Urethral cancer: a comprehensive review endorsed by the Global Society of Rare Genitourinary Tumours.

OBJECTIVE: To determine the effectiveness and adverse effects of urethrectomy alone or as part of multimodal therapy (MMT). METHODS: A comprehensive search was conducted across MEDLINE (OVID), EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL) databases, from their inception to the present date. The study cohort comprised individuals aged 16 years and older diagnosed with urethral tumours at any stage who underwent either isolated urethrectomy or urethrectomy as an integral component of MMT. RESULTS: Ninety-two studies comprising 25 480 patients met the inclusion criteria. Surgical outcomes for urethral cancer vary considerably, with 5-year overall survival (OS) ranging from 10% to 68% based on disease extent, approach, and gender. Radiotherapy (RT) alone provides 5-year OS of approximately 40%. Combined regimens provide better outcomes compared to single modalities, including reduced recurrence and enhanced survival. However, trimodal therapy showed survival benefits only for urothelial subtypes, indicating the need to tailor management according to cancer type. MMT with neoadjuvant chemotherapy prior to surgery demonstrated the most consistent survival gains. CONCLUSIONS: The management of urethral cancer demands a nuanced, personalised approach, accounting for factors such as tumour location, sex, and tumour stage. MMT combining surgery, chemotherapy and RT has shown the ability to enhance outcomes in advanced disease. More extensive collaborative studies through specialised centres are imperative to advance evidence-based protocols and refine treatment in order to improve survival.

Cancer centers of excellence for the multidisciplinary management of urologic cancers: The intersection between education, research, and healthcare.

Urologic cancers are among the leading causes of morbidity and mortality in the world, representing more than 10% of the total number of new cancer cases worldwide. These complex diseases are linked to several issues related to their diagnosis, management, monitoring, and treatment - issues that require multidisciplinary solutions that encompass and manage patients as complex entities. In response to this, the so-called cancer centers of excellence (CCEs) emerged, defined as multidisciplinary institutions specialized in the diagnosis, management, monitoring, and treatment of specific diseases, including cancer. Different institutions, such as the European Association of Urology (EAU), have proposed and encouraged its consolidation, especially for the management of prostate cancer. These institutions must be composed of three areas: healthcare, education, and research, which have complementary interactions and relationships, stimulating research and problem-solving from a multidisciplinary approach and also covering elements of basic sciences and mental health. The implementation of these CCEs has brought positive results; therefore, it is necessary to stimulate their implementation with a uro-oncologic approach.

Perspectives on prostate cancer: advances and pending challenges for a multidisciplinary oncological approach in South America.

Prostate cancer is one of the tumors with the highest incidence and mortality among men worldwide, and this situation is no different in South America. However, epidemiological data are highly variable for each country and even more so than in North America. These data may be influenced by the very low rate of early detection of disease, availability of diagnostic methods, proper data collection, and limited access to specialized multidisciplinary treatment. For many South American countries, academic referral centers can only offer state-of-the-art diagnostics and multidisciplinary cancer treatment for patients who live in or can travel to large cities, so most patients are cared for by non-expert urologists with limited resources, which can have a negative impact on their prognosis and worsen oncologic outcomes. We aimed to show the clinical management of prostate cancer patients, the current advances in management, limitations present in South America, and how a multidisciplinary approach in referral cancer centers conformed of specialized urologists, medical oncologists, and mental health professionals can maximize patient outcomes.

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Incidence of congenital heart disease in fetuses diagnosed with single isolated umbilical artery. Systematic review and meta-analysis.

OBJECTIVE: To estimate the proportion of heart disease in fetuses with a prenatal diagnosis of a single isolated umbilical artery. METHODS: We performed a search strategy in MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to the present. We assessed the risk of bias and performed a meta-analysis. We completed the subgroup analysis according to the region. RESULTS: We found 1384 studies by the search strategy. After carefully reviewing the full-text, 15 studies were included. A total of 2008 fetuses with a single isolated umbilical artery were included, and 177 had cardiac malformations. There was an overall incidence of 9% 95%CI (0.05-0.14) I2 90%. The incidence by country of origin was between 5% and 19%. The most common heart disease reported was a ventricular septal defect. Seven studies were found describing 25 cases. We described other malformations, such as tetralogy of Fallot, coarctation of the aorta, and hypoplastic left ventricle, among others. CONCLUSION: The incidence of congenital heart disease in fetuses with a single isolated umbilical artery was high. In addition, half of these correspond to significant heart disease. Based on the above, we suggest that fetuses with a single isolated umbilical artery should have a complete anatomic evaluation emphasizing cardiac evaluation.

