Human semen quality and environmental and occupational exposure to pollutants: A systematic review.

Background: The aim of the present systematic review was to evaluate the correlation between the exposure to environmental and/or occupational pollutants and possible alteration of semen quality, focalizing the attention on the studies performed using a biomonitoring approach. Methods: The review was conducted from inception to May 11 2023, according to the PRISMA Statement 2020 and using the following databases: Scopus, Pubmed and Web of Science. The protocol was registered on PROSPERO (CRD42023405607). Studies were considered eligible if they reported data about the association between exposure to environmental pollutants and alteration of semen quality using human biomonitoring. The quality assessment was carried out by the use of the Newcastle-Ottawa Quality Assessment Scale. Results: In total, 21 articles were included, conducted in several countries. The main matrices used for biomonitoring were urine and blood and the most sought-after contaminants were bisphenols, phthalates, pesticides, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, heavy metals and other inorganic trace elements. The results of the studies demonstrated a significant positive correlation between the increase of the pollutants' levels in the biological matrices examined and some alterations of the semen quality indicators, such as a decrease in motility, concentration and morphology of the spermatozoa. Conclusions: Male fertility can be negatively affected by the exposure to environmental and/or occupational pollutants. Human biomonitoring programs may be considered a useful tool for specific surveillance programs devoted to early highlight subjects who are more exposed to environmental pollutants in order to reduce risk exposure.

Percutaneous left atrial appendage closure reduces cost of care independent of the institutional cumulative caseload in patients with non-valvular atrial fibrillation.

BACKGROUND: Data on the impact of the cumulative percutaneous left atrial appendage closure (LAAC) caseload on cardiovascular outpatient and hospitalisation costs are limited. METHODS: The present single-institution analysis includes patients treated consecutively from the beginning of our LAAC experience in January 2012 until December 2016. Pre- and post-LAAC costs for hospitalisation and ambulatory visits were included. RESULTS: A total of 676 patients underwent percutaneous LAAC (using the Watchman device): 49 (2012), 78 (2013), 211 (2014), 210 (2015), and 129 (2016). LAAC procedural costs were stable over the years (overall median €9639; 2012: €9630; 2013: €10,003; 2014: €9841; 2015: €9394; 2016: €9530; p = 0.8) and there was no correlation between cumulative caseload and procedural costs (p = 0.9). Although annualised cardiovascular management costs after LAAC were lower than before LAAC (median difference between pre-LAAC and post-LAAC yearly costs: €727; 2012: €235; 2013: €1187; 2014: €716; 2015: €527; 2016: €1052; p = 0.5 among years analysed) from the beginning of the cumulative procedural experience, a significant reduction in costs was observed only from 2014 onwards. Institutional cumulative LAAC caseload and year of procedure were not related to the amount of reduction in the costs for cardiovascular care. CONCLUSION: LAAC led to cost-of-care savings from the beginning of our institutional procedural experience.

The cytokine storm and thyroid hormone changes in COVID-19.

BACKGROUND: COVID-19 is now a worldwide pandemic. Among the many extra-pulmonary manifestations of COVID-19, recent evidence suggested a possible occurrence of thyroid dysfunction. PURPOSE: The Aim of the present review is to summarize available studies regarding thyroid function alterations in patients with COVID-19 and to overview the possible physio-pathological explanations. CONCLUSIONS: The repercussions of the thyroid of COVID-19 seem to be related, in part, with the occurrence of a "cytokine storm" that would, in turn, induce a "non-thyroidal illness". Some specific cytokines and chemokines appear to have a direct role on the hypothalamus-pituitary-thyroid axis. On the other hand, some authors have observed an increased incidence of a destructive thyroiditis, either subacute or painless, in patients with COVID-19. The hypothesis of a direct infection of the thyroid by SARS-Cov-2 stems from the observation that its receptor, ACE2, is strongly expressed in thyroid tissue. Lastly, it is highly probable that some pharmaceutical agents largely used for the treatment of COVID-19 can act as confounding factors in the laboratory evaluation of thyroid function parameters.

How is small bowel permeability in endometriosis patients? a case control pilot study.

