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We investigated the efficacy and safety of continuous glucose monitoring (CGM) initiation within 1 year of type 1 diabetes (T1D) diagnosis among children, adolescents, and adults.Differences in mean A1c (primary outcome) and diabetes-related emergency visits (secondary outcome) for 2.5 years between early CGM users and non-CGM users were studied among 396 newly diagnosed patients with T1D (94% children [age18 years], 5% adults, 46% females) between January 2013 and December 2015 at Barbara Davis Center for Diabetes. The primary outcome was adjusted by age at diagnosis and gender. P 0.05 was considered significant.Gender, ethnicity, body mass index, and A1c at diagnosis were similar between the groups. Irrespective of insulin delivery methods, CGM users had a significantly greater improvement in glycemic control than non-CGM users at 1, 1.5, 2, and 2.5 years. For 2.5 years of follow-up, the multiple daily injection (MDI)+CGM group (n = 19) had 1.5% ± 0.2% lower A1c than the MDI only group (n = 225) (7.7% ± 0.2% vs. 9.2% ± 0.04%, P 0.0001), and the insulin pump (continuous subcutaneous insulin infusion [CSII])+CGM group (n = 62) had 0.7% ± 0.1% lower A1c than the CSII only group (n = 90) (8.0% ± 0.08% vs. 8.7% ± 0.07%, P 0.0001). The MDI+CGM group had significantly lower A1c than the CSII only group (7.7% ± 0.2% vs. 8.7% ± 0.07%, P 0.0001). The number of diabetes-related (severe hypoglycemia or hyperglycemia) emergency department visits was significantly lower among early CGM users compared with non-CGM users (P = 0.003).Irrespective of insulin delivery system, early initiation of CGM within 1 year from T1D diagnosis was associated with better glucose control and fewer diabetes-related emergency visits.

Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Lay summary Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis., Graphical abstract, Highlights • Under real-world conditions, OCA was effective in ~43% of patients who were non-responders to UDCA, according to Poise criteria. • Patients with cirrhosis showed lower efficacy (29.5%), mainly attributed to reduced tolerability and higher discontinuation rate. • Patients with overlap AIH-PBC showed a comparable efficacy to pure PBC, with a higher ALT reduction at 6 months. • Most patients with PBC are still in need of additional therapy if aiming to normalise liver biochemistry.

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 wellphenotyped cohorts of patients with longitudinal follow-up across sustained periods of time, application of novel image-processing technology, and biomarker discovery using multi-omics platforms.

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.

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 2/FiO2 ratio doubled from about 100 to 200 mmHg (P P 2/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

Introduction: Primary Biliary Cholangitis (PBC) is a chronic liver disease characterized by intrahepatic biliary destruction and progressive cholestasis potentially leading to end-stage liver disease and its associated complications. As for many chronic disorders, the risk of disease progression in PBC varies between patients. This has fostered the identification of disease tags defining the trajectory of the disease course. Areas covered: In this review, authors report the evidence-based parameters associated with outcomes in PBC, after an extensive literature search of the PubMed electronic database. Expert opinion: Several prognostic tools including clinical and biochemical disease parameters have been proposed. In the era of the omics science and digital innovation, biomarker discovery has sped up. Extensive data and sample collection of well-phenotyped cohorts of patients with longitudinal follow-up will guarantee an extraordinary opportunity to integrate molecular phenotyping into the clinic, thus promoting a personalized care of patients with PBC. Finally, we emphasize the need to leverage a therapeutic window of opportunity in PBC bringing a paradigm shift toward early intervention with combination therapies in individuals with a more severe phenotype to reach a deeper disease control and halt disease progression.

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., Highlights • Unusual association of two rare entities: PSC (supported by the presence of IBD) and TA. • Onset of Takayasu after PSC diagnosis. • Lack of response to UDCA and fibrates. • Improvement of liver function tests after steroid treatment. • No changes on biliary tree reported on MRCP.

Background & aims Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Non-invasive 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 at disease presentation in PBC. Approach & results We collected data from 167 consecutive treatment-naive 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 Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves(AUROCs) for advanced fibrosis (Ludwig stage≥III). The effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. Derivation cohort consisted of 126 patients with valid LSM and LB, VCTE identified patients with advanced fibrosis with AUROC of 0.89. LSM cut-offs ≤6.5kPa and >11.0kPa enabled to exclude and confirm, respectively, advanced fibrosis (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 the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. Conclusions In a multicenter study of treatment-naive PBC patients, we identified two cut-offs (LSM≤6.5kPa and>11.0kPa) able to discriminate at diagnosis the presence or the absence, respectively, of advanced fibrosis in PBC patients, with external validation. In patients with LSM between these two cut-offs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

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.