Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

Management of pleural effusion and empyema in a third-level pediatric surgical center.

BACKGROUND: Pleural effusion and empyema are frequent complications of acute bacterial pneumonia in children. To date, evidence regarding the optimal treatment of this condition is limited in the literature. METHODS: Patients with pleural effusion and empyema admitted at our Department of Pediatric Surgery over the last ten years were enrolled in this retrospective study, and successively compared with the clinical charts of patients treated before the introduction of a new diagnostic and therapeutic algorithm. In particular, primary outcomes investigated between pre- and postalgorithm period were the use of diagnostic tools and antibiotics, the need for additional therapeutic approaches, complications, and the length of stay. RESULTS: After the introduction of the new algorithm there were a decrease in the use of chest radiography for re-evaluation (100% vs. 79%, P=0.003), a more focused use of computed tomography (68% vs. 15%, P=0.001), and a decrease in the use of a second computed tomography (18% vs. 3%, P=0.07); in favor of an increase in the use of the ultrasound scan (40% vs. 100%, P=0.001). There was also a shift from the use of chest tube drainage alone to the use of drainage for urokinase administration (50% vs. 92.3%, P=0.001), and a statistically significant decrease in the need for video-assisted thoracoscopic surgery (25% vs. 7.7%, P=0.001). CONCLUSIONS: The introduction of a diagnostic and therapeutic algorithm for the management of pediatric pleural effusion and empyema has notably resulted in a decrease in the utilization of radiography and computed tomography and an increase in the use of ultrasonography, reducing unnecessary radiation exposure in children and overall costs.

Study protocol for a randomised controlled trial to determine the effectiveness of a mHealth application as a family supportive tool in paediatric otolaryngology perioperative process (TONAPP).

BACKGROUND: Otorhinolaryngology (ORL) surgery is common in children, but hospitalisation, surgery, and home care after discharge are stressful experiences for young patients and their family caregivers. Findings from literature highlight a lack of time in hospitals to support ORL surgery children and their caregivers through the perioperative process, along with the risks of caregivers' autonomous web or social media resources investigation. Therefore, this study aims to evaluate the effectiveness of a mobile health application with content to support ORL patients and their caregivers in the perioperative period to reduce caregiver anxiety and child distress compared to standard care. METHODS: An open-label, two-arm randomised control trial design is being adopted. The intervention consists of a mobile health application with content to support ORL patients and their caregivers during the perioperative period. One hundred eighty participants will be enrolled and randomly assigned to the experimental group using the mHealth application or the control group. The control group receives standard information and education about the ORL perioperative period from healthcare providers orally or through brochures. The primary outcome is the difference between the intervention and control groups in preoperative caregiver state anxiety. Secondary outcome measures include children's distress before surgery and family preparation for hospitalisation. DISCUSSION: The results of this study will be critical to the implementation of a new and safe model for the management of care and education in paediatrics. This model can achieve positive organisational and health outcomes by supporting continuity of care and empowering citizens to have informed participation and satisfaction in paediatric health promotion and management. TRIAL REGISTRATION: Trial identifier: NCT05460689 registry name: ClinicalTrials.gov. Date of registration: July 15, 2022. Last update posted: February 23, 2023.

Neoclitoral location may affect sexual function in transgender women: a preliminary pelvic MRI study.

Assigned female at birth with anorgasmia possess a smaller clitoral glans and clitoral components farther from the vagina lumen than women with normal orgasmic function. There are no studies evaluating this correlation in operated transgender women. We evaluated whether differences in MRI measurements of neoclitoris volume and distance between the neoclitoris and the neovagina were correlated with differences in sexual function. We recruited for a prospective survey study 40 operated male to female patients (oMtF) who had undergone genital gender affirming surgery and postoperative pelvic MRI. Individual pelvic MRIs were reviewed by two blinded investigators, the three axes of the neoclitoris were measured and the volume was calculated using the ellipsoid formula. The distance between the neoclitoris and the neovagina was also measured. Sexual functioning was assessed using the Female Sexual Function Index (FSFI) and the operated Male to Female Sexual Function Index (oMtFSFI). Mean scores differences in FSFI, oMtFSFI were examined; associations with clitoral size, location, sexual functioning and demographical variables were investigated as well. The response rate was 55%, 11 MtFs operated with pubic neoclitoris technique (PNT) and 11 with neo-urethroclitoroplasty according to Petrovic (NCP). The NCP group presented a neoclitoris mean volume of 1.04 (SD 0.39) cc vs 1.31 (SD 0.78) cc of the other group (p = 0.55). The mean distance between neoclitoris and neovagina was 4.20 (SD 0.57) cm in the PNT group and 2.55 (SD 0.45) in the NCP group (p < 0.001). Patients who had undergone NCP achieved a higher FSFI and oMtFSFI mean Total Score than those operated with the previous technique (FSFI 25.81 SD 3.02 vs 18.62 SD 9.92 p = 0.08; oMtFSFI 37.63 SD 8.28 vs 43.36 SD 13.02 p = 0.23). According to pelvic MRI measurements, this study suggests a correlation between neoclitoral location and oMtF sexual satisfaction.

