Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection:Bioinformatics and molecular simulation analyses

Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

Primary lymphomas of the genitourinary tract:A population-based study

Objective:We performed a population-based analysis focusing on primary extranodal lymphoma of either testis,kidney,bladder or prostate(PGUL).Methods:We identified all cases of localized testis,renal,bladder and prostate primary lymphomas(PL)versus primary testis,kidney,bladder and prostate cancers within the Surveillance,Epidemiology,and End Results database(1998e2015).Estimated annual proportion change methodology(EAPC),multivariable logistic regression models,cumulative incidence plots and multivariable competing risks regression models were used.Results:The rates of testis-PL,renal-PL,bladder-PL and prostate-PL were 3.04%,0.22%,0.18%and 0.01%,respectively.Patients with PGUL were older and more frequently Caucasian.Annual rates significantly decreased for renal-PL(EAPC:5.6%;pZ0.004)and prostate-PL(EAPC:3.6%;pZ0.03).In multivariable logistic regression models,older ager independently predicted testis-PL(odds ratio[OR]:16.4;p<0.001)and renal-PL(OR:3.5;p<0.001),while female gender independently predicted bladder-PL(OR:5.5;p<0.001).In surgically treated patients,cumulative incidence plots showed significantly higher 10-year cancer-specific mortality(CSM)rates for testis-PL,renal-PL and prostate-PL versus their primary genitourinary tumors.In multivariable competing risks regression models,only testis-PL(hazard ratio[HR]:16.7;p<0.001)and renal-PL(HR:2.52;p<0.001)independently predicted higher CSM rates.Conclusion:PGUL rates are extremely low and on the decrease in kidney and prostate but stable in testis and bladder.Relative to primary genitourinary tumors,PGUL are associated with worse CSM for testis-PL and renal-PL but not for bladder-PL and prostate-PL,even after adjustment for other-cause mortality.

Management of genitourinary syndrome of menopause in breast cancer survivors:An update

There is increasing attention about managing the adverse effects of adjuvant therapy(Chemotherapy and anti-estrogen treatment)for breast cancer survivors(BCSs).Vulvovaginal atrophy(VVA),caused by decreased levels of circulating estrogen to urogenital receptors,is commonly experienced by this patients.Women receiving antiestrogen therapy,specifically aromatase inhibitors,often suffer from vaginal dryness,itching,irritation,dyspareunia,and dysuria,collectively known as genitourinary syndrome of menopause(GSM),that it can in turn lead to pain,discomfort,impairment of sexual function and negatively impact on multiple domains of quality of life(QoL).The worsening of QoL in these patients due to GSM symptoms can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly.The diagnosis of VVA is confirmed through patient-reported symptoms and gynecological examination of external structures,introitus,and vaginal mucosa.Systemic estrogen treatment is contraindicated in BCSs.In these patients,GSM may be prevented,reduced and managed in most cases but this requires early recognition and appropriate treatment,but it is normally undertreated by oncologists because of fear of cancer recurrence,specifically when considering treatment with vaginal estrogen therapy(VET)because of unknown levels of systemic absorption of estradiol.Lifestyle modifications and nonhormonal treatments(vaginal moisturizers,lubricants,and gels)are the first-line treatment for GSM both in healthy women as BCSs,but when these are not effective for symptom relief,other options can be considered,such as VET,ospemifene,local androgens,intravaginal dehydroepiandrosterone(prasterone),or laser therapy(erbium or CO2 Laser).The present data suggest that these therapies are effective for VVA in BCSs;however,safety remains controversial and a there is a major concern with all of these treatments.We review current evidence for various nonpharmacologic and pharmacologic therapeutic modalities for GSM in BCSs and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research.We include recommendations for an approach to the management of GSM in women at high risk for breast cancer,women with estrogen-receptor positive breast cancers,women with triplenegative breast cancers,and women with metastatic disease.

