Sinonasal cancer incidence in Lombardy, Italy, 2008-20.

BACKGROUND: Epithelial sinonasal cancers (SNC) are rare tumours with recognized associations with known/suspected occupational carcinogens (wood/leather dust, nickel/chromium compounds and formaldehyde). In Italy, a national SNC registry organized as a network of regional registries was established by law in 2008. AIMS: To describe SNC time trends, occupational exposures and geographical distribution in Lombardy, North-West Italy, based on population registry data (2008-20). METHODS: The Lombardy SNC Registry records epithelial SNCs using various sources. Interviews to collect occupational history are performed using a standardized questionnaire. Using several standard populations, we calculated yearly crude and age-standardized rates (ASRs per 100,000 person-years). Standardized incidence ratios (SIR) at municipality level were calculated, and Bayesian models were fitted to produce smoothed SIR maps. RESULTS: We recorded 827 cases (553 men, 274 women). Crude (world standardized) ASRs were 0.9 (0.4) in men and 0.4 (0.2) in women, with no time trends. Interviews were obtained for 485 (88%) men and 223 (81%) women. Among men, 217 (45%) had been exposed to occupational carcinogens (wood/leather dust: 150/65 cases, 31%/13%), while only 36 women (16%) were exposed. Among 201 men with adenocarcinoma, exposure to wood/leather dust occurred in 103/50 cases (75%/50%). Areas with elevated SIRs associated with leather dust were found in the Western areas. Exposure to wood dust was more widespread. CONCLUSIONS: This study found a high frequency of occupational exposures (wood and leather dust), particularly in men with SNC. Employment in shoe industries clustered in the Western part, while work in furniture industries was less spatially structured.

Cardiopulmonary testing in adult patients with ß-thalassemia major in comparison to healthy subjects.

ß-Thalassemia patients often have a reduced capacity of exercise and abnormal respiratory function parameters, but the reasons are unclear. In order to identify the causes of the exercise limitation, we performed a cardiopulmonary exercise testing (CPET) in a group of 54 adult ß-thalassemia major (TM) patients without pulmonary arterial hypertension and in a group of healthy control subjects. All subjects underwent cardiac echocardiography and carried out pulmonary function tests. TM patients also filled an IPAQ questionnaire on usual physical activity (PA).Overall, TM patients have a diminished exercise performance in comparison to control subjects. In fact, peak oxygen uptake (V'O2 peak), expressing maximum exercise capacity, was decreased in 81.5% of the patients; similarly, anaerobic threshold (V'O2@AT) and O2 pulse also resulted lowered. In multivariable regression models adjusted for gender, age, BMI, and mean haemoglobin, V'O2 peak and O2 pulse were positively associated with cardiac iron overload (T2*). No ventilatory limitation to exercise was observed. The most important causes of exercise limitation in these patients were muscular deconditioning and reduced cardiac inotropism due to iron deposition. Only 15/54 (27.8%) TM patients used to perform vigorous physical activity. These results suggest that a program of regular physical activity may be useful to increase the tolerance to effort and therefore to improve the quality of life in these patients.

The effect of delayed umbilical cord clamping on cord blood gas analysis in vaginal and caesarean-delivered term newborns without fetal distress: a prospective observational study.

