RESUMEN
PURPOSE OF REVIEW: To correlate the resistance mechanisms and the susceptibility to new antibiotics in Pseudomonas aeruginosa. RECENT FINDINGS: Definition of antibiotic resistance in Pseudomonas aeruginosa is still debated. Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) are used but which of them better correlate with the risk of mortality remains debated. Mechanisms underlying resistance in Pseudomonas aeruginosa are complex and may be combined, resulting in unpredictable phenotype and cross-resistance. Thus, not all CRPA are alike and tailoring antibiotic therapy on resistance mechanisms is challenging. SUMMARY: Current guidelines recommend the use of new antipseudomonal agents for CRPA or DTR-PA infections but they don't provide specific information on how tailoring antibiotic therapy on underlying resistance mechanisms. This review may be useful to understand which mechanisms are involved in CRPA and may have practical implications helping clinicians to select an appropriate antibiotic regimen. Several antibiotics are now available for Pseudomonas aeruginosa but their rational use is important to avoid development of future resistance. The knowledge of local epidemiology and most common resistance mechanisms may guide empirical therapy, but targeted antibiotic therapy should be re-evaluated as soon as susceptibility testing profile is available and selected according to Pseudomonas aeruginosa phenotype.
RESUMEN
Male infertility represents a complex clinical condition that often challenges the ability of reproductive specialists to find its etiology and then propose an adequate treatment. The unexplained decline in sperm count, as well as the association between male infertility and mortality, morbidity, and cancer, has prompted researchers toward an urgent need to better understand the causes of male infertility. Therefore, molecular biologists are increasingly trying to study whether sperm epigenetic alterations may be involved in male infertility and embryo developmental abnormalities. In this context, research is also trying to uncover the hidden role of sperm RNAs, both coding and non-coding. This narrative review aims to thoroughly and comprehensively present the relationship between sperm epigenetics, sperm RNAs, and human fertility. We first focused on the technological aspects of studying sperm epigenetics and RNAs, relating to the complex role(s) played in sperm maturation, fertilization, and embryo development. Then, we examined the intricate connections between epigenetics and RNAs with fertility measures, namely sperm concentration, embryo growth and development, and live birth rate, in both animal and human studies. A better understanding of the molecular mechanisms involved in sperm epigenetic regulation, as well as the impact of RNA players, will help to tackle infertility.
RESUMEN
PURPOSE: Real-world experience with meropenem/vaborbactam (M/V) is limited. Our aim is to report a clinical experience of M/V in the treatment of resistant Gram-negative bacilli. METHODS: This is a prospective observational study including patients hospitalized in the University Hospital of Pisa (March 2021-Jan 2023) with infections by both extended-spectrum ß-lactamases (ESBL)-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae (Kp) treated with M/V. The primary outcome measure was clinical success, defined as a composite of survival, resolution of signs and symptoms and absence of microbiological failure at day 30 from infection onset. A multivariable regression analysis was performed to identify factors associated with clinical failure. Odds ratio (OR) with 95% confidence intervals (CI) was calculated. RESULTS: A total of 104 patients who received M/V were included: 24/104 (23.1%) infections were caused by ESBL non-hypervirulent Enterobacterales, 17/104 (16.3%) by ESBL-producing hypervirulent Klebsiella pneumoniae (hvKp) and 63/104 (60.6%) by CRE. The most common infections were bloodstream infections, followed by urinary tract infections, hospital-acquired pneumonia, intra-abdominal infections and others. Septic shock occurred in 16/104 (15.4%) patients. Clinical success was achieved in 77% of patients, and 30-day mortality rate was 15.4%. In patients with KPC-producing Kp infections, clinical success and 30-day mortality rates were 82% and 11.5%, respectively. On multivariable analysis, SOFA score (OR 1.32, 95% CI 1.02-1.7, p=0.032) was independently associated with clinical failure, while source control (OR 0.16, 95% CI 0.03-0.89, p=0.036) was protective. CONCLUSIONS: M/V is a promising therapeutic option against infections caused by difficult-to-treat ESBL-producing Enterobacterales and CR-Kp.
