Association between esophageal motor disorders and pulmonary involvement in patients affected by systemic sclerosis: a retrospective study.

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc. The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the HRM with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total score ≥ 7 was considered predictive of ILD, while a score ≥ 10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement. Forty-two patients were included. We found a score ≥ 7 in 11 patients with aperistalsis, in 6 subjects with IEM and in 6 patients with a normal manometry. Otherwise, a score < 7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with IEM and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline LESP and greater HrCT scores at follow-up evaluation were significantly correlated. This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.

Achalasia and Obstructive Motor Disorders Are Not Uncommon in Patients With Eosinophilic Esophagitis.

BACKGROUND: An association has been reported between achalasia and eosinophilic esophagitis (EoE). We performed a retrospective study of high-resolution manometry (HRM) patterns in a large cohort of patients with EoE. MATERIAL AND METHODS: We collected data from consecutive patients with a new diagnosis of EoE from 2012 through 2019 undergoing HRM during the initial assessment at different centers in Italy. Demographic, clinical, endoscopic and histological characteristics were recorded at baseline and during management. Diagnoses of EoE and esophageal motility disorders were made according to established criteria. Treatments offered included proton pump inhibitors and topical steroids for EoE, and pneumatic dilation and myotomy for achalasia. Response to therapy was defined as less than 15 eosinophils per high power field in esophageal biopsies. RESULTS: Of 109 consecutive patients (mean age 37 years, 82 male), 68 (62%) had normal findings from HRM. Among 41 patients with motor disorders, 24 (59%) had minor motor disorders and 17 (41%) presented with major motor disorders, including 8 with achalasia (1 with type 1, 4 with type 2, and 3 with type 3). Achalasia and nonachalasia obstructive motor disorders had 14.7% prevalence among patients with EoE. Achalasia was more frequent in women, with longer diagnostic delay and abnormal esophagogram (P < .05) compared with EoE without achalasia or obstructive motor disorders. Clinical features and endoscopic findings did not differ significantly between patients with EoE with vs without achalasia and obstructive motor disorders. A higher proportion of patients without achalasia and obstructive motor disorders responded to topical steroids than patients with these features (P < .005). Invasive achalasia management was required for symptom relief in 50% of patients with achalasia and obstructive motor disorders. CONCLUSION: Achalasia and obstructive motor disorders are found in almost 15% of patients with EoE, and esophageal eosinophilia might cause these disorders. Patients with EoE who do not respond to standard treatments might require targeted muscle disruption.

Improvement in hepatitis C virus patients with advanced, compensated liver disease after sustained virological response to direct acting antivirals.

BACKGROUND: The outcome of patients with chronic hepatitis C virus infection (HCV) and advanced, compensated liver disease after sustained virological response (SVR) to direct-acting antivirals (DAAs) has not yet been completely depicted. We aimed to assess the clinical, biochemical and instrumental outcome of patients with advanced, compensated chronic HCV-related liver disease with DAA-induced SVR to DAAs and who had at least 1-year follow-up. MATERIALS AND METHODS: Fifty-two patients with cirrhosis (n = 27) and fibrosis stage F3 (n = 25) followed up for a median of 60 weeks after successful DAA treatment were included. Laboratory work-up, including APRI and FIB-4 scores, liver transient elastography and measurement of the spleen bi-polar diameter were carried out before treatment and at the end of follow-up. RESULTS: Liver stiffness decreased (P < 0.0001) from a median baseline of 15.2 kPa (12.0-20.0) to 9.3 kPa (7.5-12.0) at follow-up. A liver stiffness value suggestive of the presence (ie, ≥21.0 kPa) of clinically significant portal hypertension was found in 13 patients (25.0%) at baseline and in seven patients (13.5%) at follow-up (P = 0.037). Both APRI (P < 0.0001) and FIB-4 score (P = 0.025) progressively decreased, while platelet count increased (143 × 109 /L [117-176] to 153 × 109 /L [139-186], P = 0.003), and spleen bi-polar diameter decreased (120 mm [112-123] to 110 mm [102-116], P = 0.0009) from baseline to the end of follow-up. CONCLUSIONS: In patients advanced, compensated chronic liver disease, liver stiffness significantly improves in the long-term after SVR, and this improvement is accompanied by an amelioration of indirect indices of liver fibrosis and function, and by a decrease in parameters of portal hypertension.

