Multicausal analysis of mortality due to diabetes mellitus in Spain, 2016-2018.

OBJECTIVES: This study aimed to assess multicausal mortality due to diabetes from 2016-2018 in Spain. Specific objectives were to quantify the occurrence of diabetes as an underlying cause or as any registered cause on the death certificate. MATERIALS AND METHODS: A cross-sectional descriptive study taking a multicausal approach. RESULTS: Diabetes appears as an underlying cause of 2.3% of total deaths in Spain, and as any cause in 6.2%. In patients in whom Diabetes appears as an underlying cause on the death certificates, the 15 most frequent immediate causes are cardiovascular diseases in men(prevalence ratio 1,59)and women (PR1,31). In men, the causes associated with diabetes as any cause were skin diseases(prevalence ratio 1.33), followed by endocrine diseases(prevalence ratio 1.26)and genitourinary diseases (prevalence ratio1.14). In women, the causes associated with the presence of diabetes as any cause were endocrine (prevalence ratio 1.13)and genitourinary (prevalence ratio 1.04)diseases. CONCLUSIONS: In patients in whom diabetes appears as an underlying cause on the death certificates, the 15 most frequent immediate causes are cardiovascular diseases. In men, the causes associated with the presence of diabetes as any cause of death are skin, endocrine and genitourinary diseases. In women, the causes associated with diabetes as any cause are endocrine and genitourinary.

The roles of pyroptosis in genitourinary diseases.

Pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, is thought to be closely associated with the pathogenesis of diseases. Recently, the association between pyroptosis and urinary diseases has attracted considerable attention, and a comprehensive review focusing on this issue is not available. In this study, we reviewed the role of pyroptosis in the development and progression of benign urinary diseases and urinary malignancies. Based on this, pyroptosis has been implicated in the development of urinary diseases. In summary, this review sheds light on future research directions and provides novel ideas for using pyroptosis as a powerful tool to fight urinary diseases.

Exploring multimorbidity profiles in middle-aged inpatients: a network-based comparative study of China and the United Kingdom.

BACKGROUND: Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). METHODS: We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40-59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. RESULTS: We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. CONCLUSIONS: Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK.

Association between air temperature and risk of hospitalization for genitourinary disorders: An environmental epidemiological study in Lanzhou, China.

OBJECTIVES: The aim of this study was to investigate the relationship between air temperature and the risk of hospitalization for genitourinary disorders. METHODS: Distributed lag non-linear models (DLNM) were used to estimate the association between air temperature and the risk of hospitalization for genitourinary disorders, with subgroup analysis by gender and age to identify the susceptible population of temperature-sensitive genitourinary system diseases. RESULTS: Low mean temperature (MT) (RR = 2.001, 95% CI: 1.856~2.159), high MT (RR = 2.884, 95% CI: 2.621~3.173) and low diurnal temperature range (DTR) (RR = 1.619, 95% CI: 1.508~1.737) were all associated with the increased risk of hospitalization for genitourinary disorders in the total population analysis, and the high MT effect was stronger than the low MT effect. Subgroup analysis found that high MT was more strongly correlated in male (RR = 2.998, 95% CI: 2.623~3.427) and those <65 years (RR = 3.003, 95% CI: 2.670~3.344), and low DTR was more strongly correlated in female (RR = 1.669, 95% CI: 1.510~1.846) and those <65 years (RR = 1.643, 95% CI: 1.518~1.780). CONCLUSIONS: The effect of high MT on the risk of hospitalization for genitourinary disorders is more significant than that of low MT. DTR was independently associated with the risk of hospitalization for genitourinary disorders.

Epidemiology Trend of Urogenital System Disorders of Hospitalized Patients in an Eastern Chinese City from 2017 to 2019.

