Response to Ustekinumab Therapy Is Associated with an Improvement of Nutritional Status in Patients with Crohn's Disease.

The presence of sarcopenia has been associated with the worst outcome of Crohn's disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p-value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p-values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients.

A prospective study of the association between living in a rural environment during childhood and risk of psoriasis.

Psoriasis is one of the most common immune-mediated inflammatory diseases (IMIDs). Living in a rural environment during childhood is associated with a decreased risk of certain IMIDs, like asthma, in adulthood. However, its role in other IMIDs, such as psoriasis is still unclear. To evaluate the relationships between different factors related to the environment during childhood and the risk of psoriasis in adulthood we conducted a study in E3N, a French prospective cohort composed of 98 995 women. During the 1990-2018 follow-up of 72 154 study participants, we identified 1 967 incident cases of psoriasis from self-reports in self-administered structured questionnaires. During the 2004-2018 follow-up of 67 917 study participants, 188 moderate-to-severe cases of psoriasis were identified through self-reports and from data from a drug reimbursement database. We fitted Cox proportional hazards regression models with age as the time scale from which we estimated hazard ratios adjusted for putative confounders (aHRs). We found inverse associations with risk of psoriasis for rural birthplace [aHR: 0.89 (95%CI: 0.79-0.96)] and for having farming parents [aHR: 0.84 (95%CI: 0.72-0.97)]. For moderate-to-severe psoriasis we found a nominally similar inverse association with rural birthplace but not with having farming parents. Our results suggest that an exposure to a rural environment during childhood may be associated with a reduced risk of psoriasis. These findings may help to improve our understanding of the pathogenesis of psoriasis.

Reorganization of Intensive Care Units for the COVID-19 pandemic: effects on nursing sensitive outcomes.

Background: Since the first months of 2020 COVID-19 patients who were seriously ill due to the development of ARDS, required admission to the intensive care unit to ensure potentially life-saving mechanical ventilation and support for vital functions. To cope with this emergency, an extremely rapid reorganization of premises, services and staff, to dedicate an entire intensive care unit exclusively to SARS-CoV-2 patients and increasing the number of beds was essential. The aim of the study was to evaluate the effects of reorganization of the COVID-19 intensive care unit in terms of nursing sensitive outcomes. Methods: a retrospective observational study was conducted to compare nursing sensitive outcomes between pre-COVID period and COVID period. Results: Falls (0.0 and 0.4%, respectively), physical restraint (1.8 and 1.1%, respectively), and pressure ulcers (8.0 and 3.0%, respectively) were similar in the COVID and in the pre-COVID group. After adjusting for gender, age, BMI, and number of comorbidities, the incidence of bloodstream infections was significantly higher in the COVID group than in the pre-COVID group. There were no statistically significant differences in the incidence between the two groups regarding other evaluated outcomes. Conclusion: The selected nursing sensitive outcomes maintained similar values in the pre-COVID and COVID patient groups. Healthcare-related infections rate must be considered an important alarm signal of quality of nursing care especially in conditions of excessive workload, stress and the presence of less experienced staff increase.

Vaccine hesitancy and cognitive biases: Evidence for tailored communication with parents.

