Human genital tracts microbiota: dysbiosis crucial for infertility.

Human body is colonized by trillions of microbes, influenced by several factors, both endogenous, as hormones and circadian regulation, and exogenous as, life-style habits and nutrition. The alteration of such factors can lead to microbial dysbiosis, a phenomenon which, in turn, represents a risk factor in many different pathologies including cancer, diabetes, autoimmune and cardiovascular disease, and infertility. Female microbiota dysbiosis (vaginal, endometrial, placental) and male microbiota dysbiosis (seminal fluid) can influence the fertility, determining a detrimental impact on various conditions, as pre-term birth, neonatal illnesses, and macroscopic sperm parameters impairments. Furthermore, unprotected sexual intercourse creates a bacterial exchange between partners, and, in addition, each partner can influence the microbiota composition of partner's reproductive tracts. This comprehensive overview of the effects of bacterial dysbiosis in both sexes and how partners might influence each other will allow for better personalization of infertility management.

Use of a systematic risk analysis method (FMECA) to improve quality in a clinical laboratory procedure.

BACKGROUND: Risk management is a set of actions to recognize or identify risks, errors and their consequences and to take the steps to counter it. The aim of our study was to apply FMECA (Failure Mode, Effects and Criticality Analysis) to the Activated Protein C resistance (APCR) test in order to detect and avoid mistakes in this process. METHODS: We created a team and the process was divided in phases and sub phases. For each phase we calculated the probability of occurrence (O) of an error, the detectability score (D) and the severity (S). The product of these three indexes yields the RPN (Risk Priority Number). Phases with a higher RPN need corrective actions with a higher priority. RESULTS: The calculation of RPN showed that more than 20 activities have a score higher than 150 and need important preventive actions; 8 have a score between 100 and 150. Only 23 actions obtained an acceptable score lower than 100. CONCLUSIONS: This was one of the first experience of application of FMECA analysis to a laboratory process, and the first one which applies this technique to the identification of the factor V Leiden, and our results confirm that FMECA could be a simple, powerful and useful tool in risk management and helps to identify quickly the criticality in a laboratory process.

Genomic and epidemiological evidence for the emergence of a L. infantum/L. donovani hybrid with unusual epidemiology in northern Italy.

Leishmania (L.) infantum is one of the main causative agents of animal and human leishmaniasis across many endemic areas in South America, Europe, North Africa, and Asia. Despite its clinical significance, little is known about the genetic diversity of L. infantum circulating in a given endemic area. Here, we investigate this important open question by applying a comparative genomics approach to seven L. infantum isolates from different hosts and Italian regions, including the northern part of the country (Emilia-Romagna, RER), Sicily, and Sardinia, as an initial attempt to explore the breadth of parasite genetic heterogeneity in Italy. Additionally, microsatellite analysis was carried out to compare the isolates from RER with other 70 L. infantum strains from the same region as well as 65 strains belonging to the L. donovani complex from other countries. We revealed important karyotypic instability and identified strain-specific changes in gene dosage, which affected important virulence factors such as amastins and surface antigen-like proteins. Single nucleotide polymorphism-based clustering analysis of these genomes together with over 80 publicly available L. infantum and L. donovani genomes placed the Italian isolates into three geographically distinct clusters within the Mediterranean basin and uncovered three isolates clustering with putative L. infantum/L. donovani hybrids isolated in Cyprus. As judged by microsatellite profiling, these hybrid isolates are representative of a sub-population of parasites circulating in northern Italy that preferentially infect humans but not dogs. Our results place Italy at the crossroads of L. infantum infection in the Mediterranean and call attention to the public health risk represented by the introduction of non-European Leishmania species.IMPORTANCEThis study closes important knowledge gaps with respect to Leishmania (L.) infantum genetic heterogeneity in a given endemic country, as exemplified here for Italy, and reveals genetic hybridization as a main cause for re-emerging human leishmaniasis in northern Italy. The observed high diversity of Leishmania parasites on the Italian peninsula suggests different geographical origins, with genomic adaptation to various ecologies affecting both pathogenicity and transmission potential. This is documented by the discovery of a putative L. infantum/L. donovani hybrid strain, which has been shown to preferentially infect humans but not dogs. Our results provide important information to health authorities, which need to consider the public health risk represented by the introduction of new Leishmania species into EU countries due to population displacement or travel from countries where exotic/allochthonous parasite species are endemic.