OBJECTIVE: To evaluate trends in the prevalence and clinical characteristics of urogenital diseases in hospitalized patients of secondary and tertiary hospitals in Ningbo, an east coast city in China, from 2017 to 2019. METHODS: We collected the data on hospitalized patients in Ningbo secondary and tertiary hospitals from January 1, 2017 to December 31, 2019. The data included age, sex, and diagnosis identified using the International Classification of Diseases (ICD) codes, which were obtained from Ningbo National Health Information Platform. We quantified the epidemiology (age/sex-specific) trend of urogenital system disorders. RESULTS: From January 2017 to December 2019, there were 256750 hospitalized patients with urogenital system disorders. These hospitalized patients comprised more women than men (1.45:1.00). The number of hospitalized patients with these diseases significantly increased over the 3 years (77505, 89167, and 90078, respectively; Z = 20.03, p < 0.001). The highest prevalence of these diseases was in the 40- to 64-year-old age group (47.37%), followed by the 18- to 39-year-old age group (23.94%). Over the 3 years, the five most common diseases in hospitalized male patients were male reproductive organ disorders, urolithiasis, tubulointerstitial disease, renal failure, and glomerular disease; Whereas the five most common diseases in hospitalized female patients were non-inflammatory disorders of the female genital tract, benign or dynamic undetermined tumors of the female reproductive organs, disorders of breast (according to ICD-10, disorders of breast (N60-N64) were involved in urogenital system diseases (N00-N99)), inflammatory diseases of female pelvic organs, and renal tubulointerstitial disease. In addition, the number of inpatients with renal tubulointerstitial disease significantly increased from 5952 to 9616 over the 3 years (rank increased from 6 to 3). CONCLUSIONS: Patients with urogenital system disorders significantly increased over the 3 years, occurring more often in women and most commonly in young and middle-aged people, which warrants more attention in clinical practice.

THE MORBIDITY RATE OF GENITOURINARY DISEASES ACCORDING TO THE DATA ON POPULATION RECEIVING MEDICAL CARE IN A MULTIFUNCTIONAL HEALTH CARE FACILITY.

OBJECTIVE: The aim: Establishing the characteristic features and morbidity rate of genitourinary diseases in order to substantiate the need for health care services. PATIENTS AND METHODS: Materials and methods: The article uses bibliographic, medical, statistical and content analysis, as well as analytical methods. We have analyzed the sex-age characteristics of the morbidity rate of genitourinary diseases, with the morbidity rates among different sex-age groups of the population in 2015-2022 evaluated. RESULTS: Results: Diseases of the genitourinary system constitute a significant share in the overall structure of the morbidity rate (7.3%-10.6%) and disease prevalence (6.1%-7.3%) among adults. In 2015-2022, the dynamics of the morbidity rate of genitourinary diseases and their prevalence were characterized by a constant increase until 2019, with a subsequent decrease until 2022. Such trends in the morbidity rate and prevalence of genitourinary diseases among people may be related to the impact of the COVID-19 pandemic, which led to the restricted access to health care services as a result of taking measures to prevent the spread of infection, excessive load on the network of health care facilities within the pandemic period, etc. The features of prevalence and dynamics of the incidence of genitourinary diseases in adolescents, adults, and persons of older age groups are determined. CONCLUSION: Conclusions: The identified sex-age characteristics of the morbidity rate of genitourinary diseases, prevailing nosologies in certain age and sex groups will become the basis for substantiating measures to improve the quality of medical care, taking into account the principle of patient centricity and integration of care.

[Position paper of the working group Urological Acute Medicine]. / Positionspapier des Arbeitskreises "Urologische Akutmedizin".

Emergency patients with acute genitourinary system diseases are frequently encountered in both outpatient and clinical emergency structures. It is estimated that one-third of all inpatients in a urology clinic initially present as an emergency. In addition to general emergency medicine knowledge, specialized urologic expertise is a prerequisite for the care of these patients, which is needed early and specifically for optimal treatment outcomes. It must be taken into account that, on the one hand, the current structures of emergency care still lead to delays in patient care despite positive developments in recent years. On the other hand, most hospital emergency facilities need urologic expertise on site. In addition, politically intended changes in our health care system, which drive an increasing ambulantization of medicine and condition a further centralization of emergency clinics, become effective. The aim of the newly established working group "Urological Acute Medicine" is to ensure and further improve the quality of care for emergency patients with acute genitourinary system diseases and, in consensus with the German Society of Interdisciplinary Emergency and Acute Medicine, to define precise task distributions and interfaces of both specialities.

Adverse events related to alpha-blockers: analysis of real-life data from Eudra-Vigilance.

