Alcohol-related diseases: from metabolism to the main effect on the body.

Alcohol consumption can cause, beyond addiction, roughly 200 different diseases and at least fourteen types of cancer. In 2016 the WHO estimated that 29% of alcohol-related deaths were mainly due to oncological diseases, liver cirrhosis (20%), and cardiovascular disorders (19%). The aim of this review was to focus on the absorption and metabolism of ethanol and discuss the main conditions caused by alcohol consumption (i.e., liver and cardiovascular diseases, and tumors). This narrative review is based on a detailed analysis of the scientific literature published before January 31, 2024 (PubMed, Web of Science, Scopus, Google Scholar). Approximately 90% of the absorbed alcohol reaches the liver where it is metabolized to acetaldehyde, a highly reactive and toxic compound. The excessive use of alcohol causes damage to several organs and systems, mainly the liver (e.g., steatosis, steato-hepatitis, fibrosis, and cirrhosis), cardiovascular system (cardiomyopathy, arrythmias, arterial hypertension, and stroke), and significantly contribute to the onset of neoplastic lesions to various organs including the esophagus, liver and breast. Even moderate drinking appears not to reduce mortality risk. Alcohol intake is one of the main risk factors for several pathological conditions and social problems, thus drastically impacting on public health. Proper awareness of the high risk related to alcohol consumption is of crucial importance to reduce the harm to public health.

Active myeloperoxidase: a promising biomarker to differentiate "acute" and "low-grade" peri-prosthetic joint infections from aseptic failures.

Introduction: The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI. Methods: Synovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant. Results: Active MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78-0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11-83.81%, positive likelihood ratio 5.88, 95% CI: 2.31-14.98 and negative likelihood ratio 0.35, 95%CI: 0.24-0.51). No difference in MPO levels was found between acute and chronic low-grade PJI. Conclusion: The proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice.

Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World?

Sex and gender are fundamental health determinants and their role as modifiers of treatment response is increasingly recognized. Norepinephrine is a cornerstone of septic shock management and its use is based on the highest level of evidence compared to dopamine. The related 2021 Surviving Sepsis Campaign (SCC) recommendation is presumably applicable to both females and males; however, a sex- and gender-based analysis is lacking, thus not allowing generalizable conclusions. This paper was aimed at exploring whether sex- and gender-disaggregated data are available in the evidence supporting this recommendation. For all the studies underpinning it, four pairs of authors, including a woman and a man, extracted data concerning sex and gender, according to the Sex and Gender Equity in Research guidelines. Nine manuscripts were included with an overall population of 2126 patients, of which 43.2% were females. No sex analysis was performed and gender was never reported. In conclusion, the present manuscript highlighted that the clinical studies underlying the SCC recommendation of NE administration in septic shock have neglected the likely role of sex and gender as modifiers of treatment response, thus missing the opportunity of sex- and gender-specific guidelines.

The role of echocardiography in pulmonary embolism for the prediction of in-hospital mortality: a retrospective study.

PURPOSE: Pulmonary Embolism (PE) is the third leading cause of cardiovascular death, following myocardial infarction and stroke. The latest European Society of Cardiology (ESC) guidelines on PE recommend short-term prognostic stratification based on right ventricular (RV) overload detected by transthoracic echocardiography (TTE) or contrast-enhanced chest CT. The aim of the study is to find out which of the signs of right ventricular dysfunction best predicts in-hospital mortality (IHM). METHODS: This is a monocentric, retrospective study including adult patients admitted from the emergency department with a c-e cCT confirmed diagnosis of PE between January 2018 and December 2022 who underwent a TTE within 48 h. RESULTS: 509 patients (median age 76 years [IQR 67-84]) were included, with 7.1% IHM. At univariate analysis, RV/LV ratio > 1 (OR 2.23, 95% CI 1.1-4.5), TAPSE < 17 mm (OR 4.73, 95% CI 2.3-9.8), the D-shape (OR 3.73, 95% CI 1.71-8.14), and LVEF < 35% (OR 5.78, 95% CI 1.72-19.47) resulted significantly correlated with IHM. However, at multivariate analysis including also haemodynamic instability, PESI class > II, and abnormal hs-cTnI levels, only LVEF < 35% (OR 5.46, 95% CI 1.32-22.61) resulted an independent predictor of IHM. CONCLUSION: Despite the recognised role of TTE in the early management of patients with circulatory shock and suspected PE, signs of RV dysfunction have been shown to be poor predictors of IHM, whereas severely reduced LVEF is an independent risk factor for in-hospital death.

