Assisted reproduction and Coronavirus in Italy.

OBJECTIVE: A novel type of Coronavirus was identified in China in December 2019. The first cases of a form of pneumonia of unknown etiology were detected at the beginning of that month in Wuhan. The virus is believed to have emerged at the Wuhan Huanan Seafood Market, where transmission of a zoonotic pathogen to humans occurred. PATIENTS AND METHODS: Some studies conducted in China during the epidemic report small numbers of pregnant women infected with SARS-CoV-2 and some pregnancy complications in patients with COVID-19. However, they fail to document the transplacental passage of the virus from mother to fetus. RESULTS: Following the COVID-19 outbreak, guidelines for couples who are undergoing treatments of assisted reproduction have been issued by the International Federation for Fertility Societies (IFFS), the American Society for Reproductive Medicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE) and the Latin American Network of Assisted Reproduction (REDLARA). They recommend couples to discuss assisted reproduction with their doctors while those at risk or with SARS-CoV-2 should consider freezing oocytes or embryos and retransferring them later. CONCLUSIONS: Other than the US, Italy is the country with the highest number of cases (197675 positives, 26644 deaths) (updated on April 26). The Italian National Transplant Centre and the Higher Institute of Health advised on March 17 to complete the cycles already started and not to start new cycles. Phase 2 will begin on 4 May with an increase in freedom of action and fertilization treatments will start again. The Society that brings together embryologists (SIERR) has issued the guidelines to be followed when this happens.

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes.

OBJECTIVES: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027- Clostridium difficile infection (CDI). METHODS: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027- CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. RESULTS: Overall, 238 patients with 027+ CDI and 267 with 027- CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549-3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906-5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051-3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281-4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437-9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155-125.000, p 0.007) were associated with recurrence in 027- CDI. CONCLUSIONS: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity.

Common medium versus advanced IVF medium for cryopreserved oocytes in heterologous cycles.

Granulocyte-macrophage colony-stimulation factor plays different crucial roles during embryo implantation and subsequent development. Here we aimed to evaluate the effects of embryo cell culture medium, with the inclusion of granulocyte-macrophage colony-stimulation factor (GM-CSF), on embryo development and pregnancy rate. To this end, we took advantage of our retrospective observational study to correlate the outcomes from two different culture media. We included in this study 25 unselected patient from our IVF Center that underwent heterologous IVF cycle with crypreserved oocytes. We analyze the fertilization rate, pregnancy rate, and embryo quality at different day of transfer obtained from two different media composition. Our results show that the rate of fertilization and the pregnancy rate were increased using medium added with this particular type of cytokines (GM-CSF).

Role of transvaginal ultrasound in evaluation of ureteral involvement in deep infiltrating endometriosis.

OBJECTIVE: To assess whether routine examination of the ureters on transvaginal sonography (TVS) can identify reliably potential silent ureteral involvement by endometriosis and should therefore be recommended in all patients with deep infiltrating endometriosis (DIE). METHODS: This was a prospective study of 200 consecutive patients scheduled for surgery for DIE, evaluated between January 2012 and December 2014 at a tertiary endometriosis center at Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. Routine TVS, abdominal ultrasound and gynecological examination were performed within 3 months before surgery, and patient history, signs and symptoms were recorded. Surgical and histological findings were compared with the preoperative ultrasonographic diagnosis. The main outcome of interest was the presence of ureteral dilatation or hydronephrosis caused by endometriosis. RESULTS: Of 200 patients with DIE, associated ureteral dilatation was diagnosed on TVS in 13 (6.5%) cases. Ureteral involvement was confirmed intraoperatively in all 13 cases by detection of ureteral dilatation caused by endometriotic tissue surrounding the ureter and causing stenosis. Of the 13 patients with ureteral dilatation, renal ultrasound detected six (46.2%) cases of hydronephrosis. Mean duration of visualization and study of dilated ureters was 5 min (range, 3-9 min). Ureteric diameter was ≥ 6 mm in all cases of ureteral dilatation, with a median diameter of 6.9 mm (range, 6-18 mm). Both ureters were identified on TVS in all 200 patients with DIE. CONCLUSIONS: Our study confirms a relatively high incidence of ureteral involvement in patients with DIE. TVS appears to be a reliable tool for the diagnosis of ureteral involvement and, additionally, it allows the detection of both the level and degree of obstruction. Our findings confirm that TVS examination is an accurate non-invasive diagnostic tool for the detection of ureteral involvement by endometriosis. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Assessment of risk factors for candidemia in non-neutropenic patients hospitalized in Internal Medicine wards: A multicenter study.

