Delayed treatment in breast cancer patients during the COVID-19 pandemic: a population health information research infrastructure (PHIRI) case study.

BACKGROUND: The indirect impact of the coronavirus disease 2019 pandemic on healthcare services was studied by assessing changes in the trend of the time to first treatment for women 18 or older who were diagnosed and treated for breast cancer between 2017 and 2021. METHODS: An observational retrospective longitudinal study based on aggregated data from four European Union (EU) countries/regions investigating the time it took to receive breast cancer treatment. We compiled outputs from a federated analysis to detect structural breakpoints, confirming the empirical breakpoints by differences between the trends observed and forecasted after March 2020. Finally, we built several segmented regressions to explore the association of contextual factors with the observed changes in treatment delays. RESULTS: We observed empirical structural breakpoints on the monthly median time to surgery trend in Aragon (ranging from 9.20 to 17.38 days), Marche (from 37.17 to 42.04 days) and Wales (from 28.67 to 35.08 days). On the contrary, no empirical structural breakpoints were observed in Belgium (ranging from 21.25 to 23.95 days) after the pandemic's beginning. Furthermore, we confirmed statistically significant differences between the observed trend and the forecasts for Aragon and Wales. Finally, we found the interaction between the region and the pandemic's start (before/after March 2020) significantly associated with the trend of delayed breast cancer treatment at the population level. CONCLUSIONS: Although they were not clinically relevant, only Aragon and Wales showed significant differences with expected delays after March 2020. However, experiences differed between countries/regions, pointing to structural factors other than the pandemic.

Understanding Patterns of Adherence to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis: Insights from an Italian Prospective Cohort Study.

Background: Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014-2021 in newly diagnosed IPF patients, using Healthcare Utilization Databases of the Marche Region, Italy. Methods: The first 12-month adherence to antifibrotic was estimated using the Proportion of Days Covered (PDC), defining adherence as PDC ≥ 75%. State Sequence Analysis over the initial 52 weeks of treatment was used to identify adherence patterns. The role of adherence patterns on acute exacerbations/death, adjusted by demographic, clinical features, and monthly adherence after the 52-week period (time-dependent variable), was assessed with Cox regression. Results: Among 667 new IPF cases, 296 received antifibrotic prescriptions, with 62.8% being adherent in the first year. Three antifibrotic utilization patterns emerged-high adherence (37.2%), medium adherence (42.5%), and low adherence (20.3%)-with median PDCs of 95.3%, 79.5%, and 18.6%, respectively. These patterns did not directly influence three-year mortality/exacerbation probability, but sustained adherence reduced risk over time. Conclusions: Good adherence was observed in in this population-based study, emphasizing the importance of continuous antifibrotics therapy over time to mitigate adverse outcomes.

Incidence of amyotrophic lateral sclerosis before and during the COVID-19 pandemic: evidence from an 8-year population-based study in Central Italy based on healthcare utilization databases.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder with a high multidimensional burden, with an obscure etiopathogenesis. METHODS: We designed a longitudinal, population-based study of people residing in Central Italy (Marche Region) who were beneficiaries of the National Health System. People with an unprecedented ALS hospitalization (335.20 ICD-9 CM) or tagged with an ALS exemption between 2014 and 2021 were considered incident cases. ALS cases residing in the region for <3 years or with an active ALS exemption or hospitalized for ALS before 2014 were excluded. We used secondary sources to identify new ALS diagnoses. The regional referral center for ALS's database was used to test the accuracy of secondary sources in detecting cases. ALS mean incidence was compared to that reported in similar studies conducted in Italy. The incidence rate trend adjusted by sex and age was evaluated using the Poisson regression model. RESULTS: We detected 425 new ALS cases (median age: 70y) in the 2014-2021 period, with a mean incidence of 3.5:100,000 py (95%CI: 3.2-3.8; M:F = 1.2), similar to that reported in similar studies conducted in Italy. No trend was observed during 2014-2019. After including 2020-2021 in the model, we observed a mean decrease in incidence of 5.8% (95% CI 2.0%; 9.5%, p = 0.003). CONCLUSION: We show a decrease in the incidence rate of ALS in Marche, during the 2014-2021 period, as a possible outcome of a delayed neurological assessment and diagnosis during the pandemic. An ad hoc developed identification algorithm, based on healthcare utilization databases, is a valuable tool to assess the health impact of global contingencies.