Epidemiology and Outcomes of Bloodstream Infections in HIV-Patients during a 13-Year Period.

No data on antibiotic resistance in bloodstream infection (BSI) in people living with HIV (PLWH) exist. The objective of this study was to describe BSI epidemiology in PLWH focusing on multidrug resistant (MDR) organisms. A retrospective, single-center, observational study was conducted including all positive blood isolates in PLWH from 2004 to 2017. Univariable and multivariable GEE models using binomial distribution family were created to evaluate the association between MDR and mortality risk. In total, 263 episodes (299 isolates) from 164 patients were analyzed; 126 (48%) BSI were community-acquired, 137 (52%) hospital-acquired. At diagnosis, 34.7% of the patients had virological failure, median CD4 count was 207/µL. Thirty- and 90-day mortality rates were 24.2% and 32.4%, respectively. Thirty- and 90-day mortality rates for MDR isolates were 33.3% and 46.9%, respectively (p < 0.05). Enterobacteriaceae were the most prevalent microorganisms (29.8%), followed by Coagulase-negative staphylococci (21.4%), and S. aureus (12.7%). In BSI due to MDR organisms, carbapenem-resistant K. pneumoniae and methicillin-resistant S. aureus were associated with mortality after adjustment for age, although this correlation was not confirmed after further adjustment for CD4 < 200/µL. In conclusion, BSI in PLWH is still a major problem in the combination antiretroviral treatment era and it is related to a poor viro-immunological status, posing the question of whether it should be considered as an AIDS-defining event.

Rhodococcus equi Pneumonia in Kidney Transplant Recipient Affected by Acute Intermittent Porphyria: A Case Report.

Rhodococcus equi is a gram-positive coccobacillus responsible for severe infections in patients with weakened immune systems. R equi generally causes pnumonia that may evolve into fatal systemic infection if left untreated. Here, we present a case of a 67-year-old woman affected by acute intermittent porphyria (AIP) who developed R equi pneumonia 7 months after kidney transplantation. Although clinical features at presentation were nonspecific, lung computed tomography showed right perihilar consolidation with a mass-like appearance causing bronchial obstruction. Appropriate antibiotic including intravenous meropenem and oral azithromycin that was then switched to oral levofloxacin and oral azithromycin along with reduction of immunosuppressive therapy resolved pneumonia without provoking an acute attack of porphyria. AIP limited the choice of antibiotics for the treatment of R equi infection because some potentially porphyrinogenic antibacterial agents were avoided. Based on this experience, azithromycin and meropenem can be safely administered for the treatment of R Equi infection in patients with AIP.

Gastric Mucormycosis in a Liver and Kidney Transplant Recipient: Case Report and Concise Review of Literature.

Mucormycosis is an uncommonly encountered fungal infection in solid organ transplantation. The infection is severe and often results in a fatal outcome. The most common presentations are rhino-sino-orbital and pulmonary disease. We describe a rare case of gastric mucormycosis in a patient with a combined liver-kidney transplant affected by glycogen storage disease type Ia. A 42-year-old female patient presented with gastric pain and melena 26 days after transplantation. Evaluation with upper endoscopy showed two bleeding gastric ulcers. Histological examination of gastric specimens revealed fungal hyphae with evidence of Mucormycetes at subsequent molecular analysis. Immunosuppressive therapy was reduced and antifungal therapy consisting of liposomal amphotericin B and posaconazole was promptly introduced. Gastrointestinal side effects of posaconazole and acute T-cell rejection of renal graft complicated management of the case. A prolonged course of daily injections of amphotericin B together with a slight increase of immunosuppression favored successful treatment of mucormycosis as well as of graft rejection. At 2-year follow-up, the woman was found to have maintained normal renal and liver function. We conclude that judicious personalization of antimicrobial and antirejection therapy should be considered to resolve every life-threatening case of mucormycosis in solid organ transplantation.