Systematic Review and Meta-analysis of Minimally Invasive Procedures for Surgical Inguinal Nodal Staging in Penile Carcinoma.

CONTEXT: There are several procedures for surgical nodal staging in clinically node-negative (cN0) penile carcinoma. OBJECTIVE: To evaluate the diagnostic accuracy, perioperative outcomes, and complications of minimally invasive surgical procedures for nodal staging in penile carcinoma. EVIDENCE ACQUISITION: A systematic review of the Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov was conducted. Published and ongoing studies reporting on the management of cN0 penile cancer were included without any design restriction. Outcomes included the false negative (FN) rate, the number of nodes removed, surgical time, and postoperative complications. EVIDENCE SYNTHESIS: Forty-one studies were eligible for inclusion. Four studies comparing robot-assisted (RA-VEIL) and video-endoscopic inguinal lymphadenectomy (VEIL) to open inguinal lymph node dissection (ILND) were suitable for meta-analysis. A descriptive synthesis was performed for single-arm studies on modified open ILND, dynamic sentinel node biopsy (DSNB) with and without preoperative inguinal ultrasound (US), and fine-needle aspiration cytology (FNAC). DSNB with US + FNAC had lower FN rates (3.5-22% vs 0-42.9%) and complication rates (Clavien Dindo grade I-II: 1.1-20% vs 2.9-11.9%; grade III-V: 0-6.8% vs 0-9.4%) in comparison to DSNB alone. Favourable results were observed for VEIL/RA-VEIL over open ILND in terms of major complications (2-10.6% vs 6.9-40.6%; odds ratio [OR] 0.18; p < 0.01). Overall, VEIL/RA-VEIL had lower wound-related complication rates (OR 0.14; p < 0.01), including wound infections (OR 0.229; p < 0.01) and skin necrosis (OR 0.16; p < 0.01). The incidence of lymphatic complications varied between 20.6% and 49%. CONCLUSIONS: Of all the surgical staging options, DSNB with inguinal US + FNAC had the lowest complication rates and high diagnostic accuracy, especially when performed in high-volume centres. If DSNB is not available, favourable results were also found for VEIL/RA-VEIL over open ILND. Lymphatic-related complications were comparable across open and video-endoscopic ILND. PATIENT SUMMARY: We reviewed studies on different surgical approaches for assessing lymph node involvement in cases with penile cancer. The results show that a technique called dynamic sentinel node biopsy with ultrasound guidance and fine-needle sampling has high diagnostic accuracy and low complication rates. For lymph node dissection in penile cancer cases, a minimally invasive approach may offer favourable postoperative outcomes.

Lymphocele Complication After Kidney Transplant: Current Literature Review and Management Algorithm.

Kidney transplant is the best treatment option for patients with end-stage renal disease. It reduces mortality and improves the quality of life. However, kidney transplant presents medical and surgical complications, and one of the most common is the posttransplant lymphocele. Lymphocele complication has an incidence of up to 20% and presents with variable clinical symptoms, which are directly associated with the size and compression effect on the adjacent organs. There are reported risk factors that favor the appearance of lymphocele. Despite known factors, there are more relevant factors (male sex, deceased donor, and corticosteroids) to carry out a stricter follow-up. The treatment of lymphoceles can vary according to the severity of the symptoms, characteristics of the collection, and the patient's clinical status. Despite the high recurrence, percutaneous intervention is the initial approach in this condition. If percutaneous aspiration, drainage, and sclerotherapy are unsuccessful, then open or laparoscopic fenestration can be performed; laparoscopy is the standard of treatment since it is highly effective and has few adverse effects.

Unveiling Disrupted Lipid Metabolism in Benign Prostate Hyperplasia, Prostate Cancer, and Metastatic Patients: Insights from a Colombian Nested Case-Control Study.

