Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation.

BACKGROUND & AIMS: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC. METHODS: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. RESULTS: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. CONCLUSION: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. IMPACT AND IMPLICATIONS: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.

Ultrasound muscle assessment for sarcopenia detection in inflammatory bowel disease: A prospective study.

BACKGROUND: Sarcopenia is prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes; thus, effective diagnostic tools are needed to assess muscle mass and function in this population. METHODS: 153 consecutive patients were included, 100 in the training cohort and 53 in the study cohort. Three superficial muscles (rectus femoris = RF, rectus abdominis = RA, and biceps brachii = BB) were selected for the detection of sarcopenia using muscle ultrasound (US). The training cohort consisted of consecutive patients with or without IBD and was used to evaluate the feasibility and inter- and intra-observer variability of the US measurement. The study cohort consisted of only IBD patients and served to test US diagnostic accuracy. In the latter, muscle US, bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were used to measure muscle parameters. RESULTS: Sarcopenia prevalence in IBD patients was 50%. Muscle US showed excellent inter-rater and intra-rater reliability (ICC >0.95) and a good diagnostic accuracy in detecting sarcopenia compared to BIA with area under the receiver operating characteristic curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined as the sum of the RA, BB, and RF thickness divided by the square of the patient's height, resulting in an AUROC of 81%. Muscle thresholds for sarcopenia were detected, with RA and USMI values correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Additionally, the agreement between the US and MRI measurements of RA was excellent (ICC 0.96). CONCLUSIONS: The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. This research has significant implications for disease management in IBD patients and underscores the need for further investigations to validate these findings in larger cohorts.

Eosinophilic esophagitis: does age matter?

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with increasing prevalence worldwide. It is a multifactorial disease caused by a combination of immunologic, genetic, and environmental factors. The clinical presentation of EoE varies largely, especially between different age groups. While diagnostic criteria and therapeutic goals are similar in children and adults, there are differences in treatment, with a more cautious approach in children to avoid growth disturbances. In addition, close monitoring and follow-up are essential in children to ensure uninterrupted growth. AREAS COVERED: A search in PubMed/MEDLINE, EMBASE, and SCOPUS databases was conducted to identify relevant studies published between January 2010 and January 2023 to give an overview of the state-of-the-art of EoE epidemiology, diagnosis, and treatment while focusing on similarities and differences between the adult and the pediatric population. EXPERT OPINION: The current state of research indicates that while significant progress has been made in understanding and treating EoE, further research and advances are needed to optimize diagnostic strategies, tailored treatment approaches, monitoring, and follow-up, and improve long-term outcomes for patients. With further innovation, the management of EoE can become more precise and tailored, leading to better patient outcomes and improved quality of life.

Mechanistic Insights into Eosinophilic Esophagitis: Therapies Targeting Pathophysiological Mechanisms.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by eosinophilic infiltration of the esophagus. It arises from a complex interplay of genetic predisposition (susceptibility loci), environmental triggers (allergens and dietary antigens), and a dysregulated immune response, mainly mediated by type 2 T helper cell (Th2)-released cytokines, such as interleukin (IL)-4, IL-5, and IL-13. These cytokines control eosinophil recruitment and activation as well as tissue remodeling, contributing to the characteristic features of EoE. The pathogenesis of EoE includes epithelial barrier dysfunction, mast cell activation, eosinophil degranulation, and fibrosis. Epithelial barrier dysfunction allows allergen penetration and promotes immune cell infiltration, thereby perpetuating the inflammatory response. Mast cells release proinflammatory mediators and promote eosinophil recruitment and the release of cytotoxic proteins and cytokines, causing tissue damage and remodeling. Prolonged inflammation can lead to fibrosis, resulting in long-term complications such as strictures and dysmotility. Current treatment options for EoE are limited and mainly focus on dietary changes, proton-pump inhibitors, and topical corticosteroids. Novel therapies targeting key inflammatory pathways, such as monoclonal antibodies against IL-4, IL-5, and IL-13, are emerging in clinical trials. A deeper understanding of the complex pathogenetic mechanisms behind EoE will contribute to the development of more effective and personalized therapeutic strategies.

Prevalence of Disease-Related Malnutrition and Micronutrients Deficit in Patients with Inflammatory Bowel Disease: A Multicentric Cross-Sectional Study by the GSMII (Inflammatory Bowel Disease Study Group).