Genitourinary function and defecation after colorectal cancer surgery with low-and high-ligation of the inferior mesenteric artery:A meta-analysis

BACKGROUND The effect of low ligation(LL)vs high ligation(HL)of the inferior mesenteric artery(IMA)on functional outcomes during sigmoid colon and rectal cancer surgery,including urinary,sexual,and bowel function,is still controversial.AIM To assess the effect of LL of the IMA on genitourinary function and defecation after colorectal cancer(CRC)surgery.METHODS EMBASE,PubMed,Web of Science,and the Cochrane Library were systematically searched to retrieve studies describing sigmoid colon and rectal cancer surgery in order to compare outcomes following LL and HL.A total of 14 articles,including 4750 patients,were analyzed using Review Manager 5.3 software.Dichotomous results are expressed as odds ratios(ORs)with 95%confidence intervals(CIs)and continuous outcomes are expressed as weighted mean differences(WMDs)with 95%CIs.RESULTS LL resulted in a significantly lower incidence of nocturnal bowel movement(OR=0.73,95%CI:0.55 to 0.97,P=0.03)and anastomotic stenosis(OR=0.31,95%CI:0.16 to 0.62,P=0.0009)compared with HL.The risk of postoperative urinary dysfunction,however,did not differ significantly between the two techniques.The meta-analysis also showed no significant differences between LL and HL in terms of anastomotic leakage,postoperative complications,total lymph nodes harvested,blood loss,operation time,tumor recurrence,mortality,5-year overall survival rate,or 5-year disease-free survival rate.CONCLUSION Since LL may result in better bowel function and a reduced rate of anastomotic stenosis following CRC surgeries,we suggest that LL be preferred over HL.

Considerations for the clinical use of stem cells in genitourinary regenerative medicine

The genitourinary tract can be affected by several pathologies which require repair or replacement to recover biological functions.Current therapeutic strategies are challenged by a growing shortage of adequate tissues.Therefore,new options must be considered for the treatment of patients,with the use of stem cells(SCs)being attractive.Two different strategies can be derived from stem cell use:Cell therapy and tissue therapy,mainly through tissue engineering.The recent advances using these approaches are described in this review,with a focus on stromal/mesenchymal cells found in adipose tissue.Indeed,the accessibility,high yield at harvest as well as anti-fibrotic,immunomodulatory and proangiogenic properties make adipose-derived stromal/SCs promising alternatives to the therapies currently offered to patients.Finally,an innovative technique allowing tissue reconstruction without exogenous material,the self-assembly approach,will be presented.Despite advances,more studies are needed to translate such approaches from the bench to clinics in urology.For the 21st century,cell and tissue therapies based on SCs are certainly the future of genitourinary regenerative medicine.

SARS-CoV-2 effects in the genitourinary system and prospects of sex hormone therapy

Object:Corona virus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which leads to acute respiratory infection symptoms.SARS-CoV-2 infection is not always limited to the respiratory tract,and renal infection and dysfunction have been shown to be specific risk factors for death.In addition,COVID-19 has a higher incidence,severity and mortality in men than women.This disparity is due to biological rather than comorbid or behavioral sex differences.Because the male reproductive system is unique,the function of sex hormones in COVID-19 infection may explain the differences between males and females.Understanding these factors will provide appropriate prevention measures and adequate triage strategies and guide the drug discovery process.Methods:An electronic search was completed in PubMed,ARXIV,MEDRXIV and BIORXIV.The most relevant articles were systematically reviewed.In addition,single cell RNA sequencing analysis of tissue samples from human cell landscape was conducted.Results:The influence of SARS-CoV-2 on the urogenital system,the possibility of urinary tract transmission and the functions of sex hormones were discussed in this review.Conclusion:Corona viruses can invade the genitourinary system,causing urological symptoms.Identifying the potential genitourinary organ impairments and protecting them from damage are necessary.Since sex hormones have potential as specific drugs,the gonadal hormones substitution therapy should be considered in both sexes in the COVID-19 pandemic.

An integrated analysis of mRNA-miRNA transcriptome data revealed hub regulatory networks in three genitourinary cancers

Bladder,kidney,prostate and testicular carcinoma are the top four genitourinary cancers in China.Here we analyzed mRNA and miRNA expression profiles of carcinomas of the bladder(TCC),kidney(ccRCC)and testis(TGCT)to uncover their specific regulatory mechanisms.The gene expression profiles of GSE31617 were downloaded from GEO database,which contained 27 samples,including 10 TCC,7 TGCT and 10 ccRCC.Specific up-and downregulated differentially expressed genes(DEGs)and differentially expressed microRNAs(DEmiRNAs)of each cancer were selected and target genes of DEmiRNAs were predicted.Gene interaction network of the shared genes and target genes of DEmiRNAs of each cancer was predicted by STRING and constructed by Cytoscape.In each cancer,we build regulatory networks of hub genes selected and conducted GO analysis of enriched genes.Furthermore,we chose four hub genes(SALL4,RHEB,CDC42 and TNN)for survival analysis in OncoLnc database,and they all had effects on the survival rate of another genitourinary cancer-kidney renal clear cell carcinoma(KIRC).In conclusion,the present study indicated that the identified hub genes promote our understanding of molecular mechanisms underlying the development of three genitourinary cancers,and might be used as molecular targets and diagnostic biomarkers for the treatment of them.

