Radiographic ratios for classifying furcation anatomy: proposal of a new evaluation method and an intra-rater and inter-rater operator reliability study.

OBJECTIVES: Even if it seems to be an important anatomical parameter for tissue regeneration, few studies in literature evaluate the "mean measure" of root divergence. Most of them are linear measurements, which hardly describe the dental furcation conformation in its entirety. It is left to the subjectivity of the operator deciding whether a furcation is convergent or divergent. The goal of this study is to create a visual evaluation method using specific measurements applied on endo-oral X-rays to overcome these problems, giving a conformation of the entire interradicular space and its divergence. MATERIAL AND METHODS: A user-friendly software (Paint®, Windows10®) was used to take three different measurements on endo-oral radiographs of upper and lower molars. Three blind operators measured 20 radiographs, to analyze the intra- and inter-operator reproducibility of the measurements. Then, the technique was repeated on 250 radiographic images to identify an average value and define a main conformation of the interradicular space. The ratio of these three measurements allowed to develop a new visual evaluation method of the interradicular space. RESULTS: Intra and inter-operator reproducibility was statistically confirmed on a sample of 20 anonymous endo-oral radiographs measured by 3 blind operators, indicating that the measurement technique was not operator dependent. Measurement made on 250 X-rays obtained with this technique permitted to subdivide in five groups the conformation of the interradicular space and define a mean value of the interradicular space. CONCLUSIONS: A new anatomical evaluation of the interradicular space in its entirety, which could help the clinicians in diagnostic and decisional phase in the therapy of furcated molars, can be obtained. CLINICAL RELEVANCE: A pre-operative evaluation of interradicular space conformation could affect therapy treatment choice.

The influence of interradicular anatomy on the predictability of periodontal regenerative therapy of furcation defects: a retrospective, multicenter clinical study.

BACKGROUND: The relationship between the anatomy of the interradicular space and success in regenerative therapy of furcation defects is discussed in this paper. The goal of this retrospective, multicenter clinical study is to clinically evaluate the relationship between the interradicular conformation and regenerative therapy success with the use of a novel measurement method. METHODS: One hundred thirty-eight radiographs of mandibular molars with furcation defects that had been treated with regenerative therapy were collected from six clinical centers. Data on the type of therapy and clinical parameters before and after treatment (follow-up of at least 12 months) were collected. The radiographs (before surgery and at least 12 months postoperatively) were measured with a visual evaluation method by a blind operator using graphics software. RESULTS: Success, defined as a reduction in horizontal and vertical furcation involvement, decrease in probing depths, and increase in clinical attachment level, was statistically assessed on 138 regenerated molars sites and were related to clinical variables such as age, sex, center, and treatment. No correlation was found between success in regenerative therapy and the conformation of the interradicular space, measured with a visual ratio method and a standard linear measurement. At the univariate analysis, the parameters that had a correlation with success were center, extent of furcation involvement, treatment, and sex. The use of enamel matrix derivative (EMD) seemed to be the most favorable therapy, with increase in CAL gain and reduction of vertical or horizontal furcation involvement. CONCLUSIONS: The regenerative outcome was not significantly influenced by the anatomy of furcation. The center, the degree of furcation involvement, sex, and treatment (EMD) were significantly associated with higher success of periodontal regeneration.

Near-infrared system's efficiency for peripheral intravenous cannulation in a level III neonatal intensive care unit: a cross-sectional study.

Venipuncture is a painful and invasive procedure for hospitalised newborns and represents a challenge for neonatal healthcare professionals. This study evaluated the most efficient cannulation method based on the proportion of success at the first attempt, standard care or near-infrared (NIR) device use, and pain assessment. An observational study with two arms was conducted in the neonatal intensive care unit (NICU) of a tertiary-care university hospital in Italy. All newborns undergoing peripheral vein cannulation and only nurses with more than 5 years of professional experience in the NICU were eligible for the first arm. Only newborns with a body weight of >2500 g at cannulation and all nurses working in the NICU were involved in the second arm. In the first arm of the study, no statistically significant differences between the NIR and control groups were found in terms of proportion of successful at the first attempt 60.6% (confidence interval [CI] 95%: 48.8; 72.4) vs. 56.1% (CI 95%: 44.1; 68.0) and the mean premature infant pain profile score 6.3 (CI 95%: 5.4-7.1) vs. 5.8 (CI 95%: 5.0-6.6). In the second arm, only among less experienced nurses (<1 year), we observed a significant increase in the proportion of success in the NIR group compared with the control group, nearly tripling the success rate (72.7% [54.1; 91.3] vs. 23.1% [0.2; 46.0]).  Conclusion: This study reported no differences between the NIR and control groups. The results also suggest that using a NIR device may be advantageous for healthcare professionals with less experience during first-time cannulation. What is Known: • Venipuncture is a painful procedure commonly used to place a peripheral venous catheter for administering nutrients or drugs. • Near-infrared light facilitates the visualisation of veins and consequently, the performance of cannulation in the paediatric population. What is New: • The near-infrared light device was not associated with fewer attempts and a lower premature infant pain profile score in placing venous access in newborns than the traditional method. • The near-infrared light device could help nurses with less professional experience place a peripheral venous catheter.

