Search

Background/Objectives : Obesity is an established risk factor for several infective conditions, including Acute Bacterial Skin and Skin Structure Infections (ABSSSIs), with a rising trend in their incidence expected in this population. Although numerous antibiotics are available for the prevention and treatment of ABSSSIs, their characterization in obese patients is not a regulatory mandate, highlighting a knowledge gap in this field. Dalbavancin (DAL) is the first approved long-acting antibiotic for the treatment of ABSSSIs. The aim of the study was to describe the clinical effectiveness of DAL in the treatment of ABSSSI, with or without concomitant osteoarticular infections (OAIs), in obese patients compared with non-obese patients. Furthermore, we compared the effectiveness of DAL and intravenous standard of care (SOC) regimens in a subgroup of obese patients with ABSSSI. Results : Overall, 45 subjects treated with DAL (12 obese and 33 non-obese) and 8 obese subjects treated with SOC regimens (1:1 ratio) were included. Obese patients treated with DAL had a similar clinical resolution to non-obese patients. However, obese patients tended to have a better cure rate in ABSSSI than OAI. The subgroup of obese patients with ABSSSI had a high clinical resolution, which was comparable to that of SOC. DAL was overall highly tolerated in obese patients. Methods : Over a three-year period, hospitalized subjects with ABSSSI who were treated with DAL were included. Patients were further divided into two groups according to the presence/absence of obesity (BMI ≥ 30 kg/m 2 ). Furthermore, obese patients treated with DAL were compared with obese patients treated with SOC (1:1 ratio). Conclusions : In our real-world study, DAL confirmed its high effectiveness in the treatment of ABSSSI, including in a difficult-to-treat population such as obese patients.

Objective: To study the effect of switching to a follicle-stimulating hormone (FSH) preparation other than that to which infertile male patients have not had an effective response. Patients and methods: Seventy-four normogonadotropinemic, non-obstructive, oligozoospermic patients who were poor responders to the administration of highly purified FSH (hpFSH) (Group 1 (n = 22) and Group 3 (n = 15)) or to recombinant human FSH (rhFSH) (Group 2 (n = 22) and Group 4 (n = 15)) were selected for this prospective study. After 3 months of washout from treatment with the first FSH preparation of choice, rhFSH was administered to patients in Groups 1 and 4 and hpFSH to those in Groups 2 and 3. Serum luteinizing hormone, FSH, total testosterone levels, conventional sperm parameters, testicular volume, and the number of pregnancies were evaluated at study entry and after the first and second treatment cycles. Results: Comparing treatment groups, the greatest improvement in sperm parameters was recorded in the groups of patients prescribed the switch in FSH preparation. Group 1 had the greatest benefit from therapy, with the highest pregnancy rate after the second treatment cycle. Indeed, eight couples achieved pregnancy (36.4%), compared to Groups 2 (n = 4; 18.2%), 3 (n = 1; 6.7%), and 4 (n = 2; 13.3%) ( p = 0.04). Conclusions: The results of this study suggest that a therapeutic scheme involving the "switching" of the FSH preparation yields better results than a protocol using the same FSH preparation for six months. These findings, if confirmed by further studies, will help us better design a treatment strategy with FSH for infertile patients with oligozoospermia.

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment performed in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections after endovascular popliteal aneurysm repair (EPAR) are the most dangerous complications to occur as they involve serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity., Case Report: We report two patients who were admitted to the emergency room of our hospital for pain and edema in the lower leg. Both patients had undergone exclusion of a ruptured PA a few years before by endovascular graft. CTA testing showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus capitis in the first case and S. aureus in the second. Prophylactic antibiotics were administered for 10 days, then patients underwent an open surgical conversion with the complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and a biological bovine pericardium prosthesis in the second case. The infective department of our hospital had defined a discharged specific antibiotic therapy for each patient, based on intraoperative microbiological samples. Furthermore, we have examined the literature and found six more cases described in case report articles that refer to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice., Conclusions: The open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection after an endovascular popliteal aneurysm repair procedure.