BACKGROUND: Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and sexual AEs associated with ABs based on Eudra-Vigilance reported AEs. METHODS: Eudra-Vigilance (EV) database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of sexual and neuro-vascular AEs for tamsulosin, alfuzosin, silodosin, prazosin and doxazosin per category and severity until July 30th, 2022. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall the number of AEs were 2842 for Alfuzosin, 11,086 for tamsulosin, 792 for terazosin, 572 for prazosin and 4641 for doxazosin. Different percentages of AEs were obtained for each drug and in different age groups according to EV sub-groups (≤65, 65-85, ≥85). On PRR analysis, the risk of ejaculatory disorders for Silodosin (11%) is 18.5 times higher (PRR 18.5 95%CI; 10.7-31.8; P<0.05) when compared to alfuzosin and the risk of orthostatic hypotension is 2 times lower (PRR=1,84 95%CI 1.32-2.57; P<0.05). CONCLUSIONS: Real life data is consistent with registry studies regarding side effects related to alpha-blockers. Alfuzosin is safer in terms of ejaculatory disorders while silodosin and tamsulosin in terms of orthostatic hypotension. Clinicians should consider these data when prescribing ABs especially in younger and older patients.

Lumbar endoscopic spine surgery for persistent genital arousal disorder/genitopelvic dysesthesia resulting from lumbosacral annular tear-induced sacral radiculopathy.

BACKGROUND: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by distressing, abnormal genitopelvic sensations, especially unwanted arousal. In a subgroup of patients with PGAD/GPD, cauda equina Tarlov cyst-induced sacral radiculopathy has been reported to trigger the disorder. In our evaluation of lumbosacral magnetic resonance images in patients with PGAD/GPD and suspected sacral radiculopathy, some had no Tarlov cysts but showed lumbosacral disc annular tear pathology. AIM: The aims were 2-fold: (1) to utilize a novel multidisciplinary step-care management algorithm designed to identify a subgroup of patients with PGAD/GPD and lumbosacral annular tear-induced sacral radiculopathy who could benefit from lumbar endoscopic spine surgery (LESS) and (2) to evaluate long-term safety and efficacy of LESS. METHODS: Clinical data were collected on patients with PGAD/GPD who underwent LESS between 2016 and 2020 with at least 1-year follow-up. LESS was indicated because all had lumbosacral annular tear-induced sacral radiculopathy confirmed by our multidisciplinary management algorithm that included the following: step A, a detailed psychosocial and medical history; step B, noninvasive assessments for sacral radiculopathy; step C, targeted diagnostic transforaminal epidural spinal injections resulting in a temporary, clinically significant reduction of PGAD/GPD symptoms; and step D, surgical intervention with LESS and postoperative follow-up. OUTCOMES: Treatment outcome was based on the validated Patient Global Impression of Improvement, measured at postoperative intervals. RESULTS: Our cohort included 15 cisgendered women and 5 cisgendered men (mean ± SD age, 40.3 ± 16.8 years) with PGAD/GPD who fulfilled the criteria of lumbosacral annular tear-induced sacral radiculopathy based on our multidisciplinary management algorithm. Patients were followed for an average of 20 months (range, 12-37) post-LESS. Lumbosacral annular tear pathology was identified at multiple levels, the most common being L4-L5 and L5-S1. Twenty-two LESS procedures were performed in 20 patients. Overall, 80% (16/20) reported improvement on the Patient Global Impression of Improvement; 65% (13/20) reported improvement as much better or very much better. All patients were discharged the same day. There were no surgical complications. CLINICAL IMPLICATIONS: Among the many recognized triggers for PGAD/GPD, this subgroup exhibited lumbosacral annular tear-induced sacral radiculopathy and experienced long-term alleviation of symptoms by LESS. STRENGTHS AND LIMITATIONS: Strengths include long-term post-surgical follow-up and demonstration that LESS effectively treats patients with PGAD/GPD who have lumbosacral annular tear-induced sacral radiculopathy, as established by a multidisciplinary step-care management algorithm. Limitations include the small study cohort and the unavailability of a clinical measure specific for PGAD/GPD. CONCLUSION: LESS is safe and effective in treating patients with PGAD/GPD who are diagnosed with lumbosacral annular tear-induced sacral radiculopathy.

Case of apparent mpox reinfection.

We present an apparent second episode of mpox (monkeypox) genital ulcerative disease in a non-immunosuppressed MSM (man who has sex with men) patient who had completely recovered from a primary mpox infection 4 months previously. The patient had also received a complete two-dose course of smallpox vaccination between the two presentations. This case highlights the importance of continuing to include mpox in the differential diagnoses for individuals presenting with genital or mucosal ulceration, regardless of assumed immunity derived from prior infection or vaccination.

Neutralizing Antibody Kinetics and Immune Protection Against Herpes Simplex Virus 1 Genital Disease in Vaccinated Women.