Cerebro-placental and umbilico-cerebral ratios in uncomplicated monochorionic twins: Longitudinal references and comparison with singletons.

OBJECTIVES: Monochorionic twins (MC) are at high risk of adverse outcomes and Doppler investigation of umbilical and cerebral flows is mandatory for their surveillance. The cerebro-placental (CPR) and umbilico-cerebral (UCR) ratios are considered non-invasive measures of fetal adaptation to hypoxemia. We aimed to provide longitudinal references for CPR and UCR from 16 to 37 weeks of gestation that are specific for MC twins, and compare these with singleton charts. METHODS: Longitudinal study of a cohort of consecutive uncomplicated MC twin pregnancies monitored at our unit from 2010 to 2018. The estimated centile curves were obtained estimating the median with fractional polynomials by a multilevel model and the external centiles through the residuals. The comparison with singletons references was made through graphic evaluation. RESULTS: One-hundred-fifty-two MC pregnancies were included with a median of 10 longitudinal ultrasounds each. References for CPR and UCR in function of gestational age are presented. Compared to singletons, MC twins showed an earlier and greater circulatory redistribution with lower CPR and higher UCR median values. CONCLUSIONS: MC twin-specific references for CPR and UCR suitable for serial monitoring are presented. The comparison with singleton references demonstrates substantial differences in the hemodynamic balance that must be considered when interpreting findings in MC twins.

Cytogenetic study in primary myelofibrosis at diagnosis: Clinical and histological association and impact on survival according to WHO 2017 classification in an Italian multicenter series.

We analyzed cytogenetic data at diagnosis in 395 primary myelofibrosis (PMF) patients to evaluate any possible association between karyotype and WHO 2017 classification and its impact on prognosis. All the cases were diagnosed and followed at five Italian Hematological Centers between November 1983 and December 2016. An abnormal karyotype (AK) was found in 69 patients and clustered differently according to bone marrow fibrosis grade as it was found in 31 (27.0%) cases with overt fibrotic and 38 (13.6%) with pre-fibrotic PMF (p = 0.001). Sex, anemia, thrombocytopenia, circulating blasts ≥1%, higher lactate dehydrogenase, and International Prognostic Scoring System risk classes were all significantly associated with karyotype. At a median follow-up of >6 years, 101 deaths were recorded. Survival was different between AK and normal karyotype (NK) patients with an estimated median overall survival (OS) of 11.6 and 25.7 years, respectively (p = 0.0148). In conclusion, in our cohort around 20% of patients had an AK, more frequently in subjects with an advanced bone marrow fibrosis grade and clinical-laboratory features indicative of a more aggressive disease. This study shows that an AK confers a more severe clinical phenotype and impacts adversely on OS, thus representing an additional parameter to be considered in the evaluation of PMF prognosis.

Integrating clinical, morphological, and molecular data to assess prognosis in patients with primary myelofibrosis at diagnosis: A practical approach.