Prostate cancer is a significant global health concern, and its prevalence is increasing worldwide. Despite extensive research efforts, the complexity of the disease remains challenging with respect to fully understanding it. Metabolomics has emerged as a powerful approach to understanding prostate cancer by assessing comprehensive metabolite profiles in biological samples. In this study, metabolic profiles of patients with benign prostatic hyperplasia (BPH), prostate cancer (PCa), and metastatic prostate cancer (Met) were characterized using an untargeted approach that included metabolomics and lipidomics via liquid chromatography and gas chromatography coupled with high-resolution mass spectrometry. Comparative analysis among these groups revealed distinct metabolic profiles, primarily associated with lipid biosynthetic pathways, such as biosynthesis of unsaturated fatty acids, fatty acid degradation and elongation, and sphingolipid and linoleic acid metabolism. PCa patients showed lower levels of amino acids, glycerolipids, glycerophospholipids, sphingolipids, and carnitines compared to BPH patients. Compared to Met patients, PCa patients had reduced metabolites in the glycerolipid, glycerophospholipid, and sphingolipid groups, along with increased amino acids and carbohydrates. These altered metabolic profiles provide insights into the underlying pathways of prostate cancer's progression, potentially aiding the development of new diagnostic, and therapeutic strategies.

Treatment of urge incontinence in postmenopausal women: A systematic review.

BACKGROUND: Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. CONCLUSIONS: The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.

Corporal Skip Metastases in Penile Squamous Cell Carcinoma: An Unknown and Distinct Pattern of Spread with Poor Prognosis.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is characterised by stepwise lymphatic dissemination. Skip metastases (SkMs) are rare metastases in the corpus cavernosum or spongiosum without continuity to the primary tumour or its resection site. OBJECTIVE: To assess the distinct pattern of spread in SkM+ patients and the effect of SkM on prognosis. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of patients with SkM+ PSCC at ten high-volume international referral centres between January 2006 and May 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated histopathological data, primary lymph node (LN) staging, and metastatic spread. We included a cohort of patients matched for pT stage, LN status, and grade who did not have SkM (SkM-) to compare the SkM prognosis and predictive value for cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Among the 63 SkM+ patients who met our inclusion criteria, the SkM diagnosis was synchronous in 54.0% and metastases were mostly located in the corpus cavernosum. SkM was symptomatic in 14% of cases, was detected on imaging in 32%, and was found incidentally on pathological examination in 27%. Fifty-one patients (81%) presented with positive LNs and 28 (44%) developed distant metastases. Seven patients (11%) presented with or developed distant metastasis without displaying any LN involvement. The 2-yr cancer-specific survival estimates were 36% (95% confidence interval [CI] 25-52%) for SkM+ and 66% (95% CI 55-80%) for matched SkM- patients (p < 0.001). On multivariable Cox regression analysis, SkM presence was an independent predictor for higher CSM (hazard ratio 2.05, 95% CI 1.06-4,12; p = 0.03). CONCLUSIONS: PSCC-related SkM is associated with aggressive disease behaviour and poor survival outcomes. Palpation of the entire penile shaft is essential, and distant staging is recommended in patients suspected of having SkM owing to the tendency for distant metastatic spread. PATIENT SUMMARY: We investigated outcomes for patients with cancer of the penis who had metastases in the tissues responsible for erection. We found that metastases in this location were associated with poor prognosis, even in the absence of more typical spread of cancer via the lymph nodes.

Effectiveness of photobiomodulation with low-level lasers on the acceleration of orthodontic tooth movement: a systematic review and meta-analysis of split-mouth randomised clinical trials.

Although several studies have evaluated the effect of low-level laser therapy (LLLT) on orthodontic movement acceleration, results are still inconsistent. Such inconsistencies may be attributed to the differences in the LLLT application protocols, especially in terms of wavelength ranges. Objective: (i) to assess the clinical effects of LLLT on the acceleration of orthodontic movement and (ii) to establish the most effective LLLT wavelength to accelerate tooth movement during orthodontic treatments. MEDLINE (PubMed), Scopus, ScienceDirect, and LILACS were searched from inception to October 2022. Inclusion criteria: Split-mouth randomised clinical trials (RCTs) on systemically healthy patients reporting the effect of LLLT in accelerating orthodontic movements, specifically retraction of canines. The risk of bias was assessed using RoB-2. A random effect model was applied. Nineteen RCTs met the inclusion criteria for qualitative synthesis, and eighteen RCTs were included in the quantitative synthesis. Seventeen studies were rated as at some concerns of bias and two studies were classified as having a low risk of bias. In general terms, this systematic review and meta-analysis presents a moderate risk of bias. Findings of this systematic review and meta-analysis point to a tendency for faster orthodontic dental movement in the groups receiving LLLT treatment during the first (OR of 0.28 95% CI (0.07 to 0.48)), second (OR of 0.52 95% CI (0.31 to 0.73)), and third (OR of 0.41 95% CI (0.03 to 0.79)) month follow-up. Wavelengths ≤ 810 nm and energy density values ≤ 5.3 J/cm2 were associated with faster orthodontic tooth movement.