Clinical and Microbiological Characteristics of Visceral Leishmaniasis Outbreak in a Northern Italian Nonendemic Area: A Retrospective Observational Study.

Background. Visceral leishmaniasis (VL) caused by Leishmania infantum is endemic in the Mediterranean area. In the last decades a northward spread of the parasite has been observed in Italy. This paper describes a VL outbreak in Modena province (Emilia-Romagna, Northern Italy) between 2012 and 2015. Methods. Retrospective, observational study to evaluate epidemiological, microbiological characteristics, and clinical management of VL in patients referring to Policlinico Modena Hospital. Results. Sixteen cases of VL occurred in the study period. An immunosuppressive condition was present in 81.3%. Clinical presentation included anemia, fever, leukopenia, thrombocytopenia, and hepatosplenomegaly. Serology was positive in 73.3% of cases, peripheral blood PCR in 92.3%, and bone marrow blood PCR in 100%. Culture was positive in 3/6 cases (50%) and all the isolates were identified as L. infantum by ITS1/ITS2 sequencing. The median time between symptom onset and diagnosis was 22 days (range 6-131 days). All patients were treated with liposomal amphotericin b. 18.8% had a VL recurrence and were treated with miltefosine. Attributable mortality was 6.3%. Conclusions. VL due to L. infantum could determine periodical outbreaks, as the one described; thus it is important to include VL in the differential diagnosis of fever of unknown origin, even in low-endemic areas.

Multidrug-resistant tuberculosis outbreak in an Italian prison: tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays.

The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the 'Casa Circondariale' of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice.

Age-related changes in the prevalence of precipitating antibodies to BK virus in infants and children.

Nearly 1000 sera from children were tested by immunoelectro-osmophoresis against BK virus, and age-specific prevalence rates were estimated from birth until the age of 12 years. Declining rates during the first 12 months showed the waning of passive immunity, which at birth reflects the mother's immune status. The changes of prevalence suggested that the peak incidence of primary infections occurred at about 2 years, with an estimated peak annual rate of 24.6%.

Pulmonary vascular disease in infants with complete atrioventricular septal defect.

In order to assess incidence and time of occurrence of pulmonary vascular disease, the lungs of 49 patients were studied histologically. Thirty-four lung specimens were obtained at autopsy, and 15 were open lung biopsies. Patients consisted of 24 males and 25 females ranging in age from 10 days to 14 years (median 9 months); 37 had Down's syndrome. Overall incidence of irreversible pulmonary vascular disease (grade 3 or more) under 1 year of age was 34.6%; grade 4 of pulmonary vascular disease was observed only in Down patients. In correlating pulmonary vascular resistance, measured during heart catheterization, with pulmonary vascular disease severity at histology, 6 out of 7 patients with pulmonary vascular resistance over 7 units per metre squared showed grade 4 of pulmonary vascular disease, and of these 4 were under 1 year of age. These findings suggest that a significant rate of pulmonary vascular disease occurs under 1 year of age, with most severe degrees in the time interval 7-12 months. They show that good correlation exists between pulmonary vascular resistance over 7 units per metre squared and grade 4 of pulmonary vascular disease. They demonstrate that the most severe pulmonary vascular disease is seen in Down's syndrome. Finally, they indicate that early surgical correction is mandatory and should be accomplished within 6 months of age.

Anatomical-echocardiographic correlations in pulmonary atresia with intact ventricular septum. Use of subcostal cross-sectional views.

Cross-sectional echocardiographic images from 26 patients presenting pulmonary atresia with intact ventricular septum were compared with anatomical findings in specimens having the same anomaly. The echocardiographic study was based on a subcostal approach using oblique projections, and specimens were cut in the same planes. Patients were classified into three groups. In the first group the morphologically right ventricle was represented by all of its three component parts: inlet, trabecular and outlet (12 cases). The second group was made up of patients with overgrowth of the apical component. Consequently the right ventricle had only two effective components: inlet and outlet (6 cases). In the third group, muscular overgrowth of both outlet and apical portions meant that the right ventricle was represented only by an inlet portion (8 cases). The good morphologic assessment and correlation with anatomic cuts, obtained in particular by using the "right oblique equivalent" view can avoid invasive study in this malformation prior to palliative surgery.