OBJECTIVE: To determine variations in cord blood gas (CBG) parameters after 3-minute delayed cord clamping (DCC) in vaginal deliveries (VDs) and caesarean deliveries (CDs) at term without fetal distress. DESIGN: Prospective observational study. SETTING: University hospital. SAMPLE: CBG from 97 VDs and 124 CDs without fetal distress. METHODS: Comparison of paired arterial-venous CBG parameters drawn at birth from the unclamped cord and after 3-minutes DCC for VDs and CDs. MAIN OUTCOME MEASURES: Base excess, bicarbonate, haematocrit and haemoglobin from both arterial and venous cord blood, lactate, neonatal outcomes, partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), pH, and postpartum haemorrhage. RESULTS: Arterial cord blood pH, bicarbonate ( HCO3- , mmol/l), and base excess (BE, mmol/l) decreased significantly after 3-minute DCC both in VDs (pH = 7.23 versus 7.27; P < 0.001; HCO3-  = 23.3 versus 24.3; P = 0.004; BE = -5.1 versus -2.9; P < 0.001) and CDs (pH = 7.28 versus 7.34; P < 0.001; HCO3-  = 26.2 versus 27.2; P < 0.001; BE = -1.5 versus 0.7; P < 0.001). After 3-minute DCC, pCO2 increased in CDs only (57 versus 51; P < 0.001), whereas lactate increased more in CDs compared with VDs (lactate, +1.1 [0.9, 1.45] versus +0.5 [-0.65, 2.35]; P = 0.01). Postpartum maternal haemorrhage, neonatal maximum bilirubin concentration, and need for phototherapy were similar between the two groups. Newborns born by CD more frequently required postnatal clinical monitoring or admission to a neonatal intensive care unit. CONCLUSIONS: After 3-minute DCC, the acid-base status shifted towards mixed acidosis in CDs and prevalent metabolic acidosis in VDs. CDs were associated with a more pronounced increase in arterial lactate, compared with VDs. TWEETABLE ABSTRACT: By 3-minute DCC, acid-base status shifts towards mixed and metabolic acidosis in caesarean and vaginal delivery, respectively.

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia.

BACKGROUND: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. METHODS: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs ≥ 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). RESULTS: Chest CT scores showed a significant correlation with FEV1 (p = 0.0002), age (p <  0.0001), BMI (p = 0.0002) and number of lung lobes involved (p <  0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation (≥ 2/year) were older (p = 0.01), had lower FEV1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED). CONCLUSIONS: In our PCD population the number of exacerbations (≥ 2/year) and PA colonization were the two most relevant factors associated with severity of disease.

Selective intrauterine growth restriction in monochorionic twins: changing patterns in umbilical artery Doppler flow and outcomes.

OBJECTIVES: To describe changes in umbilical artery (UA) Doppler flow in monochorionic diamniotic (MCDA) twins affected by selective intrauterine growth restriction (sIUGR), to correlate Doppler findings with pregnancy course and perinatal outcome, and to report postnatal follow-up. METHODS: This was a retrospective study of 140 MCDA twins with sIUGR. UA end-diastolic flow, defined as Doppler waveform pattern Type I (persistently positive), Type II (persistently absent or persistently reversed) or Type III (intermittently absent or intermittently reversed), was recorded at first examination and monitored weekly until double or single intrauterine fetal death (IUFD), bipolar cord coagulation or delivery. All neonates had an early neonatal brain scan, magnetic resonance imaging, when indicated, and neurological assessment during infancy. Rates (per 100 person-weeks) and hazard ratios (HR) of IUFD in the IUGR twin in each pregnancy were calculated considering UA Doppler pattern as a time-dependent variable. RESULTS: At first examination, there were 65 cases with UA Doppler waveform pattern Type I, 62 with Type II and 13 with Type III. Of the 65 Type-I cases, 48 (74%) remained stable, while 17 (26%) changed to either Type II absent (14%), Type II reversed (9%) or Type III (3%). Of 62 Type-II cases (47 with absent and 15 with reversed flow), 33 (53%) remained stable (18 with absent and all 15 with reversed flow). The 29 Type-II absent cases which changed became Type II reversed (24/47, 51%) or Type III (5/47, 11%). All 13 Type-III cases remained stable. Compared with Type I, the risk of IUFD (adjusted for estimated fetal weight discordance and amniotic fluid deepest vertical pocket) was highest when the pregnancy was or became Type II reversed (HR, 9.5; 95% CI, 2.7-32.7) or Type II absent (HR, 4.3; 95% CI, 1.3-14.3). Mild neurological impairment was more prevalent in the IUGR twin than in the large cotwin (7% vs 1%, P = 0.02). CONCLUSIONS: Risk stratification based on UA Doppler is useful for planning ultrasound surveillance. However, patterns can change over time, with important consequences for management and outcome. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fine airborne particles: when alarming levels are the standard.