Introduction: Real-life experience with imipenem/cilastatin/relebactam (IMI/REL) for the treatment of KPC-producing Klebsiella pneumoniae complex (KPC-Kp) and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa (DTR-PA) infections is herein described., Methods: Adult patients with KPC-Kp or DTR-PA infections who received ≥48 h of IMI/REL were included. Clinical and microbiological outcomes were retrieved through the medical records. Primary outcome was clinical cure. Secondary outcomes included mortality from infection onset and adverse effects attributable to IMI/REL., Results: We included 10 patients with different infections caused by DTR-PA ( n  = 4), KPC-Kp [ n  = 5, of which 3 ceftazidime/avibactam-resistant (CTV-R KPC-Kp), 2 CTV susceptible (CTV-S KPC-Kp)] or both DTR-PA/KPC-Kp ( n  = 1) successfully treated with IMI/REL: 3 hospital-acquired pneumonia, 1 ventilator-associated pneumonia, 2 skin and soft tissue infections, 1 osteomyelitis, 2 bloodstream infections, 1 complicated urinary tract infection. Clinical cure was achieved in all cases. No patients died and no side effect were reported., Discussion: We reported the preliminary real-life experience on the successful and safe use of IMI/REL for the treatment of KPC-Kp or DTR-PA complicated infections, including pneumonia and bone infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Leanza, Mascellino, Volpicelli, Covino, Falletta, Cancelli, Franchi, Carnevalini, Mastroianni and Oliva.)

Purpose: The mesoderm specific transcription ( MEST ) gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on MEST methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the MEST gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters., Materials and Methods: This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating MEST gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included., Results: Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of MEST gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360)., Conclusions: Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The MEST gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Background: COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients., Materials and Methods: This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients., Results: Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155-314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12-31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75-4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12-4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19-5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47-5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20-26.92), p = 0.035]. No differences were observed in hematological cohort., Conclusion: CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia., (© 2024. The Author(s).)