Background: Vaccine hesitancy (VH) remains worldwide a reason of concern. Most of the vaccination education strategies followed a "fact-based" approach, based on the assumption that decision making is a rational process, without considering the influence of cognitive biases and heuristics. Our study aimed at identifying factors involved in the parents' vaccination choice to inform and shape communication interventions. Methods: We conducted an online national survey among parents between November 2020 and April 2021. The questionnaire consisted of 42 items organised in 4 parts: (1) personal information, (2) cognitive biases and risk propension, (3) Analytic Thinking (Cognitive Reflection Test), (4) conspiracy mentality, health literacy, and VH. Exploratory factor analysis was conducted to identify latent variables underlying the 19 items related to the 6 cognitive biases. Factors were categorised in quintiles and the corresponding pseudo-continuous variables used as predictors of the VH. Logistic regression model was applied to assess the association of the VH with factors, conspiracy mentality and risk propension. We adjusted for age, gender, economic status, and education levels. Results: The study included 939 parents, 764 women (81.4%), 69.8% had a degree or higher level of education. Considering cognitive biases, four factors explaining 54% of the total variance were identified and characterised as: fear of the side effects of vaccines (scepticism factor); carelessness of the risk and consequences of infections (denial factor); optimistic attitude (optimistic bias factor); preference for natural products (naturalness bias factor). All factors were positively associated to VH (p < 0.001) as were conspiracy mentality (p = 0.007) and risk propension (p = 0.002). Conclusions: This study confirmed the need to amplify the model used to analyse the VH considering cognitive biases as important factor affecting the parents' decision making. These results may be useful to design personalised communication interventions regarding vaccines and vaccination.

Impact of low-dose acetylsalicylic acid on pregnancy outcome in systemic lupus erythematosus: results from a multicentre study.

OBJECTIVE: It is still a matter of debate whether low-dose acetylsalicylic acid (LDASA) should be prescribed to all patients with SLE during pregnancy. This study aimed at investigating the impact of LDASA on pregnancy outcomes in patients with SLE without history of renal involvement and without antiphospholipid antibodies (aPL). METHODS: This is a retrospective analysis of prospectively monitored pregnancies at seven rheumatology centres. Previous/current renal involvement and aPL positivity were the exclusion criteria. Adverse pregnancy outcome (APO) is the composite outcome of the study and included proteinuric pre-eclampsia, preterm delivery <37 weeks, small-for-gestational age infant, low birth weight <2500 g, intrauterine growth restriction and intrauterine fetal death after 12 weeks of gestation of a morphologically normal fetus. RESULTS: 216 pregnancies in 187 patients were included; 82 pregnancies (38.0%) were exposed to LDASA treatment. No differences in terms of age at conception, disease duration, clinical manifestations, comorbidities and disease flare during pregnancy were observed between patients taking LDASA and those who did not take LDASA during pregnancy. APO was observed in 65 cases (30.1%), including 13 cases (6.1%) of pre-eclampsia. The incidence of all complications was similar in the two groups. However, it is interesting to note that pre-eclampsia had lower frequency in patients taking LDASA versus those not taking LDASA (2.4% vs 8.3%, p=0.14). CONCLUSIONS: In pregnant patients with SLE without renal involvement and were aPL-negative, there is a low risk of severe obstetric complications, such as early pre-eclampsia. LDASA treatment does not provide a statistically significant advantage over these complications. However, a careful individual risk-benefit balance is warranted.

Serum oncostatin M predicts mucosal healing in patients with inflammatory bowel diseases treated with anti-TNF, but not vedolizumab.

BACKGROUND: Oncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD. METHODS: We selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54. RESULTS: Among 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts. CONCLUSION: Our study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF.

COVID-19 Infection Among Incarcerated Individuals and Prison Staff in Lombardy, Italy, March 2020 to February 2021.