BACKGROUND: An increasing prevalence of candidemia has been reported in Internal Medicine wards (IMWs). The aim of our study was to identify risk factors for candidemia among non-neutropenic patients hospitalized in IMWs. METHODS: A multicenter case-control study was performed in three hospitals in Italy. Patients developing candidemia (cases) were compared to patients without candidemia (controls) matched by age, time of admission and duration of hospitalization. A logistic regression analysis identified risk factors for candidemia, and a new risk score was developed. Validation was performed on an external cohort of patients. RESULTS: Overall, 951 patients (317 cases of candidemia and 634 controls) were included in the derivation cohort, while 270 patients (90 patients with candidemia and 180 controls) constituted the validation cohort. Severe sepsis or septic shock, recent Clostridium difficile infection, diabetes mellitus, total parenteral nutrition, chronic obstructive pulmonary disease, concomitant intravenous glycopeptide therapy, presence of peripherally inserted central catheter, previous antibiotic therapy and immunosuppressive therapy were factors independently associated with candidemia. The new risk score showed good area under the curve (AUC) values in both derivation (AUC 0.973 95% CI 0.809-0.997, p<0.001) and validation cohort (0.867 95% CI 0.710-0.931, p<0.001). A threshold of 3 leads to a sensitivity of 87% and a specificity of 83%. CONCLUSION: Non-neutropenic patients admitted in IMWs have peculiar risk factors for candidemia. A new risk score with a good performance could facilitate the identification of candidates to early antifungal therapy.

The use of r-hFSH in treatment of idiopathic male factor infertility before ICSI.

OBJECTIVE: To evaluate the efficacy of pre-treatment of idiopathic oligozoospermic patients with r-hFSH to improve the clinical results of ICSI. PATIENTS AND METHODS: 82 infertile couples due to male factor who attended our center were included in the study. Thirty-six were randomized to the treatment group (group A) and forty-six to the control group (group B). The male partners in group A were treated with recombinant human FSH (r-hFSH; Gonal F®) 150 IU subcutaneously three times a week for a 3-months period. The control group (group B) did not receive any treatment. After the treatment couples of both groups underwent a cycle of ICSI. RESULTS: The fertilization rate was comparable in both groups. However, in the treatment group (group A), the clinical pregnancy rate was significantly higher (42%) compared to the control group (group B) (20%) (p < 0.02). Also, the implantation rate was significantly higher in treatment group (26%) compared to the control (15%) (p < 0.04). Miscarriage rate was lower (15.7%) in the treatment group than in the control (43.7%), and this difference was statistically significant (p < 0.05). CONCLUSIONS: Treatment of idiopathic male factor infertility with r-hFSH before ICSI improves clinical pregnancy rate, increases implantation rate and decreases the early pregnancy loss.

Risk factors and clinical outcomes of candidaemia in patients treated for Clostridium difficile infection.

The alterations occurring in the intestinal flora during Clostridium difficile infection (CDI) may promote the translocation of Candida to the blood and the development of candidaemia. The aim of our study was to analyse clinical findings of these patients to determine the risk factors associated with the development of candidaemia subsequent to CDI. We compared 35 patients with candidaemia subsequent to CDI with 105 patients with CDI. Patients with candidaemia showed more severe infections and higher mortality. The ribotype 027 strain and vancomycin treatment at ≥ 1000 mg/day were prevalent in patients developing candidaemia. CDI may predispose to the translocation of Candida.

Role of empirical and targeted therapy in hospitalized patients with bloodstream infections caused by ESBL-producing Enterobacteriaceae.

BACKGROUND: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase (ESBL) producing Enterobacteriaceae are a major cause of in-hospital mortality. The effect on survival of empirical and targeted antibiotic therapy in these patients remains controversial. METHODS: A prospective cohort study was conducted analyzing data from 94 patients (age 59 ± 21 years) with BSI due to ESBL producing strains (Sixty-one E. coli, 26 K. pneumoniae, 4 Proteus spp and 3 Enterobacter spp). RESULTS: Risk factors associated with 21-day mortality at univariate analysis were: recent administration of antibiotic therapy (p=0.049), higher SOFA score (p=0.05), ICU stay (p <0.01), hypotension at presentation (p =0.001) or septic shock (p <0.001) and bacteremia from source other than urinary tract (p=0.03). Regardless of antibiotic class used, no differences in survival were noted between patients receiving or not adequate initial antimicrobial treatment (37.1% vs 23.7% p=0.23); on the other hand, compared with the administration of other in vitro active antibiotics, the use of carbapenem as definitive therapy was associated with a significantly lower 21-day mortality (54.3% vs 28.5% p=0.02). CONCLUSIONS: These findings suggest that the administration of an adequate initial therapy is not associated with mortality in hospitalized patients with BSI due to Enterobacteriaceae. The severity of clinical conditions at presentation and the administration of carbapenems as definitive therapy seems to be really important in affecting the outcome of patients with BSI due to ESBL producing strains.

A cluster of fulminant Clostridium difficile colitis in an intensive care unit in Italy.