Endometriosis is a chronic inflammatory disease of women of reproductive age. Small bowel (SB) permeability and lipopolysaccharides (LPS) could play a role in the perduration of low grade inflammation status and the pathogenesis of endometriosis. To clarify this hypothesis, we measured SB permeability through plasma values of LPS and urinary secretion of lactulose (La), mannitol (Ma) and their ratio (L/M) in patients with endometriosis compared with healthy controls (HC). Eight patients and 14 HC entered the study. SB permeability was evaluated by high-performance liquid chromatography of urine concentrations of La and Ma. Plasma levels of LPS were measured in the blood. Moreover, a nutritional, gastroenterological, quality of life evaluation was performed through validates questionnaires and complete gynaecological evaluations. The statistical analysis of the obtained data did not show differences in anthropometric and nutritional characteristics and gastrointestinal functional disease in the two groups. Patients reported higher levels of pelvic chronic pain (3.87 ± 2.99 vs 0.15 ± 0.55; pe = 0.001) and significantly higher LPS plasma levels (0.529 ± 0.11 vs 0.427 ± 0.08; p value = .027) than HC. Our results indicate that intestinal permeability is abnormal in endometriosis patients, and it might play a role in the pathogenesis of this chronic disease.

Transcatheter aortic valve replacement with the 34 mm Medtronic Evolut valve : Early results of single institution experience.

OBJECTIVES: To report our experience with the recently introduced 34 mm Evolut transcatheter aortic valve replacement (TAVR) prosthesis. BACKGROUND: A larger TAVR prosthesis has become available for the treatment of aortic stenosis (AVS) in larger native aortic annuli (up to 30 mm). Outcomes with this new device are still unreported. RESULTS: The first 25 transfemoral TAVRs performed by our team with the self-expandable 34 mm Evolut are presented. The majority of patients were male (84%) with a mean age of 81.3 ± 5.6 years, a median logistic euro-SCORE of 14.7 (5.4-61.0), and a computed tomography measured mean perimeter-derived aortic annulus diameter of 27.1 ± 1.4 mm (min. 25.0-max. 31.2 mm). We implanted one 34 mm Evolut in all patients. Median operative time and radiation time were 68.5 and 12.4 min respectively. To optimise final valve position and haemodynamic performance, at least one complete re-sheathing and re-positioning of the same valve was reported in 33.2%. New permanent pacemaker implantation (PPMI) was necessary in 28.5%. At Receiver Operating Characteristic (ROC) analysis, a minimal diameter of the left ventricular outflow tract <21.9 mm was a significant predictor for PPMI (specificity 82%; sensitivity 83%; p = 0.005; Area Under the Curve (AUC) = 0.9). Length of stay in hospital was 9.2 ± 5.8 days and no in-hospital death was reported. At discharge, grade 1 + para-valvular regurgitation was present in 32%, and no regurgitation in the remaining patients. Device success and early safety were 100% and 92% respectively. CONCLUSIONS: TAVR with the 34 mm Evolut prosthesis has shown satisfactory acute outcomes. Although results are consistent with those observed with smaller Evolut prostheses, a trend for a higher PPMI rate has been noticed and could derive from a higher oversizing rate.

Mitro-aortic pathology: a point of view for a fully transcatheter staged approach.

Severe aortic valve stenosis (AVS) and mitral valve regurgitation (MVR) often coexist. Although a fully percutaneous treatment for the two conditions, by means of transcatheter aortic valve implantation (TAVI) followed by MitraClip, can be appealing in selected high-risk candidates, critical and strategical reasoning should be applied. In a 3-year period we have developed a single-centre experience of 14 patients who were managed with a staged percutaneous approach to treat severe AVS and MVR. The average interval from TAVI to MitraClip repair was 101 ± 12 days. Success for TAVI was 100% and 92.9% (13/14) for MitraClip. At late follow-up, 3 patients developed MVR 3+. Estimated 1­year survival was 66.5%. Freedom from 1­year endpoint (death, stroke, major bleeding, myocardial infarction, and cardiac re-hospitalisation) was 57.9%.In our view, a fully transcatheter approach for mitro-aortic pathology is feasible and should be performed only as a staged procedure in those patients that remain symptomatic, in spite of successful TAVI. It should be emphasised that although the periprocedural success rate is satisfactory, follow-up mortality and re-hospitalisation rates remain high, even at mid-term follow-up. This most probably results from the advanced clinical picture at time of referral for treatment.