RESUMEN
INTRODUCTION: The preservation of the bladder neck during robot-assisted radical prostatectomy (RARP) could improve urinary continence recovery and limit the risk of positive surgical margins (PSMs). We refined our lateral approach to the bladder neck technique and compared its outcomes with those of the standard anterior approach. MATERIAL AND METHODS: From a retrospective analysis of 599 consecutive RARPs, 171 patients treated with the lateral and 171 patients treated with the anterior approach were pair-matched 1:1 on the basis of age, grade, and pathological stage. We described our surgical technique and compared the two approaches in terms of basal PSMs, recovery of urinary continence, and complications. RESULTS: As compared to the anterior approach, the lateral approach had shorter operative times and comparable rates of basal PSMs and postoperative complications. The rates of urinary continence after one, three, and 12 months were comparable between the two groups and were generally higher in localized disease. At regression analysis, predictors of urinary incontinence were only age, pathological stage T3b, ISUP grade 5 and nerve-sparing surgery. CONCLUSIONS: The lateral approach leads to an anatomical dissection of the bladder neck without increasing the risk of PSMs. However, no significant benefits in terms of continence recovery were demonstrated over the standard anterior approach.
RESUMEN
Peyronie's disease, a fibroinflammatory disorder, detrimentally impacts the sexual well-being of men and their partners. The manifestation of fibrotic plaques within penile tissue, attributed to dysregulated fibrogenesis, is pathognomonic for this condition. The onset of fibrosis hinges on the perturbation of the equilibrium between matrix metalloproteinases (MMPs), crucial enzymes governing the extracellular matrix, and tissue inhibitors of MMPs (TIMPs). In the context of Peyronie's disease, there is an elevation in TIMP levels coupled with a decline in MMP levels, culminating in fibrogenesis. Despite the scant molecular insights into fibrotic pathologies, particularly in the context of Peyronie's disease, a comprehensive literature search spanning 1995 to 2023, utilizing PubMed Library, was conducted to elucidate these mechanisms. The findings underscore the involvement of growth factors such as FGF and PDGF, and cytokines like IL-1 and IL-6, alongside PAI-1, PTX-3, HIF, and IgG4 in the fibrotic cascade. Given the tissue-specific modulation of fibrosis, comprehending the molecular underpinnings of penile fibrosis becomes imperative for the innovation of novel and efficacious therapies targeting Peyronie's disease. This review stands as a valuable resource for researchers and clinicians engaged in investigating the molecular basis of fibrotic diseases, offering guidance for advancements in understanding Peyronie's disease.
RESUMEN
The nocardiae are a complex group of bacteria belonging to the aerobic saprophytes actinomycetes. Although nocardiosis typically occurs in immunocompromised patients, infection may occasionally develop in immunocompetent patients as well. Here we describe a rare case of primary cutaneous nocardiosis due to Nocardia vinacea in an immunocompetent 79-year-old patient. Since cutaneous nocardiosis presents variably and mimics other cutaneous infections, acid-fast and Gram stainings on clinical samples are significant to obtain a rapid and presumptive diagnosis.
Asunto(s)
Nocardiosis , Nocardia , Enfermedades Cutáneas Bacterianas , Humanos , Nocardiosis/diagnóstico , Nocardiosis/microbiología , Nocardiosis/tratamiento farmacológico , Nocardia/aislamiento & purificación , Nocardia/genética , Nocardia/clasificación , Anciano , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Masculino , Antibacterianos/uso terapéutico , Piel/microbiología , Piel/patología , InmunocompetenciaRESUMEN
Background and objective: Nodal metastasis is a major survival and prognostic factor in penile cancer (PeCa). Thus, accurate staging, prognosis, and treatment selection require adequate inguinal lymphadenectomy (ILND). ILND surgery should balance oncologic rigor with morbidity and postoperative complications. Our aim was to compare the feasibility and safety of open ILND (OILND) and videoendoscopic ILND (VEILND) in patients with PeCa. Methods: We conducted a single-center randomized trial with a within-patient design between October 2019 and April 2023. Patients who were undergoing either staging or radical ILND for PeCa were included and randomized to receive either OILND or VEILND on one side, with the other technique then used on the contralateral side. The trial was approved by the local ethics committee and was registered on ClinicalTrials.gov (NCT05887921). The primary outcome was the safety of VEILND. Secondary outcomes included intraoperative and postoperative morbidity rates and surgical outcomes for the two procedures, as well as oncological outcomes according to survival estimates. Key findings and limitations: We included 14 patients in the study. Median follow-up was 12 mo (interquartile range [IQR] 12-17). There were no significant differences in operative time and the number of lymph nodes removed between OILND and VEILND. However, the median time to drain removal was significantly shorter in the VEILND group (15 d, IQR 13-17, 95% confidence interval [CI] 12-17) than in the OILND group (27 d, IQR 20-41, 95% CI 24-31; p = 0.025). No intraoperative complications were observed, but postoperative complications occurred in three cases (21.4%, 95% CI 8.4-37.8%) in the VEILND group and eight (57.1%, 95% CI 18.6-54.3%) in the OILND group (p = 0.032). Conclusions and clinical implications: VEILND represents a safe technique to consider for either staging or curative intent in PeCa and seems to have an advantage over OILND in terms of morbidity. Further high-powered studies are warranted to confirm these preliminary results. Patient summary: We compared the outcomes of two different surgical techniques to remove lymph nodes in patients with penile cancer. We found that a video-assisted keyhole surgery approach seems to result in a lower rate of complications than after open surgery.