Glucometrics and device satisfaction in children and adolescents with type 1 diabetes using different treatment modalities: A multicenter real-world observational study.

AIMS: To analyze metabolic outcomes, diabetes impact and device satisfaction in children and adolescents with type 1 diabetes in Italy who used different treatment modalities for diabetes care in a real-life context. METHODS: In this multicenter, nationwide, cross-sectional study, 1464 participants were enrolled at a routine visit. The following treatment modalities were considered MDI + SMBG; MDI + CGM; Sensor Augmented Pump Therapy; predictive management of low glucose; Hybrid Closed Loop (HCL); Advanced Hybrid Closed Loop (AHCL). Health related quality of life was evaluated by the Italian version of the Diabetes Impact and Device Satisfaction Scale (DIDS) questionnaire. RESULTS: Patients treated with AID systems were more likely to have HbA1c ≤ 6.5 %, higher percentage of time with glucose levels between 70 and 180 mg/dL, lower percentage of time with glucose levels above 180 mg/dL, higher device satisfaction, and reduced impact of diabetes. All the therapeutic modalities with respect to MDI + CGM, except for MDI + SMBG, contributed to increase the device satisfaction. HCL and AHCL respect to MDI + CGM were associated with lower diabetes impact. CONCLUSION: Real-life use of automated insulin delivery systems is associated with reduced type 1 diabetes impact, increased device satisfaction, and achievement of glycemic goals.

Differences in Plasma 25-Hydroxyvitamin D Levels at Diagnosis of Celiac Disease and Type 1 Diabetes.

AIM: The aim of this work is to assess the vitamin D levels, evaluated as plasma 25-hydroxyvitamin D of children with a new diagnosis of celiac disease (CD), of children with a new onset of type 1 diabetes (T1D) and in children with CD at diagnosis of T1D (T1D&CD). METHODS: In this single-center observational study, we collected data for four groups of children and adolescents: T1D, CD, T1D&CD, and a control group (CG). The CG included schoolchildren who had negative results during a mass screening campaign for CD and were not diagnosed for T1D, according to RIDI Marche registry data, were considered for the purposes of this study. Plasma 25-hydroxyvitamin D, 25(OH)D2, and 25(OH)D3 were considered as the parameters for evaluating vitamin D nutritional status, and the date of measurement was recorded to analyze vitamin D level seasonality. Vitamin D nutritional status was categorized as follows: severe deficiency (<10 ng/mL), deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), or sufficiency/adequacy (≥30 ng/mL). The Kruskal-Wallis test was used to compare the groups. The association of 25(OH)D levels with health conditions and seasonal differences of 25(OH)D levels was analyzed using a multiple linear regression model. RESULTS: The number of children enrolled for the present study was 393: 131 in the CG, 131 CD, 109 T1D, and 22 T1D&CD. Significantly lower levels of vitamin D were displayed for children with CD, T1D, or both the diseases. Interestingly, severe vitamin D deficiency was detected in no children with CD, 1.5% of children in the CG, in 24.4% with T1D, and 31.8% with T1D&CD (p < 0.001). As expected, the CG children vitamin D levels were significantly influenced by seasonality. Contrarily, no seasonal differences were reported in children with CD, T1D, and T1D&CD. Multiple regression analysis showed that children with T1D and T1D&CD had lower 25(OH)D levels of 9.9 ng/mL (95% CI: 5.4; 14.5) and 14.4 ng/mL (95% CI: 6.2-22.7) compared to CG children (p < 0.001). CONCLUSIONS: Our results showed low levels of vitamin D diagnosis of T1D, CD, and T1D&CD; however, severe deficiency was only reported in children with T1D and T1D&CD. More studies are needed to better understand the role of this deficiency in children newly diagnosed with CD and T1D.

Role of viable but non culturable cells in patients with cystic fibrosis in the era of highly effective modulator therapy.