MitraClip step by step; how to simplify the procedure.

The MitraClip system is a device for percutaneous edge-to-edge reconstruction of the mitral valve in patients with severe mitral regurgitation who are deemed at high risk for surgery. Studies have underlined the therapeutic benefit of the MitraClip system for patients at extreme and high risk for mitral valve surgery, suffering from either degenerative or functional mitral regurgitation. The MitraClip procedure shows low peri-procedural complication rates, and a significant reduction in mitral regurgitation, as well as an improvement in functional capacity and most importantly quality of life. It hereby widens the spectrum of mitral valve repair for the Heart Team. The current review underscores the efficacy of the procedure and describes the technique to simplify the procedure.

Introducing transcatheter aortic valve implantation with a new generation prosthesis: Institutional learning curve and effects on acute outcomes.

OBJECTIVES: We present our single-centre experience with the direct flow medical (DFM) trans-catheter aortic valve implantation (TAVI) prosthesis addressing the impact of learning curve upon outcomes. BACKGROUND: The DFM has been recently introduced for TAVI. The prosthesis presents original design and implantation features. METHODS: Patients were divided into three groups according to the chronological implantation sequence that reflected technical skills acquisition of the entire team. RESULTS: Group I included the first 20 patients (early learning phase), group II the second 20 patients (proctoring to other members of the team), and group III the following 93 patients (technique consolidation). Differences in baseline and procedural variables were analysed. Nonparametric correlation and linear regression were used to identify changes according to institutional cumulative experience. There was a significant correlation between catheterisation time and institutional experience (rho = -0.4; p < 0.0001) confirmed at linear regression (beta = -0.2; p = 0.001; CI: -0.3 - -0.08). Moreover, there was lower rate of valve retrieval in group III (15% vs. 20% vs. 10%; p = 0.5). No intra-procedural mortality was reported and improved early safety (at 30 days) was observed (80% vs. 85% vs. 87.1; p = 0.7). At hospital discharge, valve haemodynamic performance was satisfactory with only mild regurgitation in 10% (I), 20% (II), and 9.7% (III) (p = 0.8). CONCLUSIONS: DFM adequate sizing and implantation can be achieved after the early learning phases. A significant reduction in catheterisation time is reported after the first 20 patients. Results remain satisfactory during the proctoring and technical consolidation phase.

[We carry out too many TAVI - contra]. / Wir machen zu viele TAVI - Kontra.

Transcatheter aortic valve implantation (TAVI) is an established and approved procedure with an increasing implantation rate, whilst the number of surgical aortic valve replacements (SAVR) remained unchanged (AQUA data). This demonstrates that more patients who were unsuitable for SAVR were treated with TAVI. First randomized trials have shown a significant survival benefit for TAVI compared to conservative therapy (PARTNER B) and non-inferiority to SAVR in high-risk patients (PARTNER A). The US pivotal trials demonstrated even a significant survival benefit in TAVI patients compared to SAVR. The current 5-year data of the PARTNER trials demonstrate a long-term durability of the TAVI valves, which even have superior hemodynamic parameters. Increasing experience, optimization and evolution of the TAVI systems lead to better results and lower rates of complications and mortality, as was shown by the "real world data" from the German aortic valve registry (GARY). The analysis of the subgroups and also the Nordic aortic valve intervention (NOTION) study showed equivalent results for TAVI and SAVR in patients with intermediate and low risk. There is a trend to expand the indications to patients with intermediate risk and the currently ongoing large prospective and randomized trials SURTAVI and PARTNER II could provide greater clarity.

Cesarean section during ECMO support.

This article presents the case of a pregnant woman affected by A/H1N1 flu progressed to ARDS requiring rescue therapy by VV ECMO. Due to the early gestational age, the patient was placed on ECMO before delivery. Four weeks after VV-ECMO placement, a Cesarean section was successfully performed while on ECMO support. One week after delivery, the patient was weaned from ECMO and at 8 weeks from admission she was discharged home without O2 support. The newborn is alive and was discharged at 40 days of age on neurological follow-up.

Primary graft failure after heart transplantation: the importance of donor pharmacological management.