Currently available prognostic scoring systems in primary myelofibrosis (PMF) do not integrate clinical, histological, and molecular data, or they also required information on "other" mutations that are available in the clinical practice only in a very limited number of laboratories. In the present multicenter study, including 401 PMF patients, an integrated International Prognostic Scoring System (I-IPSS) was developed by combining IPSS, grade of bone marrow fibrosis (GBMF), and driver mutations molecular status (MS) to define PMF prognosis at diagnosis. Four prognostic categories were identified: I-IPSS-low risk (113 patients), I-IPSS-intermediate-1 risk (56 patients), I-IPSS-intermediate-2 risk (154 patients), and I-IPSS-high risk (78 patients). Median overall survival was 26.7 years in I-IPSS-intermediate-1, 10.8 in I-IPSS-intermediate-2, and 6.4 in I-IPSS-high-risk patients (log-rank test <0.0001); instead, it was not reached in the I-IPSS-low-risk cohort because of the extremely low number of registered deaths. The addition of GBMF and MS to IPSS improved the efficacy for predicting the risk of death. Indeed, the sensitivity of I-IPSS was significantly higher (P < .05) than that of IPSS, considering both total deaths and 5- and 10-year mortality. This comprehensive approach allows clinicians to evaluate mutual interactions between IPSS, GBMF, and MS and identify high-risk patients with poor prognosis who may benefit from aggressive treatments. More importantly, this integrated score can be easily applicable worldwide as it only required information that represent the good clinical practice in the management of PMF patients.

Minimal increases of serum alpha-foetoprotein herald HCC detection in Caucasian HBV cirrhotic patients under long-term oral therapy.

BACKGROUND & AIMS: In Caucasian patients with compensated cirrhosis caused by hepatitis B virus (HBV), the risk of hepatocellular carcinoma (HCC) developing persist despite long-term nucleos(t)ide analogs (NUC) treatment. In the surveillance of this population with persistently normal transaminases because of NUCs, the added value of serum alpha-foetoprotein (AFP) monitoring is poorly defined. METHODS: Two hundred and fifty-eight Caucasian HCC-free patients with HBV-compensated cirrhosis who started tenofovir or entecavir while having normal serum AFP levels (≤7 ng/mL) at baseline or within the first year of treatment underwent HCC surveillance by semiannual ultrasound evaluation and serum AFP determination. RESULTS: During 96 (18-120) months of antiviral therapy, 3947 AFP values were collected, median AFP level was 2 ng/mL. Thirty-five patients developed an HCC at an overall 8-year crude cumulative incidence of 14% (annual incidence of 2%). HCC incidence increased in parallel with increasing AFP thresholds: 24%, 36%, 64% and 92% for AFP levels after exceeding 2, 4, 6 and 7 ng/mL for the first-time. Of the 12 patients who experienced an AFP rise > 7 ng/mL, 11 developed an HCC and one had liver metastases of lung cancer. Overall, an AFP > 7 ng/mL had 99.6% specificity, 31.4% sensitivity, 91.7% PPV, 90.2% NPV, LR+ 70.1 and LR- 0.69 for HCC; this excellent specificity was maintained up to 18 months before HCC detection. CONCLUSIONS: In Caucasian patients with HBV-compensated cirrhosis on long-term NUC, an increase in AFP over 7 ng/mL shows excellent specificity, heralding HCC development within 1 year.

Blunt bowel and mesenteric trauma: role of clinical signs along with CT findings in patients' management.

BACKGROUND: Bowel and/or mesentery injuries represent the third most common injury among patients with blunt abdominal trauma. Delayed diagnosis increases morbidity and mortality. The aim of our study was to evaluate the role of clinical signs along with CT findings as predictors of early surgical repair. MATERIAL AND METHODS: Between March 2014 and February 2017, charts and CT scans of consecutive patients treated for blunt abdominal trauma in two different trauma centers were reread by two experienced radiologists. We included all adult patients who underwent contrast-enhanced CT of the abdomen and pelvis with CT findings of blunt bowel and/or mesenteric injury (BBMI). We divided CT findings into two groups: the first included three highly specific CT signs and the second included six less specific CT signs indicated as "minor CT findings." The presence of abdominal guarding and/or abdominal pain was considered as "clinical signs." Reference standards included surgically proven BBMI and clinical follow-up. Association was evaluated by the chi-square test. A logistic regression model was used to estimate odds ratio (OR) and confidence intervals (CI). RESULTS: Thirty-four (4.1%) out of 831 patients who sustained blunt abdominal trauma had BBMI at CT. Twenty-one out of thirty-four patients (61.8%) underwent surgical repair; the remaining 13 were treated conservatively. Free fluid had a significant statistical association with surgery (p = 0.0044). The presence of three or more minor CT findings was statistically associated with surgery (OR = 8.1; 95% CI, 1.2-53.7). Abdominal guarding along with bowel wall discontinuity and extraluminal air had the highest positive predictive value (100 and 83.3%, respectively). CONCLUSION: In patients without solid organ injury (SOI), the presence of free fluid along with abdominal guarding and three or more "minor CT findings" is a significant predictor of early surgical repair. The association of bowel wall discontinuity with extraluminal air warrants exploratory laparotomy.