Low Fibrinogen Levels Are Associated with Bleeding After Varices Ligation in Thrombocytopenic Cirrhotic Patients.

INTRODUCTION AND AIM: EVBL is a procedure frequently performed in cirrhotic patients for primary prophylaxis of bleeding. Patients with cirrhosis display various degrees of alteration of common coagulation parameters, and it is not known whether these alterations may predict post-EVBL bleeding. To evaluate factors predictive of post-endoscopic variceal band ligation (EVBL) bleeding in cirrhotic patients with thrombocytopenia. METHODS: We included 109 patients with cirrhosis undergoing EVBL for primary prophylaxis of variceal bleeding. Common coagulation parameters (INR, fibrinogen levels) and complete haemogram were obtained in all patients and evaluated subdividing patients in bleeders and non bleeders following EVBL. RESULTS: The incidence of post-EVBL bleeding was 5.5% (6 patients). INR and platelet counts, considered as continuous or dichotomous variables according to common cut-offs (i.e., INR>1.5, platelet count <50x109/L) were not predictors of post-EVBL bleeding. Patients who bled had significantly lower fibrinogen levels [146 mg/dL (98 - 262) versus 230 mg/dL (104 - 638), P=0.009], and no other biochemical or clinical predictors of bleeding were identified. A fibrinogen cut-off of 179 mg/dL had 98.6% negative predictive value for bleeding. CONCLUSION: low fibrinogen levels are associated with an increased risk of bleeding following prophylactic EVBL in cirrhotic patients, and might be used to stratify patients' risk. However, due to their preliminary nature, these findings need to be confirmed in larger populations.

Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity.

Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (±SE) Cr(VI)-reducing ability of post-meal samples (20.4±2.6µgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2±2.3µgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3±1.9 and 25.6±2.8µgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water.

Diagnostic delay in achalasia.

BACKGROUND: Achalasia is a rare disorder characterized by impaired esophageal motility and symptoms like dysphagia, regurgitation, chest pain, and weight loss. A timely diagnosis is crucial to adequately manage this condition. AIMS: This study aimed to assess the diagnostic delay from symptom onset to a definite diagnosis of achalasia, and to identify associated factors. METHODS: This retrospective, single-center study included patients diagnosed with achalasia between January 2013 and September 2023. Demographic data, symptoms, manometric, endoscopic, and radiological findings were collected. We also considered socio-economic deprivation. Early diagnosis was defined as occurring within 12 months of symptom onset, while late diagnosis was defined as occurring more than 12 months. RESULTS: We included 278 patients (142 males, median age 58 years). Dysphagia was the most common symptom (96 %), followed by regurgitation (70.1 %). The median diagnostic delay was 24 months (IQR 12-72, range 0-720), with 213 patients (76.6 %) experiencing late diagnosis. Early diagnosis was more common in patients with weight loss (63.1% vs. 42.0 %, p = 0.003). Lower material deprivation correlated with shorter diagnostic delay (24 months, IQR 10-60 vs. 60 months, IQR 18-300, p = 0.001). CONCLUSIONS: Achalasia diagnosis is often delayed. Weight loss along with socio-economic factors, influence the timeliness of diagnosis. Improving awareness of disease and relevance of initial symptoms may facilitate earlier diagnosis and treatment.

Expression of epidermal growth factor receptor (EGFR) in systemic sclerosis patients (SSc) and gastro-oesophageal reflux disease (GORD).

INTRODUCTION: Systemic sclerosis (SSc) affects the connective tissue and leads to an abnormal fibrotic process in the skin and internal organs. Epidermal Growth Factor Receptor (EGFR) is able to induce cell proliferation and differentiation, and its expression is increased in SSc patients with pulmonary artery hypertension and in skin biopsies in patients with scleroderma. To date, no data on esophageal expression of EGFR are available in SSc patients. We aimed to evaluate whether the pro-fibrogenic pathways of SSc may affect EGFR expression in the esophagus. METHODS: A retrospective analysis included patients with SSc and control subjects suffering from gastroesophageal reflux symptoms. Endoscopic assessment and histopathologic analyses were performed in all subjects and the presence of microscopic esophagitis was used to distinguish patients with normal esophageal mucosa and subjects with non-erosive reflux disease. EGFR expression was measured in all subjects. RESULTS: A total of 35 patients with SSc were included, while the control group included 67 non-SSc patients. EGFR expression at the Z-line was higher in SSc patients than non-SSc patients in absence of microscopic esophagitis (median 65 %, IQR 56-71 % vs 42 %, IQR 37-54 %, p < 0.001). Microscopic esophagitis was found in 60 % of patients with SSc and 62.7 % of control patients, and EGFR expression was significantly higher in patients presenting microscopic esophagitis both in SSc and non-SSc patients. CONCLUSION: The EGFR hyperexpression may be due to SSc and/or reflux-related damage in patients with microscopic esophagitis. Further studies are warranted to answer open questions and provide a possible role of EGFR in terms of diagnosis, prognosis, and therapy.

