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Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.
Bapir, R, Bhatti, KH, Eliwa, A, García-Perdomo, HA, Gherabi, N, Hennessey, D, Magri, V, Mourmouris, P, Ouattara, A, Perletti, G, et al
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2023;(2):11509
Abstract
UNLABELLED 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.
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Treatment of urge incontinence in postmenopausal women: A systematic review.
Bapir, R, Bhatti, KH, Eliwa, A, García-Perdomo, HA, Gherabi, N, Hennessey, D, Magri, V, Mourmouris, P, Ouattara, A, Perletti, G, et al
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2023;(3):11718
Abstract
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.
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3.
Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis.
Bapir, R, Bhatti, KH, Eliwa, A, García-Perdomo, HA, Gherabi, N, Hennessey, D, Magri, V, Mourmouris, P, Ouattara, A, Perletti, G, et al
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2022;(4):507-514
Abstract
OBJECTIVE Proton pump inhibitors are widely used as treatment of acid-related disorders. They are considered safe although their long-term use has been associated with some adverse effects including an increased propensity for urinary calculi formation. The aim of this study was to systematically review available data from studies evaluating the association of PPIs and nephrolithiasis. MATERIALS AND METHODS We searched two electronic databases (PubMed and EMBASE) for cohort studies or case-control studies evaluating the relationship between treatment with proton pump inhibitors and the risk of stone formation published up to 31 October 2022. The overall association of PPIs and urinary calculi was analyzed using a random effects model (RevMan5). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS A total of 550 studies were retrieved; 7 were selected by title and abstract screening; after removal of duplicates, 4 records were evaluated by full-text examination. An additional study was retrieved by handsearching the references included in screened studies. In the unadjusted analysis, the odds of urinary calculi were greater in subjects taking PPIs compared to controls (unadjusted OR = 2.10, 95% CI 1.74-2.52, p < 0.00001). The pooled odds ratio of two case-control studies confirmed that use of PPIs increased the odds of urinary calculi compared with non-use (OR 2.44, 95% CI 2.29 to 2.61). Pooled analysis of three cohort studies evaluating incident nephrolithiasis showed an overall hazard ratio estimate of 1.34 (95% CI = 1.28-1.40). One study found lower urinary citrate and urinary magnesium levels in subjects exposed to PPIs. The Newcastle-Ottawa Quality Assessment Scale scores ranged between 6 and 8. CONCLUSIONS PPIs showed an association with urinary calculi in patients included in the studies included in this review. If these data will be confirmed in adequately powered randomized trials, clinicians may consider limiting the long-term use of PPIs, to avoid unnecessary prolongation of treatment. Urinary magnesium and citrate should be evaluated in renal stone forming patients taking PPIs to supplement their intake when requested.
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The impact of nutrition and lifestyle on male fertility.
Benatta, M, Kettache, R, Buchholz, N, Trinchieri, A
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2020;92(2)
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The impact of environmental, lifestyle and nutritional factors on unexplained male fertility has long been acknowledged. Yet, little research had been dedicated to the topic, despite declining semen quality having become a worldwide phenomena. Available studies have yielded limited, and at times conflicting, evidence. Hence this literature review sought to capture the current knowledge around unexplained male infertility and environmental, lifestyle, diet and nutrients factors. Summarized is the evidence from 69 studies, including population observations and clinical trials. The collected outcomes showed that a Western-type diet, rich in red and processed meats, refined grains, high-energy drinks and sweets, trans and saturated fats was associated with poor semen quality. Whereby higher intakes of fruits and vegetables, whole grains, omega-3 and poultry showed beneficial effects. However, as only selected groups were examined, more research is needed to project such findings onto the wider population. The reviewed evidence also included alcohol consumption, which showed high alcohol intake closely correlated to declining sperm concentrations. Whilst the verdict on caffeine consumption and the impact on sperm quality was inconclusive. In addition, several interventional studies evaluated the effect of dietary supplementation on various parameters of semen, where coenzyme Q10, L-carnitine, vitamin E, antioxidants, combined nutrient formulations and herbal blends all had positive outcomes. The review on zinc and folic acid supplementation yielded mixed results. This brief recap of the current evidence on environmental, lifestyle and nutritional influences on male infertility summarises the dietary foundations for the support of unexplained male infertility.