Chronic intestinal pseudo-obstruction: associations with gut microbiota and genes expression of intestinal serotonergic pathway.

BACKGROUND: Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes. Gut microbiota and its interplay with ENS affect 5-HT synthesis, release, and the subsequent serotonin receptor activation. To date, the interplay between 5-HT and gut microbiota in PIPO remains largely unclear. This study aimed to assess correlations between mucosa associated microbiota (MAM), intestinal serotonin-related genes expression in PIPO. To this purpose, biopsies of the colon, ileum and duodenum have been collected from 7 PIPO patients, and 7 age-/sex-matched healthy controls. After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16 S, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, and correlations with MAM and clinical parameters of PIPO have been evaluated. RESULTS: Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection. CONCLUSIONS: For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.

Chronic constipation in Parkinson's disease: clinical features and molecular insights on the intestinal epithelial barrier.

Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities.

Predicting in-hospital mortality in patients admitted from the emergency department for pulmonary embolism: Incidence and prognostic value of deep vein thrombosis. A retrospective study.

BACKGROUND: Pulmonary embolism (PE) is one of the most common causes of death from cardiovascular disease. Although deep vein thrombosis (DVT) is the leading cause of PE, its prognostic role is unclear. This study investigated the incidence and prognostic value of DVT in predicting in-hospital mortality (IHM) in patients admitted from the emergency department (ED) for PE. METHODS: This retrospective cohort study was conducted in the ED of a third-level university hospital. Patients over 18 years admitted for PE between 1 January 2018 and 31 December 2022 were included. RESULTS: Five hundred and thirty patients (mean age 73.13 years, 6% IHM) were included. 69.1% of cases had DVT (36.4% unilateral femoral vein, 3.6% bilateral, 39.1% unilateral popliteal vein, 2.8% bilateral, 45.7% distal vein thrombosis and 7.4% iliocaval involvement). Patients who died in hospital had a higher Pulmonary Embolism Severity Index (PESI) (138.6 vs. 99.65, p < 0.001), European Society of Cardiology risk class (15.6% vs. 1%, intermediate-high in 50% vs. 6.4%, p < 0.001) and more DVT involving the iliac-caval vein axis (18.8% vs. 6.6%, p = 0.011). PESI class >II, right ventricular dysfunction, increased blood markers of myocardial damage and involvement of the iliocaval venous axis were independent predictors of IHM on multivariate analysis. CONCLUSIONS: Although further studies are needed to confirm the prognostic role of DVT at PE, involvement of the iliocaval venous axis should considered to be a sign of a higher risk of IHM and may be a key factor in prognostic stratification.

Diagnostic accuracy of Point Of Care UltraSound (POCUS) in clinical practice: A retrospective, emergency department based study.

AIMS: Point-of-care ultrasound (POCUS) is the acquisition and interpretation of ultrasound imaging at the bedside to solve specific clinical questions based on signs and symptoms of presentation. While several studies evaluated POCUS diagnostic accuracy for a variety of clinical pictures in the emergency department (ED), only a few data are available on POCUS diagnostic accuracy performed by physicians with different POCUS skills. The objective of this research was to evaluate the diagnostic accuracy of POCUS compared to standard diagnostic imaging in the ED. MATERIALS AND METHODS: This was a retrospective study conducted in the ED of a third-level university hospital. Patients who underwent cardiac, thoracic, abdominal, or venous lower limb POCUS and a standard imaging examination between June 2021 and January 2022 were included. RESULTS: 1047 patients were screened, and 844 patients included. A total of 933 POCUS was included (102, 12.09%, cardiac; 466, 55.21%, thoracic; 336, 39.8%, abdominal; 29, 3.44%, lower limb venous POCUS), accounting for 2029 examinations. POCUS demonstrated 96.6% (95% CI 95.72-97.34) accuracy, 47.73 (95% CI 33.64-67.72) +LR, 0.09 (95% CI 0.06-0.12) -LR. +LR was greater than 10 for all investigations but for hydronephrosis (5.8), and -LR never exceeded 0.4. CONCLUSIONS: POCUS exhibited high diagnostic accuracy for virtually all conditions when performed by emergency department physicians.

Liquorice Toxicity: A Comprehensive Narrative Review.

