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.

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study.

OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

Ovarian fibrosarcoma: case report and latest trends in diagnostic and therapeutic management.

The authors describe a rare case of primary ovarian fibrosarcoma and the latest trends in diagnosis and therapy. The rarity of this dis-ease and the scarce number of reported cases pose serious problems in differentiating it from other fibrous forms. A 58-year-old woman presented intermittent pelvic pain and a demarcated, mobile, and solid lump in the right adnexa. Diagnostic imaging revealed a solid- cystic inhomogeneous mass occupying the right adnexa and the CA125 level was elevated. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy. Histological findings with immunomarkers led to the final diagnosis of low-grade malignant mesenchymal neoplasm derived from the ovarian stroma compatible with fibrosarcoma. Twenty-four months follow-up showed no recurrence of disease. Ovarian fibrosarcoma is very uncommon neoplasm with a poor prognosis. Despite the efforts of several authors in reporting morphological, histological, and immunohistochemical features of this neoplasm, nowadays, the diagnosis, treatment, and prognosis are unresolved issues. The present case highlights the important role of immunohistochemistry to define histological type and differential diagnosis. As demonstrated by the authors' experience, they believe that surgery is curative in the early stages with low immunohistochemical positivity for ki67 and that chemotherapy should be reserved in advanced stages with regimens in use for the treatment of sarcomas.

Asthma management among different specialists: results from a national Italian survey.

In Europe more than 50% of asthmatic treated patients have a not well-controlled asthma. The present survey aims at investigating how different specialists approach asthmatic patients. A web anonymous questionnaire was randomly administered to 604 General Practitioners (GPs), 241 Pneumologists and 131 Allergists. It concerned: epidemiology, diagnostic workup, follow-up and risk factors, treatment and future risk. A general agreement emerges about asthma diagnostic work-up. All categories are aware of the impact of comorbidities on asthma. LABA/inhaled steroids combination is considered the first choice treatment. Surprisingly, depot steroids and long-acting beta2 agonists (LABA) alone are still prescribed by GPs. Concerning monitoring tools, Allergists rely on inflammation biomarkers, whereas reduction of rescue medication is more relevant for GPs. Asthma Control Test (ACT) is considered time consuming by more than 50% of all physicians and is not known by most of GPs. Adherence is considered a crucial problem in asthma management. All categories seem to have a good knowledge about asthma. The cultural background may account for mild differences in asthma control tools and treatment options. GPs have a pivotal role in discriminating patients who need specific assessment by specialists. It is thus important that GPs and specialists share common tools for recognizing and managing those patients.

The possible role of zinc in the etiopathogenesis of endometriosis.

PURPOSE OF INVESTIGATION: Aim of the study was to evaluate the possible involvement of zinc in the complex pathogenic process behind the onset and perpetuation of endometriotic lesions. To study the level of zinc serum between a group of patients affected by endometriosis and a group of healthy patients. MATERIALS AND METHODS: The study included 86 women: 42 patients whose histodiagnosis had revealed pelvic endometriosis and 44 healthy patients. The authors measured the serum zinc concentration for all patients. RESULTS: The group of patients with endometriosis presented serum zinc concentration of 1010 +/- 59.24 microg/l. The observation group presented a serum zinc concentration of 1294 +/- 62.22 microg/l. CONCLUSION: The results showed that serum zinc levels in women with endometriosis are decreased and this seems to actually confirm that this microelement can possibly affect the multifactorial pathogenesis of the disease. As a matter of fact, zinc interferes with many biological processes, among which inflammation and immunity, which seem to be the base of the development of the lesions. Therefore, the authors believe that this hypothesis requires more attention and further investigation to determine its reasonableness. If the results are confirmed, this study opens up future prospects as for the treatment of endometriosis, taking into account also the role of zinc in the onset of male sterility and the development of testicles. Zinc could in fact be used as marker to detect women at high risk of endometriosis and for the elaboration of a new treatment for sterility, from which these women often suffer.

The history of mast cell and basophil research - some lessons learnt from the last century.

This year (2013) marks the 50th anniversary of death of Otto Carl Willy Prausnitz (1876-1963) and Heinz Küstner (1897-1963). The two physicians, when working at the Hygiene Institute at the University of Breslau, Germany (Prausnitz was the Head of the Institute), described in 1921 what is still called today the Prausnitz-Küstner or PK reaction showing that allergy could be transferred from the allergic person by transferring serum to a healthy person. Their discovery ended the belief that an anaphylactic/allergic reaction was caused by poisons, but to the contrary showed that the presence of the hypersensitivity factor could be transferred to other people. We know now that this factor is immunoglobulin E (IgE), sensitizing mast cells and basophils to respond to an allergic stimulus. We take this occasion to retrace some of the important discoveries and lessons learnt from the last century relating to the function of these two cell types as effectors of the IgE system and the mediators they produce.