BACKGROUND: Lung infections antibiotic treatment in Cystic Fibrosis patients (pwCF) is often complicated by bacterial persisters, including the so-called Viable but Non Culturable (VBNC) forms, live cells undetected by the routine cultural microbiological methods. This study investigated the occurrence of VBNC cells of five CF bacterial pathogens in 94 pwCF over one year and the possible associations with the patients' clinical features. METHODS: Sputum samples, recovered at routine visits and during exacerbation episodes, were analyzed for the presence of the five pathogens by both routine culture-based assays and species-specific qPCR. VBNC cells were estimated as the difference between molecular and cultural counts and their presence was matched with the clinical data in particular the therapeutic regimens. RESULTS: All but ten pwCF showed the presence of VBNC cells at least once during the study. Pseudomonas aeruginosa and methicillin-susceptible Staphylococcus aureus were the species most frequently found in the VBNC state. Only the former showed a significant association between chronic infection and VBNC cells presence; VBNC-MSSA positive patients significantly increased overtime. The presence of non culturable bacteria was generally concurrent with poor lung functionality and more frequent pulmonary exacerbations. No significant association with modulator treatment was evidenced. CONCLUSIONS: The obtained data demonstrated the overwhelming occurrence of bacterial VBNC cells in CF lung infections, warranting a constant monitoring of pwCF and underlining the need of implementing the routine culture-based assays with culture-independent techniques. This is pivotal to understand the CF bacterial population dynamics and to efficiently contrast the lung infection progression and worsening.

Effects of the supplementation with a multispecies probiotic on clinical and laboratory recovery of children with newly diagnosed celiac disease: A randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of a multispecies probiotic on clinical and laboratory recovery of children with celiac disease (CeD) at diagnosis. METHODS: Children with newly diagnosed CeD entered a randomized double-blind placebo-controlled trial. A gluten-free diet (GFD) plus a multispecies probiotic or placebo were administered for 12 weeks. Growth, laboratory, and clinical parameters were recorded at enrollment, after 3 and 6 months of follow-up. RESULTS: Overall, 96 children completed the study: 49 in group A (placebo) and 47 in group B (probiotic). A significant increase of BMI-Z score was found in both groups after 3 and 6 months of treatment (p < 0.001), however the increase of BMI-Z score was significantly higher and faster in Group B than in Group A. Other clinical and laboratory parameters improved in both groups after 3 and 6 months (p<0.001), but no difference was found between the groups and a comparable time trend was observed in both groups. CONCLUSIONS: Treatment with a multispecies probiotic induced a higher and faster increase of BMI in children with newly diagnosed CeD. The mechanism of this positive effect remains to be elucidated.

Downregulation of argininosuccinate synthase 1 (ASS1) is associated with hypoxia in placental development.

Argininosuccinate synthase (ASS1) is involved in nitric oxide production, which has a key role in placental development improving pregnancy outcomes. Syncytiotrophoblast and extravillous trophoblast differentiations are milestones of placental development and their impairment can cause pathologies, such as preeclampsia (PE) and fetal growth restriction (FGR). Immunohistochemistry and Western blotting were used to localize and quantify ASS1 in first trimester (8.2 ± 1.8 weeks), third trimester (38.6 ± 1.1 weeks), and PE (36.3 ± 1.5 weeks) placentas. In addition, cell cultures were used to evaluate ASS1 expression under hypoxic conditions and the syncytialization process. Our data showed that ASS1 is localized in the villous cytotrophoblast of first trimester, third trimester, and PE placentas, while the villous cytotrophoblast adjacent to the extravillous trophoblast of cell columns as well as the extravillous trophoblast were negative for ASS1 in first trimester placentas. In addition, ASS1 was decreased in third trimester compared to the first trimester placentas (p = 0.003) and no differences were detected between third trimester and PE placentas. Moreover, ASS1 expression was decreased in hypoxic conditions and syncytialized cells compared to those not syncytialized. In conclusion, we suggest that the expression of ASS1 in villous cytotrophoblast is related to maintaining proliferative phenotype, while ASS1 absence may be involved in promoting the differentiation of villous cytotrophoblast in extravillous cytotrophoblast of cell columns in first trimester placentas.