Solid State Vaginal Laser for the Treatment of Genitourinary Syndrome of Menopause: A Preliminary Report

Background: Genitourinary syndrome of menopause (GSM) is the new term for vulvovaginal atrophy (VVA). The condition is relevant in more than 50% of women, having an adverse impact on quality of life and sexual relationships. Objective: To assess the efficacy and safety of a new type of non-ablative laser, Solid State Vaginal Laser (SSVL), for vaginal tissue regeneration and rejuvenation. Method: Eighty participants with GSM symptoms were treated with a total of 4 treatments in about two months (every 15 - 20 days) of a non-ablative SSVL (LASEmaR 1500TM-EUFOTON). A cumulative intensity of GSM symptoms using a 10-cm VAS (dryness and/or burning and/or dyspareunia), the vaginal health index (VHI), the Female Sexual Function Index (FSFI) were evaluated. Urinary Incontinence Short Form (ICIQ-UI SF) and vaginal bioptic samples were also collected. Results: Improvement following the SSVL was observed on VHIS, VVA symptoms and sexual female function. This finding was also ratified by the improvement of vaginal histological features. After the SSVL treatment, almost all patients (91%) affected by urinary incontinence obtained the complete remission of symptoms. Conclusion: The objective evaluation of VHIS, FSFI and ICIQ-UI SF scores and the histological results indicates a real favorable effect of SSVL on GSM and on urinary incontinence.

Radiological Evaluation of Lower Genitourinary Tract Cysts in Males

Aim of the Work: The present wok aims to assess how to reach the optimum diagnosis of the nature and the complications of lower genitourinary tract cyst in male patient using different radiological imaging modalities. Patients and Methods: 1000 male patients were evaluated with pelvic ultrasound and if lower genitourinary tract cysts were present, the patients were further subjected to either trans-rectal ultrasound (TRUS), TRUS guided aspiration for presence of spermatozoa, TRUS guided seminal vesiculography or CT urography in order to reach the origin of the cyst and the complications of its presence. Results: 14 cases were detected with lower genitourinary tract cysts among our patients with an overall incidence 1.4%;among them 3 patients with mid line prostatic cysts showed normal seminal analysis;1 patient with prostatic cyst was infertile;3 patients were detected with infravesical cysts after transurethral resection prostatectomy;2 cases with small retention cysts were associated with benign prostatic hyperplasia;1 case was detected with prostatic abscess;1 patient was detected with unilateral ureterocele;1 patient was detected with large pelvi abdominal unilateral seminal vesicle cyst;1 patient was with unilateral ejaculatory duct cyst;1 patient with small cystic dilation of prostatic urethra was associated with urethral stone.

Management of genitourinary trauma – current evaluation from the Sub-Saharan region: A systematic review

BACKGROUND Trauma is a major cause of morbidity globally and the sixth leading cause of death,accounting for 10%of all mortalities.The genitourinary trauma is estimated for approximately 10%of all patients presenting with trauma,and the kidney is the most injured genitourinary organ globally.However,there is a paucity of data on genitourinary injury from the Sub-Saharan,and there may be variations from common genitourinary organs injured in developed nations.AIM To provide insight on the epidemiology and management of genitourinary trauma in Sub-Saharan Africa with recommendations based on international guidelines.METHODS A thorough literature search of genitourinary trauma was conducted using PubMed,Google Scholar and African Journal Online.RESULTS A total of 30 studies from the Sub-Saharan region were eligible for the study and reviewed for epidemiology,biodata,types of injury,mechanisms of injury,treatment and follow-up.After evaluating 21904 patients presenting with urological emergencies,approximately 6.6%of cases were due to genitourinary trauma.The commonest injury was urethral 42.9%(22.2-62.2%)followed by injury to the external genitalia(penis,scrotum,testes)25.1%(8.8-67.7%).CONCLUSION Genitourinary injury in Sub-Saharan Africa is underreported,and the presence of more trauma registries,trained urologists and trauma facilities could improve the overall standard of care as well as providing data for research and development in the field.