RESUMEN
Monoclonal antibodies (mAbs) are one of the most important classes of biologics with high therapeutic and diagnostic value, but traditional methods for mAbs generation, such as hybridoma screening and phage display, have limitations, including low efficiency and loss of natural chain pairing. To overcome these challenges, novel single B cell antibody technologies have emerged, but they also have limitations such as in vitro differentiation of memory B cells and expensive cell sorters. In this study, we present a rapid and efficient workflow for obtaining human recombinant monoclonal antibodies directly from single antigen-specific antibody secreting cells (ASCs) in the peripheral blood of convalescent COVID-19 patients using ferrofluid technology. This process allows the identification and expression of recombinant antigen-specific mAbs in less than 10 days, using RT-PCR to generate linear Ig heavy and light chain gene expression cassettes, called "minigenes", for rapid expression of recombinant antibodies without cloning procedures. This approach has several advantages. First, it saves time and resources by eliminating the need for in vitro differentiation. It also allows individual antigen-specific ASCs to be screened for effector function prior to recombinant antibody cloning, enabling the selection of mAbs with desired characteristics and functional activity. In addition, the method allows comprehensive analysis of variable region repertoires in combination with functional assays to evaluate the specificity and function of the generated antigen-specific antibodies. Our approach, which rapidly generates recombinant monoclonal antibodies from single antigen-specific ASCs, could help to identify functional antibodies and deepen our understanding of antibody dynamics in the immune response through combined antibody repertoire sequence analysis and functional reactivity testing.
Asunto(s)
Anticuerpos Monoclonales , Células Productoras de Anticuerpos , COVID-19 , Proteínas Recombinantes , SARS-CoV-2 , Humanos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/biosíntesis , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Células Productoras de Anticuerpos/inmunología , SARS-CoV-2/inmunología , COVID-19/inmunología , Anticuerpos Antivirales/inmunología , FemeninoRESUMEN
INTRODUCTION: The emergence of multidrug-resistant Gram-negative bacilli and the development of new antibiotics have complicated the selection of optimal regimens. International guidelines are valuable tools, but are limited by the scarcity of high-quality randomized trials in many situations. METHODS: A panel of experts from the French and Italian Societies of Infectious Diseases aimed to address unresolved issues in clinical practice based on their experience, an updated literature review and open discussions. RESULTS: The panel reached consensus for the following 'first choices': (i) cefepime for ventilator-acquired pneumonia due to AmpC ß-lactamase-producing Enterobacterales; (ii) the ß-lactam/ß-lactamase inhibitor combination most active in vitro, or cefiderocol combined with fosfomycin, and aerosolized colistin or aminoglycosides, for severe pneumonia due to Pseudomonas aeruginosa resistant to ceftolozane-tazobactam; (iii) high-dose piperacillin-tazobactam (including loading dose and continuous infusion) for complicated urinary tract infections (cUTIs) caused by extended-spectrum ß-lactamase-producing Enterobacterales with piperacillin-tazobactam minimum inhibitory concentration (MIC) ≤8 mg/L; (iv) high-dose cefepime for cUTIs due to AmpC ß-lactamase-producing Enterobacterales other than Enterobacter spp. if cefepime MIC ≤2 mg/L; (v) ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections (IAIs) due to third-generation cephalosporin-resistant Enterobacterales; (vi) ceftazidime-avibactam plus aztreonam plus metronidazole for IAIs due to metallo-ß-lactamase-producing Enterobacterales; (vii) ampicillin-sulbactam plus colistin for bloodstream infections (BSIs) caused by carbapenem-resistant Acinetobacter baumannii; (viii) meropenem-vaborbactam for BSIs caused by Klebsiella pneumoniae carbapenemase-producing Enterobacterales; and (ix) ceftazidime-avibactam plus fosfomycin for neurological infections caused by carbapenem-resistant P. aeruginosa. CONCLUSIONS: These expert choices were based on the necessary balance between antimicrobial stewardship principles and the need to provide optimal treatment for individual patients in each situation.
Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Italia , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Combinación de Medicamentos , Francia , Cefalosporinas/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/microbiología , Cefepima/uso terapéutico , Cefepima/farmacología , Fosfomicina/uso terapéutico , Fosfomicina/farmacología , Colistina/uso terapéutico , Colistina/farmacología , Tazobactam , Ceftazidima , Compuestos de AzabicicloRESUMEN
Background: Penile shortening, frequently resulting from end-stage Peyronie's disease (PD), has a negative impact on patients' sexual activity and overall quality of life, especially when accompanied by Erectile dysfunction (ED). Various surgical techniques have been described to manage concomitant ED and penile shortening through penile prosthesis (PP) implantation. Objectives: To evaluate the benefits and risks of different penile length preservation techniques during PP implantation. Design: A systematic review of the available literature on the use of penile length preservation maneuvers in conjunction with PP implantation was conducted. Data sources and methods: For this systematic review, three databases (Medline, Embase and Cochrane) and clinical trial.gov were queried for relevant publications from 1 January 1990 to 1 September 2022. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: The qualitative analysis included 15 relevant articles involving 1186 adult patients who underwent penile length preservation techniques during PP implantation. Penile lengthening of 1-7 cm was reported. Overall, postoperative complications were described in up to 21.7% of cases. Only five studies reported functional outcomes, showing a significant improvement in postoperative period based on the administered questionnaire (e.g. IIEF - International Index of Erectile Function, EDITS - Erectile Dysfunction Inventory of Treatment Satisfaction). Conclusion: Penile length preservation procedures appear to offer a viable option for managing acquired penile shortening, particularly in cases of PD. However, they are associated with a significant risk of complications. Proper patient selection, thorough discussion of risks and benefits, and referral to high-volume centers are mandatory to achieve optimal outcomes and minimizing complications. Trial registration: PROSPERO database registration CRD42022360758.
RESUMEN
Adult Acquired Buried Penis (AABP) is a pathological condition necessitating surgical correction, ranging from simple to complex procedures involving the utilization of full-thickness (FTSG) or split-thickness (STSG) skin grafts especially in cases of substantial viable penile skin loss. In this retrospective study, we aimed to compare the surgical, functional, and patient-reported outcomes (PROs) of graft types that were utilized to treat AABP among 39 patients at a single center between November 2017 and May 2023. Among these patients, 22 needed skin grafts, with 9 undergoing FTSG and the remainder receiving STSG. Lichen Sclerosus (LS) was the primary cause (54.6%) of AABP requiring skin grafts. Patients primarily presented with voiding (63.6%) and sexual (27.3%) dysfunction. The STSG group had a lower mean age (64.7 ± 11.6) than the FTSG group (66.7 ± 11.6; P = 0.015), with no significant differences in BMI (p = 0.643). Complex repairs (Santucci grade ≥3) were performed in 81.0% of cases, with 88.9% in the FTSG group and 75.0% in the STSG group. Operative times were similar (160.2 ± 31.7 vs 161.5 ± 50.3, p = 0.945). No significant differences in preoperative penis length were found between the FTSG and STSG groups (P = 0.918). Postoperative complications occurred in 36.4% of patients, with severe complications (Clavien grade ≥3) in 9.1%. General postoperative complications and recurrence rates did not significantly differ between groups (P = 0.397 and 0.375; respectively). Functional outcomes, evaluated using the International Index of Erectile Function and the International Prostate Symptom Score, improved significantly in both groups after surgical procedures (P < 0.001 for all). Patient-reported satisfaction for the operation was 81.3% calculated by ad-hoc questionnaire. In conclusion, no discernible differences in outcomes were observed between STSG and FTSG. Larger comparative studies with extended follow-up periods and validated questionnaires are warranted for confirmation. Physicians should consider specialized centers for AABP surgical repair due to its intricacies.