Importance: Owing to infrastructural and population characteristics, the prison setting is at increased risk for transmission of SARS-CoV-2 and for severe clinical outcomes. Because of structural and operational reasons, research in prison settings is challenging and available studies are often monocentric and have limited temporal coverage; broader-based research is necessary. Objectives: To assess the extent and dynamics of the COVID-19 pandemic within the prison system of a large Italian region, Lombardy, and report the infection prevention and control measures implemented. Design, Setting, and Participants: This repeated cross-sectional study was carried out from March 1, 2020, through February 28, 2021 (first wave, March-June 2020; second wave, October 2020-February 2021) in the prison system of Lombardy, which includes 18 detention facilities for adults. All incarcerated persons and the prison staff of the penitentiary system of the Lombardy region participated in the study. Exposures: The main exposures of interest were the weekly average number of incarcerated individuals placed in quarantine in single or shared isolation rooms, the rate of sick leave by symptomatic and asymptomatic prison staff reported to the prison occupational medicine department on a weekly basis, and the level of overcrowding. Main Outcomes and Measures: The primary outcome measures were weekly COVID-19 crude case rates, weekly test positivity rate, and the relative risk of acquiring the infection for prison staff, incarcerated persons, and the general population. Results: The study population comprised a mean of 7599 incarcerated individuals and 4591 prison staff. Approximately 5.1% of the prison population were women; demographic characteristics of the prison staff were not available. During the study, COVID-19 occurred in 1564 incarcerated individuals and 661 prison staff. Most of these cases were reported during the second wave (1474 in incarcerated individuals, 529 in prison staff), when stringent measures previously enforced were relaxed. During both epidemic waves, incarcerated individuals and prison staff had a higher relative risk for COVID-19 infection than the general population during both the first wave (incarcerated individuals: 1.30; 95% CI, 1.06-1.58; prison staff: 3.23; 95% CI, 2.74-3.84) and the second wave (incarcerated individuals: 3.91; 95% CI, 3.73-4.09; prison staff: 2.61; 95% CI, 2.41-2.82). Conclusions and Relevance: The findings of this study suggest that the prison setting was an element of fragility during COVID-19 pandemic, with a high burden of COVID-19 cases among both the incarcerated individuals and prison staff. The prison setting and prison population need to be included and possibly prioritized in the response during epidemic events.

Can the computed tomography texture analysis of colorectal liver metastases predict the response to first-line cytotoxic chemotherapy?

BACKGROUND: Artificial intelligence in radiology has the potential to assist with the diagnosis, prognostication and therapeutic response prediction of various cancers. A few studies have reported that texture analysis can be helpful in predicting the response to chemotherapy for colorectal liver metastases, however, the results have varied. Necrotic metastases were not clearly excluded in these studies and in most studies the full range of texture analysis features were not evaluated. This study was designed to determine if the computed tomography (CT) texture analysis results of non-necrotic colorectal liver metastases differ from previous reports. A larger range of texture features were also evaluated to identify potential new biomarkers. AIM: To identify potential new imaging biomarkers with CT texture analysis which can predict the response to first-line cytotoxic chemotherapy in non-necrotic colorectal liver metastases (CRLMs). METHODS: Patients who presented with CRLMs from 2012 to 2020 were retrospectively selected on the institutional radiology information system of our private radiology practice. The inclusion criteria were non-necrotic CRLMs with a minimum size of 10 mm (diagnosed on archived 1.25 mm portal venous phase CT scans) which were treated with standard first-line cytotoxic chemotherapy (FOLFOX, FOLFIRI, FOLFOXIRI, CAPE-OX, CAPE-IRI or capecitabine). The final study cohort consisted of 29 patients. The treatment response of the CRLMs was classified according to the RECIST 1.1 criteria. By means of CT texture analysis, various first and second order texture features were extracted from a single non-necrotic target CRLM in each responding and non-responding patient. Associations between features and response to chemotherapy were assessed by logistic regression models. The prognostic accuracy of selected features was evaluated by using the area under the curve. RESULTS: There were 15 responders (partial response) and 14 non-responders (7 stable and 7 with progressive disease). The responders presented with a higher number of CRLMs (P = 0.05). In univariable analysis, eight texture features of the responding CRLMs were associated with treatment response, but due to strong correlations among some of the features, only two features, namely minimum histogram gradient intensity and long run low grey level emphasis, were included in the multiple analysis. The area under the receiver operating characteristic curve of the multiple model was 0.80 (95%CI: 0.64 to 0.96), with a sensitivity of 0.73 (95%CI: 0.48 to 0.89) and a specificity of 0.79 (95%CI: 0.52 to 0.92). CONCLUSION: Eight first and second order texture features, but particularly minimum histogram gradient intensity and long run low grey level emphasis are significantly correlated with treatment response in non-necrotic CRLMs.