BACKGROUND: Previously, our group conducted the Herpevac Trial for Women, a randomized efficacy field trial of type 2 glycoprotein D (gD2) herpes simplex virus (HSV) vaccine adjuvanted with ASO4 in 8323 women. Study participants were selected to be seronegative for HSV-1 and HSV-2. We found that the vaccine was 82% protective against culture-positive HSV-1 genital disease but offered no significant protection against HSV-2 genital disease. Efficacy against HSV-1 was associated with higher levels of antibody to gD2 at enzyme-linked immunosorbent assay (ELISA). METHODS: To better understand the results of the efficacy study, we measured postvaccination concentrations of neutralizing antibody (nAb) to either HSV-1 and HSV-2 from HSV-infected study participants and matched uninfected controls. Statistical modeling was used to determine whether these responses were correlated with protection against HSV. RESULTS: nAbs to either HSV-1 or HSV-2 were correlated with ELISA binding antibodies to gD2. HSV-1 or HSV-2 nAb findings support the observation of protection by higher levels of antibody against HSV-1 infection, but the lack of protection against HSV-2 remains unexplained. CONCLUSIONS: The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with nAbs directed against the virus, although the power to assess this was lower in the nAb study compared with the ELISA results owing to smaller sample size. CLINICAL TRIALS REGISTRATION: NCT00057330.

Bovine campylobacteriosis in bulls: insights in the conventional and molecular diagnosis.

Campylobacter fetus is a gram-negative motile bacterium, with two subspecies relevant to cattle health: C. fetus subsp. venerealis (Cfv) and C. fetus subsp. fetus (Cff). Both subspecies are associated with reproductive losses in cattle. In this study, we evaluated the identification of C. fetus for the diagnosis of bovine campylobacteriosis through bacteriological culture, direct immunofluorescence (DIF) and molecular tests in preputial smegma (PS) samples of three Angus bulls challenged with Cfv, Cfv biovar intermedius (Cfvi) or Cff, respectively, in an experiment imitating the natural infection. Two DNA extraction protocols were tested (in-house thermal extraction and commercial kit). Aspiration and scraping collection for PS were compared by conventional tests. Additionally, bacteremia was also evaluated in blood samples. Bulls were challenged by natural mating with heifers that had been experimentally infected with C. fetus subspecies; which led to infection. The Cfv- and Cfvi-bulls were positive for at least 9 months. Although Cff is not considered a venereal strain, in this study it was transmissible to bull from heifers experimentally infected, as evidenced by its colonization and persistence in the preputial cavity for 5 to 6 months. This finding suggests a potential risk of dissemination within herds. The results obtained by bacteriological culture or direct immunofluorescence (DIF) showed no significant differences, regardless the sampling device used (aspiration with Cassou pipette, metal and plastic scraper). C. fetus qPCR, on the other hand, yielded better results with an in-house DNA extraction method than with a commercial kit (75% vs 66.6%). Furthermore, qPCR diagnosis was more efficient than culture (66.6%) or DIF (56%). Bacteremia in whole blood samples was negative by qPCR and bacteriological culture in all samples. Altogether, this study demonstrated the transmission of Cff from heifers to bull and also showed that PCR-based methods are promising for the diagnosis of Bovine Genital Campylobacteriosis from clinical samples of PS.

Cone-beam CT delta-radiomics to predict genitourinary toxicities and international prostate symptom of prostate cancer patients: a pilot study.

For prostate cancer (PCa) patients treated with definitive radiotherapy (RT), acute and late RT-related genitourinary (GU) toxicities adversely impact disease-specific quality of life. Early warning of potential RT toxicities can prompt interventions that may prevent or mitigate future adverse events. During intensity modulated RT (IMRT) of PCa, daily cone-beam computed tomography (CBCT) images are used to improve treatment accuracy through image guidance. This work investigated the performance of CBCT-based delta-radiomic features (DRF) models to predict acute and sub-acute International Prostate Symptom Scores (IPSS) and Common Terminology Criteria for Adverse Events (CTCAE) version 5 GU toxicity grades for 50 PCa patients treated with definitive RT. Delta-radiomics models were built using logistic regression, random forest for feature selection, and a 1000 iteration bootstrapping leave one analysis for cross validation. To our knowledge, no prior studies of PCa have used DRF models based on daily CBCT images. AUC of 0.83 for IPSS and greater than 0.7 for CTCAE grades were achieved as early as week 1 of treatment. DRF extracted from CBCT images showed promise for the development of models predictive of RT outcomes. Future studies will include using artificial intelligence and machine learning to expand CBCT sample sizes available for radiomics analysis.