Changing constituents of genitourinary cancer in recent 50 years in Beijing

Objective To assess the changes in constituents of genitourinary cancer inpatients in Beijing following the growing economy of China.Methods Urological inpatients treated from January 1951 to December 2000 at the Institute of Urology, Peking University were studied restrospectively.Results In the period of about 50 years 28 474 urological inpatients were reviewed. Cancer patients aged 0 -25 years and 26 -50 years comprised 19. 5% and 28. 2% , respectively. Since the 1970s the incidence rates of renal cancer and prostate cancer increased dramatically from 10. 4% to 28. 7% and from 3. 3% to 13. 4% , respectively.Conclusion The introduction of new diagnostic instruments, the expansion of the aged population and a high fat diet are considered to be responsible for the change of constituents of genitourimary concer inpatients.

Pediatric genitourinary tumors:Distribution,demographics,and outcomes

Importance:The diversity of pediatric genitourinary malignancies requires a timely resource detailing tumor characteristics and survival.Objective:To determine the incidence,demographics,and outcomes of all pediatric genitourinary tumors within the United States.Methods:A population-based search for patients diagnosed with genitourinary cancers under age 15 was performed using the National Cancer Institute’s Surveillance,Epidemiology,and End Results 18 registry.Information on primary tumor location,histologic type,patient age,sex,year of diagnosis,race,treatment,cause of death,and survival months was extracted.Descriptive epidemiological and survival statistics were calculated for all variables.Results:A total of 4576 cases from 1973 through 2015 were identified.The most common primary tumor sites were the kidney(80.3%),testis(12.3%),bladder(2.8%),and vagina(1.5%).Nephroblastoma(87.9%)and sarcoma(3.4%)were the most common renal malignancies.Rhabdomyosarcoma was common in the vagina,bladder,and testis at rates of 66.2%,61.2%,and 24.6%,respectively.Germ cell tumors(71.0%)were the most common primary tumor of the testis.Ten-year overall survival(OS)for renal nephroblastoma and sarcoma was 88%and 82%,respectively.Ten-year OS for RMS of the testis was 91%,the bladder was 79%,the vagina was 79%,and the prostate was 56%.Germ cell tumor 10-year OS were 96%in the testis and 100%in the vagina.Interpretation:A better understanding of the overall distribution and outcomes associated with pediatric genitourinary cancers allows physicians to best understand the patient’s disease in the context of current frequency in a genitourinary setting and reported outcomes.

Royal jelly for genitourinary syndrome of menopause:A randomized controlled trial

Objective:Genitourinary syndrome of menopause is a progressive condition characterized by a decrease in estrogen,which causes bothersome genital symptoms.The purpose of the study was to determine the effect of royal jelly on the genitourinary syndrome of menopause.Materials and methods:A randomized controlled trial was carried out from November 2018 to June 2019 in Bandar Abbas,Iran.The trial was registered in the Iranian Registry of Clinical Trials(1RCT20181107041585N1)with the main objective of determining if royal jelly could reduce the genitourinary syndrome of menopausal women.Eligible women were randomly assigned to receive either daily 1g of oral royal jelly or placebo for 8 weeks.The urogenital subscale of the Menopausal Rating Scale was used to determine genitourinary syndrome.Independent samples t-test was used for inter-group comparisons and paired samples t-test for pre-and post-treatment comparisons.Results:There were no differences in the severity of sexual problems,bladder complications,or vaginal dryness between groups before intervention.Although the intervention group's bladder complications improved slightly after eight weeks of royal jelly treatment compared to the control group(p?0.04),there were no significant changes in vaginal dryness,sexual problems,or total urogenital score.The within-group changes(before and after treatment)also showed no differences in urogenital symptoms.Conclusions:A daily dose of 1g royal jelly taken orally for 8 weeks did not alleviate menopausal genitourinary syndrome.No serious side effects were observed.To make more reliable decisions about the use and safety of royal jelly in the future,different doses of royal jelly and longer trials are required.