BACKGROUND: Primary graft failure (PGF) remains the strongest determinant of perioperative mortality after heart transplantation (HT). Donor management may play an important role in the incidence of PGF. MATERIALS AND METHODS: Multivariate analysis was used to identify PGF determinants after HT. Donor and recipient data were analyzed together with preharvest management information and perioperative results. PGF was defined as the need for mechanical circulatory support immediately post-HT. RESULTS: Isolated HT was performed in 54 consecutive patients from January 2006 to June 2009. PGF occurred in 11 (20%) patients. Upon univariate analysis, preoperative mean pulmonary arterial pressure was significantly higher among patients developing PGF (P=.02). The donors for PGF patients had more often been managed with high inotropic support (dopamine>10 microg/kg/min and/or alpha agonists>0.06 microg/kg/min; P=.008). In contrast, death for head trauma was more common among donors for patients who did not develop PGF (P=.02). In-hospital mortality was 13% (7/54); 71% of these deceased patients displayed PGF (5/7). Upon multivariate analysis, preharvest high donor inotropic support was the strongest determinant of PGF (P=.01, odds ratio [OR]=7.5). Donor death due to head trauma showed a protective effect against PGF (P=.03, OR=0.1). CONCLUSION: PGF remains a lethal perioperative complication despite modern tools for prompt cardiac mechanical assistance. As a result of the organ shortage, many centers accept marginal hearts assuming that donor hemodynamic management shows a reduced impact on PGF. We suggest a timely evaluation of the hazards for PGF whenever high inotropic support is used, especially among donors dying for causes other than head trauma.

Successful lung transplantation in an HIV- and HBV-positive patient with cystic fibrosis.

Prior to the advent of highly active antiretroviral therapy (HAART), HIV-infected patients were usually not considered as transplant candidates because of the poor prognosis of their underlying disease and concerns regarding the potential detrimental effects of immunosuppression on viral load and immune status. However, with the significant HAART-associated improvements in morbidity and mortality, good short-term outcomes after liver and kidney transplantation for patients with HIV infection have been reported. Nevertheless, HIV infection is currently considered a contraindication to lung transplantation in most transplant centers worldwide. The results of a double lung transplant performed in an HIV and HBV co-infected patient with cystic fibrosis (CF) and end-stage respiratory failure (ESRF) are presented after a 2-year follow-up. Approval of and recommendations for the management of this patient were obtained from the Italian National Center for Transplantation as an extension of the ongoing Italian protocol for liver and kidney transplantation in HIV-infected individuals. The operation was successful and the patient recovered rapidly after surgery. A cautious infectious and immunosuppressive management allowed so far the avoidance of major infectious complications and rejection. To the best of our knowledge, this is the first report of lung transplantation in an HIV and HBV co-infected patient.

Regulation of lysophosphatidic acid receptor-stimulated response by G-protein-coupled receptor kinase-2 and beta-arrestin1 in FRTL-5 rat thyroid cells.

Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that activates a variety of biological activities including cell proliferation. Three mammalian LPA receptor (LPAr) subtypes have been identified by molecular cloning, named lp(A1), lp(A2) and lp(A3), that are coupled to heterotrimeric G-proteins for signal transduction. The LPAr are endogenously expressed in the rat thyroid cell line FRTL-5 and we used the FRTL-5 cells permanently transfected to obtain moderate overexpression of G-protein-coupled receptor kinase-2 (GRK2) or beta-arrestin1 to study whether GRK2 and beta-arrestin1 desensitise LPAr-mediated signalling and regulate LPA-stimulated functional effects. Using RT-PCR we documented that lp(A1), lp(A2) and lp(A3) receptors are all expressed in FRTL-5 cells. We then analysed the signal transduction of the LPAr in FRTL-5 cells. Exposure to LPA did not stimulate inositol phosphate formation nor cAMP accumulation but reduced forskolin-stimulated cAMP. LPA was also able to stimulate MAP kinase activation and this effect was abolished by pertussis toxin pretreatment. These results suggest that LPAr are mainly coupled to a pertussis toxin-sensitive G-protein in FRTL-5 cells. In order to investigate whether GRKs and arrestins are involved in the regulation of LPAr-mediated signalling, we used the FRTL-5 cell line permanently transfected to overexpress GRK2 (named L5GRK2 cells) or beta-arrestin1 (L5betaarr1 cells). The ability of LPA to inhibit forskolin-stimulated cAMP accumulation was blunted in L5GRK2 and more markedly in L5betaarr1. The MAP kinase activation was also blunted in L5GRK2 and in L5betaarr1B cells. Exposure to 20 microM LPA increased the phosphorylation of extracellular signal-regulated kinases ERK1/2 by approximately 3-fold in L5pBJI cells (FRTL-5 cells transfected with the empty vector pBJI) while it induced a modest increase in L5betaarr1 and was ineffective in L5GRK2. We measured [3H]thymidine uptake in L5betaarr1B and in L5 GRK2 cells to test whether GRK2 and beta-arrestin1 could have a role in the regulation of LPAr-mediated cell proliferation. The mitogenic response induced by 35 microM LPA was substantially blunted in L5betaarr1 (-69+/-6%) and in L5GRK2 (-69.8+/-4.5%) cells as compared with L5pBJI. Our findings document that the receptor-mediated responses elicited by LPA are regulated by GRK2 and beta-arrestin1 in FRTL-5 cells and indicate that this mechanism is potentially important for the control of the LPA-stimulated proliferative response.