BACKGROUND: Renowned since ancient times for its medical properties, liquorice is nowadays mainly used for flavoring candies or soft drinks. Continuous intake of large amounts of liquorice is a widely known cause of pseudo-hyperaldosteronism leading to hypertension and hypokalemia. These manifestations are usually mild, although in some cases may generate life-threatening complications, i.e., arrhythmias, muscle paralysis, rhabdomyolysis, and coma. In addition, liquorice has an important estrogenic-like activity. METHODS: We summarized the current knowledge about liquorice and reviewed 104 case reports in both the English and Italian languages from inception to June 2023 concerning complications due to an excess of liquorice intake. RESULTS: In contrast to most published data, female sex and old age do not appear to be risk factors. However, hypertension and electrolyte imbalance (mainly hypokalemia) are prevalent features. The detection of glycyrrhetinic acid in blood is very uncommon, and the diagnosis is essentially based on an accurate history taking. CONCLUSIONS: Although there is not a significant mortality rate, liquorice toxicity often requires hospitalization and therefore represents a significant health concern. Major pharmaceutical drug regulatory authorities should solicit public awareness about the potentially dangerous effects caused by excessive use of liquorice.

Acute Prosthetic Joint Infections with Poor Outcome Caused by Staphylococcus Aureus Strains Producing the Panton-Valentine Leukocidin.

The aim of this study was to investigate whether the presence of Staphylococcus aureus (SA) producing the Panton-Valentine leukocidin (PVL) affects the outcome of Prosthetic Joint Infection (PJI). Patients with acute and chronic PJI sustained by SA were prospectively enrolled at the orthopedic unit of "Casa di Cura Santa Maria Maddalena", from January 2019 to October 2021. PJI diagnosis was reached according to the diagnostic criteria of the International Consensus Meeting on PJI of Philadelphia. Synovial fluid obtained via joint aspirations was collected in order to isolate SA. The detection of PVL was performed via real-time quantitative PCR (RT-qPCR). The outcome assessment was performed using the criteria of the Delphi-based International Multidisciplinary Consensus. Twelve cases of PJI caused by SA were included. Nine (75%) cases were acute PJI treated using debridement, antibiotic and implant retention (DAIR); the remaining three (25%) were chronic PJI treated using two-stage (n = 2) and one-stage revision (n = 1), respectively. The SA strains that tested positive for PVL genes were 5/12 (41.6%,). Treatment failure was documented in three cases of acute PJI treated using DAIR, all supported by SA-PVL strains (p < 0.045). The remaining two cases were chronic PJI treated with a revision arthroplasty (one and two stage, respectively), with a 100% eradication rate in a medium follow-up of 24 months. Although a small case series, our study showed a 100% failure rate in acute PJI, probably caused by SA PVL-producing strains treated conservatively (p < 0.04). In this setting, toxin research should guide radical surgical treatment and targeted antibiotic therapy.

Markers of liver function as potential prognostic indicators of SARS-CoV-2 infection: A retrospective analysis during the first and second waves of COVID-19 pandemic.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is known to cause a predominant respiratory disease, although extrapulmonary manifestations can also occur. One of the targets of Coronavirus disease 2019 (COVID-19) is the hepatobiliary system. The present study aims to describe the correlation between the increase of liver damage markers (i.e. alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin [TB]) and COVID-19 outcomes (i.e., in-hospital mortality [IHM] and intensive care unit [ICU] transfer). Methods: All patients with confirmed SARS-CoV-2 infection admitted to the Infectious Diseases Unit of the St. Anna University-Hospital of Ferrara from March 2020 to October 2021 were retrospectively included in this single-centre study. ALT, AST and TB levels were tested in all patients and IHM or ICU transfer were considered as main outcomes. Co-morbidities were assessed using Charlson Comorbidity Index. Results: A total of 106 patients were retrieved. No hepatic marker was able to predict IHM, whereas all of them negatively predicted ICU transfer (ALT: OR 1.005, 95%CI 1.001-1.009, p= 0.011; AST: OR 1.018, 95%CI 1.006-1.030, p= 0.003; TB: OR 1.329, 95%CI 1.025-1.724, p= 0.032). Age was the only parameter significantly related to mortality. Conclusions: The present study, by correlating liver damage markers with COVID-19 outcome, showed that an increase of ALT, AST and TB predicted patients' severity, although not mortality.

Comparison between Capillary and Serum Lactate Levels in Predicting Short-Term Mortality of Septic Patients at the Emergency Department.