Non-Ablative Transvaginal Radiofrequency in the Treatment of Stress Urinary Incontinence: Review of the Literature

Background: Urinary incontinence is defined as the involuntary loss of urine, which can affect up to 45% of women after menopause. Radiofrequency is a non-invasive procedure that involves the application of an electromagnetic wave that through heat generation promotes neocollagenesis and neoeslatinogenesis in the vaginal epithelium. This energy-based technology has been studied as a potential alternative for the treatment of genitourinary syndrome of menopause and urinary incontinence. Objective: To review the recent literature (from 2020 to June 2022) on the use of transvaginal radiofrequency in the treatment of stress urinary incontinence, by searching articles at databases of Capes, PubMed Cochrane and Scielo. Methods: The descriptor terms “Urinary Incontinence/therapy” [Majr] AND “Urinary Incontinence, Stress/therapy” [Majr] AND RADIOFREQUENCY-Search Results-PubMed, [“woman” OR “women”] AND [“urinary incontinence” OR “stress urinary incontinence”] AND Radiofrequency were used, with a filter for the period 2020 to 2022. Conclusion: The studies evaluated in this review demonstrated significant results of radiofrequency in the resolution or reduction of complaints of women with urinary incontinence, especially stress urinary incontinence, but most of these studies presented a low methodological quality. There is, therefore, a lack of studies with longer follow-ups, evaluation of cost-effectiveness, randomized clinical trials with objective outcomes and the use of validated questionnaires with international acceptance.

Research progress on the application of the main components of Cuscuta sinensis in the urogenital system

Cuscuta sinensis is a traditional Chinese medicine commonly used in traditional medicine,known for its liver and kidney tonifying effects,sperm fixing and urine reduction properties,fetus calming abilities,eye brightening qualities,and diarrhea stopping capabilities.Modern pharmacological studies have focused on its chemical components such as flavonoids,polysaccharides,alkaloids,steroids,and other bioactive compounds.These studies have revealed its various pharmacological effects,including hormone secretion regulation,ovulation promotion,sperm protection,testicular development promotion,and sperm formation.It is extensively utilized in the treatment of urological and reproductive system diseases,such as male sexual dysfunction,polycystic ovary syndrome,premature ovarian failure,weak spermatozoa,and infertility.This article provides a review of recent advancements in the application of Cuscuta sinensis in the genitourinary system,aiming to enhance the clinical application of Cuscuta sinensis preparations.

Extramammary Paget’s disease: Updates in the workup and management

Objective:Extramammary Paget’s disease(EMPD)is a rare cutaneous malignant disease.Due to its rarity,there is a paucity of data regarding best treatment strategy.EMPD primarily affects apocrine gland-bearing skin areas such as the vulva,scrotum,and penis.Our objective was to provide a present-day rationale for diagnosis,pathogenesis,and treatment of EMPD with a focus on recent progress in workup and management of the disease.Methods:Literature on EMPD until February 2022 was assessed through PubMed,MEDLINE databases,and Google scholar.A narrative review of the most relevant articles was provided.Results:EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ.The foundation of EMPD treatment centers around prompt and accurate diagnosis,wide local or Mohs micrographic surgical excision with proper management towards the margin status,and careful consideration for lymphadenectomy in patients with regionally positive disease.Conventional chemotherapies are alternative treatments modality for patients with distant metastases;however,they sometimes have suboptimal efficacy.At present,there is no agreement regarding adjuvant or systemic therapies,although recent studies have shown several insights into the molecular pathogenesis,tumor biology,and genomics of the development and advancement of EMPD,which may lead to novel and targeted treatment approaches for metastatic EMPD in the future.Conclusion:Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling.These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression.Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors,and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

Probiotics to counteract biofilm-associated infections: promising and conflicting data

Altered bowel flora is currently thought to play a role in a variety of disease conditions, and the use of Bifidobacterium spp. and Lactobacillus spp. as probiotics has been demonstrated to be health-promoting, even if the success of their administration depends on the applied bacterial strain（s） and the targeted disease. In the last few decades, specific probiotics have been shown to be effective in the treatment or the prevention of acute viral gastroenteritis, pediatric post-antibiotic-associated diarrhea, some pediatric allergic disorders, necrotizing enterocolitis in preterm infants, inflammatory bowel diseases and postsurgical pouchitis. The potential application of probiotics is continuously widening, with new evidence accumulating to support their effect on the prevention and treatment of other disease conditions, including several oral diseases, such as dental caries, periodontal diseases and oral malodor, as well as genitourinary and wound infections. Considering the increasingly widespread ability of pathogens to generate persistent biofilm-related infections, an even more attractive proposal is to administer probiotics to prevent or counteract biofilm development.The response of biofilm-based oral, intestinal, vaginal and wound infections to probiotics treatment will be reviewed here in light of the most recent results obtained in this field.