Esophageal motor disorders across ages: A retrospective multicentric analysis.

BACKGROUND: Age-related changes in the gastrointestinal system are common and may be influenced by physiological aging processes. To date, a comprehensive analysis of esophageal motor disorders in patients belonging to various age groups has not been adequately reported. METHODS: We conducted a retrospective assessment of high-resolution manometry (HRM) studies in a multicenter setting. HRM parameters were evaluated according to the Chicago Classification version 4.0. Epidemiological, demographic, clinical data, and main manometric parameters, were collected at the time of the examination. Age groups were categorized as early adulthood (<35 years), early middle-age (35-49 years), late middle-age (50-64 years), and late adulthood (≥65 years). RESULTS: Overall, 1341 patients (632, 47.0% male) were included with a median age of 55 years. Late adulthood patients reported more frequently dysphagia (35.2%) than early adulthood patients (24.0%, p = 0.035), early middle-age patients (21.0%, p < 0.0001), and late middle-aged patients (22.7%, p < 0.0001). Esophagogastric junction outflow obstruction was more prevalent in late adulthood (16.7%) than in early adulthood (6.1%, p = 0.003), and in early middle-age (8.1%, p = 0.001). Patients with normal esophageal motility were significantly younger (52.0 years) than patients with hypercontractile esophagus (61.5 years), type III achalasia (59.6 years), esophagogastric junction outflow obstruction (59.4 years), absent contractility (57.2 years), and distal esophageal spasm (57.0 years), in multivariate model (p < 0.0001). CONCLUSION: The rate of esophageal motor disorders is higher in older patients, in particular esophagogastric junction outflow obstruction and hypercontractile esophagus. Future prospective studies are necessary to confirm our results and to find tailored strategies to improve clinical outcomes.

Applying Lyon consensus criteria in the work-up of patients with extra-oesophageal symptoms - A multicentre retrospective study.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) based on otolaryngologist's assessment of laryngoscopic findings remains contentious in terms of sensitivity and specificity. AIMS: To evaluate GERD prevalence, applying Lyon 2.0 Consensus criteria, in patients with extra-oesophageal symptoms undergoing laryngoscopic examination and impedance-pH monitoring. METHODS: In this retrospective assessment, we included 470 patients with extra-oesophageal symptoms, either isolated or combined with typical symptoms, who had been referred to six tertiary Italian Gastroenterology Units between January and December 2020. Of these, 274 underwent 24-h impedance-pH monitoring and laryngoscopy off PPI therapy. GERD diagnosis followed Lyon Consensus 2.0 criteria, incorporating mean nocturnal baseline impedance when pH-impedance monitoring was inconclusive. RESULTS: Laryngoscopic examination revealed pathological findings (predominantly posterior laryngitis) in 71.2% (195/274). GERD was diagnosed in 29.2% (80/274) via impedance-pH monitoring. The prevalence of GERD in patients with positive or negative laryngoscopy was similar (32.3% vs. 21.5%, p = 0.075). No significant difference in proximal reflux occurrences was noted between positive and negative laryngoscopy groups (33.3% vs. 24.1%, p = 0.133). Laryngoscopy demonstrated sensitivity and specificity of 78.8% and 32.0%, respectively, with a positive predictive value (PPV) of 32.3% and negative predictive value (NPV) of 28.4%. In contrast, a threshold of four concurrent laryngoscopic signs, identified in only eight patients, demonstrated a PPV of 93.8% and a NPV of 73.6% (sensitivity 25.4%, specificity 99.2%). CONCLUSION: This study underscores the limited diagnostic accuracy of laryngoscopy, emphasising the necessity of impedance-pH monitoring for confirming GERD diagnoses using Lyon 2.0 criteria in patients with suspected extra-oesophageal symptoms.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis.