The role of basophils in the pathogenesis of allergic disease.

There has been much controversy surrounding the importance of basophils in allergy. These cells are, after all, comparatively rare and yet they display remarkable potential to contribute to the symptoms of allergic inflammation. Furthermore, by virtue of their ability to rapidly elaborate T helper type 2 (Th2)-type cytokines, they are well endowed to support ongoing allergic immunity. Despite this, basophils have often been regarded as redundant in this function as in murine models of allergy, their more numerous tissue-fixed mast cell counterparts also display Th2-type cytokine-releasing potential, which is rather different in most human mast cells. Surprisingly, it is from murine models that the basophil has re-surfaced as a key orchestrator of Th2-type immunity and chronic allergic inflammation, a property that has long been hypothesized by researchers into human basophil function but never demonstrated. Moreover, murine experimental models also highlighted the ability of basophils to take up and present antigens in an MHC-dependent manner. Controversy regarding basophils, however, has remained as recent methods for depleting these cells in murine models of allergy and parasitic infection have yielded conflicting results, where the role for this cell oscillates from essential antigen-presenting cells to mere supporting functions in controlling Th2 responses. This review highlights the recent advances in understanding the role of this rather enigmatic cell in allergy.

Experimental hookworm infection: a randomized placebo-controlled trial in asthma.

BACKGROUND: Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma. OBJECTIVES: To determine the effects of experimental hookworm infection in asthma. METHODS: Thirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD(20)AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects. RESULTS: Mean PD(20)AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: -1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated. CONCLUSIONS: Experimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken.

Single negative birefringence in stacked spoof plasmon metasurfaces by prism experiment.

We report negative and positive refraction in a prism made of stacked perforated thin surfaces for s and p polarization, respectively. By corrugating the subwavelength slits of a free-standing periodic arrangement, geometrically induced surface-plasmon-like currents are excited and transmission is allowed under s polarization (electric-field vector parallel to the slit). When several of those corrugated slit arrays are subwavelength stacked, the stack behaves as a negative effective index medium (because of double negativity) under s polarization, whereas it behaves as a positive effective index medium under p polarization. The birefringence has been confirmed by the usual wedge experiment in the millimeter-wave range.

An unusual case of asymptomatic appendicular cutting foreign body.

Foreign body ingestion is a common problem in pediatric age. Foreign bodies in the lumen of appendix is a well known event. In this condition perforation or appendicitis may occur even for blunt or sharp objects. For these reasons, in case of stasis of foreign body in the lumen of appendix a prophylactic appendectomy is recommended. A case of asymptomatic ingested cutting foreign body in the appendix is presented and the approach is discussed according to the literature data.

Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study.

BACKGROUND: Epidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration. OBJECTIVE: To determine whether hookworm larval migration through the lungs increases airway responsiveness in allergic individuals with measurable airway responsiveness but not clinical asthma, and investigate the general tolerability of infection and effect on allergic symptoms. METHODS: Thirty individuals with allergic rhinoconjunctivitis and measurable airway responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomized, double-blind to cutaneous administration of either 10 hookworm larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce 1-s forced expiratory volume by 10% (PD(10)AMP) measured at any time over the 4 weeks after active or placebo infection. Secondary outcomes included peak flow variability in the 4 weeks after infection, rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12-week study period, and change in allergen skin test responses between baseline and 12 weeks. RESULTS: Mean maximum change in PD(10)AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (-1.67 and -1.16 doubling doses; mean difference -0.51, 95% confidence interval -1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. There were no significant differences in peak-flow variability, rhinoconjunctivitis symptoms or skin test responses between groups. CONCLUSION: Hookworm infection did not cause clinically significant exacerbation of airway responsiveness and was well tolerated. Suitably powered trials are now indicated to determine the clinical effectiveness of hookworm infection in allergic rhinoconjunctivitis and asthma.

Electroinductive waves role in left-handed stacked complementary split rings resonators.