Sepsis is a time-dependent and life-threating condition related to macro- and micro-circulatory impairment leading to anaerobic metabolism and lactate increase. We assessed the prognostic accuracy of capillary lactates (CLs) vs. serum ones (SLs) on 48-h and 7-day mortality in patients with suspected sepsis. This observational, prospective, single-centre study was conducted between October 2021 and May 2022. Inclusion criteria were: (i) suspect of infection; (ii) qSOFA ≥ 2; (iii) age ≥ 18 years; (iv) signed informed consent. CLs were assessed with LactateProTM2®. 203 patients were included: 19 (9.3%) died within 48 h from admission to the Emergency Department, while 28 (13.8%) within 7 days. Patients deceased within 48 h (vs. survived) had higher CLs (19.3 vs. 5 mmol/L, p < 0.001) and SLs (6.5 vs. 1.1 mmol/L, p = 0.001). The best CLs predictive cut-off for 48-h mortality was 16.8 mmol/L (72.22% sensitivity, 94.02% specificity). Patients within 7 days had higher CLs (11.5 vs. 5 mmol/L, p = 0.020) than SLs (2.75 vs. 1.1 mmol/L, p < 0.001). The multivariate analysis confirmed CLs and SLs as independent predictors of 48-h and 7-day mortality. CLs can be a reliable tool for their inexpensiveness, rapidity and reliability in identifying septic patients at high risk of short-term mortality.

Performance of five serological tests in the diagnosis of visceral and cryptic leishmaniasis: a comparative study.

INTRODUCTION: Leishmaniasis is a major health problem and its diagnosis still represents a challenge. Since consistent evidence on the comparison of serological methods is lacking, our work aims to compare five serological tests for the diagnosis of visceral and asymptomatic leishmaniasis in southern France, a region where leishmaniasis is endemic. METHODOLOGY: Serum samples from 75 patients living in Nice, France were retrospectively analyzed. They included patients affected by visceral leishmaniasis (VL; n = 25), asymptomatic carriers (AC; n = 25) and negative controls (n = 25). Each sample was tested using two immunochromatographic tests (ICT; IT LEISH® and TruQuick IgG/IgM®), an indirect fluorescent antibody test (IFAT) and two Western Blotting (WB; LDBio BIORAD® and an in-house method). RESULTS: Diagnosis of VL with IFAT and TruQuick® showed the highest diagnostic performance parameters. IFAT had 100% sensitivity and specificity, while TruQuick had 96% sensitivity and 100% specificity. Finally, the two tests showed high accuracy (100% for IFAT and 98% for TruQuick) for the AC group. WB LDBio® was the only method able to detect Leishmania latent infection, with a sensitivity of 92%, and a specificity of 100%, with a Negative Predictive Value (NPV) of 93%. This performance is reflected in the high accuracy of the test. CONCLUSIONS: The data obtained with TruQuick® supports its application in the rapid diagnosis of leishmaniasis in endemic areas, a feature not shown by IFAT despite its high diagnostic performance. Regarding the diagnosis of asymptomatic leishmaniasis, the best results were obtained with WB LDBio®, confirming previous studies.

2023 Update on Sepsis and Septic Shock in Adult Patients: Management in the Emergency Department.

BACKGROUND: Sepsis/septic shock is a life-threatening and time-dependent condition that requires timely management to reduce mortality. This review aims to update physicians with regard to the main pillars of treatment for this insidious condition. METHODS: PubMed, Scopus, and EMBASE were searched from inception with special attention paid to November 2021-January 2023. RESULTS: The management of sepsis/septic shock is challenging and involves different pathophysiological aspects, encompassing empirical antimicrobial treatment (which is promptly administered after microbial tests), fluid (crystalloids) replacement (to be established according to fluid tolerance and fluid responsiveness), and vasoactive agents (e.g., norepinephrine (NE)), which are employed to maintain mean arterial pressure above 65 mmHg and reduce the risk of fluid overload. In cases of refractory shock, vasopressin (rather than epinephrine) should be combined with NE to reach an acceptable level of pressure control. If mechanical ventilation is indicated, the tidal volume should be reduced from 10 to 6 mL/kg. Heparin is administered to prevent venous thromboembolism, and glycemic control is recommended. The efficacy of other treatments (e.g., proton-pump inhibitors, sodium bicarbonate, etc.) is largely debated, and such treatments might be used on a case-to-case basis. CONCLUSIONS: The management of sepsis/septic shock has significantly progressed in the last few years. Improving knowledge of the main therapeutic cornerstones of this challenging condition is crucial to achieve better patient outcomes.

Predicting in-hospital mortality in patients with acute pancreatitis in the ED: a direct, retrospective comparison of four clinical and radiological prognostic scores.