The myeloproliferative neoplasms, unclassifiable: clinical and pathological considerations.

This corrects the article DOI: 10.1038/modpathol.2016.182.

The myeloproliferative neoplasms, unclassifiable: clinical and pathological considerations.

In this study, we investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. We performed a meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow (70%) with normal erythropoiesis without left-shifting (59%), increased granulopoiesis with left-shifting (73%) and increased megakaryocytes with loose clustering (96%). Megakaryocytes displayed frequent giant forms with hyperlobulated or bulbous nuclei and/or other maturation defects. Interestingly, more than half of the cases displayed severe bone marrow fibrosis (59%). Median values of hemoglobin level and white blood cells count were all within the normal range; in contrast, median platelets count and lactate dehydrogenase were increased. Little less than half of the patients (44%) showed splenomegaly. JAK2V617F mutation was detected in 72% of all patients. Among the JAK2-negative cases, MPLW515L mutation was found in 17% and CALR mutations in 67% of the investigated cases, respectively. Finally, by multiple correspondence analysis of the morphological profiles, we found that all but four of the cases could be grouped in three morphological clusters with some features similar to those of the classic BCR-ABL1-negative myeloproliferative neoplasms. Analysis of the clinical parameters in these three clusters revealed discrepancies with the morphological profile in about 55% of the patients. In conclusion, we found that the category of myeloproliferative neoplasm, unclassifiable is heterogeneous but identification of different subgroups is possible and should be recommended for a better management of these patients.

Prognostic significance of a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in primary myelofibrosis patients.

AIMS: To evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. METHODS AND RESULTS: Reticulin fibrosis, collagen deposition and osteosclerosis were graded from 0 to 3 in a series of 122 baseline BMBs. Then, we assigned to each case a comprehensive score [reticulin, collagen, osteosclerosis (RCO) score, ranging from 0 to 9] that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was associated more frequently with anaemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. The RCO score was correlated strictly with overall mortality (P = 0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (log-rank test: P < 0.001). Moreover, it proved to be more accurate than the European Consensus on Grading of Bone Marrow Fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. CONCLUSION: The comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis was prognostically significant and more accurate than ECGMF grade in identifying high-risk patients and improved PPV when applied in addition to IPSS.

Propranolol 0.1% eye micro-drops in newborns with retinopathy of prematurity: a pilot clinical trial.

BACKGROUND: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. This study evaluated safety and efficacy of propranolol eye micro-drops in preterm newborns with ROP. METHODS: A multicenter open-label trial, planned according to the Simon optimal two-stage design, was performed to analyze safety and efficacy of propranolol micro-drops in newborns with stage 2 ROP. To this end, hemodynamic and respiratory parameters were monitored, and blood samples were collected weekly, for 3 wk. Propranolol plasma levels were also monitored. The progression of the disease was evaluated with serial ophthalmologic examinations. RESULTS: Twenty-three newborns were enrolled. Since the fourth of the first 19 newborns enrolled in the first stage of the study showed a progression to stage 2 or 3 with plus, the second stage was prematurely discontinued. Even though the objective to complete the second stage was not achieved, the percentage of ROP progression (26%) was similar to that obtained previously with oral propranolol administration. However, no adverse effects were observed and propranolol plasma levels were significantly lower than those measured after oral administration. CONCLUSION: Propranolol 0.1% eye micro-drops are well tolerated, but not sufficiently effective. Further studies are required to identify the optimal dose and administration schedule.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

BACKGROUND: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Effects of Red Blood Cell Transfusions on the Risk of Developing Complications or Death: An Observational Study of a Cohort of Very Low Birth Weight Infants.