Rapid Immunochromatography on Fresh Intestinal Biopsy Is Highly Accurate in Detecting Intestinal Antitransglutaminase Antibodies.

INTRODUCTION: Intestinal antitransglutaminase antibodies (I-anti-TG2) are a specific marker of celiac disease (CeD). The aim of this study was to evaluate the diagnostic accuracy of a novel application of an immunochromatographic assay referred to as Rapid_AntiTG2 to detect I-anti-TG2 on intestinal biopsy lysate. METHODS: Consecutive pediatric patients referred to a single center for elective upper endoscopy were enrolled. Biopsies were taken from duodenal bulb and distal duodenum. For each sampling site, 2 biopsies were analyzed for standard histology, 1 biopsy was cultured to perform the reference standard assay for I-anti-TG2 detection (endomysium [EMA] biopsy), and 1 biopsy was mechanically lysed to perform Rapid_AntiTG2. The primary outcome was the diagnostic accuracy of Rapid_AntiTG2 on biopsy lysate compared with that of the gold standard (serology + histopathology) for CeD diagnosis. The secondary outcome was the agreement of Rapid_AntiTG2 with EMA biopsy. RESULTS: One hundred forty-eight patients were included. Of them, 79 were those with CeD (64 classical CeD, 2 seronegative CeD, and 13 potential CeD) and 69 were controls. Rapid_AntiTG2 on biopsy lysate had very high diagnostic accuracy (sensitivity 100%, specificity 97%, LR+ 34.1, LR- 0.01) in separating patients with CeD from controls. Diagnostic accuracy was unchanged in patients with potential and seronegative CeD. Rapid_AntiTG2 on biopsy lysate had almost perfect agreement with the EMA biopsy reference test (99% agreement, Cohen K 0.97). DISCUSSION: I-anti-TG2 can be detected with an immunochromatographic assay after simple mechanical lysis of fresh intestinal biopsy with very high diagnostic accuracy. The test is quick and easy to perform and can be widely available in any endoscopy unit. Its implementation would allow a better understanding of the prognostic value of I-anti-TG2 and help clinicians in cases of suspected CeD that are difficult to classify.

Management of Primary Spontaneous Pneumothorax in a Third-Level Pediatric Surgical Center: A Retrospective Study.

Introduction: The management of primary spontaneous pneumothorax (PSP) in pediatrics remains controversial. The aim of this study was to investigate the risk of recurrence after non-surgical treatment vs. surgery, the difference in the length of stay (LOS) between various treatment options, and the role of computed tomography (CT) in the management of PSP. Materials and Methods: We retrospectively reviewed patients admitted to our Pediatric Surgery Unit for an episode of PSP between June 2009 and July 2020. Medical records including clinical presentation at admission, diagnostics, treatments, complications, and LOS were collected. Results: Twenty-three patients (22 males and 1 female) were included in this study. Median age was 15.65 (range 9-18). Chest X-rays were performed in all patients and showed 5 small (22%) and 18 large (78%) PSP. Chest drain was used for large PSP (≥2 cm) if the patient was clinically unstable. Eleven patients (48%) were managed non-operatively with observation alone and a recurrence rate of 18%, chest drain was used in 11 patients with a recurrence rate of 36%, and surgery was deemed necessary as a first treatment choice in one case. Six patients (27%) had an episode of relapse after non-operative management or chest drain placement. Following surgery, a relapse occurred in 2 of the 6 patients. Chest drain insertion was associated with a longer LOS than observation alone (6.36 vs. 2.4 days), and surgery resulted in a longer LOS than other types of treatment (P = 0.001). Conclusion: According to our experience, small PSP or clinically stable larger PSP can be treated conservatively with observation alone. Operative management should be taken into consideration in children with large symptomatic PSP, persistent air leak, and/or relapse after chest drain insertion.