[Role of viruses in acute gastroenteritis]. / Inquadramento etiopatogenetico delle enteriti acute virali.

In a two years screening carried out on Florentine children we confirmed that Rotaviruses are the most important ethiological agents of acute gastroenteritis in infants less than two years old, irrespective of sex. We had evidence that Rotavirus diarrhea does not occur with the same incidence every year. Rotavirus gastroenteritis is characterized by profuse diarrhea, vomiting, fever and often by respiratory symptoms. Severe complications have not been observed.

Coronary angioplasty in single-vessel complex lesions: short- and long-term outcome and factors predicting acute coronary occlusion.

Percutaneous transluminal coronary angioplasty (PTCA) of complex coronary lesions (plaque ulceration and/or thrombus) has an increased risk of procedural complications. To assess the influence of these angiographic features on immediate and long-term results of PTCA, we prospectively compared the success rate, incidence of procedural complications, and restenosis rate in two groups of patients selected on the basis of the presence (study group = 30 patients) or absence (control group = 200 patients) of complex morphology at the time of angioplasty. The two groups were similar with regard to extent of coronary artery disease and site of coronary stenosis. Patients in the study group had a higher incidence of periprocedural acute coronary occlusion (47% vs 6%; p less than 0.01), which in 78% of the cases was successfully treated with repeat angioplasty and intracoronary thrombolysis. Univariate correlates of this complication were Canadian Cardiovascular Society class IV (57% vs 19%; p less than 0.05) and recent (less than 30 days) onset of worsening of symptoms (71% vs 31%; p less than 0.05). The incidence of acute myocardial infarction was slightly higher in the study group (6.7% vs 2%; p = NS), and the success rate with redilatation was the same (90%). Clinical and angiographic follow-up data were obtained from all patients in whom the procedure was successful; the restenosis rate was 55% in the study group compared with 36% in the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Type A aortic dissection: the role of angiography in identifying morphologic features in comparison with autopsy and surgical findings]. / Dissecazione aortica di tipo A: ruolo della angiografia nella valutazione delle caratteristiche morfologiche; confronto con i reperti anatomici e chirurgici.

To evaluate the reliability of cineangiography in identifying some morphologic characteristics of type A aortic dissection, the angiograms of 36 consecutive patients were retrospectively revised and compared with the surgical of necropsy findings. The following features were examined: site and extension of intimal tear (s); extension of the wall dissection; coronary and brachiocephalic arteries involvement; coexisting anuloaortic ectasia; aortic valve state. The angiographic diagnosis of site and extension of the intimal tear was correct in 97 (35/36) and 100% of cases respectively. In one case the presence of an intimal tear at the level of the aortic arch was missed because of the superimposition of the innominate artery. The extension of the wall dissection was correctly identified in 24 out of 25 patients. In one case the presence of distal false lumen thrombosis made the correct diagnosis impossible. The brachiocephalic arteries involvement was always correctly stated while the coronary involvement was suspected in 6 and confirmed in 5 (1 false positive). Anuloectasia was suspected in 12 and confirmed in 10 (2 false positives). In our experience the most challenging diagnosed were the presence of aortic arch tears and the aortic arch and coronary arteries involvement in the dissection. This study confirms that many morphologic features of type A aortic dissection can be adequately assessed by cineangiography.

[Serodiagnosis of rotavirus infections in gastroenteritis of infants]. / Sierologia diagnostica di infezioni da rotavirus in casi di gastroenterite infantile.

We report the use of the line immunoelectroosmophoresis (LIEOP), a modification of the immunoelectroosmophoresis (IEOP), for the serodiagnosis of rotavirus infection, in comparison with the complement fixation test. We tested 17 paired and 29 single sera from hospitalized children affected by acute gastroenteritis; rotavirus had been searched in the stools both by electron microscopy and IEOP. The LIEOP showed seroconversion in all the 11 cases with positive stools and also in 5 out of 5 patients whose stool sample had been negative. Either we had not been able to detect the virus, or there was an intervening (nosocomial) rotavirus infection. All sera which were reactive by complement fixation with bovine rotavirus were also reactive by LIEOP. Some of the sera which reacted by LIEOP, both with the homologous and the heterologous antigen, were negative by complement fixation.