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) patients might experience disease-related malnutrition (DRM), but prevalence and risk factors are not well defined. The primary aim of the study was to define the prevalence of DRM and micronutrient deficiency in IBD patients; the secondary aim was to assess variables related to DRM. MATERIALS AND METHODS: A multicenter, cross-sectional study was performed including consecutive adult IBD patients during a period of 2 weeks. Nutritional status was assessed with the body mass index (BMI) and the Malnutrition Universal Screening Tool. DRM was defined according to European Society for Clinical Nutrition and Metabolism guidelines. RESULTS: Among the 295 enrolled patients, the prevalence of DRM was 23%, with no statistical difference between Crohn's disease and ulcerative colitis. Compared with well-nourished patients, patients with DRM showed higher rate of hospitalization in the previous month, were more often receiving systemic steroids, and had lower hemoglobin, albumin, and prealbumin levels and higher median C-reactive protein levels. At univariate logistic regression, current hospitalization, hospitalization in the previous month, low serum albumin, low BMI, high C-reactive protein, high Crohn's Disease Activity Index, and female sex were variables related to DRM. At the multivariate logistic regression, low BMI, current hospitalization and hospitalization in the previous month were significantly associated with DRM. In 23% of IBD patients, a deficiency of at least 1 micronutrient was observed, with no difference between ulcerative colitis and Crohn's disease. CONCLUSIONS: DRM and microelements malnutrition are frequent conditions in the IBD population. DRM seems to be associated with disease activity and hospitalization.

Colonic ductal adenocarcinoma case report: New entity or rare ectopic degeneration?

BACKGROUND: Ectopic pancreatic tissue is a congenital anomaly where a part of pancreatic tissue is located outside of the pancreas and lacks vascular or anatomical communication with it but shows the same histological features. Currently, the literature reports only two anecdotal cases of malignant transformation of colonic ectopic pancreas. CASE SUMMARY: We present a case of an 81-year-old patient presenting with anemia, with right colonic neoplasia and carbohydrate antigen 19-9 above the normal values. She underwent laparoscopic right hemicolectomy. The final histology was consistent with a primitive adenocarcinoma with ductal morphology and solid-predominant growth pattern. Benign ectopic pancreatic tissue was absent in the surgical specimen. CONCLUSION: The case describes a very rare complete degeneration of a colonic ectopic pancreatic tissue. However, the absence of benign ectopic pancreatic tissue in the surgical specimen is suggestive of the first description of a primitive ductal adenocarcinoma of the colon.

Inflammation and malnutrition in inflammatory bowel disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, has become increasingly prevalent worldwide in the past decade. The nutritional status of patients with IBD is often impaired, with malnutrition presenting as imbalanced energy or nutrient intake, including protein-energy malnutrition, disease-related malnutrition, sarcopenia, and micronutrient deficiency. Additionally, malnutrition can manifest as overweight, obesity, and sarcopenic obesity. Malnutrition can lead to disturbances in gut microbiome composition that might alter homoeostasis and cause a dysbiotic state, potentially triggering inflammatory responses. Despite the clear link between IBD and malnutrition, little is known about the pathophysiological mechanisms beyond protein-energy malnutrition and micronutrient deficiencies that could promote inflammation through malnutrition, and vice versa. This Review focuses on potential mechanisms that trigger a vicious cycle between malnutrition and inflammation, and their clinical and therapeutic implications.

The oft-overlooked cardiovascular complications of inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel disease (IBD) may be associated with several extraintestinal comorbidities, including cardiovascular disease (CVD). Chronic inflammation is recognized as an important factor in atherogenesis, thrombosis, and myocarditis. AREAS COVERED: IBD patients may be at increased risk for developing early atherosclerosis, cardiovascular events, peripheral artery disease, venous thromboembolism, myocarditis, and arrhythmias. Anti-tumor necrosis factor agents and thiopurines have been shown to have a protective effect against acute arterial events, but more research is needed. However, an increased risk of venous thromboembolism and major cardiovascular events has been described with the use of Janus kinase inhibitors. EXPERT OPINION: CVD risk is slightly increased in patients with IBD, especially during flares. Thromboprophylaxis is strongly recommended in hospitalized patients with active disease as the benefit of anticoagulation outweighs the risk of bleeding. The pathogenetic relationship between CVD and IBD and the impact of IBD drugs on CVD outcomes are not fully elucidated. CVD risk doesn't have the strength to drive a specific IBD treatment. However, proper CVD risk profiling should always be done and the best strategy to manage CVD risk in IBD patients is to combine appropriate thromboprophylaxis with early and durable remission of the underlying IBD.