Reduction in pediatric growth hormone deficiency and increase in central precocious puberty diagnoses during COVID 19 pandemics.

BACKGROUND: While several studies have been published so far on the effect of COVID-19 pandemic on health care for non-COVID-19 diseases, to date no study evaluated the impact of the COVID-19 pandemic on the entire field of pediatric endocrinology. This study aimed to evaluate differences in pediatric endocrine stimulation tests after the advent of COVID-19 pandemics. METHODS: Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 and 2020 in a tertiary center. RESULTS: Overall, 251 tests were performed on 190 patients in 2020, compared to 278 tests on 206 patients in 2019 (- 10% tests; - 8% children evaluated). A significant reduction was found in tests to diagnose growth hormone deficiency (GHD) (- 35%), while LHRH tests increased (+ 22%). A reduction of 30% in GHD diagnosis was observed. Central precocious puberty (CPP) diagnosis increased by 38% compared to 2019, mainly in females. CONCLUSION: This study found a significant reduction of tests investigating GHD during COVID-19 pandemics. It also showed a clinically meaningful increase in cases of CPP in girls. These results suggest the need for families and pediatricians to monitor children's growth during isolation and enlighten new perspectives towards conditions associated with lockdown restrictions as increased screen time, social isolation, and children's anxiety as possible triggers of CPP.

Minimally-Invasive Surgical Approach to Congenital Dacryostenosis: Proposal for a New Protocol.

Background: Congenital dacryostenosis is one of the most common ophthalmological disorders in infants, with a high spontaneous resolution rate. In patients unresponsive to conservative treatment, the first-line approach is lacrimal drainage system probing, thought there is no clear consensus on optimal timing of surgery. The optimal treatment of patients unresponsive to primary probing is also controversial. Objectives: The aim of this study is to assess the optimal timing of probing in children with congenital dacryostenosis. Other purposes are to evaluate the efficacy of repeated probing and dacryointubation in patients unresponsive to the initial surgery without evident lacrimal outflow dysgenesis, and to determine the epidemiology of these maldevelopments. Methods: A retrospective consecutive cohort study was conducted in 625 eyes of 457 patients aged 7-48 months who underwent surgery for dacryostenosis. Patients were divided into 4 cohorts according to the timing of surgery. Data were analyzed using Fisher's test. Results: The success rate of primary probing was high, without significant differences between cohorts. One-third of recurrences were related to maldevelopments, the other two-thirds were treated with a second probing or dacryointubation, with high success rates, that did not significantly differ between the procedures. All cases unresponsive to the second surgery were resolved with dacryointubation. Conclusions: Probing is highly effective and its outcome is not affected by timing of surgery. Nevertheless, we advocate for early intervention, in order to identify possible maldevelopments, which require more invasive management. In patients unresponsive to primary probing, without evident maldevelopments, repeated probing should still be considered as the first-line approach, since it's less invasive but similarly effective to dacryointubation.

Is ultrasonography mandatory in all children at their first febrile urinary tract infection?

BACKGROUND: This study investigated whether performing kidney ultrasound (KUS) only in children presenting either a pathogen other than E. coli at their first febrile urinary tract infection (fUTI) or experiencing fUTI recurrence would increase missed diagnoses of kidney anomalies. METHODS: Patients aged 2-36 months with fUTI who underwent KUS evaluation from 2 January 2013 to 31 June 2018 were enrolled. Cystourethrography was performed after pathological KUS or recurring fUTIs. Thereafter, we retrospectively assessed the detection rate of kidney anomalies through performing KUS only in patients with atypical pathogen at first fUTI or with recurring fUTIs. RESULTS: In 263 patients included, the isolated pathogen was E. coli in 223 cases (84.8%) and atypical in 40 cases (15.2%). KUS detected kidney anomalies in 14/223 (6.3%) of fUTIs caused by E. coli and in 11/40 (27.5%) of fUTIs caused by an atypical pathogen (OR 5.5, 95%CI 2.5-14.5). Cystourethrography was performed in 40 patients and vesicoureteral reflux (VUR) found in 20 cases. None of the high grade VUR diagnoses or other kidney anomalies would have been lost through a different diagnostic protocol that required the presence of an atypical pathogen at the first fUTI or a fUTI recurrence to perform the KUS. CONCLUSIONS: A diagnostic protocol that requires presence of an atypical pathogen at the first fUTI or a second episode of fUTI to perform the KUS would allow a reduction in the number of negative ultrasounds with a negligible risk of missed diagnoses of kidney anomalies.