RESUMEN
PURPOSE: Augmented adiposity may negatively impact sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones. Moreover, a dysregulated metabolic pathway may promote apoptosis among spermatogenic cells. Based on these premises, a relation between weights loss and ameliorate semen parameters seems beneficial. To investigate if physical activity may affect semen parameters and fertility rate, a systematic literature search on major dataset has been performed. MATERIALS AND METHODS: The search terms included: "Assisted reproduction therapies," "fertility," "semen parameters," "sperm parameters," and "physical activity." This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and it was registered on PROSPERO (CRD42023384471). A total of 47 studies have been identified; 1 reference has been eliminated after duplication check. After preliminary screening 32 papers have been excluded. Considering the exclusion criteria, 15 full-text articles were evaluated for eligibility. After a full-text review, six studies published during a span of eight years (2014-2022) have been included in the meta-analysis. Semen parameters, pregnancy and birth rates were investigated. The revised Cochrane risk of bias tool (Rob2) has been used to check the risk of bias. RESULTS: The number of patients enrolled in studies ranges from 17 to 521; in the end, a total of 1,637 patients have been enrolled in the study. Fertility parameters investigated were semen quality parameters and pregnancy rates and live births. A statistically significant relationship between physical exercise and sperm concentration (p=0.02), total sperm motility (p<0.01), total sperm count (p<0.01), normal morphology (p<0.01) has been established. Moreover, the study registered a statistically significant association within physical activity and total pregnancy rate (p<0.01) and live birth rate (p<0.01). CONCLUSIONS: We demonstrated that physical activity is significantly associated with amelioration of semen parameters and may be crucial in improving or even reverting male infertility.
RESUMEN
INTRODUCTION: Placebo influence on such objective indicators, as sperm quality and infertility, has not been studied previously, but some studies report that placebo may distort even objective outcomes. The aim of current study is to assess the placebo effect on fertility in patients suffering from sperm abnormalities and/or infertility. EVIDENCE ACQUISITION: We conducted a search of two databases (Scopus and MEDLINE) and identified placebo-controlled clinical trials which focused on sperm abnormalities and/or male infertility treatment. Primary outcomes included changes in semen parameters (volume, total count, sperm concentration in semen, progressive motility, morphology (normal cells)). Secondary outcomes included DNA fragmentation and change in pregnancy rate. EVIDENCE SYNTHESIS: Seventy-seven articles published from 1983 to 2022 were included. Statistically significant changes were observed for the following values: total sperm count, mean change 0.16 (95% CI 0.05, 0.26); P=0.004, I2=75.1%; and progressive motility, mean change 0.13 (95% CI 0.02, 0.24); P=0.026, I2=84.9%. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology or DNA fragmentation index. The publication bias for all the values measured with Egger's test and funnel plots was low. CONCLUSIONS: The current meta-analysis indicated a statistically significant increase of total sperm count and progressive motility in the placebo group. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology and DNA fragmentation index. These findings should be considered while planning or analyzing placebo-controlled clinical trials.
Asunto(s)
Infertilidad Masculina , Efecto Placebo , Análisis de Semen , Humanos , Masculino , Infertilidad Masculina/tratamiento farmacológico , Fragmentación del ADN/efectos de los fármacos , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacosRESUMEN
Peyronie's disease (PD) is a condition of penile connective tissue affecting up to 10% of men worldwide. In the complexity of its management, nonsurgical treatments, such as intraplaque injections, are gaining attention. The current literature shows data on the efficacy of intraplaque injections of hyaluronic acid (HA) mainly in acute-phase PD. However, data on injections of HA in stable-phase PD are lacking. Data for this retrospective study were derived from a prospectively maintained database of private patients presenting at a private medical practice affiliated to the University of Naples "Federico II" (Naples, Italy) with stable-phase PD between January 2020 and March 2023. Patients underwent a standard protocol of three injections, each administered at a two-week interval. During the intervals, patients performed vacuum device therapy, penile stretching, and modeling exercises. All patients compiled the Peyronie's Disease Questionnaire (PDQ) and Global Assessment of Peyronie's Disease (GAPD) at baseline and 2 weeks after the third injection. A penile Doppler ultrasound was performed 2 weeks after the last injection to record the final curvature. Overall, we recruited 62 patients with stable-phase PD and a mean (±standard deviation [s.d.]) curvature of 52.7° (±9.7°). After 6 weeks, eight (12.9%) patients did not experience any curvature improvement. The remaining 54 patients had a final mean (±s.d.) curvature of 40.3° (±9.1°) with P < 0.001, compared to that before treatment. We found improvement in all PDQ domains (all P ≤ 0.01), and 50 (80.6%) patients reported subjective improvement of the penile curvature according to the GAPD. In conclusion, we demonstrated that after three injections of HA administered according to the adopted protocol, patients with stable-phase PD could experience significant improvements in penile curvature, and physical and psychological consequences of the disease without significantly relevant side effects.