In this letter it is presented a Left-Handed Metamaterial design route based upon stacked arrays of screens made of complementary split rings resonators under normal incidence in the microwave regime. Computation of the dispersion diagram highlights the possibility to obtain backward waves provided the longitudinal lattice is small enough. The experimental results are in good agreement with the computed ones. The physics underlying the Left-Handed behavior is found to rely on electroinductive waves, playing the mutual capacitive coupling the major role to explain the phenomenon. Our route to Left-Handed metamaterial introduced in this paper based on stacking CSRRs screens can be scaled to millimeter and terahertz for future applications.

A rapid two-step procedure for the purification of human peripheral blood basophils to near homogeneity.

BACKGROUND: Basophils are increasingly utilized as indicators of allergic inflammation and as primary allergic effector cells to study signalling pathways. However, until the present, their enrichment has been time consuming, costly and limited to relatively few specialized laboratories. OBJECTIVE: We have therefore devised a reproducible and rapid method for the purification of human basophils from small quantities of peripheral blood within 1.5 h, which does not require the use of specialized equipment such as elutriators. METHODS: Human basophils were obtained from healthy volunteers undergoing venipuncture. Heparinized or K3-ethylenediaminetetraacetic acid blood samples were first subjected to centrifugation in Hetasep, directly followed by negative selection using immunomagnetic beads. Basophil morphology and purity were assessed by May-Grünwald staining of cytospins. IgE-mediated histamine release was analysed spectrofluorometrically and IL-4 and IL-13 production by quantitative RT-PCR. CD203c and CD63 surface expression was measured using flow cytometry before and after activation with anti-IgE. RESULTS: Using this protocol, basophils were enriched close to homogeneity in most cases with a mean purity of 99.34+/-0.88% (range 97-100%, n=18) and a mean recovery of 75.6 (range 39-100%, n=8). Basophil viability following purification was 99.6+/-0.89% using Trypan blue exclusion. The purification procedure gave rise to basophils with normal functional responses to anti-IgE regarding histamine release as well as IL-4 and IL-13 mRNA expression. Moreover, constitutive cell-surface CD203c/CD63 expressions were not elevated before anti-IgE stimulation. CONCLUSION: The rapidity, simplicity and reproducibility of this method will facilitate the employment of basophils in high-output ex vivo studies.

Total internal reflection microscopy for live imaging of cellular uptake of sub-micron non-fluorescent particles.

This paper presents a simple, high-resolution, non-fluorescent imaging technique called total internal reflection microscopy (TIRM) and demonstrates its potential application to real-time imaging of live cellular events. In addition, a novel instrument is introduced that combines the simplicity of TIRM with the specificity afforded by dual-colour total internal reflection fluorescence (TIRF) microscopy and allows sequential imaging with the two modalities. The key design considerations necessary to apply these imaging modes in a single instrument are discussed. The application of TIRM alone yielded high-resolution live images of cell adherence to a poly-L-lysine modified substrate, whereby fine cellular structures are imaged. Non-fluorescent imaging of the uptake of sub-micron-sized polymeric particles by live cells is also demonstrated. Finally, images of fluorescently labelled cells were obtained in TIRF mode, sequentially to images obtained of the same cell in TIRM mode. Visual information gained using TIRF is compared with TIRM to demonstrate that the level of cell structure information obtainable with our total internal reflection microscope is comparable with the TIRF technique.

[Methods for microbiological control of textiles]. / Evaluation des méthodes de prélèvement pour le contrôle microbiologique des textiles.

Our laboratory is requested more and more by the establishments of health and the industrial laundries for the microbiological realization of control on the textile articles after completion. We checked the effectiveness of the techniques of the bacteriol prints or rodac and the bacterial extraction after maceration for the realization of these controls. The output of extraction of the bacteriol prints applied to woven material samples sterilized and then artificially contaminated by a titrated Staphylococcal suspension is lower than 1%. The technique recommended and largely used for the study in particular of the contamination of the blouses of doctor in the establishments of health thus does not appear to be relevant. We propose for the quality control of the linen a technique of maceration then extraction by the ultra sounds whose output is evaluated to 62% which requires to sacrifice the controled textile article. The choice of the bacteriological techniques as controls ultimate of a procedure must be carried out carefully to meet the needs for quality. Conclusions, when with the effectiveness of a process, deduced from results obtained by a bad method could be wrongfully reassuring.

A novel tool for the detection of allergic sensitization combining protein microarrays with human basophils.

BACKGROUND: Protein microarray (PM) is a powerful alternative to costly or labour-intensive diagnostic for the large-scale detection of allergen-specific IgE. In this study, we established a proof-of-concept that coupling the diversity of protein array with the biological output of basophilic cells is a feasible proposition. METHOD: Human basophils purified from the peripheral blood of healthy donors were stripped, re-sensitized with the serum or IgE preparation to be tested, and incubated with manually spotted protein array chips (FAST slides). The basophilic cell lines KU-812 and RBL-703/21 likewise sensitized were compared with peripheral blood basophils by the same approach. Purified basophils or other basophilic cells were incubated with FAST slides for various periods of time, washed, and cell binding was visualized by light microscopy. Basophil activation, indicating the effective cross-linking of IgE by allergens, was monitored via up-regulation of basophil activation surface marker (CD 63). RESULTS: Purified stripped peripheral basophils, re-sensitized with the serum of a grass pollen-allergic patient, displayed strong binding to anti-IgE antibody and grass pollen extract with relatively low unspecific binding. Similar results were obtained with RBL-703/21, which may be a good replacement for peripheral basophils to avoid the costly, cumbersome and time-consuming basophil purification. CONCLUSION: Our data suggest that coupling the diversity of a PM approach with the potential functionality and biological activity of a cell-based test is feasible and may result in a new system to detect allergic sensitization.

Barriers to effective tuberculosis control: a qualitative study.

SETTING: Emilia Romagna region, Italy. OBJECTIVE: To explore chest and infectious disease physicians' views of barriers to effective tuberculosis (TB) control and possible solutions. DESIGN: A series of nine focus groups including a total of 49 physicians. RESULTS: Three categories of barriers to effective TB control were identified: 1) uncertainty about appropriate clinical practice in the treatment of specific sub-groups of patients, such as the elderly or immigrants; 2) organisational factors, such as the availability of diagnostic services and of sufficient resources; and 3) multiple barriers to a viable and effective TB control programme in a country with a low prevalence of TB. CONCLUSIONS: The lack of integration and coordination of health services, as well as the scarcity of dedicated TB nurses, were perceived by the participants as crucial barriers to effective TB control. As a result of this study, a regional programme was started with the goals of quantifying the need for TB nurses and developing a better network for required health services. Qualitative studies such as this can be useful in improving TB control in a low-prevalence TB country, to identify problems and increase the participation of key professionals.

Asthma is not a common cause of severe chronic respiratory failure in non-smokers: ALOT study.

BACKGROUND: Little is known about the long-term natural history of asthma and the long-term clinical and functional consequences in non-smoking patients. From a functional point of view, non-smoking asthmatic patients may have a significantly greater decline in forced expiratory volume in one second (FEV1) compared with non-asthmatic subjects and may develop chronic irreversible (fixed) airflow limitation. This has been related to the physiological consequences of chronic airway inflammation causing airway remodeling. However these lesions are all potentially reversible and there is little radiological evidence indicating lung destruction (pulmonary emphysema), which is potentially irreversible, in non-smoking asthmatics. Severe chronic respiratory failure is the major cause of mortality in patients with severe chronic lung diseases. Domiciliary long-term oxygen therapy (LTOT) is an accepted treatment for patients with severe chronic respiratory failure. Our reasoning, therefore, was that if asthma is a cause of severe chronic respiratory failure in non-smokers we should be able to find non-smoking asthmatics within a large population of patients on LTOT. The aim of our study (Asthma and Long-term Oxygen Therapy, "ALOT") was to investigate the prevalence of non-smoking asthmatics in patients on LTOT in a multi-centre, cross-sectional study. METHODS: Between June and September 2003 we screened all subjects on long-term domiciliary oxygen therapy in three different hospitals in the North-East area of Italy (within the provinces of Ferrara and Bologna). Taken collectively, we have found one-hundred and eighty-four patients on LTOT. We have reviewed their clinical data (age, sex, smoking, history and physical examination, arterial blood gas analysis, pulmonary function). RESULTS: 114 patients (all smokers) fulfilled the diagnostic criteria for COPD. Seventy patients (all smokers) had other diseases. We were unable to find any non-smokers in our screened population of subjects on long-term domiciliary oxygen therapy. Furthermore, there was no past history of asthma and/or acute wheezing episodes in either of the patient groups. CONCLUSIONS: This data suggests that asthma is an uncommon cause of severe chronic respiratory failure necessitating long-term domiciliary oxygen therapy in non-smokers and supports the current consensus that asthma and COPD are different diseases with differing stages of severity and the concept that long-term avoidance of active smoking is fundamental for the prevention of severe chronic respiratory failure.