Incidence, predictive factors and survival outcomes of incidental prostate cancer in patients who underwent radical cystectomy for bladder cancer.

BACKGROUND: The aim of this study was to analyze the incidence, preoperative findings, pathological features and prognosis in patients with incidental prostate cancer (iPCa) detected at radical cystectomy (RC) for bladder cancer (BCa). METHODS: We retrospectively reviewed data of patients who underwent RC for BCa at our Institution between January 2005 and March 2018. Data regarding patient's history, preoperative digital rectal examination (DRE), total serum PSA level were collected from the chart review. Univariable and multivariable Cox regression models addressed the association of iPCa with recurrence-free survival (RFS) and overall survival (OS). RESULTS: We obtained a final study cohort of 177 patients. Median age was 69 years (IQR 42-89) and 80(45.2%) patients had iPCa. Patients with iPCa had higher age, preoperative PSA levels and a significant rate of suspicious DRE (all P<0.05). Four patients had BCR during a median follow-up of 28 months (IQR 6-159) and none died for prostate cancer. In multivariable analyses adjusted for age, bladder cancer BCa pT and pN stage and LVI the ten-years RFS and OS rates were not impacted by iPCa regardless of whether it is a clinically significant cancer or not (HR=1.25, 95% CI: 0.65-2.38, P=0.51 vs. HR=1.37, 95% CI: 0.71-2.64, P=0.35) (HR=1.04, 95% CI: 0.53-1.86, P=0.89 vs. HR=1.20, 95% CI: 0.22-6.72, P=0.83). CONCLUSIONS: iPCa is quite common in our study group and most of cases are organ-confined and well differentiated. Regardless of clinical relevance, iPCa does not have an impact on survival outcomes as BCa is driving the prognosis of these patients.

Strabismus surgery in Angelman syndrome: More than ocular alignment.

PURPOSE: To report and evaluate strabismus surgery in children with Angelman syndrome, in order to optimize and standardize surgical approach. Other purposes are to understand the possible relation between ocular findings and motor ability, and between improvement in ocular alignment and changes in motor skills in this population. DESIGN: Observational cross-sectional study. METHODS: Medical records of pediatric patients with Angelman syndrome, who underwent strabismus surgery, were investigated. Collected data included: genotype, gender, age at the time of surgery, refractive error, pre-operative strabismus, surgical procedure, surgical outcome, gross and fine motor development assessment pre- and post-operatively. RESULTS: Seventeen subjects, aged 3-15 years, were investigated. Fourteen patients were exotropic, three esotropic. Most patients presented astigmatism. Considering the exaggerated response to standard amounts of surgery and the risk of consecutive strabismus on long term follow-up reported by previous studies in children with developmental delay, a reduction of the amount of strabismus surgery was applied. Post-operatively, all patients presented with a significative reduction of the baseline deviation angle, with all esotropic patients and 7 exotropic patients (59%) achieving orthotropia. The surgical outcomes were variable according to the type and the amount of baseline strabismus, but no case presented with exaggerated surgical response. At baseline, patients showed important delays in all motor abilities, and, post-operatively, presented a significant improvement in walking and fine motor tasks. Pre- and post-operative motor abilities were negatively correlated to astigmatism, anisometropia, and amount of deviation. CONCLUSIONS: According to our data, the standard nomograms for strabismus surgery may be successfully applied in subjects with Angelman syndrome and exotropia. Our data suggest that the reduction of the deviation angle improves motor skills in strabismic pediatric patients with Angelman syndrome.

Mid-term outcome after arthroscopic treatment of femoroacetabular impingement: development of a predictive score.

PURPOSE: To build a post-arthroscopy outcome-predictive score (POPS) associated with the likelihood of lasting benefit after arthroscopic treatment of femoroacetabular impingement (FAI) and based solely on unambiguous preoperative information. METHODS: A population of 220 FAI patients, operated on with standard techniques by orthopaedic surgeons trained in hip arthroscopy in 6 different centres, was evaluated physically or by telephone interview 2 to 5 years after surgery. The criteria of successful mid-term outcome (SMO) were agreed upon by all authors. A multivariate logistic regression, adjusted for patient's age and centre, was applied to predict SMO. In the model, the variables associated with the outcome were included and the relative ORs (odds ratios) were used to compute the FAI-POPS (FAI - post-arthroscopy outcome-predictive score). A ROC (receiver operating characteristic) curve was plotted and the optimum cut-off was calculated. RESULTS: 155 patients out of 220 showed a successful mid-term outcome. The optimum cut-off of FAI-POPS was calculated to be 6.3 and with this threshold it proved a sensitivity of 0.66 and a specificity of 0.69, a positive predictive value of 0.84 and a negative predictive value of 0.46. CONCLUSIONS: The standard arthroscopic treatment of FAI resulted in satisfactory persistent symptom relief for about 70% of patients. No or minimal osteoarthritis, short time elapsed from the appearance of symptoms and high preoperative modified Harris Hip Score are independent predictive factors of SMO. The FAI-POPS is obtained as sum of 3 odds ratios corresponding to the above prognostic factors and is a useful predictor of mid-term outcome after conventional arthroscopic FAI treatment.