Asunto(s)
Ácido Hialurónico , Induración Peniana , Humanos , Induración Peniana/tratamiento farmacológico , Masculino , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Inyecciones Intralesiones , Pene/efectos de los fármacos , Pene/diagnóstico por imagen , AdultoRESUMEN
Background: In vitro-in vivo discordance in ß-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is attributed to the supra-physiologic zinc concentration in in vitro testing media. Methods: A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active ß-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active ß-lactam therapy (ceftazidime/avibactam + aztreonam) were documented. The patients' isolates were used to induce septicemia in mice, and survival upon meropenem treatment was recorded. Meropenem minimum inhibitory concentrations (MICs) were determined in standard media and in the presence of physiological zinc concentrations. Results: Twenty-nine patients receiving empiric non-MBL-active ß-lactams (median duration, 4 days) were compared with 29 receiving MBL-active ß-lactams. The 14-day mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality (P < .0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower vs MICs in zinc-unadjusted broth (≥64â mg/L). Conclusions: Our data provide foundational support to establish pharmacokinetic/pharmacodynamic relationships using MICs derived in physiologic zinc concentration, which may better predict ß-lactam therapy outcome.
RESUMEN
OBJECTIVES: To retrospectively describe the patterns of use of dalbavancin for treating infections in diabetic patients in Italian and Spanish standard clinical practice. METHODS: DALBADIA [NCT04959799] was a multicentre, observational, retrospective cohort study, conducted in Italy and Spain. The study enrolled 97 adults with type 1 or 2 diabetes mellitus, treated with dalbavancin as per standard clinical practice for a Gram-positive bacterial infection or the Gram-positive component of a mixed infection. RESULTS: Dalbavancin was used to treat cellulitis (18/92 patients, 19.6%), followed by prosthetic joint infection (14 patients, 15.2%), endocarditis (13 patients, 14.1%), and primary bacteraemia (10 patients, 10.9%); 78/92 (84.8%) patients had Gram-positive infections only, and 14 (15.2%) had mixed infections. The most frequently isolated microorganisms were Staphylococcus aureus in 43 (55.8% of the patients with microbial isolation), 25.6% of which methicillin-resistant; Staphylococcus epidermidis in 13 (16.9%), 53.8% of which methicillin-resistant; Enterococcus faecalis in 11 (14.3%). The main reason for the dalbavancin choice was the intent to simplify the antibiotic regimen (81.5% of cases). A multidisciplinary team participated in the treatment choice process for 53 (57.6%) patients. Dalbavancin was given as first-line antibiotic in 34 (37.0%) patients and administered as one infusion in 32 (34.8%), and as two infusions in 39 (42.4%). In total, 57/62 (91.9%) eligible patients with available assessment were judged clinically cured or improved at the end of observation. CONCLUSION: In clinical practice, dalbavancin was used in diabetic patients to treat ABSSSIs and other difficult-to-treat infections with a favourable safety profile and a high rate of positive clinical responses.