Background The aim of this study was to evaluate the association between red blood cell (RBC) transfusions on the risk of death, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Study Design and Methods This is an observational study. Data were entered prospectively into the study database at the time of the first transfusion. Clinical characteristics, adverse events, and outcomes of the patients transfused in the first 28 days of life were compared with the population of VLBW infants not transfused during the same period. The association among birth weight, gestational age, comorbidities, and the number of transfusions was estimated with a Poisson regression model. The association between the composite outcome and the occurrence of death, ROP, or BPD separately considered and a set of covariates was estimated with a logistic regression model. Results We enrolled 641 VLBW infants, 42% of whom were transfused. Transfusions were associated with the risk of developing the composite outcome, independently from other conditions; this risk correlated with several transfusions ≥ 3 (odds ratio: 5.88, 95% confidence interval: 2.74-12.6). ROP and BPD were associated with several transfusions ≥ 3. Conclusion We observed an association between RBC transfusions and the composite risk of death or ROP, BPD, and NEC.

Impact of Mode of Delivery on Female Postpartum Sexual Functioning: Spontaneous Vaginal Delivery and Operative Vaginal Delivery vs. Cesarean Section.

INTRODUCTION: Several studies have explored the association between modes of delivery and postpartum female sexual functioning, although with inconsistent findings. AIM: To investigate the impact of mode of delivery on female postpartum sexual functioning by comparing spontaneous vaginal delivery, operative vaginal delivery, and cesarean section. METHODS: One hundred thirty-two primiparous women who had a spontaneous vaginal delivery, 45 who had an operative vaginal delivery, and 92 who underwent a cesarean section were included in the study (N = 269). Postpartum sexual functioning was evaluated 6 months after childbirth using the Female Sexual Function Index. Time to resumption of sexual intercourse, postpartum depression, and current breastfeeding also were assessed 6 months after delivery. MAIN OUTCOME MEASURES: Female Sexual Function Index total and domain scores and time to resumption of sexual intercourse at 6 months after childbirth. RESULTS: Women who underwent an operative vaginal delivery had poorer scores on arousal, lubrication, orgasm, and global sexual functioning compared with the cesarean section group and lower orgasm scores compared with the spontaneous vaginal delivery group (P < .05). The mode of delivery did not significantly affect time to resumption of sexual intercourse. Women who were currently breastfeeding had lower lubrication, more pain at intercourse, and longer time to resumption of sexual activity. CONCLUSION: Operative vaginal delivery might be associated with poorer sexual functioning, but no conclusions can be drawn from this study regarding the impact of pelvic floor trauma (perineal laceration or episiotomy) on sexual functioning because of the high rate of episiotomies. Overall, obstetric algorithms currently in use should be refined to decrease further the risk of operative vaginal delivery.

Variable Lifting Index for Manual-Lifting Risk Assessment: A Preliminary Validation Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of the new Variable Lifting Index (VLI) method, theoretically based on the Revised National Institute for Occupational Safety and Health [NIOSH] Lifting Equation (RNLE), in predicting the risk of acute low-back pain (LBP) in the past 12 months. BACKGROUND: A new risk variable termed the VLI for assessing variable manual lifting has been developed, but there has been no epidemiological study that evaluates the relationship between the VLI and LBP. METHOD: A sample of 3,402 study participants from 16 companies in different industrial sectors was analyzed. Of the participants, 2,374 were in the risk exposure group involving manual materials handling (MMH), and 1,028 were in the control group without MMH. The VLI was calculated for each participant in the exposure group using a systematic approach. LBP information was collected by occupational physicians at the study sites. The risk of acute LBP was estimated by calculating the odds ratio (OR) between levels of the risk exposure and the control group using a logistic regression analysis. Both crude and adjusted ORs for body mass index, gender, and age were analyzed. RESULTS: Both crude and adjusted ORs showed a dose-response relationship. As the levels of VLI increased, the risk of LBP increased. This risk relationship existed when VLI was greater than 1. CONCLUSION: The VLI method can be used to assess the risk of acute LBP, although further studies are needed to confirm the outcome and to define better VLI categories.

"You can't always get what you want": from doctrine to practicability of study designs for clinical investigation in endometriosis.