Use of the Internet by patients before and after cardiac surgery: telephone survey.

BACKGROUND: Little is known about to what extent patients who underwent medical treatment access the Internet and whether they benefit from consulting the Internet. OBJECTIVE: To understand if cardiopathic patients use the Internet for health-related information and whether they find retrieved information understandable and useful. METHODS: Telephone interviews, using a semi-structured questionnaire, were conducted with 82 patients who had undergone off-pump coronary-artery bypass grafting at the Center for Less Invasive and Robotic Heart Surgery in Buffalo, New York, USA. Study design was multidisciplinary, combining expertise of medical and communication science. Sources of medical information were identified (doctor, Internet, magazines, newspapers, television, radio, family members). Accessibility, quality, and readability of Internet medical information from the patients point of view were investigated. RESULTS: Out of 82 patients, 35 (35/82, 42.7%) were Internet users. Internet users had a significantly higher education level than Internet non-users (college education: 42.9% of users, 10.6% of non-users; P <.001). Among the Internet users, 18 (18/35, 51.4%) had used the Internet for retrieving medical information; 17 (17/35, 48.6%) had not. No statistically significant differences in demographic data were found when comparing these 2 sub-groups of patients. Family-members involvement was high (15/18, 83.3%). Internet medical information was rated helpful in most cases; readability was acceptable for only 3 patients (3/18, 16.7%). To improve on-line medical information, all patients interviewed suggested sites designed by their physicians. CONCLUSIONS: Although 1 in 5 patients in our sample has used the Internet to retrieve medical information, the majority of them experiences difficulties comprehending the information retrieved. Health-care providers should provide Internet medical information that is adequate for the non-medical public's needs.

Thyrotropin activates mitogen-activated protein kinase pathway in FRTL-5 by a cAMP-dependent protein kinase A-independent mechanism.

The involvement of mitogen-activated protein (MAP) kinases in the mitogenic effect of thyrotropin (TSH) is not fully elucidated. In FRTL-5 cells, we found that the MAP kinase kinase (MEK) inhibitors UO126 and PD98059 substantially decreased TSH-induced DNA synthesis, indicating that MAP kinases are involved in the TSH-stimulated proliferative response. Accordingly, TSH, forskolin (FSK) and 8-bromo-cAMP induced a rapid (3 min) and transient activation of ERK1/2, as assessed by phosphorylation of myelin basic protein and ERK1/2. This effect was cAMP-dependent and protein kinase A (PKA)-independent. The activation of Rap1 and B-Raf was involved in the mechanism of MAP kinase stimulation by TSH. TSH induced rapid (3 min) GDP/GTP exchange and activation of Rap1. After a 3-min exposure to FSK, B-Raf was recruited to a vesicular compartment, where it colocalized with Rap1. Both activation of Rap1 and translocation of B-Raf were PKA-independent. The Rap1 dominant negative Rap1N17 significantly reduced TSH-stimulated but not insulin-like growth factor 1-stimulated ERK1/2 phosphorylation, whereas the Ras dominant negative RasN17 inhibited the effect of both agonists. In conclusion, our results document that TSH increases intracellular cAMP, which rapidly stimulates MAP kinase cascade independent of PKA. This novel mechanism could integrate other pathways involved in TSH-stimulated proliferative response.