Impact of low-dose computed tomography screening on lung cancer mortality among asbestos-exposed workers.

Background: We previously showed that low-dose computed tomography (LDCT) screening in asbestos-exposed workers is effective in detecting lung cancer (LC) at an early stage. Here, we evaluate whether LDCT screening could reduce mortality from LC in such a high-risk population. Methods: Within a cohort of 2433 asbestos-exposed men enrolled in an Occupational Health surveillance programme, we compared mortality between the participants in the ATOM002 study (LDCT-P, N = 926) and contemporary non-participants (LDCT-NP, N = 1507). We estimated standardized mortality ratios for the LDCT-P and LDCT-NP populations using regional and national rates (SMR_FVG and SMR_ITA, respectively). We compared survival for all causes, all neoplasms, LC and malignant neoplasm of pleura (MNP) between LDCT-P and LDCT-NP using Cox proportional hazard models adjusted for age, smoking history, asbestos exposure level and comorbidities. Results: A reduction in mortality from LC was observed in the LDCT-P group compared with regional and national figures (SMR_FVG = 0.55, 95% confidence interval (CI) 0.24-1.09; SMR_ITA = 0.51, 95% CI 0.22-1.01); this was not the case for the LDCT-NP group (SMR_FVG = 2.07, 95% CI 1.53-2.73; SMR_ITA = 1.98, 95% CI 1.47-2.61). A strong reduction in LC mortality was observed for the LDCT-P compared with the LDCT-NP [hazard ratio (HR) = 0.41, 95% CI 0.17-0.96]. Mortality was also reduced for all causes (HR = 0.61, 95% CI 0.44-0.84), but not for all neoplasms (HR = 0.97, 95% CI 0.62-1.50) and MNP (HR = 0.86, 95% CI 0.31-2.41) within the LDCT-P population. Conclusions: In our cohort, participation in the LDCT screening study was associated with reduced mortality from LC. This finding supports the use of LDCT in surveillance programmes for asbestos-exposed workers.

Cancer incidence in a cohort of asbestos-exposed workers undergoing health surveillance.

OBJECTIVES: To compare a local cohort of 2488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995-2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study. METHODS: Standardized incidence ratios (SIRs), with 95% confidence interval (95% CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974 and 1994. For internal comparisons, we calculated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up. RESULTS: Among cohort members the SIR was 8.82 (95% CI 5.95-12.61) for mesothelioma and 1.61 (95% CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974 and 1984 was 2.09 (95% CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR = 1.53 95% CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost threefold for lung cancer (IRR = 2.94 95% CI 1.01-8.57). CONCLUSIONS: This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974 and 1984.

Mortality in a cohort of asbestos-exposed workers undergoing health surveillance.

BACKGROUND: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health surveillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality. OBJECTIVES: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy. METHODS: Standardized Mortality Ratios (SMR), with 95% Confidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994). RESULTS: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60). CONCLUSIONS: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure.

Comparison of primary breast cancer and paired metastases: biomarkers discordance influence on outcome and therapy.

AIM: Discordance between primary tumor and paired metastases biology has been widely detected in metastatic breast cancer. The aim of this study was to evaluate the prognostic impact of Ki67, estrogen receptor (ER), progesterone receptor (PR) and HER2 discordance. METHODS: We retrospectively analyzed a cohort of 544 patients affected by metastatic breast cancer. Variation in ER, PR, Ki67 and HER2 expression between primary site and recurrence was tested through the McNemar test. RESULTS: A significant variation was observed in respect to ER, PR and Ki67 status (12.65%, p = 0.0072; 49.71%, p < 0.0001; 35%, p < 0.0001, respectively). Among patients with ER or PR discordance, the driver of therapeutic decisions was the ER status. Moreover, we observed a therapy-related reduction of ER in taxanes or aromatase inhibitors-exposed patients (odds ratio: 3.59; 95% CI: 1.66-7.77; p = 0.001 and odds ratio: 2.07; 95% CI: 0.96-4.44; p = 0.06, respectively). CONCLUSION: Biopsy of metastatic lesions may influence the decision-making process translating into better outcome.