OBJECTIVES: To quantify the contribution of each individual month to the annual mortality burden attributable to particulate matter (PM) in 2015 in Milan, Italy, after authorities and media considered December 2015 as an outlying month carrying an exceptional population exposure to PM. STUDY DESIGN: We used routinely available daily time series of air pollution and mortality to perform an assessment of the impact of PM exposure on population health. METHODS: By combining daily death counts with daily PM levels, as well as the yearly average of the number of deaths with the yearly average of PM concentrations, impact estimates were calculated in terms of deaths attributable (AD) to levels of PM10 and PM2.5 exceeding the daily or the annual European Union (EU) exposure limits. RESULTS: On a monthly basis, the estimated AD for exceeding the daily EU limits for more than 35 days were 18.4 (PM10) and 33.2 (PM2.5) between January and March, and 20.0 and 31.9 between October and December, respectively. On an annual basis, the EU limit for PM10 was almost met and, therefore, the estimated impact in terms of AD was practically null. CONCLUSIONS: Impact results should be interpreted in the light of the skewness of the daily PM concentration distribution. The number of days above the limits is more important than the average annual concentration in determining the number of attributable deaths. The impact of PM on mortality is substantial during the whole winter season irrespective of its annual average concentration. Our estimates further stress the need for a revision of the current European air quality standards.

Amyotrophic lateral sclerosis: a comparison of two staging systems in a population-based study.

BACKGROUND AND PURPOSE: To compare two recently developed staging systems for amyotrophic lateral sclerosis (ALS) [King's College and Milano-Torino staging (MITOS) systems] in an incident, population-based cohort of patients with ALS. METHODS: Since 2009, a prospective registry has been recording all incident cases of ALS in the Emilia Romagna region in Italy. For each patient, detailed clinical information, including the ALS functional rating scale score, is collected at each follow-up. RESULTS: Our study on 545 incident cases confirmed that King's College stages occurred at predictable times and were quite evenly spaced out throughout the disease course (occurring at approximately 40%, 60% and 80% of the disease course), whereas MITOS stages were mostly skewed towards later phases of the disease. In the King's College system there was a decrease in survival and an increase in deaths with escalating stages, whereas in the MITOS system survival curves pertaining to intermediate stages overlapped and the number of deaths was fairly homogenous throughout most stages. CONCLUSIONS: The King's College staging system had a higher homogeneity (i.e. smaller differences in survival among patients in the same stage) and a higher discriminatory ability (i.e. greater differences in survival among patients in different stages), being more suitable for individualized prognosis and for measuring efficacy of therapeutic interventions.

A 5-year follow-up in deferasirox treatment: improvement of cardiac and hepatic iron overload and amelioration in cardiac function in thalassemia major patients.

Deferasirox (DFX) is an oral iron chelator with established efficacy and safety. We evaluated by T2* cardiovascular magnetic resonance (CMR) the efficacy of DFX in preventing and removing cardiac and liver iron load and cardiac volume changes, along 5 years in adult thalassemia major (TM) patients. Twenty-three TM patients (9 males/14 women, mean age 36 ± 4 years) were included in this study. Repeated CMR was performed to assess myocardial and liver iron load (baseline t0, after 2.5 years t1, after 5 years t2). Myocardial T2* values changed progressively and increased significantly between t0 and t2 (t0: 27.15 ± 9.58 vs t2: 36.64 ± 6.68, p = 0.0001). At baseline evaluation, a cardiac T2* value <20 ms was detected in six patients (26 %): they showed an improvement of cardiac T2* values between t0 and t1, with normal T2* levels reached in all patients at t2. In the overall population, a significant reduction of both end-diastolic and end-systolic left ventricular volumes (EDV, ESV) were detected between t0 and t2 (EDV, t0: 132 ± 31 ml vs t2: 124 ± 22 ml, p = 0.033; ESV, t0: 48 ± 14 ml vs t2: 41 ± 10 ml, p = 0.0007). A significant reduction in liver iron concentration (LIC) was detected at t1 (5.36 ± 3.58 mg/g dw at baseline vs 3.35 ± 2.68 mg/g dw at t1, p = 0.004). In patients with cardiac iron overload at baseline (n.6), mean cardiac T2* values doubled at t2, and mean LIC value is reduced of 29 %. After 5 years of treatment, DFX continually and significantly reduced myocardial and liver iron overload, and it prevented further iron deposition.