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis-Current Treatment and Monitoring.

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

Gastro-oesophageal reflux and gastric aspiration in idiopathic pulmonary fibrosis patients.

The aim of the study was to characterise gastro-oesophageal reflux (GOR) in idiopathic pulmonary fibrosis (IPF). 40 consecutive IPF patients underwent pulmonary high-resolution computed tomography (HRCT) scan and impedance-pH monitoring while off antisecretory therapy. The presence of pulmonary fibrosis was assessed using validated HRCT scores. Reflux features included distal oesophageal acid exposure, number of acid/weakly acidic reflux episodes and their proximal migration. 40 consecutive patients with interstitial lung disease other than IPF (non-IPF patients) and 50 healthy volunteers were also enrolled. IPF patients had significantly higher (p<0.01) oesophageal acid exposure (median (interquartile range (IQR)) 9.25 (4.7-15.4)% versus 3.3 (1.4-7.4)% versus 0.7 (0.2-4.2)%, number of acid (median (IQR) 45 (23-55) versus 32 (19-44) versus 18 (10-31)), weakly acidic (median (IQR) 34 (19-43) versus 21 (11-33) versus 18 (15-28)) and proximal reflux (median (IQR) 51 (26.5-65.5) versus 20 (9.5-34.5) versus 9 (5-20)) events compared to non-IPF patients and healthy volunteers, respectively. Pulmonary fibrosis HRCT scores correlated well with reflux episodes in both the distal (r(2)=0.567) and proximal (r(2)=0.6323) oesophagus. Patients with IPF had more bile acids and pepsin (p<0.03) in bronchoalveolar lavage fluid (BALF) (62% and 67%, respectively) and saliva (61% and 68%, respectively) than non-IPF patients (25% and 25% in BALF, and 33% and 36%, respectively, in saliva) and controls (0% and 0% in BALF and saliva, respectively). Acid GOR is common in IPF, but weakly acidic GOR may also occur. Patients with IPF had a risk of pulmonary aspiration of gastric contents. Outcome studies with intense antireflux therapy are needed.

How safe are heartburn medications and who should use them?

INTRODUCTION: Heartburn is a frequent symptom occurring in daily clinical practice and is mainly associated with gastroesophageal reflux disease (GERD). However, it can be stimulated by various factors and diseases other than GERD can present with heartburn. Therefore, physicians must be very careful in distinguishing GERD from non-GERD conditions in their patients, particularly when heartburn is refractory to anti-reflux medications. AREAS COVERED: The aim of this narrative review was to analyze the medical literature regarding the prevalence of heartburn and the various clinical disorders which can be present with this symptom. The type of medications usually adopted for treating heartburn and their grade of safety have been reviewed using an extensive computerized (Medline/PubMed) search with particular focus on the last 20 years. EXPERT OPINION: Many drugs can be used for relieving heartburn in patients with GERD, although PPIs are the pharmacological agents with the greatest efficacy. However, it must be highlighted that many non-GERD conditions may present clinically with this symptom whose intensity does not differ between GERD and functional esophageal disorders, which represent about 50% of all patients with suspected GERD. It is very important to identify these functional conditions because their treatment differs completely from that of GERD.

Pharmacotherapies in eosinophilic esophagitis: state of the art.

Eosinophilic esophagitis is a chronic immune-mediated esophageal disease with a Th2 inflammatory response to inhalant and food allergens that cause an eosinophilic infiltration of esophageal mucosa. The diagnosis requires an upper endoscopy with esophageal bioptic samples, in particular the number of eosinophils must be >15 eos/high power field. The main symptoms of EoE in adults are dysphagia and food impaction, and its incidence is growing. Nowadays, the etiology of EoE is not well understood and no standard therapy is available. Therefore, the aim of this review was to analyze the major studies present in literature regarding the various therapeutic approaches to this disease.

An update of pharmacology, efficacy, and safety of vonoprazan in acid-related disorders.