Bladder stones in a closed diverticulum caused by Schistosoma mansoni: A case report

BACKGROUND Genitourinary(GU)schistosomiasis is a chronic infection caused by a parasitic trematode,with Schistosoma haematobium(S.haematobium)being the prevalent species.The disease has a variable prevalence around the world,with a greater burden on,but not limited to Africa,South America,Asia,and the Middle East.CASE SUMMARY We report the case of a 30-year-old man who presented with symptoms of bladder stones.During endoscopic cystolithalopaxy,we did not detect any stones in the bladder.Upon careful scanning of the urinary bladder trigone,sandy patches were detected.We performed endoscopic resection,which revealed a closed diverticulum with bladder stones.The diverticular wall was sent for histopathology and revealed features of chronic granulomatous inflammation with numerous embedded Schistosoma eggs,with some of the eggs having lateral spines.The patient was treated with praziquantel,and his symptoms completely resolved.CONCLUSION GU schistosomiasis is primarily caused by S.haematobium.However,Schistosoma mansoni mediated GU schistosomiasis is unusual,making this a quite interesting case.

How low do we fall to lower hemoglobin A1c? SGLT2 inhibitors: Effective drugs or expensive toxins!

SGLT2 inhibitors improve hyperglycemia with a decline in body weight and blood pressure, the outcomes touted to be of major importance in management of type 2 diabetes. However, the efficacy in lowering glycemia is very modest and imparts an undue cost burden on patients. Moreover, the declines in body weight and blood pressure are slight at best and orthostatic hypotension and its manifestations including syncope at worst, are all secondary to dehydration and probable total body electrolyte depletion caused by polyuria and nocturia as anticipated and established consequences of glycolsuria induced by SGLT2 inhibitors via their mechanism of action. Moreover, frequent adverse effects including impaired renal function as expressed by rises in serum creatinine and urea nitrogen, hyperkalemia and recurrent genitourinary infections are certainly likely to lead to the decline in quality of life. Finally, a rise in LDL cholesterol accompanied by increased serum viscosity secondary to dehydration may compromise cardiovascular safety as well. Thus, use of these expensive agents with modest efficacy and with established significant pathologic side effects escalating costs even further and unknown long term safety may be contradictory to the tenets of ethical medical practice established by “Hippocratic oath”. Recent approval of SGLT2 inhibitors by regulatory agencies in Europe and USA for treatment of hyperglycemia in type 2 diabetes is therefore surprising and disheartening.

Global,regional,and national burden of kidney,bladder,and prostate cancers and their attributable risk factors,1990–2019

Background:The burden of kidney,bladder,and prostate cancers has changed in recent decades.This study aims to investigate the global and regional burden of,and attributable risk factors for genitourinary cancers during the past 30 years.Methods:We extracted data of kidney,bladder,and prostate cancers from the Global Burden of Disease 2019 database,including incidence,mortality,disability-adjusted life-years(DALYs),and attributable risk factors from 1990 to 2019.Estimated annual percentage changes(EAPC)were calculated to assess the changes in age-standardized incidence rate,age-standardized mortality rate(ASMR),and age-standardized DALYs rate(ASDR).The associations between cancers burden and socio-demographic index(SDI)were also analyzed.Results:Compared with 1990,the global incident cases in 2019 were higher by 154.78%,123.34%,and 169.11%for kidney,bladder,and prostate cancers,respectively.During the 30-year study period,there was a downward trend in ASMR and ASDR for bladder cancer(EAPC=–0.68 and–0.83,respectively)and prostate cancer(EAPC=–0.75 and–0.71,respectively),but an upward trend for kidney cancer(EAPC=0.35 and 0.12,respectively).Regions and countries with higher SDI had higher incidence,mortality,and DALYs for all three types of cancers.The burden of bladder and prostate cancers was mainly distributed among older men,whereas the burden of kidney cancer increased among middle-aged men.Smoking related mortality and DALYs decreased,but high body mass index(BMI)and high fasting plasma glucose(FPG)related mortality and DALYs increased among kidney,bladder,and prostate cancers during the study period.Conclusions:Kidney,bladder,and prostate cancers remain major global public health challenges,but with distinct trend for different disease entity across different regions and socioeconomic status.More proactive intervention strategies,at both the administrative and academic levels,based on the dynamic changes,are needed.