III Italian Consensus Conference on Malignant Mesothelioma of the Pleura. Epidemiology, Public Health and Occupational Medicine related issues.

The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up-to-date methodology; 4) Necroscopy should be practiced for validation. Expert referral centres could contribute to the definition of uncertain cases. Health surveillance should aim to all asbestos effects. No diagnostic test is recommended for MM screening. Health surveillance should provide information on risks, medical perspective, and smoking cessation. The economic burden associated to MM was estimated in 250,000 Euro per case.

Breast density in NF1 women: a retrospective study.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were compared with those from 300 healthy subjects to verify differences in breast density. Mammograms were independently reviewed and scored by a radiologist and using a Computer-Aided Detection (CAD) software. The comparison of breast density between NF1 patients and controls was performed through Chi-squared test and with multivariable ordinal logistic models adjusted for age, body mass index (BMI), number of pregnancies, and menopausal status.breast density was influenced by BMI and menopausal status in both NF1 patients and healthy subjects. No difference in breast density was observed between NF1 patients and the healthy female population, even after considering the potential confounding factors.Although NF1 and a highly fibroglandular breast are known risk factors of BC, in this study, NF1 patients were shown to have comparable breast density to healthy subjects. The presence of pathogenic variants in the NF1 gene does not influence the breast density value.

Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO).

BACKGROUND: The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated. METHODS: We performed a pooled analysis of six case-control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types. RESULTS: A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68-0.97) and HRT ever users (OR=0.77; 95% CI: 0.66-0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61-0.94, and OR=0.66; 95% CI: 0.49-0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37-0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66-0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19-0.71) in HRT users. No interaction with smoking status or BMI was observed. CONCLUSION: Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women.

Surgical versus low-dose progestin treatment for endometriosis-associated severe deep dyspareunia II: effect on sexual functioning, psychological status and health-related quality of life.

STUDY QUESTION: Does surgical and low-dose progestin treatment differentially affect endometriosis-associated severe deep dyspareunia in terms of sexual functioning, psychological status and health-related quality of life? SUMMARY ANSWER: Surgery and progestin treatment achieved essentially similar benefits at 12-month follow-up, but with different temporal trends. WHAT IS ALREADY KNOWN: Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. STUDY DESIGN, SIZE, DURATION: Patient preference, parallel cohort study with 12-month follow-up. The effect of conservative surgery at laparoscopy versus treatment with a low dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery was compared. PARTICIPANTS/MATERIALS AND SETTING, METHODS: A total of 51 patients chose repeat surgery and 103 progestin treatment. Variations in sexual function, psychological well-being and quality of life were measured by means of the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression Scale (HADS) and the Endometriosis Health Profile-30 (EHP-30). MAIN RESULTS AND THE ROLE OF CHANCE: Four women in the surgery group and 21 women in the progestin group withdrew from the study for various reasons. Total FSFI scores, anxiety and depression scores and EHP-30 scores improved immediately after surgery, but worsened with time, whereas the effect during progestin use increased more gradually, but progressively, without overall significant between-group differences at 12-month follow-up. A tendency was observed towards a slightly better total FSFI score after surgery at the end of the study period. LIMITATIONS, REASONS FOR CAUTION: Treatments were not randomly allocated, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions. WIDER IMPLICATIONS OF THE FINDINGS: Both surgery and medical treatment with progestins are valuable options for improving the detrimental impact of endometriosis-associated dyspareunia on sexual functioning and quality of life. Women should be aware of the pros and cons of both options to decide which one best suits their needs. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.

Update of the mortality study of workers exposed to polychlorinated biphenyls (Pcbs) in two Italian capacitor manufacturing plants.