BACKGROUND: Patients, now generally well informed through dedicated websites and support organizations, are beginning to look askance at clinical experimentation. We conducted a survey investigation to verify whether women with endometriosis would still accept to participate in a randomized controlled trial (RCT) on treatment for pelvic pain. METHODS: A total of 500 patients consecutively self-referring to an academic outpatient endometriosis clinic, were asked to compile two questionnaires focused on hypothetical comparisons between a new drug and a standard drug, and between medical and surgical treatment, for endometriosis-associated pelvic pain. The main outcome measure was the percentage of patients willing to participate in a theoretical RCT. RESULTS: A total of 239 (48 %) women would decline participation in a comparative study on a new drug and a standard drug, as 204 (41 %) would prefer the former medication, and 35 (7 %) the latter. Fifty women (10 %) would participate in a RCT, but only 24 (5 %) would accept blinding. The most frequently chosen option was the patient preference trial (211; 42 %). No significant differences were observed in demographic and clinical characteristics between the 50 women who would accept and the 450 who would decline to be enrolled in a RCT. A total of 229 women (46 %) would decline participation in a comparative study on medical versus surgical treatment, as 186 (37 %) would prefer pharmacological therapy and 43 (9 %) a surgical procedure. Only 11 (2 %) women would participate in such a RCT. More than half of the women (260; 52 %) selected the patient preference trial. No significant variations in distributions of answers were observed between women who did or did not undergo a previous surgical procedure. CONCLUSION: Only a small minority of the women included in our study sample would accept randomization, and even less so blinding. Patient preference appears to play a central role when planning interventional trials on endometriosis-associated pelvic pain. Adequately designed observational analytic studies could be considered when recruitment in a RCT appears cumbersome.

Neurodevelopmental outcome of extremely low birth weight infants at 24 months corrected age: a comparison between Griffiths and Bayley Scales.

BACKGROUND: The availability of accurate assessment tools for the early detection of infants at risk for adverse neurodevelopmental outcomes is a major issue. The purpose of this study is to compare the outcomes of the Bayley Scales (Bayley-II vs Bayley-III) in a cohort of extremely low birth weight infants at 24 months corrected age, to define which edition shows the highest agreement with the Griffiths Mental Development Scales Revised. METHODS: We performed a single-centre cohort study. We prospectively enrolled infants with a birth weight of 401-1000 g and/or gestational age < 28 weeks. Exclusion criteria were the presence of neurosensory disabilities and/or genetic abnormalities. Infants underwent neurodevelopmental evaluation at 24 months corrected age using the Griffiths and either the Bayley-II (birth years 2003-2006) or the Bayley-III (birth years 2007-2010). RESULTS: A total of 194 infants were enrolled. Concordance was excellent between the Griffiths and the Bayley-III composite scores for both cognitive language and motor abilities (weighted K = 0.80 and 0.81, respectively) but poorer for the Bayley-II (weighted K = 0.63 and 0.50, respectively). The Youden's Index revealed higher values for the Bayley-III than for the Bayley-II (75.9 vs 69.6%). Compared with the Griffiths, the Bayley-III found 3% fewer infants as being severely impaired in cognitive-language abilities and 7.8% fewer infants as being mildly impaired in motor skills while the Bayley-II showed, compared with the Griffiths, higher rates of severely impaired children both for cognitive-language and motor abilities (14.1 and 15.3% more infants respectively). DISCUSSION: Our study suggests that the Bayley-III, although having a higher agreement with the Griffiths compared to the Bayley-II, slightly tends to underestimate neurodevelopmental impairment compared with the Griffiths, whereas the Bayley-II tends to overestimate it. CONCLUSIONS: On the basis of these findings, we recommend the use of multiple measures to assess neurodevelopmental outcomes of extremely low birth weight infants at 24 months.

Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms.

This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n=34), primary myelofibrosis (n=44) and polycythaemia vera (n=25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group was asked to reach a collegial 'consensus' diagnosis. The second group reviewed individually all the cases to recognize the main morphological parameters indicated by the WHO classification and report their results in a database. They were subsequently instructed to individually build a 'personal' diagnosis of myeloproliferative neoplasms subtype just assembling the parameters collected in the database. Our results indicate that high levels of agreement (≥70%) have been reached for about all of the morphological features. Moreover, among the 18 evaluated histological features, 11 resulted statistically more useful for the differential diagnosis among the different Philadelphia chromosome-negative myeloproliferative neoplasms. Finally, we found a high percentage of agreement (76%) between the 'personal' and 'consensus' diagnosis (Cohen's kappa statistic >0.40). In conclusion, our results support the use of the histological criteria proposed by the WHO classification for the Philadelphia chromosome-negative myeloproliferative neoplasms to ensure a more precise and early diagnosis for these patients.