Trends and cyclic variation in the incidence of childhood type 1 diabetes in two Italian regions over 33 years and during the COVID-19 pandemic.

AIM: There is conflicting evidence about the impact of the COVID-19 pandemic on the incidence of type 1 diabetes. Here, we analysed long-term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID-19 pandemic with that estimated from long-term data. MATERIALS AND METHODS: This was a population-based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 to 31 December 2019 were estimated using Poisson and segmented regression models. RESULTS: There was a significant increasing trend in the incidence of type 1 diabetes of 3.6% per year [95% confidence interval (CI): 2.4-4.8] between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95% CI: -1.3 to 2.4). There was a significant 4-year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95% CI: 23.0-30.9) was significantly higher than expected (19.5, 95% CI: 17.6-21.4; p = .010). CONCLUSION: Long-term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to understand better the impact of COVID-19 on new-onset type 1 diabetes in children.

Combining Bayesian Calibration and Copula Models for Age Estimation.

Accurately estimating and predicting chronological age from some anthropometric characteristics of an individual without an identity document can be crucial in the context of a growing number of forced migrants. In the related literature, the prediction of chronological age mostly relies upon the use of a single predictor, which is usually represented by a dental/skeletal maturity index, or multiple independent ordinal predictor (stage of maturation). This paper is the first attempt to combine a robust method to predict chronological age, such as Bayesian calibration, and the use of multiple continuous indices as predictors. The combination of these two aspects becomes possible due to the implementation of a complex statistical tool as the copula. Comparing the forecasts from our copula-based method with predictions from an independent model and two single predictor models, we showed that the accuracy increased.

Ciliary Neurotrophic Factor Modulates Multiple Downstream Signaling Pathways in Prostate Cancer Inhibiting Cell Invasiveness.

BACKGROUND: Prostate cancer (PCa) remains the most common diagnosed tumor and is the second-leading cause of cancer-related death in men. If the cancer is organ-confined it can be treated by various ablative therapies such as RP (radical prostatectomy), RT (radiation therapy), brachytherapy, cryosurgery or HIFU (High-Intensity Focused Ultrasound). However, advanced or metastatic PCa treatment requires systemic therapy involving androgen deprivation, but such patients typically progress to refractory disease designated as castration-resistant prostate cancer (CRPC). Interleukin-6 (IL-6) has been established as a driver of prostate carcinogenesis and tumor progression while less is known about the role of ciliary neurotrophic factor (CNTF), a member of the IL-6 cytokine family in prostate cancer. Moreover, MAPK/ERK, AKT/PI3K and Jak/STAT pathways that regulate proliferative, invasive and glucose-uptake processes in cancer progression are triggered by CNTF. METHODS: We investigate CNTF and its receptor CNTFRα expressions in human androgen-responsive and castration-resistant prostate cancer (CRPC) by immunohistochemistry. Moreover, we investigated the role of CNTF in proliferative, invasive processes as well as glucose uptake using two cell models mimicking the PCa (LNCaP cell line) and CRPC (22Rv1 cell line). CONCLUSIONS: Our results showed that CNTF and CNTFRa were expressed in PCa and CRPC tissues and that CNTF has a pivotal role in prostate cancer environment remodeling and as a negative modulator of invasion processes of CRPC cell models.

Prognosis and Survival in Idiopathic Pulmonary Fibrosis in the Era of Antifibrotic Therapy in Italy: Evidence from a Longitudinal Population Study Based on Healthcare Utilization Databases.

The aim was to evaluate the determinants of acute exacerbation (AE) and death in new cases of idiopathic pulmonary fibrosis (IPF) using administrative databases in the Marche Region. Adults at their first prescription of antifibrotics or hospitalization with a diagnosis of IPF occurring in 2014-2019 were considered as new cases. Multiple Cox regression was used to estimate the risk of AE and of all-cause mortality adjusted by demographic and clinical characteristics, stratifying patients according to antifibrotic treatment. Overall, 676 new cases of IPF were identified and 276 deaths and 248 AE events occurred. In never-treated patients, the risk of AE was higher in patients with poor health conditions at diagnosis; the risk of death was higher in males, in patients aged ≥75 and in those with poor health conditions at baseline. The increasing number of AEs increased the risk of death in treated and never-treated patients. Within the limits of an observational study based on secondary data, the combined use of healthcare administrative databases allows the accurate analysis of progression and survival of IPF from the beginning of the antifibrotic therapy era, suggesting that timely and early diagnosis is critical to prescribing the most suitable treatment to increase survival and maintain a healthy life expectancy.