Advanced breast, cervical and prostate cancer- Patient needs: systematic review.

BACKGROUND: There are high rates registered globally of breast cancer, cervical and prostate. People going through have needs that cause an impact in their life's quality, especially in the final stages of the illness. GOAL: To characterise the most evaluated and afflicted physical, emotional, roll, cognitive, social and spiritual needs of patients in the final stages of breast, cervical and prostate cancer. INTERVENTIONS/METHODS: A thorough systematic search of databases such as Medline (Ovid) and Embase, from databases' creation throughout 31 December 2021. Quantitative studies were included to evaluate, from the adoption of tools, the dimensions or needs of people going under three types of cancer on final stages. RESULTS: Twelve studies were included. More common symptoms such as nausea/vomiting and pain were the most evaluated with 83%. Fifty-eight per cent of papers studied the emotional function of people with breast and prostate cancer. Other 42% included roll, cognitive and social appreciations. Sexual, cognitive and physical, in that line, were the most affected. The most common questionnaires used to measure oncological patients on final stages were those from European Organisation for Research and Treatment of Cancer on its C-30, BR-23, C-15 PAL and CR-25 versions. CONCLUSIONS: On breast and prostate cancer, the most affected aspect was the sexual dysfunction, while for cervical cancer, the physical function was the most altered one. Spiritual dimension was not included in any of the evaluated literature.

Reporting of costs and economic impacts in randomized trials of de-implementation interventions for low-value care: a systematic scoping review.

BACKGROUND: De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. METHODS: We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. RESULTS: We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). CONCLUSION: De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. TRIAL REGISTRATION: OSF (Open Science Framework): https://osf.io/ueq32 .

Effectiveness of Virtual Reality in Balance Training for Fall Prevention in Older Adults: Systematic Review.

OBJECTIVE: The purpose of this study was to determine the effectiveness of virtual reality (VR) in balance training for the prevention of falls in older adults. METHODS: We included studies with experimental designs, cohort studies, and quasi-experimental studies of older adults who underwent balance training associated with the use of VR for the prevention of falls. The comparison of control and intervention groups in the studies reported statistically significant improvements in terms of balance for VR. RESULTS: The effects and benefits from the use of VR were seen by the fourth week of intervention, with significant improvements in balance and lower fall rates, the improvements became greater for groups using VR. CONCLUSIONS: The benefits presented by the studies were related not only to balance but also to fear of falling, reaction time, gait, physical fitness, independence in activities of daily living, muscle strength, and even quality of life.

Effectiveness and safety of prophylactic phototherapy to prevent jaundice in premature newborns: Systematic review and meta-analysis.

To determine the effectiveness and safety of prophylactic phototherapy compared with conventional phototherapy for the prevention of neonatal jaundice. We included clinical trials comparing prophylactic phototherapy to conventional phototherapy to prevent jaundice in premature newborns. We searched Embase, MEDLINE, LILACS, Central, and others. The statistical analysis was performed in RevMan (Review Manager 5.3). Outcomes were analyzed according to the type of variable: risk difference (RD) and mean difference (MD). A random effects model was used due to heterogeneity. We reported results in forest plots. Risk of bias was evaluated, and a sensitivity analysis was made. 1127 articles were found, and six studies (2332 patients) were included in the meta-analysis. Five studies evaluated the need for exchange transfusion as the primary outcome RD -0.01, 95% CI [-0.05 to 0.03]. One study evaluated bilirubin encephalopathy RD -0.04, 95% CI [-0.09 to 0.00]. Five studies evaluated the duration of phototherapy, MD 38.47, 95% CI [1.28 to 55.67]. Four studies evaluated levels of bilirubin (MD -1.23, 95% CI [-2.25 to -0.21]. Two studies evaluated mortality, RD 0.01, 95% CI [-0.03 to 0.04]. As a conclusion, compared to conventional phototherapy, prophylactic phototherapy decreases the last measured level of bilirubin, as well as the probability of neurodevelopmental disturbances. However, it increases phototherapy duration.