INTRODUCTION: Patients with acid-related disorders (ARDs) of the upper digestive tract remain highly prevalent and need to be continuously investigated to improve their management. AREAS COVERED: This review provides a summary of the most recent advancements in the treatment of ARDs with particular focus on the new drugs available to overcome the unmet needs of traditional therapies. EXPERT OPINION: Proton pump inhibitors remain the best therapy in treating ARDs, but a consistent proportion of these patients continues to present mucosal lesions or to experience symptoms despite treatment. These cases pertain mainly to the most severe forms of erosive esophagitis or to non-erosive reflux disease. Also, the increasing rate of patients with H. pylori infection not responding to eradication therapy represents a difficult clinical condition. The recent advent of a new class of antisecretory drugs, such as the potassium competitive acid blockers and, among them the most studied vonoprazan, which are characterized by a better pharmacological profile than PPIs (rapid onset of action, longer lasting acid suppression, control of nocturnal acidity), has the potential to overcome the above-mentioned unmet needs. More research should be done to assess their efficacy in Western populations and their safety in patients treated in the long term.

Prevalence of Lactose Intolerance in Patients with Hashimoto Thyroiditis and Impact on LT4 Replacement Dose.

Purpose: to determine lactose intolerance (LI) prevalence in women with Hashimoto's thyroiditis (HT) and assess the impact of LI on LT4 replacement dose. Methods. consecutive patients with HT underwent Lactose Breath Test and clinical/laboratory data collection. Unrelated gastrointestinal disorders were carefully ruled out. Lactose-free diet and shift to lactose-free LT4 were proposed to patients with LI. Results: we enrolled 58 females (age range, 23−72 years) with diagnosis of HT. In total, 15 patients were euthyroid without treatment, and 43 (74%) euthyroid under LT4 (30 of them with a LT4 formulation containing lactose). Gastrointestinal symptoms were present in 84.5% of patients, with a greater prevalence in change in bowel habits in lactose-intolerant patients (p < 0.0001). The cumulative LT4 dose required did not differ in patients with or without LI. No significant difference in both TSH values and LT4 dose were observed in patients shifted to lactose-free LT4 and diet at 3 and 6 months compared to baseline. Conclusion: the prevalence of LI in patients with HT was 58.6%, not different from global prevalence of LI. In the absence of other gastrointestinal disorders, LI seems not to be a major cause of LT4 malabsorption and does not affect the LT4 required dose in HT patients.

Achalasia with dense eosinophilic infiltrate responds to steroid therapy.

A patient presented with chronic substernal discomfort and intermittent dysphagia for solids. High-resolution impedance manometry (HRIM) of the esophagus showed that there was no peristalsis in the esophageal body but incomplete relaxation of the lower esophageal sphincter and incomplete bolus transit, so the patient was diagnosed with achalasia. Moreover, probably because of esophageal stasis, eosinophilic infiltration that mimicked a pattern of eosinophilic esophagitis was observed, on the basis of multiple biopsies of the esophagus. The patient was given 50 mg prednisolone once daily; the symptoms improved dramatically, and HRIM showed complete recovery of esophageal peristalsis, deeper relaxation of the lower esophageal sphincter, and complete bolus transit profile. HRIM can therefore be used to assess dysmotility abnormalities in patients with achalasia and eosinophilic-like esophagitis, and steroids relieve these symptoms. Treatment with a high dose of prednisolone resulted in a complete disappearance of dysphagia because of improved esophageal motility and reduced eosinophilic infiltrate. It is therefore important to control the inflammatory process in patients with idiopathic achalasia, which is likely to result from an autoimmune reaction.

Pharmacological Management of Gastro-Esophageal Reflux Disease: An Update of the State-of-the-Art.

Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic disorder, whose knowledge remains limited and the management of these patients changes continuously. This review provides a summary of the most recent advancements in the pathogenesis of this disease and the new drugs introduced into the market to overcome some of the unmet needs of traditional therapies. Nowadays, the most fruitful diagnostic examinations are 24-hour impedance-pH monitoring, which allows us to separate true NERD from esophageal functional disorders and high-resolution manometry, which helps to exclude the existence of motility disorders sharing the same symptoms of GERD. Proton pump inhibitors (PPIs) remain the first-choice therapy in the treatment of GERD, but a consistent proportion of these patients continue to experience symptoms despite their intake. These cases pertain mainly to the subpopulation with non-erosive reflux disease (NERD) and represent very challenging clinical situations, because it is mandatory to understand the reasons for PPI failure. The management of these difficult patients requires necessarily to test them and avoid the use of empiric treatments that are often unsuccessful, costly and potentially dangerous. Recently, several new drugs have been used to increase the defensive properties of this mucosa with promising results in randomized clinical trials.