Myeloid neoplasms and autoimmune diseases: markers of association.

OBJECTIVES: To investigate the prognostic significance of concomitant autoimmune diseases (ADs) in myeloproliferative neoplasms (MPNs). METHODS: 435 subjects with a diagnosis of MPNs were included in this observational single institution longitudinal study. Of them, 34 patients presented an overt AD at diagnosis of MPN. Clinical presenting features, progression-free and overall survival were compared between MPN subgroups in relation to co-existence of AD at diagnosis of MPN. RESULTS: Compared to cases without ADs, the subjects with ADs were significantly younger, had lower haemoglobin and haematocrit levels and more frequently presented with splenomegaly. The clinical and biological features associated to progression-free and overall survival were: age, presence of splenomegaly, histotype (MF vs. PV vs. ET), anaemia, high platelet count and presence of any AD at diagnosis of MPN. The age-adjusted hazard ratio (HR) of progression for the presence of AD at diagnosis of MPN was 2.76. Overall survival was not significantly associated to AD at diagnosis, but the HR of progression for the presence of AD at diagnosis of MPN was 2.18. CONCLUSIONS: A possible common genetic predisposition, the inflammatory bone marrow microenvironment and the activation of theJAK/STAT pathway could be considered as responsible for the observed association between MPNs and ADs.

Trajectories of Adherence to Biologic Disease-Modifying Anti-Rheumatic Drugs in Tuscan Administrative Databases: The Pathfinder Study.

Scanty information on clustering longitudinal real-world data is available in the medical literature about the adherence implementation phase in rheumatoid arthritis (RA). To identify and characterize trajectories by analyzing the implementation phase of adherence to biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), we conducted a retrospective cohort drug-utilization study using Tuscan administrative databases. RA patients were identified by a validated algorithm, including the first biologic DMARD supply from 2010 to 2015, RA specialist visit in the year before or after the first supply date and RA diagnosis in the five years before or in the year after the first supply date. We observed users for three years or until death, neoplasia, or pregnancy. We evaluated adherence quarterly through the Medication Possession Ratio. Firstly, we identified adherence trajectories and described the baseline characteristics; then, we focused on the trajectory most populated to distinguish the related sub-trajectories. We identified 952 first ever-biologic DMARD users in RA (712 females, mean age 52.7 years old, standard deviation 18.8). The biologic DMARD mostly supplied was etanercept (387 users) followed by adalimumab (233). Among 935 users with at least 3 adherence values, we identified 49 fully-adherent users, 829 continuous users, and 57 early-discontinuing users. Significant differences were observed among the index drugs. After focusing on the continuous users, three sub-trajectories were identified: continuous-steady users (556), continuous-alternate users (207), and continuous-declining users (66). No relevant differences emerged at the baseline. The majority of first ever-biologic DMARD users showed a continuous adherence behavior in RA. The role of adherence potential predictors and the association with effectiveness and safety outcomes should be explored by further studies.

Association between telomere length and mitochondrial copy number and cancer risk in humans: A meta-analysis on more than 300,000 individuals.

In the last decades the association of leukocyte telomere length (LTL) and mitochondrial copy number (mtDNAcn) with cancer risk has been the focus of many reports, however the relation is not yet completely understood. A meta-analysis of 112 studies including 64,184 cancer cases and 278,641 controls that analysed LTL and mtDNAcn in relation to cancer risk has been conducted to further our understanding of the topic. Stratified analyses for tumor type were also performed. Overall, no association was observed for all cancer combined neither for LTL nor mtDNAcn. Significant associations were detected for these biomarkers and specific cancer type; however, a large degree of heterogeneity was present, even within the same tumor type. Alternatives approaches based on polymorphic variants, such as polygenic risk scores and mendelian randomization, could be adopted to unravel the causal correlation of telomere length and mitochondrial copy number with cancer risk.

