In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy ...and to estimate the proportion of TC cases potentially attributable to overdiagnosis.
Data on TC cases reported to Italian cancer registries during 1998–2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region.
In Italy between 1998–2002 and 2008–2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998–2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008–2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders.
Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.
•Incidence rates of thyroid cancer (TC) in Italy are among the highest worldwide.•Cancer data were collected from Italian cancer registries for the period 1998–2012, and time trends were analysed.•Large increasing heterogeneity of TC incidence rates was observed across regions and areas in Italy.•We used a previously developed method to estimate overdiagnosis of TC.•The steady increases of TC incidence in Italy are largely due to overdiagnosis.
PurposeThe Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE) cohort was established in Italy in 2016 to evaluate the overall efficacy and ...tolerability of dolutegravir (DTG)-based antiretroviral (ARV) regimens in clinical practice.ParticipantsThe ODOACRE cohort enrols all adult HIV-1-infected patients, both treatment-naïve and treatment-experienced, starting a DTG-based ARV regimen, in 11 clinical centres in Italy from 2014.Findings to dateIn recent years, various works by the ODOACRE cohort have been produced, demonstrating the high efficacy and tolerability of DTG-based ARV regimens in clinical practice, both in ART-naïve (in the setting of acute HIV-1 infection and late presenters patient) and experienced patients. We confirmed the virological efficacy of DTG-based regimens and we evaluated predictors of virological failure. We investigated cause of discontinuation and evaluated tolerability and metabolic profile of the regimens. Within these investigations, we explored particularly the use of DTG in simplification in two-drug regimen with either rilpivirine or lamivudine. We also compared DTG-based regimens with other integrase inhibitors in clinical practice.Future plansTo continue to study long-term efficacy and tolerability of DTG-based regimens is the purpose of the ODOACRE cohort.
Summary Background & aims A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with ...carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. Methods Sixty eligible patients were randomly assigned to: arm 1, l -carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, l -carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. Results The results did not show a significant difference between treatment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. Conclusions The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.
Abstract Objective In April 2005 a phase III randomized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative ...stress in improving identified primary endpoints: increase of lean body mass, decrease of resting energy expenditure (REE), increase of total daily physical activity, decrease of interleukin-6 and tumor necrosis factor-α, and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF). Methods All patients were given as basic treatment polyphenols plus antioxidant agents α-lipoic acid, carbocysteine, and vitamins A, C, and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) l -carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus l -carnitine plus thalidomide. Treatment duration was 4 mo. The sample comprised 475 patients. Results By January 2007, 125 patients, well balanced for all clinical characteristics, were included. No severe side effects were observed. As for efficacy, an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3, 4, and 5, whereas arm 2 showed a significant worsening of lean body mass, REE, and MFSI-SF. Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1, 3, and 5 versus arm 2. A significant inferiority of arm 2 versus arms 3, 4, and 5 for the primary endpoints lean body mass, REE, and MFSI-SF was observed on the basis of t test for changes. Conclusion The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen. The study is still in progress and the final results should confirm these data.
Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes ...are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes.
Frailty affects physical, cognitive, and social domains exposing older adults to adverse health outcomes. High physical frailty with increased S100A8/A9 alarmins level in HSPCs (Hematopoietic Stem/Progenitor cells) and blood identify subjects with early cardiorespiratory dysfunctions. Low HSPCs count and high S100A8/A9 levels in the bloodstream associate with more advanced, multidomain frailty predicting major adverse cardiovascular events (MACE).
OBJECTIVE:Assessment of the feasibility and effectiveness of a brief intervention for smoking cessation in people living with HIV (PLWH).
SETTING:Multicenter cohort prospective study involving PLWH ...from 10 Italian infectious disease centers.
METHODS:During routine HIV care, clinicians delivered the 5As brief intervention (Ask, Advise, Assess, Assist, Arrange) to each patient who enrolled in the study, following the European AIDS Clinical Society guidelines. At study end, participating clinicians evaluated their own adherence to intervention“standard” if counseling was delivered in at least half of the follow-up visits, “soft” if less. The main outcome measure was smoking abstinence ≥6 months. Abstinence predictors were evaluated using a Cox-proportional hazard regression model.