To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT) <12 nmol l -1 , we performed a meta-analysis following the Population Intervention Comparison Outcome model. Population: men with TT <12 nmol l -1 or clear mention of hypogonadism in the inclusion criteria of patients; intervention: TRT; comparison: placebo or no therapy; outcomes: arterial thrombotic events (stroke, myocardial infarction [MI], upper limbs, and lower limbs), VTE (deep vein thrombosis [DVT], portal vein thrombosis, splenic thrombosis, and pulmonary embolism), and mortality. A total of 2423 abstracts were assessed for eligibility. Twenty-four studies, including 14 randomized controlled trials (RCTs), were finally included, with a total of 4027 and 310 288 hypotestosteronemic male patients, from RCTs and from observational studies, respectively. Based on RCT-derived data, TRT did not influence the risk of arterial thrombosis (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 0.47-3.43, P = 0.64), stroke (OR = 1.34, 95% CI: 0.09-18.97, P = 0.83), MI (OR = 0.51, 95% CI: 0.11-2.31, P = 0.39), VTE (OR = 1.42, 95% CI: 0.22-9.03, P = 0.71), pulmonary embolism (OR = 1.38, 95% CI: 0.27-7.04, P = 0.70), and mortality (OR = 0.70, 95% CI: 0.20-2.38, P = 0.56). Meanwhile, when only observational studies are considered, a significant reduction in the risk of developing arterial thrombotic events, MI, venous thromboembolism, and mortality was observed. The risk for DVT remains uncertain, due to the paucity of RCT-based data. TRT in men with TT <12 nmol l -1 is safe from the risk of adverse cardiovascular events. Further studies specifically assessing the risk of DVT in men on TRT are needed., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: The Small Nuclear Ribonucleoprotein Polypeptide N ( SNRPN ) gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted reproductive techniques (ART), such as Angelman and Prader-Willi. Data present in the literature suggest the association between aberrant sperm SNRPN gene methylation and abnormal sperm parameters. The latest meta-analysis on the methylation pattern of this gene in spermatozoa of infertile patients published in 2017 reported a higher degree of methylation in the spermatozoa of infertile patients compared to fertile controls. Objectives: Here we provide an updated and comprehensive systematic review and meta-analysis of the sperm methylation pattern of the SNRPN gene in patients with abnormal sperm parameters/infertility compared to men with normal sperm parameters/fertile. For the first time in the literature, we performed a meta-regression analysis to evaluate whether age or sperm concentration could influence the methylation status of this gene at the sperm level. Methods: This meta-analysis was registered in PROSPERO (n. CRD42023397056). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the MOOSE guidelines for meta-analyses and systematic reviews of observational studies were strictly followed in our meta-analysis. According to our Population Exposure Comparison Outcome (PECO) question, we included data from original articles assessing the levels of SNRPN gene methylation at the sperm level in infertile patients or patients with abnormalities in one or more sperm parameters compared to fertile or normozoospermic men. Results: Only six of 354 screened studies were included in the quantitative synthesis. Our analysis showed significantly higher levels of SNRPN gene methylation in patients compared to controls. However, significant heterogeneity was found between studies. In sensitivity analysis, no studies were sensitive enough to skew the results. The Egger test showed no publication bias. In the meta-regression analysis, the results were independent of age and sperm concentration in the overall population. The same results were found in the control group. However, when analyzing the patient group, a direct correlation was found between SNRPN methylation and age, indicating that the degree of methylation of the SNRPN gene increases with advancing age. Conclusions: Fertility status or abnormality of sperm parameters is associated with a change in the methylation pattern of the SNRPN gene, with higher levels found in infertile patients or those with abnormal sperm parameters compared to fertile men or men with normal sperm parameters. In the group of infertile patients/patients with abnormal sperm parameters, age was directly correlated to the degree of SNRPN methylation, highlighting the presence of a mechanism that explains the age-related altered sperm quality and the risk of ART. Despite some limitations present in the analyzed studies, our results support the inclusion of SNRPN methylation in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to analyze in couples who want to undergo ART.

Introduction: The long interspersed nuclear element-1 (LINE1) gene is a retrotransposon whose methylation status appears to play a role in spermatogenesis, the outcome of assisted reproductive techniques (ART), and even in recurrent pregnancy loss (RPL). Advanced paternal age appears associated with altered sperm parameters, RPL, poor ART outcomes, and compromised offspring health. The methylation status of LINE1 has been reported to be affected by age. The latest meta-analysis on the LINE1 methylation pattern in spermatozoa found no significant differences in methylation levels between infertile patients and fertile controls. However, to the best of our knowledge, no updated meta-analysis on this topic has been published recently. Furthermore, no comprehensive meta-regression analysis was performed to investigate the association between sperm LINE1 methylation pattern and age., Objectives: To provide an updated and comprehensive systematic review and meta-analysis on sperm LINE1 gene methylation degree in patients with abnormal sperm parameters compared to men with normal sperm parameters and to probe the association between sperm LINE1 methylation status and age and/or sperm concentration., Methods: This meta-analysis was registered in PROSPERO (registration n. CRD42023397056). It was performed according to the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating LINE1 gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included., Results: Of 192 abstracts evaluated for eligibility, only 5 studies were included in the quantitative synthesis, involving a total of 340 patients and 150 controls. Our analysis showed no significant difference in LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters compared to fertile controls and/or men with normal sperm parameters, although there was significant heterogeneity across studies. No significant evidence of publication bias was found, and no study was sensitive enough to alter the results. In meta-regression analysis, we found that the results were independent of both ages and sperm concentration. A sub-analysis examining patients and controls separately was also conducted and we found a trend for a positive correlation between LINE1 methylation and sperm concentration in the control group only., Conclusions: The results of this systematic review and meta-analysis do not suggest a determining role of sperm LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters. Therefore, we do not suggest including LINE1 in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART cycles., (© 2023. The Author(s).)