Telomere Length and Male Fertility.

Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2-rs11125529 and decreased sperm motility (p = 0.03); PXK-rs6772228 with a lower sperm count (p = 0.02); NAF1-rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208-rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process.

Psychological distress in the academic population and its association with socio-demographic and lifestyle characteristics during COVID-19 pandemic lockdown: Results from a large multicenter Italian study.

Measures implemented in many countries to contain the COVID-19 pandemic resulted in a change in lifestyle with unpredictable consequences on physical and mental health. We aimed at identifying the variables associated with psychological distress during the lockdown between April and May 2020 in the Italian academic population. We conducted a multicenter cross-sectional online survey (IO CONTO 2020) within five Italian universities. Among about 240,000 individuals invited to participate through institutional communications, 18 120 filled the questionnaire. Psychological distress was measured by the self-administered Hospital Anxiety and Depression Scale (HADS). The covariates collected included demographic and lifestyle characteristics, trust in government, doctors and scientists. Associations of covariates with influenza-like symptoms or positive COVID-19 test and with psychological distress were assessed by multiple regression models at the local level; a meta-analysis of the results was then performed. Severe levels of anxiety or depression were reported by 20% of the sample and were associated with being a student or having a lower income, irrespective of their health condition and worries about contracting the virus. The probability of being severely anxious or depressed also depended on physical activity: compared to those never exercising, the highest OR being for those who stopped during lockdown (1.53; 95% CI, 1.28 to 1.84) and the lowest for those who continued (0.78; 95% CI, 0.64 to 0.95). Up to 21% of severe cases of anxiety or depression might have been avoided if during lockdown participants had continued to exercise as before. Socioeconomic insecurity contributes to increase mental problems related to the COVID-19 pandemic and to the measures to contain it. Maintaining or introducing an adequate level of physical activity is likely to mitigate such detrimental effects. Promoting safe practice of physical activity should remain a public health priority to reduce health risks during the pandemic.

Investigation of circulating metabolites associated with breast cancer risk by untargeted metabolomics: a case-control study nested within the French E3N cohort.

BACKGROUND: Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease. METHODS: Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression. RESULTS: Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49-0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19-2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18-1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11-2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05-1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women. CONCLUSIONS: Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake.

Association between the glyco-metabolic adverse effects of antipsychotic drugs and their chemical and pharmacological profile: a network meta-analysis and regression.

BACKGROUND: Glyco-metabolic deteriorations are the most limiting adverse reactions to antipsychotics in the long term. They have been incompletely investigated and the properties of antipsychotics that determine their magnitude are not clarified.To rank antipsychotics by the magnitude of glyco-metabolic alterations and to associate it to their pharmacological and chemical properties, we conducted a network meta-analysis. METHODS: We searched PubMed, Embase, and Psycinfo on 10 September 2020. We selected studies containing the endpoint-baseline difference or the distinct values of at least one outcome among glucose, HbA1c, insulin, HOMA-IR, triglycerides, total/HDL/LDL cholesterols. Of 2094 articles, 46 were included in network meta-analysis. Study quality was assessed by the RoB 2 and ROBINS-I tools. Mean differences (MD) were obtained by random-effects network meta-analysis; relations between MD and antipsychotic properties were analyzed by linear regressions. Antipsychotic properties investigated were acidic and basic pKa, polar surface area, polarizability, and occupancies of D2, H1, M1, M3, α1A, α2A, 5-HT1A, 5-HT2A, 5-HT2C receptors. RESULTS: We meta-analyzed 46 studies (11 464 patients); on average, studies lasted 15.47 weeks, patients had between 17.68 and 61.06 years of mean age and 61.64% were males. Olanzapine and clozapine associated with greater deteriorations, aripiprazole and ziprasidone with smaller deteriorations. Higher polarizability and 5-HT1A receptor occupancy were associated with smaller deteriorations, H1, M1, and M3 receptor occupancies with larger deteriorations. CONCLUSIONS: Drug rankings may guide antipsychotic switching toward metabolically safer drugs. Mechanistic insights may suggest improvements for combination therapies and drug development. More data are required regarding newer antipsychotics.