Correlation Between Skin and Affected Organs in 52 Sclerodermic Patients Followed in a Diseases Management Team: Development of a Risk Prediction Model of Organ-Specific Complications.

Objective: To identify the existence of a correlation among the various organs affected, focusing primarily on immuno-dermatological aspects, and to create a risk prediction model of organ-specific complications. Material and Methods: Fifty-two patients with stable scleroderma, followed between 2015 and 2019, were investigated through an extensive multidisciplinary evaluation in the last year. Results: Patients with lung involvement presented a worse degree of skin fibrosis than patients without it (p <0.001). No relationship was observed for the heart, kidney, and esophagus. Patients with pulmonary involvement had a lower pressure of the low esophagus sphincter and a higher Warrick score than patients without it (p <0.05). Age was significantly higher in patients with kidney involvement. Diffuse scleroderma patients had a worse pulmonary impairment than limited scleroderma patients (p <0.05). The manometric "sclerodermic" pattern was observed to be the most frequent (55.6%, p <0.05) in dcSSc patients while the sclerodermic and normal pattern were equally represented (41.2 and 32.4% respectively, p <0.05) in lcSSc patients. When compared to the negative serological groups, anti-Scl-70 positive patients presented a worse lung involvement while anti-centromere patients presented a better lung outcome (p <0.05). PM-Scl 100/75 positive patients presented mostly a pulmonary fibrotic pattern (p <0.05) and, also, heart complications were more likely associated with anti PM-Scl 100/75 positivity (p <0.05). The risk prediction model for organ-specific complications had an accuracy of 84.4% (95%CI 78, 89) in complication-site prediction, AUC of 0.871, 86% of sensitivity, and 83% of specificity, Cohen's Kappa (k) of 0.68. Conclusions: Out of all the organs studied, the skin is the one that correlates with the lung. Patients with a diffuse form of disease presented more frequently the anti Scl-70 antibody and had a worse lung and esophageal involvement (scleroderma pattern) than the negative group. Conversely, patients with limited disease presented all positive for the anti-centromere antibody with a better lung involvement than the negative group, without any difference among the esophageal manometric pattern. Anti PM-Scl 100/75 antibody patients were associated with pulmonary fibrosis and presented cardiac involvement. The model created has demonstrated excellent values of sensitivity, specificity, and accuracy, but further studies are needed for validation.

A Machine Learning Application to Predict Early Lung Involvement in Scleroderma: A Feasibility Evaluation.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic immune-mediated disease, featuring fibrosis of the skin and organs, and has the greatest mortality among rheumatic diseases. The nervous system involvement has recently been demonstrated, although actual lung involvement is considered the leading cause of death in SSc and, therefore, should be diagnosed early. Pulmonary function tests are not sensitive enough to be used for screening purposes, thus they should be flanked by other clinical examinations; however, this would lead to a risk of overtesting, with considerable costs for the health system and an unnecessary burden for the patients. To this extent, Machine Learning (ML) algorithms could represent a useful add-on to the current clinical practice for diagnostic purposes and could help retrieve the most useful exams to be carried out for diagnostic purposes. METHOD: Here, we retrospectively collected high resolution computed tomography, pulmonary function tests, esophageal pH impedance tests, esophageal manometry and reflux disease questionnaires of 38 patients with SSc, applying, with R, different supervised ML algorithms, including lasso, ridge, elastic net, classification and regression trees (CART) and random forest to estimate the most important predictors for pulmonary involvement from such data. RESULTS: In terms of performance, the random forest algorithm outperformed the other classifiers, with an estimated root-mean-square error (RMSE) of 0.810. However, this algorithm was seen to be computationally intensive, leaving room for the usefulness of other classifiers when a shorter response time is needed. CONCLUSIONS: Despite the notably small sample size, that could have prevented obtaining fully reliable data, the powerful tools available for ML can be useful for predicting early lung involvement in SSc patients. The use of predictors coming from spirometry and pH impedentiometry together might perform optimally for predicting early lung involvement in SSc.