Risk stratification in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic liver disorder commonly affecting young patients and associated with uncertain prognosis and elevated risk of end-stage liver disease and hepatobiliary cancer. Rate of progression in PSC is heterogeneous and accurately predicting the disease course is of paramount importance to clinical practice and interventional trial design. So far, efforts have brought to the development of models looking at short-to-middle-term outcome using composite models including clinical, laboratory, radiological and histological parameters with limited performance. In the era of whole genome sequencing and digital innovation, the time is ripe for the development of stratified medicine in PSC. Efforts should be directed toward developing well-phenotyped cohorts of patients with longitudinal follow-up across sustained periods of time, application of novel image-processing technology, and biomarker discovery using multiomics platforms.

Use of IBD Drugs in Patients With Hepatobiliary Comorbidities: Tips and Tricks.

Advanced therapies (biologic agents and small molecules) for inflammatory bowel diseases (IBD) have radically changed the management of these diseases during the last decade. Data about these drugs in patients with hepatic disorders derive mainly from real-life studies, as these conditions often represent an exclusion criterion from pivotal drug developmental trials. However, IBD patients sometimes have concomitant liver diseases. Nonalcoholic fatty liver disease is the most prevalent hepatic comorbidity, whereas viral hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, and hepatic vascular disorders are less frequent. This review aimed at describing the real-life data about the use of advanced therapies for IBD in patients with concomitant hepatobiliary disorders. Hepatitis B virus and hepatitis C virus infections do not represent an absolute contraindication for novel IBD therapeutic agents. Data from the literature suggest a safe hepatobiliary profile of biologic agents and small molecules in the case of nonalcoholic fatty liver disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and portal vein thrombosis. Consequently, although the liver disease does not affect a different therapeutic approach in patients with concomitant IBD and liver disease, a close risk/benefit analysis for each drug should be performed in these patients, especially in cirrhotic patients and in the postliver transplant setting.

This review focuses on the efficacy and safety of IBD-approved biologic agents and small molecules in patients with common hepatobiliary disorders that may coexist in IBD patients, focusing in particular on liver-related side effects. Even if IBD treatment choices should not be substantially different based on the underlying liver disease, each agent's overall risk/benefit profile should be carefully considered, especially in cirrhotic patients and postliver transplant settings.

A quantitative MRCP-derived score for medium-term outcome prediction in primary sclerosing cholangitis.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is the gold standard for diagnosis of patients with primary sclerosing cholangitis (PSC). The semi-quantitative MRCP-derived Anali scores proposed for risk stratification, have poor-to-moderate inter-reader agreement. AIMS: To evaluate the prognostic performance of quantitative MRCP metrics in PSC. METHODS: This is a retrospective study of PSC patients undergoing MRCP. Images were processed using MRCP+ software (Perspectum Ltd, Oxford) that provides quantitative biliary features, semi-automatically extracted by artificial intelligence-driven analysis of MRCP-3D images. The prognostic value of biliary features has been assessed for all hepato-biliary complications. RESULTS: 87 PSC patients have been included in the analysis. Median follow-up from MRCP to event/censoring of 30.9 months (Q1-Q3=13.6-46.6). An adverse outcome occurred in 27 (31.0%) patients. The number of biliary strictures (HR=1.05 per unit, 95%CI 1.02-1.08, p < 0.0001), spleen length (HR=1.16 per cm, 95%CI 1.01-1.34, p = 0.039), adjusted for height, age at MRCP, and time from diagnosis to MRCP predicted higher risk of hepatobiliary complications. These were incorporated into a the quantitative MRCP-derived PSC (qMRCP-PSC) score (C-statistic=0.80). After 3-fold cross-validation, qMRCP-PSC outperformed the Anali score in our cohort (C-statistic of 0.78 vs 0.64) and enabled the discrimination of survival of PSC patients (log-rank p < 0.0001). CONCLUSIONS: The qMRCP-PSC score identified patients at higher risk of hepatobiliary complications and outperformed the available radiological scores. It represents a novel quantitative biomarker for disease monitoring and a potential surrogate endpoint for clinical trials.

New insights on the role of human leukocyte antigen complex in primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a rare autoimmune cholangiopathy. Genetic studies have shown that the strongest statistical association with PBC has been mapped in the human leukocyte antigen (HLA) locus, a highly polymorphic area that mostly contribute to the genetic variance of the disease. Furthermore, PBC presents high variability throughout different population groups, which may explain the different geoepidemiology of the disease. A major role in defining HLA genetic contribution has been given by genome-wide association studies (GWAS) studies; more recently, new technologies have been developed to allow a deeper understanding. The study of the altered peptides transcribed by genetic alterations also allowed the development of novel therapeutic strategies in the context of immunotolerance. This review summarizes what is known about the immunogenetics of PBC with a focus on the HLA locus, the different distribution of HLA alleles worldwide, and how HLA modifications are associated with the pathogenesis of PBC. Novel therapeutic strategies are also outlined.