Thymoma-associated myasthenia gravis: Clinical features and predictive value of antiacetylcholine receptor antibodies in the risk of recurrence of thymoma.

BACKGROUND: Thymoma-associated myasthenia gravis (TAMG) is one of the subtypes of myasthenia gravis with autoantibodies against the acetylcholine receptor (AChR-Ab). We analyzed the clinical features of our cohort of TAMG patients and the changes in AChR-Ab titer before and after thymectomy in order to identify factors predicting thymoma relapses. METHODS: We retrospectively assessed: age of MG onset, MG clinical status according to MGFA (Myasthenia Gravis Foundation of America), epoch of thymectomy, post-thymectomy status, oncological features and surgical approach. AChR-Ab dosages were measured both before and after thymectomy. Linear regression models were applied to identify clinical determinants of AChR-Ab titers and the Cox regression model was fitted to estimate the factors associated with the risk of thymoma recurrence. RESULTS: The study sample included 239 MG patients, 27 of whom experienced one or more recurrences (median follow-up time: 4.8 years). The AChR-Ab titers decreased after first thymectomy (P < 0.001); the decrease was more pronounced in female patients (P = 0.05), in patients diagnosed with MG at an older age (P = 0.003), and in those who had lower MG stage before surgery (P = 0.02) or higher Masaoka-Koga stage (P = 0.005). The risk of relapse was closely linked with the age of the patient, the Masaoka-Koga stage and the surgical approach. CONCLUSIONS: Presurgery levels of AChR-Ab or their change after surgery were not associated with thymoma recurrence. The reduction of AChR-Ab titers after thymectomy confirms an immunological role of thymoma in the pathogenesis of MG. KEY POINTS: Significant findings of the study: Young MG patients with an advanced Masaoka staging score of the primary tumor who underwent thymectomy with approaches different from sternotomy and VATS should be monitored for high risk of recurrence. WHAT THIS STUDY ADDS: No other study has ever investigated the changes in AChR-Ab titers before and after thymectomy in a large cohort of TAMG patients. The reduction of AChR-Ab titers after thymectomy suggests an immunological role of thymoma in the pathogenesis of MG.

Invasive Pneumococcal Disease in Tuscany Region, Italy, 2016-2017: Integrating Multiple Data Sources to Investigate Underreporting.

Invasive pneumococcal disease (IPD) is a vaccine-preventable disease characterized by the presence of Streptococcus pneumoniae in normally sterile sites. Since 2007, Italy has implemented an IPD national surveillance system (IPD-NSS). This system suffers from high rates of underreporting. To estimate the level of underreporting of IPD in 2016-2017 in Tuscany (Italy), we integrated data from IPD-NSS and two other regional data sources, i.e., Tuscany regional microbiological surveillance (Microbiological Surveillance and Antibiotic Resistance in Tuscany, SMART) and hospitalization discharge records (HDRs). We collected (1) notifications to IPD-NSS, (2) SMART records positive for S. pneumoniae from normally sterile sites, and (3) hospitalization records with IPD-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9) codes in discharge diagnoses. We performed data linkage of the three sources to obtain a combined surveillance system (CSS). Using the CSS, we calculated the completeness of the three sources and performed a three-source log-linear capture-recapture analysis to estimate total IPD underreporting. In total, 127 IPD cases were identified from IPD-NSS, 320 were identified from SMART, and 658 were identified from HDRs. After data linkage, a total of 904 unique cases were detected. The average yearly CSS notification rate was 12.1/100,000 inhabitants. Completeness was 14.0% for IPD-NSS, 35.4% for SMART, and 72.8% for HDRs. The capture-recapture analysis suggested a total estimate of 3419 cases of IPD (95% confidence interval (CI): 1364-5474), corresponding to an underreporting rate of 73.7% (95% CI: 34.0-83.6) for CSS. This study shows substantial underreporting in the Tuscany IPD surveillance system. Integration of available data sources may be a useful approach to complement notification-based surveillance and provide decision-makers with better information to plan effective control strategies against IPD.