BACKGROUND: Acute pancreatitis can be a severe disease that significantly impacts patients' quality of life and outcome. The clinical course is variable and predictive scoring systems have a debated role in early prognosis. This study aims to compare the prognostic accuracy of Balthazar, BISAP, HAPS and SOFA scores in the prediction of in-hospital mortality in patients with acute pancreatitis. METHODS: This is a retrospective, single-center cohort study conducted in the Emergency Department of a third-level university hospital. Patients aged >18 years admitted from 1st January 2018 to 31st December 2021 for the first episode of acute pancreatitis were included. RESULTS: A total of 385 patients (mean age of 65.4 years and 1.8% in-hospital mortality) were studied. Balthazar, BISAP and SOFA scores were significantly higher in patients with in-hospital mortality and AUROCs were equal to 0.95 (95% CI 0.91-0.99, P<0.001), 0.96 (95% CI 0.89-1, P=0.001), 0.91 (95% CI 0.81-1, P=0.001) with no differences among them and absence of in-hospital mortality in patients with HAPS=0. CONCLUSIONS: Our data support the concept that clinical prediction scores can be useful for risk stratification in the Emergency Department. However, no single score has shown superiority in predicting acute pancreatitis-related in-hospital mortality among tested tools.

Special Issue: Advances in SARS-CoV-2 Infection.

Coronavirus Disease 2019 (COVID-19) is a life-threatening disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus which was first reported in late 2019 in China, from where it then spread worldwide [...].

Pharmacological and nutritional therapy of children and adults with chronic intestinal pseudo-obstruction.

INTRODUCTION: Chronic intestinal pseudoobstruction (CIPO) is a rare, heterogenous, and severe form of gastrointestinal dysmotility. AREAS COVERED: Pertinent literature on pediatric and adult CIPO management has been assessed via PubMed, Scopus, and EMBASE from inception to June 2022. Prokinetics, aimed at restoring intestinal propulsion (e.g. orthopramides and substituted benzamides, acetyl cholinesterase inhibitors, serotonergic agents, and others), have been poorly tested and the available data showed only partial efficacy. Moreover, some prokinetic agents (e.g. orthopramides and substituted benzamides) can cause major side effects. CIPO-related small intestinal bacterial overgrowth requires treatment preferably via poorly absorbable antibiotics to avoid bacterial resistance. Apart from opioids, which worsen gut motility, analgesics should be considered to manage visceral pain, which might dominate the clinical manifestations. Nutritional support, via modified oral feeding, enteral, or parenteral nutrition, is key to halting CIPO-related malnutrition. EXPERT OPINION: There have been significant roadblocks preventing the development of CIPO treatment. Nonetheless, the considerable advancement in neurogastroenterology and pharmacological agents cast hopes to test the actual efficacy of new prokinetics via well-designed clinical trials. Adequate dietary strategies and supplementation remain of crucial importance. Taken together, novel pharmacological and nutritional options are expected to provide adequate treatments forthese patients.

Osteoporosis and Celiac Disease: Updates and Hidden Pitfalls.

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD.

Evaluation of Anti-SARS-CoV-2 IgA Response in Tears of Vaccinated COVID-19 Subjects.

Secretory IgA (sIgA), which may play an important role in the early defense against SARS-CoV-2 infection, were detected in the eye of COVID-19 patients. However, an evaluation of the sIgA response in the tears of vaccinated or non-vaccinated COVID-19 subjects is still lacking. Aimed at characterizing sIgA mucosal immunity in the eye, this study analyzed tear samples from 77 COVID-19 patients, including 63 vaccinated and 14 non-vaccinated subjects. The groups showed similar epidemiological features, but as expected, differences were observed in the percentage of asymptomatic/pauci-symptomatic subjects in the vaccinated vs. non-vaccinated cohort (46% and 29% of the total, respectively). Consistent with this, ocular sIgA values, evaluated by a specific quantitative ELISA assay, were remarkably different in vaccinated vs. non-vaccinated group for both frequency (69.8% vs. 57.1%, respectively) and titer (1372.3 U/mL vs. 143.7 U/mL, respectively; p = 0.01), which was significantly differently elevated depending on the type of administered vaccine. The data show for the first time significant differences of available vaccines to elicit sIgA response in the eye and suggest that quantitative tear-based sIgA tests may potentially serve as a rapid and easily accessible biomarker for the assessment of the development of a protective mucosal immunity toward SARS-CoV-2.