Applications of endoscopic ultrasound elastography in pancreatic diseases: From literature to real life.

Elastography is a non-invasive method widely used to measure the stiffness of the tissues, and it is available in most endoscopic ultrasound machines, using either qualitative or quantitative techniques. Endoscopic ultrasound elastography is a tool that should be applied to obtain a complementary evaluation of pancreatic diseases, together with other imaging tests and clinical data. Elastography can be informative, especially when studying pancreatic masses and help the clinician in the differential diagnosis between benign or malignant lesions. However, further studies are necessary to standardize the method, increase the reproducibility and establish definitive cut-offs to distinguish between benign and malignant pancreatic masses. Moreover, even if promising, elastography still provides little information in the evaluation of benign conditions.

Impact of COVID-19 on inflammatory bowel disease practice and perspectives for the future.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); since its first description in December 2019, it has rapidly spread to a global pandemic. Specific concerns have been raised concerning patients with inflammatory bowel diseases (IBD), which are chronic autoimmune inflammatory disorders of the gut that frequently require immunosuppressive and biological therapies to control their activity. Accumulating evidence has so far demonstrated that patients with IBD are not at increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection. As for the general population, the identified risk factors for severe COVID-19 course among IBD patients have been established to be advanced age and the presence of comorbidities. Treatment with high-dose corticosteroids has also been associated with an increased risk of death in IBD patients with COVID-19. Information on COVID-19 is constantly evolving, with data growing at a rapid pace. This will guarantee better knowledge and stronger evidence to help physicians in the choice of the best therapeutic approach for each patient, concurrently controlling for the risk of IBD disease under treatment and the risk of COVID-19 adverse outcomes and balancing the two. Moreover, the impact of the enormous number of severe respiratory patients on healthcare systems and facilities has led to an unprecedented redeployment of healthcare resources, significantly impacting the care of patients with chronic diseases. In this newly changed environment, the primary aim is to avoid harm whilst still providing adequate management. Telemedicine has been applied and is strongly encouraged for patients without the necessity of infusion therapy and whose conditions are stable. The severe acute respiratory syndrome coronavirus 2 pandemic has already revolutionized the management of patients with chronic immune-mediated diseases such as IBD. Direct and indirect effects of the COVID-19 pandemic will be present for some time. This is the reason why continuous research, rapid solutions and constantly updated guidelines are of utmost importance. The aim of the present review is, therefore, to point out what has been learned so far as well as to pinpoint the unanswered questions and perspectives for the future.

Acute mesenteric ischemia and small bowel imaging findings in COVID-19: A comprehensive review of the literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19), an infectious condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread worldwide since its first description in Wuhan in December 2019. Even though respiratory manifestations are the most prevalent and responsible for disease morbidity and mortality, extrapulmonary involvement has progressively gained relevance. In particular, gastrointestinal (GI) signs and symptoms, reported in up to two-thirds of patients with COVID-19, might represent the first and, in some cases, the only disease presentation. Their presence has been associated in some studies with an increased risk of a severe disease course. Proposed pathogenic mechanisms explaining GI tract involvement are either direct viral access to intestinal cells via angiotensin-converting enzyme 2 or indirect damage of the intestinal wall through mesenteric ischemia induced by the hypercoagulable state associated with COVID-19 infection. Although not typical of SARS-CoV-2 infection, several small bowel manifestations have been described in infected patients who underwent any form of abdominal imaging. The radiological findings were mainly reported in patients with abdominal symptoms, among which abdominal pain was the most common. AIM: To discuss small bowel radiological manifestations of SARS-CoV-2 infection in abdominal imaging studies. METHODS: Bibliographical searches were performed in PubMed, using the following keywords: "COVID-19" AND "imaging" AND "gastrointestinal" OR "abdominal" OR "small bowel". RESULTS: Of 62 patients with described radiologic small bowel alterations, mesenteric ischemia was diagnosed in 31 cases (50%), small bowel wall thickening in 10 cases (16%), pneumatosis in nine cases (15%), intussusception in eight cases (13%), pneumoperitoneum in two cases (3%) and paralytic ileus in two cases (3%). We also reported mesenteric adipose tissue hypertrophy and lymph nodes enlargement in a young woman. CONCLUSION: So far it is difficult to establish whether these manifestations are the direct consequence of SARS-CoV-2 infection or collateral findings in infected patients, but their recognition would be pivotal to set a closer follow-up and to reduce missed diagnoses.

Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach.

BACKGROUND AND AIMS: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. APPROACH AND RESULTS: We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. CONCLUSIONS: In a multicenter study of treatment-naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

Helmet CPAP to treat hypoxic pneumonia outside the ICU: an observational study during the COVID-19 outbreak.

BACKGROUND: Respiratory failure due to COVID-19 pneumonia is associated with high mortality and may overwhelm health care systems, due to the surge of patients requiring advanced respiratory support. Shortage of intensive care unit (ICU) beds required many patients to be treated outside the ICU despite severe gas exchange impairment. Helmet is an effective interface to provide continuous positive airway pressure (CPAP) noninvasively. We report data about the usefulness of helmet CPAP during pandemic, either as treatment, a bridge to intubation or a rescue therapy for patients with care limitations (DNI). METHODS: In this observational study we collected data regarding patients failing standard oxygen therapy (i.e., non-rebreathing mask) due to COVID-19 pneumonia treated with a free flow helmet CPAP system. Patients' data were recorded before, at initiation of CPAP treatment and once a day, thereafter. CPAP failure was defined as a composite outcome of intubation or death. RESULTS: A total of 306 patients were included; 42% were deemed as DNI. Helmet CPAP treatment was successful in 69% of the full treatment and 28% of the DNI patients (P < 0.001). With helmet CPAP, PaO2/FiO2 ratio doubled from about 100 to 200 mmHg (P < 0.001); respiratory rate decreased from 28 [22-32] to 24 [20-29] breaths per minute, P < 0.001). C-reactive protein, time to oxygen mask failure, age, PaO2/FiO2 during CPAP, number of comorbidities were independently associated with CPAP failure. Helmet CPAP was maintained for 6 [3-9] days, almost continuously during the first two days. None of the full treatment patients died before intubation in the wards. CONCLUSIONS: Helmet CPAP treatment is feasible for several days outside the ICU, despite persistent impairment in gas exchange. It was used, without escalating to intubation, in the majority of full treatment patients after standard oxygen therapy failed. DNI patients could benefit from helmet CPAP as rescue therapy to improve survival. TRIAL REGISTRATION: NCT04424992.

Takayasu arteritis and primary sclerosing cholangitis: A casual association or different phenotypes of the same disease?

Takayasu arteritis and primary sclerosing cholangitis are two rare disorders. The pathogenesis of Takayasu arteritis involves immune-mediated mechanisms, and corticosteroids represent the mainstay for treatment. Conversely, the aetiology of primary sclerosing cholangitis remains elusive, even if dysimmunity seems to be one of the contributors to bile duct damage. Despite this, immunosuppressants do not alter disease course. In this paper we describe the association of these two rare disorders, with an unexpected normalization of cholestatic enzymes following steroid treatment. This might hint a novel subtype of sclerosing cholangitis with a prevalent immunebackground, or a local manifestation of Takayasu arteritis.

Morphofunctional analysis of the retina in patients with type 1 diabetes without complications after 30 years of disease.

There is a lack of studies evaluating the sub-clinical retinal changes in patients with long-term type 1 diabetes mellitus (T1DM) and without history of systemic/ocular complications. The aim of this cross-sectional study was to investigate sub-clinical structural and/or vascular retinal changes in patients with long-term (≥30 years) T1DM and without systemic/ocular complications ("happy few" patients) using structural optical coherence tomography (OCT), OCT-angiography and microperimetry. Twelve eyes of 12 consecutive T1DM patients (mean age 52 ± 12 years, mean duration of disease 35 ± 3 years, mean HbA1c level 7.3 ± 2.8%), without micro/macrovascular complications associated with long-standing T1DM, and twelve healthy subjects were consecutively included. No statistically significant differences were disclosed comparing patients and controls for age, sex, best-corrected visual acuity, central macular thickness, and choroidal thickness. Using OCT-angiography, we did not find any significant difference in foveal avascular zone area, perfusion density, vessel length density, and tortuosity. Moreover, no significant differences were disclosed in retinal nerve fiber layer and ganglion cell complex thickness using structural OCT. No differences were disclosed in retinal sensitivity by microperimetry. New diagnostic tools are able to confirm the presence of a particular population of patients with type 1 diabetes who have been completely spared from diabetic retinal complications. The finding of these "happy few" patients could help us to better understand and target future treatments for diabetes.