HtrA1 in Gestational Diabetes Mellitus: A Possible Biomarker?

BACKGROUND: The high-temperature requirement A 1 (HtrA1) is a multidomain secretory protein with serine-protease activity, expressed in many tissues, including placenta, where its expression is higher in the first trimester, suggesting an association of this serine protease in early phases of human placenta development. In this study, we evaluated maternal serum HtrA1 levels in the first and third trimester of gestation. In particular, we evaluated a possible role of HtrA1 as an early marker of gestational diabetes mellitus (GDM) in the first trimester of gestation. METHODS: We evaluated HtrA1 serum levels in the third trimester (36-40 weeks) in normal pregnancies (n = 20) and GDM pregnancies (n = 20) by using ELISA analysis. Secondly, we performed the same analysis by using the first trimester sera (10-12 weeks) of healthy pregnant women that will develop a normal pregnancy (n = 210) or GDM (n = 28) during pregnancy. RESULTS: We found that HtrA1 serum levels in the third trimester were higher in pregnancies complicated by GDM. Interestingly, higher HtrA1 serum levels were also found in the first trimester in women developing GDM later during the second-third trimester. No significant differences in terms of maternal age and gestational age were found between cases and controls. Women with GDM shown significantly higher pre-pregnancy BMI values compared to controls. Moreover, the probability of GDM occurrence significantly increased with increasing HtrA1 levels and BMI values. The ROC curve showed a good accuracy in predicting GDM, with an AUC of 0.74 (95%CI: 0.64-0.92). CONCLUSIONS: These results suggest an important role of HtrA1 as an early predictive marker of GDM in the first trimester of gestation, showing a significative clinical relevance for prevention of this disease.

Impact of the COVID-19 pandemic on long-term trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes: an international multicentre study based on data from 13 national diabetes registries.

BACKGROUND: An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic. METHODS: For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker. FINDINGS: 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27·3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1·6% (95% CI 1·3 to 1·9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39·4% (95% CI 34·0 to 45·6) in 2020 and 38·9% (33·6 to 45·0) in 2021, significantly higher than the predicted prevalence of 32·5% (27·8 to 37·9) for 2020 and 33·0% (28·3 to 38·5) for 2021 (p<0·0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1·037 (95% CI 1·024 to 1·051; p<0·0001) per ten-unit increase in the Stringency Index for 2020 and 1·028 (1·009 to 1·047; p=0·0033) for 2021, but was not significantly associated with excess all-cause mortality. INTERPRETATION: During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents. FUNDING: German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.

Is Primary Bone Marrow Edema of the Knee Associated with Thyroid Disorders? A Retrospective Clinical Study.

Primary bone marrow edema (BME) of the knee is still an elusive condition. This retrospective study was undertaken to gain insight into its characteristic features. The records of 48 patients with primary BME of the knee diagnosed by magnetic resonance imaging were reviewed. Demographic data, medical history, current medications, pain type, smoking and drinking habits, allergies, occupation, sports practiced, environmental factors, and life events predating symptom onset were examined. Data analysis demonstrated that 56.3% of patients had experienced a stressful event before BME pain onset and that 50% suffered from thyroid disorders. Standard conservative treatment resulted in pain resolution irrespective of the use of anti-inflammatories. However, most patients reported new persistent symptoms: dysesthesia/hypoesthesia on palpation in the skin area overlying the previous edema and a reduced ipsilateral patellar reflex. To our knowledge, this is the first study characterizing a substantial cohort of patients with BME. We found that middle-aged, sedentary, and slightly overweight women smokers are the typical patients with primary BME of the knee. The appearance and persistence of cutaneous dysesthesia/hypoesthesia at the site of the earlier lesion and ipsilateral patellar hyporeflexia implicate an autonomous nervous system dysfunction in BME pathogenesis and warrant further investigation.