We describe, for the first time, a cluster of lethal fulminant health-care associated Clostridium difficile (CD) colitis in Italy, observed in the intensive care unit (ICU) of an Italian tertiary care hospital in Rome. For all cases the cause of ICU admission was CD-related septic shock. Three out of seven patients were residents in a long-term care facility in Rome, and the others had been transferred to the ICU from different medical wards of the same hospital. Five patients died within 96 h of ICU admission. Because of a clinical deterioration after 4 days of adequate antibiotic therapy, two patients underwent subtotal colectomy: both of them died within 30 days of surgical intervention. In four cases, ribotyping assay was performed and ribotype 027 was recognized. This high mortality rate could be attributable to three findings: the extent of disease severity induced by the strain 027, the delay in antimicrobial therapy administration, and the lack of efficacy of the standard antibiotic treatment for fulminant CD colitis compared to an earlier surgical approach. In order to contain a CD infection epidemic, control and surveillance measures should be implemented, and empirical therapy should be administered. Because of potential 027 ribotype CD spread in Italy, CDI should be regarded with a high index of suspicion in all patients presenting with shock and signs or symptoms suggesting abdominal disease, and an early surgical approach should be considered.

Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients.

Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

Plasminogen activator production in a rat model of Pneumocystis carinii pneumonia.

Several studies have indicated that the serine protease urokinase-plasminogen-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (BAL) samples of immunosuppressed rats both with and without PCP, we observed a decrease in uPA activity as well as a decrease in cell number. Urokinase-PA production by AMs was reduced in rats treated with cortisone alone. However, an increase in cell-associated uPA was observed in rats with PCP. This increase appears to be produced in response to P carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed uninfected rats were challenged with P carinii, a significant increase in PA activity in cell lysates was observed, though a lower response was obtained in cortisone-treated animals. Our results suggest that healthy AMs respond to the presence of P carinii with an increase in uPA production and that this response in immunodepressed rat-AMs is partially impaired.

Arthritis as a rare side effect of phenytoin therapy.

Anticonvulsant hypersensitivity syndrome is an uncommon side effect of phenytoin. It is characterized by fever, skin reactions, lymphadenopathy, and severe multiorgan involvement. Atypical clinical features have rarely been described. We observed a unique case of anticonvulsant hypersensitivity syndrome in a 77-year-old woman in whom fever and monoarthritis were the main clinical features. Symptoms dramatically subsided after phenytoin withdrawal.

CD4(+) T-lymphocytopenia and Pneumocystis carinii pneumonia in a patient with miliary tuberculosis.

We report a case of miliary tuberculosis (MTB) occurring after extracorporeal shock-wave lithotripsy in a 51-year-old man. The MTB was complicated by pancytopenia and CD4(+) T-lymphocytopenia, which was responsible for Pneumocystis carinii pneumonia. Hematological parameters returned to normal in response to antituberculous treatment.

Prosthetic biologic valve endocarditis caused by a vancomycin-resistant (vanA) Enterococcus faecalis: case report.

We recently observed (February 1999) a 68-year old patient with endocarditis on a prosthetic biologic valve caused by a vancomycin-resistant Enterococcus faecalis. Broth dilution tests showed susceptibility to ampicillin (MIC=0.5 microg/ml), no high resistance to aminoglycosides (MIC for gentamicin <500 microg/ml) and resistance to vancomycin (MIC >256 microg/ml) and teicoplanin (MIC >16 microg/ml). A PCR assay detected vanA gene in this strain. A transthoracic echocardiogram did not show valvular vegetations. A possible endocarditis was diagnosed and the patient received ampicillin for 8 weeks and gentamicin for 6 weeks. The patient remained afebrile after a 4-month follow-up when he underwent surgical replacement of the dysfunctional bioprosthetic valve. Mitral valve was sterile on culture, but histology confirmed the diagnosis of previous endocarditis. This is the third case of endocarditis caused by vancomycin-resistant E. faecalis reported to date.

[New therapeutic prospects in heart failure. ACE inhibitors and beta blockers]. / Nuove prospettive terapeutiche dello scompenso cardiaco. ACE-inibitori e beta-bloccanti.

Heart failure, still nowadays an important cause of morbidity and mortality in many countries, is a complex of symptoms related to inadequate peripheric perfusion and often to the retention of fluid, that results from an impaired left ventricular pump function. Treatment of heart failure has seen considerable changes in the last years. Short term goals of therapy are directed towards the relieve of symptoms that can be commonly managed by the use of vasodilators, diuretics, digoxin, in order to obtain an improvement in myocardial functional capacity and quality of life of patients. Nevertheless, it is important to recognize that improvement of symptoms is not necessarily correlated with correction of left ventricular dysfunction and, most important, with improvement of survival. In late 1980s both experimental and clinical observations carried out in an attempt to explain the progression of the disease and its poor long-term survival, led the physicians to think about heart failure as a neurohormonal disorder. This new conceptual model has first led to the widespread introduction of angiotensin converting inhibitors in clinical practice; then, the evidence that sympathetic activation might play an important role in the progression of heart failure, led the investigators to propose that beta-blocking agents might be useful in the management of heart failure. Accumulating clinical evidence indicates that beta blocker therapy, particularly with third generation beta-blocking agents, not only improves left ventricular function but also may reduce and reverse pathological remodeling in the heart. Ongoing large scale clinical trials may confirm the mounting evidence, from numerous clinical studies, that these agents may prolong survival in patients with heart failure.