Genital labial phyllodes tumour recurring during pregnancy - does pregnancy impact recurrence?

SUMMARY: Phyllodes tumours (PT) of the vulva are uncommon tumours. The gold standard treatment for these lesions is unknown but is intuitively presumed to be wide local excision. Incomplete resection is associated with recurrence although the time to recurrence is not known. Pregnancy is hypothesised to increase recurrence due to the production of steroid hormones oestrogen and progesterone. We report on a patient who had recurrence of a PT at a rare site (labia minora) and on the contralateral side from the original lesion, during pregnancy. These findings support that oestrogen and progesterone hormones could have played a role in the recurrence of the PT although margins were not free at the initial surgery.

Re-Analysis of Published Datasets in Search of Novel Urogenital Diseases Biomarkers.

BACKGROUND: Exosome research is a current trend in functional proteomics as it provides important data on the pathophysiology and pathogenesis of diseases. The scientific outputs regarding these topics often only approach disease-protein/peptide/exosome or mechanismprotein/ peptide/exosome association. Approaching all three aspects could be the key to a better understanding of the pathophysiology and uncovering novel biomarkers for urogenital diseases. The focus of this work is to study exosome datasets to understand the possible role of underlying proteins in disease manifestation. We also attempt to link 4 different diseases that affect renal functions and are genetically inherited. METHODS: For this purpose, the existing literature is consulted to understand the importance of exosomes in disease prediction, diagnosis and therapy. Available biotechnological methods of exosome analysis and the tools of proteomic analysis, data mining and visualization are discussed. The database PRIDE is selected to query the information of several datasets related to urinary exosome analysis. RESULTS: We have obtained a list of 19 proteins/genes involved in the mentioned diseases. On this list, we found a proteomic fingerprint consisting of Rab-7a, PDCD6, and CDC42, among others, and we are exploring their biological significance and underlying processes. CONCLUSION: APOA1, CD59, CD9, IGHG1, RAB7A, RAP1A, SEMG1 and SEMG2 are common in four urogenital diseases, and are involved in interactions with podosomes and endosomes, remodeling of chylomicrons, regulation of interleukin production, regulation of endopeptidase activity, and establishment of apical/basal polarity of epithelial cells.

Monkeypox: a new differential diagnosis when addressing genital ulcer disease.

We describe a case of genital ulcer and inguinal adenopathies that were attributable to monkeypox virus infection. We suggest clinicians adopt a low threshold for suspicion, particularly when evaluating genital ulcer disease.

The association of endosalpingiosis with gynecologic malignancy.

OBJECTIVE: Endosalpingiosis is a poorly understood condition of ectopic epithelium resembling the fallopian tubes. It has been described as an incidental pathology finding, a disease similar to endometriosis, and in association with malignancy. The objective of this study is to determine if endosalpingiosis (ES) has an increased association with gynecologic malignancy when compared to endometriosis (EM). METHODS: This is a retrospective case-control analysis of patients with a histologic diagnosis of endosalpingiosis or endometriosis at three affiliated academic hospitals between 2000 and 2020. All ES patients were included, and 1:1 matching was attempted to obtain a comparable cohort of EM patients. Demographic and clinical data were obtained, and statistical analysis was performed. RESULTS: A total of 967 patients (515 ES and 452 EM) were included. ES patients were significantly older than EM patients (median age 52 vs 48 years, p < 0.001). The ES group had significantly more cancer diagnoses at surgery than the EM group (40.1% vs 18.1%, p < 0.001); this difference persisted in a sub-analysis excluding patients with known or suspected malignancy (20.9% vs 5.6%, p < 0.001). ES patients had lower overall survival (10-year freedom from death: 77.0% vs 90.5%, p < 0.001). After adjusting for confounders, multivariable analysis showed that ES patients had increased cancer diagnosed at surgery (OR = 2.48, p < 0.001) and greater risk of death (OR = 1.69, p = 0.017). CONCLUSIONS: Endosalpingiosis was found concurrently with malignancy in 40% of cases, and this effect was preserved in multi-variable and sub-group analyses. Further research consisting of longer follow-up and exploration of molecular relationships between ES and cancer are forthcoming.