BACKGROUND: PCB carcinogenicity to humans is still controversial. Cohort mortality studies in PCB-exposed workers reported elevated risks for the following causes of death: liver, stomach, digestive, brain, prostate cancers and non-Hodgkin lymphoma. OBJECTIVES: The purpose of this study was to update as of December 2006 the mortality experience of two Italian cohorts of workers employed in the manufacture of capacitors impregnated with PCBs. METHODS: Age-gender-and calendar period adjusted Standardized Mortality Ratios (SMRs) and 95% Confidence Intervals (CI) were calculated using regional rates. Analyses by duration of employment and time since first employment were performed Results: Vital status was ascertained for 98.9% of the study subjects. Mortality from biliary tract cancer among males (SMR 3.91; 95%CI 1.47-10.41), digestive cancer "not otherwise specified" in the whole cohort (SMR 2.54; 95%CI 1.21-5.34), and brain cancer in Plant I (SMR 2.13; 95%CI 1.02-4.48), were significantly increased. Increased risks were also observed for Hodgkin's and non-Hodgkin lymphoma. No linear associations between mortality and duration of employment or latency were observed for these cancers. Mortality from stomach cancer did not differ from expectation in the whole cohort, however an increasing risk with increasing duration of employment was detected (p for trend=0.02). CONCLUSIONS: The current update suggests possibly increased cancer risks in PCB-exposed workers, affecting in particular the digestive system, brain, and lymphohemopoietic tissue. However the limited sample size, the lack of clear trends with duration of employment or with latency period, preclude to derive definite conclusions about PCB exposure and the increased cancer risks.

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study.

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.

Surgical versus medical treatment for endometriosis-associated severe deep dyspareunia: I. Effect on pain during intercourse and patient satisfaction.

STUDY QUESTION: Does surgical or medical treatment for endometriosis-associated severe deep dyspareunia achieve better results in terms of patients' satisfaction (main study outcome), variation of coital pain and frequency of intercourse? SUMMARY ANSWER: Surgery and progestin therapy were equally effective in the treatment of deep dyspareunia in women with rectovaginal endometriosis, whereas medical therapy performed significantly better than excisional treatment in those without deeply infiltrating lesions. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. This study reports a direct comparison between the two treatment options in women with severe pain during intercourse. DESIGN: Patient preference, parallel cohort study with a 12-month follow-up. The effect of conservative surgery at laparoscopy was compared with treatment with a low-dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery. PARTICIPANTS AND SETTING: A total of 51 patients chose repeat surgery and 103 progestin treatment. Patient satisfaction was graded according to a five-category scale. Variations in pain during intercourse were measured by means of a 100-mm visual analogue scale. MAIN RESULTS AND THE ROLE OF CHANCE: In the surgery group, a marked and rapid short-term dyspareunia score reduction was observed, followed by partial recurrence of pain. The pain relief effect of the progestin was more gradual, but progressive throughout the study period. At a 12-month follow-up, the frequency of intercourse per month (mean ± SD) was 4.6 ± 1.8 in the surgery group and 5.3 ± 1.5 in the norethisterone acetate group (P = 0.02). A total of 22/51 (43%) women were satisfied in the surgery group compared with 61/103 (59%) in the progestin group [adjusted odds ratios (OR), 0.36; 95% confidence interval (CI), 0.16-0.82; P = 0.015]. Corresponding figures in women with and without rectovaginal endometriotic lesions were, respectively, 13/24 (54%) versus 18/35 (51%; adjusted OR, 0.77; 95% CI, 0.22-2.67; P = 0.68), and 9/27 (33%) versus 43/68 (63%; adjusted OR, 0.23; 95% CI, 0.07-0.76, P = 0.02). BIAS, CONFOUNDING, AND OTHER REASONS FOR CAUTION: Treatments were not randomly assigned, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions. GENERALIZABILITY TO OTHER POPULATIONS: Caucasian patients able to choose their treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.

Central nervous system bleeding in patients with rare bleeding disorders.