Introduction: Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients., Methods: The mRNA levels of IFN-I, IFN-related genes and cytokines were evaluated using RT/real-time quantitative PCR., Results: Vaccinated patients showed increased rate of negative SARS-CoV-2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN-α/ω and higher IFN-related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL-6, IL-10 and TGF-β) mRNA levels compared to vaccinated individuals before mAbs (p < .05 for all genes). Increased IFN-α/ω, IFNAR1, IFNAR2 and IRF9 levels were observed in unvaccinated patients after mAbs treatment, while the mRNA expression ISGs and IL-10 were reduced in all patients., Conclusion: These data suggest that anti-S vaccinated patients have increased levels of innate immune genes compared to unvaccinated ones. Also, gene expression changes in IFN genes after mAbs administration are different according to the vaccination status of patients., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Vitamin D deficiency (VDD) and erectile dysfunction (ED) heavily burden the male population. The higher prevalence of both conditions in the elderly suggests a possible relationship between the two conditions. In addition, in vitro, animal, and human studies have revealed several mechanisms that may relate VDD to ED. The main mechanism by which vitamin D might exert its action on sexual function appears to be through the regulation of endothelial function. Indeed, VDD correlates with several markers of endothelial function. The action of vitamin D on the endothelium would be exercised both indirectly through its intervention in inflammatory processes and through the production of oxygen free radicals, and directly through the regulation of vascular stiffness, the production of nitric oxide, and the regulation of vessel permeability. Furthermore, the ubiquitous distribution of the vitamin D receptor in the human body means that this hormone can also exert a beneficial effect on erectile function by interfering with those comorbidities significantly associated with ED, such as hypertension, diabetes mellitus, hypercholesterolemia, chronic kidney disease, and hypogonadism. In this review, we thoroughly and carefully presented the evidence and mechanisms that would appear to relate vitamin D levels to erectile function. Furthermore, we have summarized the meta-analytic evidence for and against this association to provide a true representation of this topic. Data published to date suggest that low levels of vitamin D could contribute to worsening erectile function through several mechanisms. Therefore, vitamin D levels should be measured in patients with ED and maintained at adequate levels by specific supplementation in case of deficiency. However, the low quality and heterogeneity of clinical trials evaluating the effects of vitamin D administration on erectile function and ED-associated comorbidities do not allow for a univocal conclusion, and indicate the need for further studies to analyze these aspects.

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.

3,3',5-triiodo-L-thyronine (T3) improves hepatic lipid accumulation by increasing lipid catabolism but it also increases lipogenesis, which at first glance appears contradictory. Recent studies have shown that 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, also has the capacity to stimulate hepatic lipid catabolism, however, little is known about its possible effects on lipogenic gene expression. Because genes classically involved in hepatic lipogenesis such as SPOT14, acetyl-CoA-carboxylase (ACC), and fatty acid synthase (FAS) contain thyroid hormone response elements (TREs), we studied their transcriptional regulation, focusing on TRE-mediated effects of T3 compared to T2 in rats receiving high-fat diet (HFD) for 1 week. HFD rats showed a marked lipid accumulation in the liver, which was significantly reduced upon simultaneous administration of either T3 or T2 with the diet. When administered to HFD rats, T2, in contrast with T3, markedly downregulated the expression of the above-mentioned genes. T2 downregulated expression of the transcription factors carbohydrate-response element-binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c) involved in activation of transcription of these genes, which explains the suppressed expression of their target genes involved in lipogenesis. T3, however, did not repress expression of the TRE-containing ChREBP gene but repressed SREBP-1c expression. Despite suppression of SREBP-1c expression by T3 (which can be explained by the presence of nTRE in its promoter), the target genes were not suppressed, but normalized to HFD reference levels or even upregulated (ACC), partly due to the presence of TREs on the promoters of these genes and partly to the lack of suppression of ChREBP. Thus, T2 and T3 probably act by different molecular mechanisms to achieve inhibition of hepatic lipid accumulation.

Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3'-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through "non-genomic" pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism.