Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Perceived triggers of primary headache disorders: A meta-analysis.

Objective To quantitatively synthesize extant literature on perceived triggers of primary headache disorders. Methods A meta-analytic review of headache trigger survey studies was conducted. Endorsement rates, assessment method, and headache and sample characteristics were extracted from included articles. Separate random-effects models were used to assess trigger endorsement rates and post-hoc meta-regressions examined potential moderator variables. Results 85 articles from 1958 to 2015 were included, involving 27,122 participants and querying 420 unique triggers (collapsed into 15 categories). Four-fifths (0.81; 95% CI .75 to .86) of individuals with migraine or tension-type headache endorsed at least one trigger. Rates increased with the number of categories queried (OR: 1.18, 1.08-1.30) and year of publication (OR: 1.04, 1.00-1.08). The triggers most commonly endorsed were stress (.58, .53-.63) and sleep (.41, .36-.47). Conclusions Extreme heterogeneity characterizes the headache trigger literature. Most individuals with a primary headache disorder perceive their attacks to be triggered by one or more precipitants, the most common of which are stress and sleep. However, trigger endorsement is influenced by method of assessment. Enhancing methodological consistency and prioritizing experimental studies would improve our understanding of headache triggers.

Conventional fascial technique versus mesh repair for advanced pelvic organ prolapse: Analysis of recurrences in treated and untreated compartments.

117 women with severe pelvic organ prolapse (POP; stage > 2) were enrolled to elucidate a 24-month outcome of POP surgery, using conventional or mesh repair with 3 techniques. 59 patients underwent conventional repair and 58 underwent mesh repair. Two types of mesh were used: a trocar-guided transobturator polypropylene (Avaulta, Bard Inc.) and a porcine dermis mesh (Pelvisoft, Bard Inc.). Women with recurrences, who underwent previous unsuccessful conventional repair, were randomised. Primary outcome was the evaluation of anatomic failures (prolapse stage > 1) in treated and untreated compartments. Anatomic failure was observed in 11 of 58 patients (19%; CI 8.9-29) in the mesh group and in 16 of 59 patients (27.1%; p value = 0.3) in the conventional group. 9 of 11 failures in the mesh group (15.5%; CI 6.2-24.8) were observed in the untreated compartment (de novo recurrences), 14.3% in Pelvisoft and 16.7% in Avaulta arm, while only 1 recurrence in the untreated compartment (1.7%) was observed in the conventional group (odds ratio 10.6, p = 0.03).

Pivotal points in interstitial pregnancy: new insights in conservative medical treatment of non-ruptured interstitial pregnancy.

We report the efficacy of a minimally invasive approach of the multidose protocol with methotrexate (MTX) in the management of three cases of interstitial pregnancy (IP), with elevated serum ß-hCG in two cases. New considerations and management strategies are discussed. Successful termination of IP and in one case, a subsequent successful pregnancy, was achieved. The process led to the development of an enhanced understanding of diagnostic modalities and their limitations, with regard to the particular entities under discussion. We also focused attention on pivotal points and anatomical features in the management of this dangerous occurrence. Long-term results with careful follow-up were analysed by instrumental procedure. This hazardous type of ectopic pregnancy can be managed with systemic administration of MTX, also in patients with elevated ß-hCG values. The present report underlines that an integrated approach in early diagnosis, multidose treatment and close follow-up, are essential forms of medical management.

Trace metals, peroxidase activity, PAHs contents and ecophysiological changes in Quercus ilex leaves in the urban area of Caserta (Italy).

Trace metals and polycyclic aromatic hydrocarbons, severely affecting human, animal and plants health, highly contribute to the air pollution in urban areas mainly due to car traffic. In this study the air biomonitoring of the city of Caserta (South Italy) has been performed by using Quercus ilex L., a widespread ornamental plant in parks, gardens and avenues. The plant leaves from different sites within the urban area were collected and used to determine the concentrations of V, Cd, Cr, Pb, Ni, Cu, and PAHs as well as the free amino acid content and peroxidase enzyme activity as indices of the leaf physiological conditions. All the tested trace metals showed concentrations higher than the control site. Lead was positively correlated to Cd and Cr and showed, also, a positive trend with Ni and Cu that, in their turn, were highly correlated between them. Positive and significant correlations were evidenced between total PAHs and carcinogenic PAHs and negative correlations between those and all trace metals assayed except V. Cu and Cd contents evidence negative correlations with peroxidase activity, and the free amino acid contents. The PAHs, in particular Carc-PAHs, were negatively correlated to the tested heavy metals. POD was positively correlated only with V and negatively correlated with Cu and Cd.

Multidetector computed tomographic coronary angiography as an alternative to conventional coronary angiography in non-coronary surgical patients.

AIM: Aim of our study was to evaluate multidetector 64-slice spiral computed tomography (MSCT) as an alternative to traditional coronary angiography (CA) to detect concomitant coronary artery disease (CAD) in patients initially admitted for non-coronary surgical procedures. METHODS: We have analyzed data of 380 consecutive patients operated from 2006 to 2008 initially admitted for aortic (N.=170) or mitral (N.=67) valve disease, ascending aorta aneurysm ± aortic valve disease (N.=99), and other (combined valve diseases, tumors; N.=44). These patients were submitted either to MSCT (Group CT, N.=112) or to CA (Group A, N.=268). Inclusion criteria to perform MSCT were no previous myocardial infarction or documented CAD, normal left ventricular function, sinus rhythm, less than 2-3 premature ventricular or atrial contractions /min. RESULTS: In Group CT, CAD was definitively excluded in 95 patients (85%) and was detected in 17; 8 of those 17 patients were subsequently submitted to CA and coronary artery bypass surgery for significant CAD. As compared to those in Group A, patients in Group CT were younger (64±15 vs. 70±10 years, P<0.0001), had less hypertension (P=0.0001), chest pain (P<0.05), peripheral vascular disease (P<0.05). NYHA class, incidence of diabetes, smoking habit, family history of CAD were similar. The incidence of operative mortality, postoperative myocardial infarction was not significantly different in both Group CT (0%) and A (0.4%) (P=NS). CONCLUSION: In selected cardiac surgical patients less invasive 64-slice MSCT can be with some limits an alternative to CA to rule out CAD, as confirmed by the absence of postoperative ischemic complications.

Antihypertensive treatment during pregnancy and functional development at primary school age in a historical cohort study.

OBJECTIVE: To determine the functional development of children born after treatment of mild-to-moderate gestational hypertension with labetalol versus methyldopa, and no antihypertensive treatment. DESIGN: Historical cohort study. SETTING: Twelve Dutch hospital departments of obstetrics. POPULATION: Live-born children born in these hospitals and prenatally exposed to labetalol, methyldopa, or bed rest because of mild-to-moderate gestational hypertension. METHODS: Central nervous system development was measured with standard tests at 4-10 years of age. Linear regression techniques and Pearson's chi-square tests were used to compare the groups with regard to the outcome measures. MAIN OUTCOME MEASURES: Intelligence quotient (IQ), concentration, motor development, and behaviour at primary school age. RESULTS: A total of 202 children were included in the analyses. More children exposed to labetalol had attention deficit hyperactivity disorder (ADHD) than those exposed to methyldopa (OR 2.3; 95% CI 0.7-7.3), or those born to women who had been admitted for bed rest (OR 4.1; 95% CI 1.2-13.9). Sleeping problems seemed to be reported more frequently after prenatal methyldopa exposure than after exposure to labetalol (OR 3.2; 95% CI 0.6-16.7) or bed rest (OR 4.5; 95% CI 0.9-23.2), although the differences were not statistically significant. Test scores on other aspects of functional development did not differ between the three groups. CONCLUSIONS: In this hypothesis-generating study, labetalol exposure in utero seemed to increase the risk of ADHD among children of primary school age, whereas prenatal methyldopa exposure might influence sleep. Further studies with appropriate sample sizes are warranted to determine the long-term effects of antihypertensive medications.

Microbial activities and trace element contents in an urban soil.

Soil biological properties are influenced by trace metals. The main sources of these pollutants in the urban areas are industrial plants, power stations, domestic heating systems and motor vehicles. The aim of this work was to evaluate, in relation to distance from urban roads, soil trace metal concentrations (Pb, Cu, Cr, Cd and V) and their influence on C-microbial biomass as well as on soil respiration and enzyme activities (phosphatase glucosidase, galactosidase, xylanase, cellulase, trealase, protease and invertase). The samplings were carried out at four sites, along a route that goes from Giannone Street to Passionisti Street, two heavily travelled roads at two different times of the year (spring and autumn). Heavy metal contents and microbial activities were highest at the sites near the roads. The highest values of microbial activities were found in the inner site; here, on the contrary, the lowest concentrations of heavy metals were measured. Significant and negative correlations were found between microbial activity and heavy metal contents.

[Environmental spread of Taenia proglottids: an atypical yet interesting public health problem in schools]. / Dispersione ambientale di proglottiti di Taenia: un'atipica ed interessante problematica di sanità pubblica in ambiente scolastico.

We report herein a new case of teniasis caused by Taenia saginata (tapeworm) in a pediatric patient with done-on-purpose dispersion of proglottids happened in an elementary school inside the health district ASL CN-1. This new case highlights how teniasis in children is not as rare, as it is not so rare dispersal of proglottids in the environment, made on purpose, by the same subjects that have been parasitized. The environmental dispersion of proglottids is an important public health problem that requires a rapid and joint management of the problem aiming to identify the parasite as quickly as possible, given the different pathogenic larval stage of three species of tapeworm that can infest the man.

A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study.

BACKGROUND: The efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control. PATIENTS AND METHODS: In all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with < or = 3 mm stromal invasion (PR1)] or suboptimal response. RESULTS: Patient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III-IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP. CONCLUSION: TP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.

[Teniasis in a child with finding of Taenia saginata proglottids in the school environment: a case report]. / Un caso pediatrico di teniasi con reperimento di proglottidi di Taenia saginata in ambiente scolastico.

We describe a case of teniasis in a child, associated to the finding of Taenia proglottids in a classroom of a primary school in the area of Cuneo (Local Health Unit Cn-1, Piedmont Region, Italy). Several proglottids had been repeatedly found by cleaners on the bookbox of several schooldesks in the same classroom. Laboratory investigation was able to identify Taenia saginata proglottids and cooperation of the local Public Health Unit with the school management allowed to identify and treat the affected child. Laboratory investigation was crucial to exclude a Taenia solium infection, which should have had important public health implications. In fact, infection among humans can follow the ingestion of Taenia solium eggs and in this case larval forms in several tissues can occur (cysticercosis). Moreover the disease can be particularly severe when cysticerci invade the brain, causing seizures and hydrocephalia.

A new technique for tensile testing of engineering materials and composites at high strain rates.

A new test technique and bespoke apparatus to conduct high strain rate measurements of the tensile response of materials are presented. The new test method is applicable to brittle solids and composites as well as high-performance fibres, yarns and tapes used in composite construction. In this study, the dynamic response of monolithic poly(methyl methacrylate) and unidirectional composites based on Dyneema® tape, Dyneema® SK75 yarn and Kevlar® 49 yarn are explored. The technique allows early force equilibrium and yields valid tensile stress-strain curves, which include part of the elastic material response. The new method also enables investigation of size effects in tape and yarn materials, allowing testing of specimens of arbitrary length.

Binocular cyclotorsion in superior vestibular neuritis.

SUMMARY: Conjugated cyclotorsion of the eyes toward the affected side can commonly be observed in vestibular neuritis. The aim of this study was to assess the differences in cyclotorsion between the ipsi- and contralesional eye during selective involvement of the superior branch of the vestibular nerve. We studied binocular cyclotorsion through ocular fundus photographs in 10 patients affected by acute superior vestibular neuritis (SVN). Cyclotorsion was also studied in 20 normal subjects. All SVN patients showed an ipsilesional cycloversion of the eyes. Normal subjects exhibited a constant mild excyclovergence (6.42 ± 2.34°). In SVN patients, contralateral incyclotorsion (8.4 ± 8.14°) was lower and not normally distributed compared to ipsilateral eye excyclotorsion (17.9 ± 4.36°) with no correlation between them. The interocular difference in cyclodeviation could be related to the starting physiological excyclovergence, to different tonic effects on the extraocular muscles of the two eyes and to the different influence of spontaneous nystagmus on cyclodeviation in the two eyes. We recommend referring only to ipsilateral excyclotorsion in the evaluation of utricular function during SVN and its subsequent compensation. Further studies are required to determine the binocular cyclotorsion in the case of other kinds of selective involvement of the vestibular nerve.

Deposition of metallic silver coatings by Aerosol Assisted MOCVD using two new silver ß-diketonate adduct metalorganic precursors.

This work reports two new silver metalorganic precursors for the chemical vapor deposition of Ag metallic coatings. Both precursors are based on ß-diketonate adducts, namely, Ag(hfac)(L) (H-hfac = 1,1,1,5,5,5-hexafluoro-2,4-pentanedione), where L is 1,10-phenanthroline (phen) or 2,5,8,11-tetraoxadodecane (triglyme). Using these ligands, the designed precursors have better solubility in alcoholic solvents and are less toxic and costly than previously reported ones. The new precursors have been characterized and their crystallographic structure solved. With the new triglyme precursor, [Ag(triglyme)2]+[Ag(hfac)2]-, pure metallic Ag coatings made of Ag nanoparticles about 20 nm in diameter were succesfully deposited on glass and Si substrates using Aerosol Assisted Metalorganic CVD (AA-CVD).

Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study.

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR(4) (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10,000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal.

Effect of acetylsalicylate on cardiac and muscular pain induced by intracoronary and intra-arterial infusion of bradykinin in humans.

OBJECTIVES: This study assessed the algesic activity of bradykinin (BK) in humans and the effects of acetylsalicylate on muscular and cardiac BK-induced pain. BACKGROUND: Bradykinin is released by the ischemic myocardium and may be involved in the genesis of ischemic pain. METHODS: Increasing doses of BK (from 30 to 960 ng/min) were randomly infused, for periods of 2 min each, into the iliac artery of 10 patients. The same protocol was repeated 30 min after the IV administration of 1 g of acetylsalicylate. In eight other patients with coronary artery disease, the same increasing doses of BK, for periods of 2 min each, were infused into the left coronary artery. The same protocol was repeated 30 min after the IV administration of 1 g of acetylsalicylate. Time to pain onset and maximal pain severity were obtained. RESULTS: Before acetylsalicylate administration, all patients experienced pain during intra-iliac infusion of BK. After acetylsalicylate, eight patients did not experience any pain during BK infusion (p = 0.0014), and in the two remaining patients, time to pain onset and maximal pain severity were similar to those recorded before acetylsalicylate. Before acetylsalicylate administration, all patients experienced pain similar to their habitual angina during intracoronary BK infusion. After acetylsalicylate, six patients did not experience any pain during BK infusion (p = 0.0098), whereas in the two remaining patients time to pain onset and maximal pain severity were similar to those recorded before acetylsalicylate. CONCLUSIONS: Intra-iliac infusion of BK causes muscular pain, and its intracoronary infusion in patients with coronary artery disease causes cardiac pain, which is similar to their habitual angina. The BK-induced pain is abolished or reduced by acetylsalicylate, thus suggesting that acetylsalicylate-sensitive mediators, such as prostaglandins, are involved in its pathogenesis.

Ecteinascidin-743, a new marine natural product with potent antitumor activity on human ovarian carcinoma xenografts.

The antitumor activity of ecteinascidin (ET)-743, a novel marine natural product, was evaluated against a panel of human ovarian carcinoma xenografts characterized by different malignant behaviors and drug responsiveness in nude mice. These tumor models included three xenografts transplanted s.c. (HOC18, HOC22-S, and MNB-PTX-1) into nude mice, representing different levels of sensitivity to cisplatinum (DDP), which was used as reference drug for ovarian carcinoma, and two other xenografts (HOC22 and HOC8), which are highly malignant in the peritoneal cavity of nude mice, representing the growth pattern of this neoplasm. At the maximum tolerated dose of 0.2 mg/kg using an intermittent schedule of one i.v. injection every 4 days, ET-743 was highly active against HOC22-S (sensitive to DDP), inducing long-lasting, complete regressions, and against HOC18 (marginally sensitive to DDP), inducing partial tumor regressions. Moreover, significant growth delay was observed in mice bearing late-stage HOC18 tumor (400-mg tumor weight; nonresponsive to DDP). ET-743, however, was not active against MNB-PTX-1, a tumor that is highly resistant to chemotherapy, including DDP. In the i.p. ovarian carcinoma xenograft model, ET-743 at the maximum tolerated dose induced complete tumor remissions in all mice bearing HOC22 tumor, with 25% histopathologically confirmed cures, and produced marginal tumor growth delay against HOC8. These results indicate that ET-743 is a potent drug against ovarian carcinoma xenografts, being equally as active or more efficacious than DDP in the same tumor line. Our findings with human ovarian carcinoma xenografts justify clinical assessment of this drug with this tumor target.

Antiangiogenesis by cyclosporine.

The effects of cyclosporine on certain endothelial cell functions, namely matrix metalloprotease (MMP)-2 and MMP-9 secretion, proliferation, chemotaxis, and morphogenesis, were investigated in vitro, and its effects on angiogenesis were studied in vivo by using the chick embryo chorioallantoic membrane (CAM) model. In vitro, at low noncytotoxic doses (2, 4, 8, and 16 microg/mL), cyclosporine inhibited all these functions in a dose-dependent manner, although MMP-2 secretion was inhibited only at 16 microg/mL. The absence of cytotoxicity was confirmed morphologically and also because inhibition was rapidly reversed as soon as cyclosporine was removed. In vivo, cyclosporine at 0.012 and 0.024 microg per CAM displayed noncytotoxic, dose-dependent antiangiogenic activity. Biochemically, the drug inhibited the activity of the endothelial cell respiratory chain enzymes succinate oxidase and cytochrome-c oxidase, again in a dose-dependent manner. This finding could explain the effects observed in vitro and in vivo. These antiangiogenic properties of low-dose cyclosporine warrant further investigation in certain autoimmune and neoplastic diseases characterized by enhanced angiogenesis.