosis resource-intensive. Oral manifestations of GERD can be easily examined; therefore, their exploration might be a cheap, widely available, and useful tool in the differentiation of GERD and FHB. To evaluate the prevalence of dental erosions (DE) and periodontal diseases (PD) in patients with heartburn and their association with GERD and FHB. A total of 116 [M/F: 51/65, mean age: 54 (17-80) years] consecutive patients with heartburn were enrolled for detailed esophageal function and orodental examinations. Dental disorders were detected in 89% (103/116). Patients with PD + DE had significantly more often pathologic reflux (90.0% vs 27.8%; P < 0.05), higher esophagitis scores (1.8 vs 0.9; P < 0.05), and a significantly different mean impedance curve (P = 0.04) than those without any dental diseases. The opposite approach established that patients with GERD had significantly higher prevalence of DE and PD, especially if both were present (28.9% vs 2.0%; P < 0.01), more severe PD (1.5 vs 1.0; P < 0.01), and longer history of heartburn (15 years vs 9 years; P < 0.01) than those with FHB. The dental evaluation of patients with heartburn seems to be useful in the differential diagnosis of GERD and FHB. Among the studied parameters, the co-appearance of DE and PD seems to be the best predictor of GERD, whereas the absence of dental disorders was mostly observed in FHB.

Gastroesophageal reflux in children with recurrent and chronic respiratory diseases: non-acid or acid?

In some cases, gastroesophageal reflux (GER) may be accompanied by duodenogastric reflux, forming non-acid reflux, which has a certain influence on the clinical presentation and the response to anti-reflux therapy. The study aimed to determine the role of non-acid reflux in children with recurrent and chronic respiratory diseases (RCRD). All children with RCRD, for unknown reason, poorly responding to respiratory-specific therapy, hospitalized for gastroesophageal reflux disease (GERD) screening, using dual pH-multichannel intraluminal impedance (pH-MII). The study was conducted in 42 children at the age Me – 2.75; IQR 1.08-9.42. The most common type of reflux was weakly acid reflux - 62.25 [36.425-121.225], then acid - 34.05 [12.875-71.65], alkaline - 1.75 [0 - 12.375] episodes per day (p &lt;0.05). Non-acid reflux was more common in children with only respiratory symptoms - no esophageal manifestations of GERD. All types of refluxes were more often recorded in the upright compared to the supine position. In 70% patients, cough could be associated with reflux, while in 88% children reflux was non-acid (including 69% - weakly acid, 19% - alkaline), in 38% - acid. Non-acid reflux is the main type of GER in children with RCRD refractory to standard therapy, which could be associated with cough in this patient population.