Asunto(s)
Antibacterianos , Diabetes Mellitus , Teicoplanina , Adulto , Humanos , Italia , Estudios Retrospectivos , España , Teicoplanina/análogos & derivadosRESUMEN
Purpose: This study aimed to investigate the effects of ejaculatory abstinence on sperm parameters. Methods: This analysis was registered in PROSPERO (CRD42023472124). We performed a search on PubMed using the following text terms: (("sperm parameters" OR "sperm analysis" [Mesh]) AND ("sperm DNA fragmentation" OR "DNA fragmentation" [Mesh]) AND ("sexual abstinence" [Mesh] OR "abstinence")) and an advanced search in Scopus using the terms ("sperm parameters" OR "sperm parameters" OR "DNA fragmentation") AND ("abstinence"). The sperm parameters that were investigated were sperm volume, total sperm motility, progressive sperm motility, sperm concentration, sperm morphology, and sperm DNA fragmentation (SDF). A two-day cut-off as a "short" or "long" abstinence period has been defined. Results: Thirteen studies published between 2013 and 2022 were included in this meta-analysis. A total of 2,315 patients, ranging from 6 to 836 from each cohort, were enrolled in the study. We showed that longer abstinence time was associated with greater sperm concentration (mean difference [MD]: 8.19; p <0.01), sperm volume (MD: 0.96; p <0.01), and higher SDF (MD: 3.46; p <0.01), but lower progressive sperm motility (MD: -1.83; p <0.01). Otherwise, no statistically significant difference was observed in patients with longer vs. shorter abstinence times regarding total sperm motility (MD: -1.83; p = 0.06). Meta-regression analysis showed that days of abstinence were positively and linearly related to sperm concentration (slope: 3.74; p <0.01) and SDF (slope: 0.65; p = 0.044). Conclusions: According to our data, short ejaculatory abstinence is associated with better sperm quality. Indeed, a higher percentage of progressive sperm motility and lower levels of SDF have been reported in a short abstinence cohort. In contrast, the long abstinence group reported a higher sperm concentration. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472124.
Asunto(s)
Eyaculación , Ensayos Clínicos Controlados Aleatorios como Asunto , Abstinencia Sexual , Recuento de Espermatozoides , Motilidad Espermática , Espermatozoides , Masculino , Humanos , Eyaculación/fisiología , Espermatozoides/fisiología , Análisis de Semen , Fragmentación del ADN , Factores de TiempoRESUMEN
PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, its association with anti-sperm antibodies (ASA) remains controversial. This systematic review and meta-analysis (SRMA) aims to investigate the frequency of ASA positivity in men with varicocele. MATERIALS AND METHODS: This SRMA is conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We investigated the frequency of ASA positivity in ejaculates or serum of men with varicocele as compared to men without varicocele (controls). A literature search was performed using the Scopus and PubMed databases following the Population Exposure Comparison Outcome, Study Design model. Data extracted from eligible studies were meta-analyzed and expressed as odds ratios (ORs) and confidence intervals (CIs). RESULTS: Out of 151 abstracts identified during the initial screening, 6 articles met the inclusion criteria and were included in the meta-analysis. Using mixed antiglobulin reaction (MAR) assay, 61 out of the 153 (39.8%) patients with varicocele tested positive for ASA in their ejaculates as compared to 22 out of the 129 control subjects (17%, OR=4.34 [95% CI: 1.09-17.28]; p=0.04). Using direct or indirect immunobead test, 30 out of 60 cases diagnosed with varicocele (50%) had shown ASA positivity in their ejaculates as compared to 16 out of 104 controls (15.4%, OR=3.57 [95% CI: 0.81-15.68]; p=0.09). Using enzyme-linked immunosorbent assay (ELISA), out of 89 varicocele patients, 33 (37.1%) tested positive for serum ASA as compared to 9 out of 57 participants in the control group (15.8%, OR=7.87 [95% CI: 2.39-25.89]; p<0.01). CONCLUSIONS: This SRMA indicates that ASA positivity is significantly higher among men with varicocele when tested by direct method (MAR) or indirect method (ELISA). This data suggests an immunological pathology in infertile men with varicocele and may have implications for the management of these patients.
RESUMEN
We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who received prophylaxis (cases) were compared to those who did not (controls). The main outcome was SARS-CoV-2 infection in the subsequent 6 months. Inverse probability weighting (IPW) was used to adjust for confounders. A multivariable analysis was performed to identify variables associated with SARS-CoV-2 infection. We recruited 462 patients: 228 received prophylaxis, 234 were controls. COVID-19 was lower in cases compared to controls (16.7% vs 24.8%, p = 0.03, after IPW 14.3% vs 24.6%, p = 0.01). On multivariable analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, p = 0.037) were associated with increased risk of COVID-19, while tixagevimab/cilgavimab prophylaxis (HR 0.45, 95%CI 0.27-0.73, p = 0.001) and previous SARS-CoV-2 infection (HR 0.27, 95%CI 0.14-0.51, p < 0.001) were protective. In conclusion, prophylaxis with monoclonal antibodies may reduce the risk of COVID-19 in hematological patients.