[Aortic dissection: an incidence study based on hospital cases]. / Dissecazione aortica: studio dell'incidenza basato su una casistica ospedaliera.

To ascertain the incidence of aortic dissection, we retrospectively studied the data base of our hospital (Ospedale di Treviso-ULSS n 10). The population in the Treviso area is well defined as a geographic settlement and was sufficiently stable from a demographic point of view in the period examined (1976-1988). Patients were selected on the basis of established aortic dissection diagnosed by angiography, surgical inspection or autopsy. One hundred eighty-seven patients were included: 126 of them lived in the hospital-referring area (mean annual population of 239824 people in the study period). The calculated incidence of aortic dissection was 40.4 new cases/million inhabitants/year. This figure is consistently higher than that reported in the literature. The outcome of the study is discussed and data are compared with those of previously published papers.

Clinical and angiographic follow-up after coronary angioplasty in patients with two-vessel disease: influence of completeness and adequacy of revascularization on long-term outcome.

To assess the influence of the degree of revascularization on long-term results with angioplasty in multivessel disease, 151 consecutive patients with double-vessel disease and successful angioplasty in at least one vessel were prospectively followed up for a mean of 14 months (range 6 to 30 months) with clinical evaluation, an exercise stress test, and routine angiography. Patients were divided into three groups according to completeness and adequacy of revascularization: group 1--complete revascularization (no residual stenosis > or = 70%, 51 patients); group 2--incomplete but functionally adequate revascularization (residual stenosis > or = 70% in a vessel < 2 mm in diameter or supplying akinetic or dyskinetic segments of the left ventricle, 56 patients); group 3--incomplete and inadequate revascularization (residual stenosis > or = 70% in a vessel > or = 2 mm in diameter supplying normal or hypokinetic segments, 45 patients). There were no late deaths; one myocardial infarction occurred in group 1 patients, three in group 2, and two in group 3 patients (p = NS). Recurrence of angina was lower in group 1 (13 of 51 or 26%) and group 2 (16 of 56 or 28%) compared with group 3 (23 of 45 or 51%, p < 0.01). A positive stress test for ischemia was present in 20 patients (39%) of group 1, in 30 (54%) of group 2, and in 26 patients (58%) of group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Image analysis quantification of substance P immunoreactivity in the trapezius muscle of patients with fibromyalgia and myofascial pain syndrome.

OBJECTIVE: Substance P (SP), a neurotransmitter stored within the afferent nociceptive fibers, is likely to be involved in the pathogenesis of musculoskeletal pain. We investigated SP immunoreactive (SP-ir) nerve fibers in the upper trapezius of patients with fibromyalgia (FM) and myofascial pain syndrome (MPS) by immunochemistry. METHODS: Trapezius muscle obtained from tender points of 9 women with primary FM, from trigger points of 9 women with regional myofascial pain, and from 9 control women were immunostained with anti-SP sera. Quantitative evaluation was performed by computerized image analysis. RESULTS: No significant differences in the number of SP-ir areas were detected between groups (one way ANOVA: p = 0.2); in contrast, mean optical density (OD) of SP-ir showed a significant difference comparing the groups (one way ANOVA: p < 0.0001). Mean OD of the immunostaining for SP was statistically greater in trapezius muscle of patients with MPS (0.594 +/- 0.096) compared to specimens from patients with FM (0.436 +/- 0.140) (p < 0.05) and controls (0.314 +/- 0.105) (p < 0.05); mean OD of immunostaining for SP was greater in FM specimens than in controls (p < 0.05). CONCLUSION: Our results point to a peripheral hyperactivity of the peptidergic nervous system in FM as well as in MPS. These findings support the notion of pathogenetic involvement of the afferent nervous system in the development and perception of myofascial pain.