Advances in high-risk localized prostate cancer: Staging and management.

Nearly 15% of individuals with localized prostate cancer are identified as high risk for recurrence and progression of the disease, which is why the correct staging is vital for the definition of correct treatment-also developing novel therapeutic strategies to find a balance between getting better outcomes without sacrificing the quality of life (QoL). In this narrative review, we introduced the current standards of staging and primary treatment of high-risk localized prostate cancer (PCa), based on international guidelines and arguments in the debate, under the light of the most recent literature. It brings essential tools such as PSMA PET/CT and different nomograms (Briganti. MSKCC, Gandaglia) for accurate staging and selecting wisely the definitive therapy. Even though there is a broad discussion over the best local treatment in curative-intent treatment, it looks more important to define which patient profile would adapt correctly to every different treatment, highlighting the benefits and superior outcomes with multimodal treatment.

Incidence of urological tumors in Down's syndrome: a systematic review and meta-analysis.

BACKGROUND: Some authors have estimated that the incidence of testicular germ cell tumors in individuals with trisomy 21 is more than fivefold higher than that in the general population. OBJECTIVE: This systematic review aimed to estimate the incidence of urological tumors in patients with Down's syndrome. STUDY DESIGN: We conducted a search strategy in MEDLINE (OVID), EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. We assessed the risk of bias and performed a meta-analysis. Also, the heterogeneity between trials was evaluated by the I2 test. We completed the subgroup analysis based on the type of urological tumor (testis, bladder, kidney, upper urological tract, penile, retroperitoneum). RESULTS: We found 350 studies by the search strategy. After carefully reviewing, full-text studies were included. 16,248 individuals with Down's syndrome were included, and 42 patients presented with urological tumors. There was a total incidence of 0.1%, 95%CI (0.06-0.19), I2 61%. The most common urological tumor reported was testicular. We found six studies describing 31 events and an overall incidence of 0.19%, 95%CI (0.11-0.33), I2: 51%. Other studies reported kidney, penile, upper urinary tract, bladder, and retroperitoneum tumors with a very low incidence, 0.02%, 0.06%, 0.03%, 0.11%and 0.07%, respectively. DISCUSSION: Regarding non-testicular urological tumors, we found incidences as low as 0.02% in kidney cancer or 0.03% in the upper-urothelial tract tumors. It is also lower than the general population. Compared to the age of onset of patients, it is also lower than the general population, perhaps related to a shorter life expectancy. As a limitation, we found a high heterogeneity and a lack of information regarding non-testicular tumors. CONCLUSION: There was a very low incidence of urological tumors in people with Down's syndrome. Testis tumor was the most frequently described in all cohorts and within a normal distribution range.

Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.

Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. CONCLUSIONS: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.

Lipoxins and their relationship with inflammation-associated diseases. A systematic review.

AIM: To determine the relationship of lipoxin levels with inflammation and disease development in adults and children. METHODS: We conducted a systematic review. The search strategy included Medline, Ovid, EMBASE, LILACS, The Cochrane Central Register of Controlled Trials, and Open Gray. We included Clinical trials, cohort studies, case-control studies, and cross-sectional studies. Animal experiments were excluded. RESULTS: We included fourteen studies in this review, nine consistently showing decreased lipoxin levels and anti-inflammatory markers or increased pro-inflammatory markers in cardiovascular disease, metabolic syndrome, Alzheimer's disease, periodontitis, or autism. Five studies showed increased lipoxin levels and pro-inflammatory markers in pre-eclampsia, asthma, and coronary disease. On the other hand, one showed increased lipoxin levels and decreased pro-inflammatory marker levels. CONCLUSIONS: Decreases in lipoxins are associated with developing pathologies such as cardiovascular and neurological diseases, indicating that lipoxins protect against these pathologies. However, in other pathologies, such as asthma, pre-eclampsia, and periodontitis, which are associated with chronic inflammation despite increased levels of LXA4, the increase in inflammation suggests a possible failure of this regulatory pathway. Therefore, further studies are necessary to evaluate the role of LXA4 in the pathogenesis of inflammatory diseases.

Management of Lymph Node-positive Penile Cancer: A Systematic Review.

CONTEXT: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. OBJECTIVE: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EVIDENCE ACQUISITION: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. CONCLUSIONS: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. PATIENT SUMMARY: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.