HCV micro-elimination in two prisons in Milan, Italy: A model of care.

People in prison represent a high-risk population for HCV infection control. With the advent of new direct antiviral agents (DAAs) HCV micro-elimination in prison setting became a feasible strategy. We assessed the impact of an intervention for HCV testing and treatment in 2017 and 2018 in a jail (San Vittore,SV) and a prison for sentenced individuals (Opera,OP). A dedicated protocol was applied and implemented over the two years. We collected data on demographics, HCV testing and treatment on all inmates present on 31 October 2017 and 2018. In the two facilities, there were 2,366 and 2,369 inmates in 2017 and 2018 respectively; the majority were men (95.6%; 96.4%) and Italians (57.0%; 61.9%) with a median age of 41 years. Prevalence of lifetime reported drug use remained high (46.5%; 44.2%). HCV screening coverage was 89% in both years, while HCV RNA test coverage increased (90.6%; 99.0%). HCV seroprevalence remained stable (10.1%; 9.2%). In 2017 among inmates with HCV chronic infection 90 (42.4%) individuals had started DAAs treatment and 106 (54.6%) in 2018; of whom 38 (17.9%) and 74 (38.1%) achieved the SVR. The viremic pool decreased significantly over time (SV,24.4%; 15.4%;OP, 16.1%; <1%). Among inmates with HCV-positive serology in 2018, 121 (81.0%) were never linked to care before incarceration. Our study showed how a targeted and well-implemented HCV test-and-treat intervention in prison was feasible and effective in achieving micro-elimination. Viral hepatitis elimination agenda may help drawing interest onto this neglected population and bringing prison health higher up in the global public health agenda.

Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index.

PURPOSE: Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel-based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI). PATIENTS AND METHODS: We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655; N = 2,887) comparing non-docetaxel- to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. RESULTS: There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). CONCLUSION: This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition-based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.

Serum oncostatin M at baseline predicts mucosal healing in Crohn's disease patients treated with infliximab.

BACKGROUND: Oncostatin M is upregulated in Crohn's disease inflamed intestinal mucosa, and has been suggested as a promising biomarker to predict responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases. AIM: To evaluate the suitability of serum oncostatin M as a predictive marker of response to infliximab in Crohn's disease. METHODS: We included patients treated with infliximab monotherapy. All patients underwent colonoscopy at week 54 to evaluate mucosal healing. Serum oncostatin M and faecal calprotectin were measured at baseline and after 14 weeks of treatment. Mann-Whitney test was used to evaluate correlation of oncostatin M and faecal calprotectin at baseline and week 14 with mucosal healing at week 54. Their accuracy in predicting mucosal healing was assessed by area under the curve (AUC). RESULTS: In a cohort of 45 included patients, 27 displayed mucosal healing. At both baseline and week 14, oncostatin M levels were significantly lower in patients with mucosal healing than in patients not achieving this endpoint (P < 0.001). Faecal calprotectin levels at week 14 were lower also in responders than nonresponders (P < 0.001). Oncostatin M values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, P < 0.001). The diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing (AUC = 0.91) was greater than faecal calprotectin (AUC = 0.51, P < 0.001). CONCLUSION: These results suggest that oncostatin M can predict the outcome of infliximab treatment. Compared with faecal calprotectin, the predictive capability of oncostatin M was appreciable at baseline, thus indicating oncostatin M as a promising biomarker for driving therapeutic choices in Crohn's disease.