Central nervous system (CNS) bleeding is one of the most severe and debilitating manifestations occurring in patients with rare bleeding disorders (RBDs). The aim of this study was to retrospectively collect data on patients affected with RBDs who had CNS bleeding, to establish incidence of recurrence, death rate, neurological sequences, most frequent location, type of bleeding and efficacy of treatments. Results pertained to 36 CNS bleeding episodes in 24 patients with severe deficiency except one with moderate factor VII (FVII) deficiency. Six patients (25%) experienced a recurrence and two had more than one recurrence. Seven patients (29%) had an early onset of CNS bleeding before the first 2 years of life, others (71%) later in life. In 76% of cases, CNS bleeding was spontaneous. CNS bleeding was intracerebral in 19 cases (53%), extracerebral in 10 (28%) and both intracerebral and extracerebral in two cases (6%). Neurosurgery was performed in 11 cases, in association with replacement therapy in seven cases. Seizures were noted in four patients. Residual psychomotor abnormalities were seen in two patients. No death was recorded. To prevent recurrence, 17/24 patients (71%) were put on secondary prophylaxis. In conclusion, recurrence of CNS bleeding was confirmed to be relatively frequent in patients with severe FV, FX, FVII and FXIII deficiencies. Most patients were managed with replacement therapy alone, surgery being reserved for those with worsening neurological conditions. Our results indicate that some RBDs require early prophylactic treatment to prevent CNS bleeding. Optimal dosage and frequency of treatment need further evaluation.

Bipolar cord coagulation for selective feticide in complicated monochorionic twin pregnancies: 118 consecutive cases at a single center.

OBJECTIVE: To review the experience of performing selective feticide with bipolar cord coagulation (BCC) in complicated monochorionic (MC) twin pregnancies at a single center. METHODS: This was a retrospective analysis of BCC performed using 3-mm bipolar forceps under ultrasound control in cases complicated by twin-to-twin transfusion syndrome, selective growth restriction, discordant anomaly or twin reversed arterial perfusion sequence. RESULTS: The series comprised 118 cases with a median gestational age at the time of the procedure of 22 (range, 16-30) weeks. There were 14 (12%) intrauterine deaths of the cotwin, eight (7%) miscarriages and one (1%) termination of pregnancy. When BCC was performed before 19 weeks of gestation, the rate of miscarriage was 45%, whereas it was 3% (P < 0.001) when BCC was performed after 19 weeks. Preterm prelabor rupture of membranes (PPROM) occurred in 45 (38%) cases. The median interval between BCC and PPROM was 4 (interquartile range, 2-9) weeks. In 15 (13%) cases, PPROM occurred within 2 weeks after the procedure. Median gestational age at delivery was 34 (range, 24-41) weeks. The median birth weight was 2103 (range, 480-3875) g. Neonatal death occurred in 11 (9%) cases, and two (2%) children had severe neurologic morbidity. The overall survival rate was 71% (84/118). CONCLUSION: BCC is an effective procedure in complicated MC twin pregnancies for selective feticide or when one fetus is severely jeopardized and delivery is not yet an option. Better outcomes can be achieved when this procedure is performed after 19 weeks.

Fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome: a single-center experience.

OBJECTIVE: To report the incidence of fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS). METHODS: A total of 150 cases of TTTS were treated from January 2004 to June 2009 (period 1, 2004-2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal complications (double and single intrauterine fetal death, recurrence of TTTS, twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in one twin) and maternal complications were recorded, and retrospectively analyzed. RESULTS: Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were classified preoperatively as Quintero stage I, II, III and IV, respectively. The anterior placenta was described in 73 cases (48.6%). Double and single fetal death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8 bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at a median gestational age of 30.2 weeks compared to 32.1 weeks for those not repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1 to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries performed, there was an average improvement of 1.5% in the predicted percentage of survival of at least one twin (OR 1.09, 95% CI 1.00-1.19). Major maternal complications occurred in 9 cases (6.0%), 3 of which required admission to intensive care unit. CONCLUSIONS: Fetal complications are common after fetoscopic laser surgery. In this experience, an increasing number of procedures improved the performance of a new fetoscopic laser center.