RESULTS:One thousand eighty-seven PLWH-patients (age 47.9 ± 10.8, male 73.5%) were followed for a median of 23 months (interquartile range 21–25). At baseline, current smokers were 561 (51.6%). Standard intervention was performed in 4 of 10 centers and included 343 smokers; soft intervention was performed in 6 centers (218 smokers). At last visit, 35 patients in standard (10.8%) and 6 in soft intervention (2.8%) achieved self-reported tobacco abstinence ≥6 months (P = 0.0009). Overall, the 5As intervention led to 7.3% 6-month interruptions. In the multivariable analysis, significant predictors for 6-month smoking cessation werelower Fagerström score, stage of change (preparation/contemplation vs. precontemplation), and standard intervention.
CONCLUSION:Adherence to the 5As brief intervention emerged as a critical factor for success. In fact, compared with soft intervention, the standard intervention significantly increased abstinence, highlighting that clinicians need more time and supporting tools to encourage PLWH to quit smoking.
Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate ...the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting.
Background: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of ...mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM. Methods: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice. Results: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment. Conclusions: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.
Summary
Objective Given that few and controversial data have been reported on thyroid function in human immunodeficiency virus (HIV) patients on highly active antiretroviral therapy (HAART), we ...further investigated whether HAART affects thyroid hormones.
Design and patients Two hundred two consecutive adult HIV patients in stable clinical condition were enrolled, 182 on HAART and 20 naïve; 128 were rechecked during follow‐up. Body mass index (BMI), CD4 cell count, HIV RNA, hepatitis C and B virus status and infection duration were determined in all HIV patients and HAART duration in treated patients. In all patients and in 60 controls, the following were measured: FT4 and FT3 by radioimmunoassay; TSH, antithyroid peroxidase (TPO) and antithyroglobulin (TG) antibodies by immunoradiometric assay.
Results Abnormalities in thyroid function tests were found in 23/182 (12·6%) HAART patients, but not in naïve patients. Most abnormalities were subclinical hypothyroidism, with mean FT4 and TSH levels lower and higher, respectively, in HAART patients compared to naïve patients and controls, FT4 levels being significantly lower than controls. TSH negatively correlated with CD4 count nadir and positively with HAART duration. During follow‐up, FT4 and FT3 significantly decreased and TSH increased in patients continuing HAART, whereas CD4 counts were unmodified; subclinical hypothyroid conditions persisted and further cases occurred, whereas the only hypothyroid patient who interrupted HAART shows a normalization of thyroid tests. Patients on stavudine, included in most hypothyroid patient protocols, had significantly lower FT4 levels with prolonged treatment.
Conclusions HAART, particularly stavudine, is associated with a high prevalence of subclinical hypothyroidism. Hypotheses are made regarding responsible mechanisms and risk factors. Thyroid function should be tested and sequentially rechecked in HAART patients.
Abstract
Background
An unexpected excess in weight gain has recently been reported in the course of dolutegravir (DTG) treatment. The aim of the present study was to investigate whether weight gain ...differs among different DTG-containing regimens.
Methods
Adult naïve and experienced people with HIV (PWH) initiating DTG-based antiretroviral therapy (ART) between July 2014 and December 2019 in the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) prospective cohort were included. We used an adjusted general linear model to compare weight change among backbone groups and a Cox proportional hazard regression model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for weight increases >10% from baseline.
Results
A total of 713 participants, 25.3% women and 91% Caucasian, were included. Of these, 195 (27.4%) started DTG as their first ART regimen, whereas 518 (72.6%) were ART-experienced. DTG was associated with abacavir/lamivudine in 326 participants, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 148, boosted protease inhibitors in 60, rilpivirine in 45, lamivudine in 75, and tenofovir alafenamide (TAF)/FTC in 59. At 6 and 12 months, weight gain was highest among PWH on TDF/FTC+DTG and TAF/FTC+DTG. Baseline CD4 <200 cells/mm3 (HR, 1.84; 95% CI, 1.15 to 2.96), being ART-naïve (HR, 2.24; 95% CI, 1.24 to 4.18), and treatment with TDF/FTC+DTG (HR, 1.92; 95% CI, 1.23 to 2.98) or TAF/FTC+DTG (HR, 3.80; 95% CI, 1.75 to 8.23) were associated with weight gain >10% from baseline. Higher weight (HR, 0.97 by 1 kg; 95% CI, 0.96 to 0.99) and female gender (HR, 0.54; 95% CI, 0.33 to 0.88) were protective against weight gain.
Conclusions
Naïve PWH with lower CD4 counts and those on TAF/FTC or TDF/FTC backbones were at higher risk of weight increase in the course of DTG-based ART.
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