Health care organization and use of technological devices in people with diabetes in Italy: Results from a survey of the Working Group on Diabetes and Technology.

BACKGROUND AND AIM: The use of technology offers recognized benefits to persons with diabetes. The aim of this study was to evaluate the organization of healthcare facilities, the composition of the diabetes team, and the use of Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM) in Italy. METHODS AND RESULTS: Diabetes care centers were asked to complete a web survey based on information collected in 2018. Sixty-one pediatric and 243 adult centers participated in the survey, accounting for 507,386 patients, mostly with type 2 diabetes (86.4%). Fifty-three percent of pediatric centers and 11% of adult centers reported a team composed of diabetologists, nurses, and psychologists. Overall, 13,204 patients (2.6%) were using CSII (95% with type 1 diabetes), and 28,936 (5.7%), were using CGM (74% with type 1 diabetes). When stratifying for the type of diabetes, 24% and 40.8% of patients with type 1 were using CSII and CGM, respectively, whereas low use of technology was reported for patients with type 2 and women with gestational diabetes. The percentage of adult and pediatric patients with type 1 diabetes on CSII and CGM was respectively 21% and 32%, and 35% and 57%. CONCLUSIONS: The spread of CGM and CSII increased in Italy between 2013 and 2018. However, the percentage of users is still lower than what is expected based on clinical indications for use of technology. The inadequate number of professionals in the diabetes care team and insufficient economic resources are relevant barriers to disseminating technology for diabetes management.

Ciliary neurotrophic factor is increased in the plasma of patients with obesity and its levels correlate with diabetes and inflammation indices.

To establish whether obesity involves activation of endogenous ciliary neurotrophic factor (CNTF) signalling, we evaluated its plasma levels in patients with obesity and correlated its values with the major clinical and haematological indices of obesity, insulin resistance and systemic inflammation. This study involved 118 subjects: 39 healthy controls (19 men), 39 subjects with obesity (19 men) and 40 subjects with obesity and diabetes (20 men). Plasma CNTF and CNTF receptor α (CNTFRα) were measured using commercial ELISA kits. The results showed that plasma CNTF was significantly higher in males and females with obesity with and without diabetes than in healthy subjects. Women consistently exhibited higher levels of circulating CNTF. In both genders, CNTF levels correlated significantly and positively with obesity (BMI, WHR, leptin), diabetes (fasting insulin, HOMA index and HbA1c) and inflammation (IL-6 and hsCRP) indices. Circulating CNTFRα and the CNTF/CNTFRα molar ratio tended to be higher in the patient groups than in controls. In conclusion, endogenous CNTF signalling is activated in human obesity and may help counteract some adverse effects of obesity. Studies involving a higher number of selected patients may reveal circulating CNTF and/or CNTFRα as potential novel diagnostic and/or prognostic markers of obesity, diabetes and associated diseases.

Occurrence of Idiopathic Pulmonary Fibrosis in Italy: Latest Evidence from Real-World Data.

The aim of the study was to evaluate the trend in the incidence of idiopathic pulmonary fibrosis (IPF) in a real-world setting of the Marche region, a region of Central Italy, between 2014 and 2019. This observational prospective study was based on administrative databases of hospital discharges and drug prescriptions. All adult residents in the Marche Region with a first prescription of antifibrotic drugs, or a first hospitalization with a diagnosis of IPF during the study period, were identified as incident cases of IPF. A multiple Poisson regression analysis was used to estimate the IPF incidence trend, adjusted for age, sex, and health conditions. The mean incidence rate was 9.8 cases per 100,000 person-years. A significant increasing trend of 6% per year was observed. The incidence rates were significantly higher in males than females, older subjects, and those with poorer health conditions. To our knowledge, this is the first study evaluating incidences of IPF over a 6-year period in Italy, combining hospital discharge and drug prescription databases. The study highlights that the combined use of two secondary sources is a reliable strategy to accurately identify new cases of IPF when the appropriate disease registry is lacking.