[Not Available]. / Standardization of incidence rates of mesothelioma in the absence of national standards: sensitivity analysis in a cohort formerly exposed to asbestos.

INTRODUCTION: The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006. OBJECTIVES: To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort. METHODS: We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate. RESULTS: During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively. CONCLUSIONS: Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available.

Polypharmacy and the use of medications in inpatients with acquired brain injury during post-acute rehabilitation: A cross-sectional study.

BACKGROUND: This study assessed the use of medications during inpatient post-acute rehabilitation for acquired brain injury (ABI). MATERIALS AND METHODS: All inpatients with ABI undergoing post-acute rehabilitation in centres identified through the roster of the Italian Society for Rehabilitation Medicine were included. A designated physician in each centre collected information through a structured questionnaire. This study calculated (a) prevalence of medication use, (b) logistic regression Odds Ratio (OR), with 95% confidence interval (95% CI), of polypharmacy (≥ 6 medications). RESULTS: A total of 484 patients (median age = 52 years, 63.4% men, median time from acute event = 18.5 weeks) were included; 33.8% had Rancho Los Amigos Levels of Cognitive Functioning Scale (RLAS) score 1-2, 8.1% had a score of 7-8, of whom 92.0% received medications, 51.8% had a score of 6-10, of whom 83.9% had at least one psychotropic medication and 66.9% had two or more; 51.8% received anti-epileptics, 32.1% anti-depressants, 14.5% anti-psychotics, peaking in RLAS 4 (37.3%) and decreasing in RLAS 7-8. Polypharmacy was directly associated with age (55-64 years, OR = 2.1; 95% CI = 1.1-4.1; ≥ 65 years, OR = 1.7; 95% CI = 0.9-3.3), inversely with RLAS score (1-2 vs 7-8, OR = 4.3; 95% CI = 1.9-9.8). CONCLUSION: Polypharmacy and concurrent use of psychotropic medications was common, raising concern about drug-drug interactions. Safety and effectiveness of medications should be monitored, particularly when used concurrently.

Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer.

AIM: To explore the prognostic value of extended mutational profiling for metastatic colorectal cancer (mCRC). MATERIALS & METHODS: We retrospectively reviewed survival results of 194 mCRC patients that were assigned to four molecular subgroups: BRAF mutated; KRAS mutated codons 12-13 only; any of KRAS codons 61-146, PIK3CA or NRAS mutations and all wild-type. Point mutations were investigated by pyrosequencing. RESULTS: BRAF (5.2%) and KRAS 12-13 (31.9%) mutations were associated with poorer survival (HR 2.8 and 1.76, respectively). Presenting with right-sided colon cancer, not resected primary tumor, WBC >10 × 10(9)/l, receiving less chemotherapy or no bevacizumab were all associated with inferior outcome. The all-wild-type subgroup (39.2%) reported the longest survival. CONCLUSION: Extended mutational profile combined with clinical factors may impact on survival in mCRC.

Measures of outcome in metastatic breast cancer: insights from a real-world scenario.

No gold standard treatment exists for metastatic breast cancer (MBC). Clinical decision making is based on knowledge of prognostic and predictive factors that are extrapolated from clinical trials and, sometimes, are not reliably transferable to a real-world scenario. Moreover, misalignment between endpoints used in drug development and measures of outcome in clinical practice has been noted. The roles of overall survival (OS) and progression-free survival (PFS) as primary endpoints in the context of clinical trials are the subjects of lively debate. Information about these parameters in routine clinical practice is potentially useful to design new studies and/or to interpret the results of clinical research. This study analyzed the impact of patient and tumor characteristics on the major measures of outcome across different lines of treatment in a cohort of 472 patients treated for MBC. OS, PFS, and postprogression survival (PPS) were analyzed. The study showed how biological and clinical characteristics may have different prognostic value across different lines of therapy for MBC. After first-line treatment, the median PPS of luminal A, luminal B, and human epidermal growth factor receptor 2 (HER2)-positive groups was longer than 12 months. The choice of OS as a primary endpoint for clinical trials could not be appropriate with these subtypes. In contrast, OS could be an appropriate endpoint when PPS is expected to be low (e.g., triple-negative subtype after the first line; other subtypes after the third line). The potential implications of these findings are clinical and methodological.