Abstract
BACKGROUND AND AIMS Male unexplained infertility has long been suspected to result from environmental, lifestyle and nutritional factors. However, the literature on the subject is still scarce, and clinical studies providing robust evidence are even scarcer. In addition, some similar studies come to different conclusions. Dietary pattern can influence spermatogenesis by its content of fatty acids and antioxidants. Yet, in an age of industrialized mass food production, human bodies become more exposed to the ingestion of xenobiotics, as well as chemicals used for production, preservation, transportation and taste enhancement of foods. We attempted in this paper to collect the available evidence to date on the effect of nutritional components on male fertility. MATERIAL AND METHODS A systematic search of the relevant literature published in PubMed, ScienceDirect and Cochrane Central Register of Controlled Trials Database was conducted. Literature was evaluated according to the Newcastle-Ottawa- Scale. RESULTS Epidemiological observations are concordant in demonstrating an association of low-quality sperm parameters with higher intake of red meat, processed and organ meat and fullfat dairy. On the contrary, better semen parameters were observed in subjects consuming a healthy diet, rich in fruit, vegetables, whole grains and fish. Evidences of the negative impact on male fertility of by-products of water disinfection, accumulation in food chain of persistent organochlorine pollutants, pesticides, phthalates from food and water containers and hormones used in breeding cattle have been reported. Clinical trials of the effects of micronutrients on semen parameters and outcomes of assisted fertilization are encouraging, although optimal modality of treatment should be established. CONCLUSIONS Although quality of evidence should be ameliorated, it emerges that environmental factors can influence male fertility. Some nutrients may enhance fertility whereas others will worsen it. With diagnostic analysis on a molecular or even sub-molecular level, new interactions with micronutrients or molecular components of our daily ingested foods and leisure drugs may lead to a better understanding of so far suspected but as yet unexplained effects on male spermatogenesis and fertility.
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Nutrients, vitamins, probiotics and herbal products: an update of their role in urolithogenesis.
Pedro, RN, Aslam, AU, Bello, JO, Bhatti, KH, Philipraj, J, Sissoko, I, Vasconcellos, GS, Trinchieri, A, Buchholz, N
Urolithiasis. 2020;(4):285-301
Abstract
Nutrients, vitamins, probiotics, and herbal products may be risk factors, or alternately, protect against the formation of urinary stones. The purpose of this review was to update knowledge of the role of nutraceuticals in renal stone formation. A systematic search of the relevant literature published in PubMed in the last ten years was conducted and a narrative review of the data from the included studies was done. Search screened 513 studies that were reduced to 34 after evaluation by title and abstract; other 38 studies were retrieved by references of the selected studies. Beverages high fluid intake confirmed protective effect; orange juice protective effect; apple or grapefruit juice not confirmed as risk factors; sugar-sweetened soda and punch increased risk of stone formation. Energy intake: very high energy intake increased risk factor for women (especially after menopause); dietary acid load increased risk at equal levels of energy intake. Macronutrients confirmed increased risk of high protein intake. Calcium and Oxalate: calcium intake protective effect; oxalate intake only modest increase of risk in men and older women. Metal cations zinc and iron intake no clear impact on the risk of stone formation, dietary copper increased risk; manganese intake reduced risk of stone formation. Fruits and Vegetables decreased risk. Vitamins B6 intake not associated to risk of stone formation; vitamin C intake increased risk in men; vitamin D or supplemental vitamin D intake not associated to increased risk in men and younger women, suggestion of a higher risk in older women; Probiotics Gut colonization with Oxalobacter formigenes associated to lower risk of stone formation, effect of oxalate-degraders probiotics on urinary oxalate equivocal. Herbal products efficacy of some herbal products demonstrated in some trials, more investigations needed to confirm their efficacy and safety.
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Circadian, Sleep and Caloric Intake Phenotyping in Type 2 Diabetes Patients With Rare Melatonin Receptor 2 Mutations and Controls: A Pilot Study.
Imam, A, Winnebeck, EC, Buchholz, N, Froguel, P, Bonnefond, A, Solimena, M, Ivanova, A, Bouvier, M, Plouffe, B, Charpentier, G, et al
Frontiers in physiology. 2020;:564140
Abstract
BACKGROUND Melatonin modulates circadian rhythms in physiology and sleep initiation. Genetic variants of the MTNR1B locus, encoding the melatonin MT2 receptor, have been associated with increased type 2 diabetes (T2D) risk. Carriers of the common intronic MTNR1B rs10830963 T2D risk variant have modified sleep and circadian traits such as changes of the melatonin profile. However, it is currently unknown whether rare variants in the MT2 coding region are also associated with altered sleep and circadian phenotypes, including meal timing. MATERIALS AND METHODS In this pilot study, 28 individuals [50% male; 46-82 years old; 50% with rare MT2 mutations (T2D MT2)] wore actigraphy devices and filled out daily food logs for 4 weeks. We computed circadian, sleep, and caloric intake phenotypes, including sleep duration, timing, and regularity [assessed by the Sleep Regularity Index (SRI)]; composite phase deviations (CPD) as well a sleep timing-based proxy for circadian misalignment; and caloric intake patterns throughout the day. Using regression analyses, we estimated age- and sex-adjusted mean differences (MD) and 95% confidence intervals (95%CI) between the two patient groups. Secondary analyses also compare T2D MT2 to 15 healthy controls. RESULTS Patients with rare MT2 mutations had a later sleep onset (MD = 1.23, 95%CI = 0.42;2.04), and midsleep time (MD = 0.91, 95%CI = 0.12;1.70), slept more irregularly (MD in SRI = -8.98, 95%CI = -16.36;-1.60), had higher levels of behavioral circadian misalignment (MD in CPD = 1.21, 95%CI = 0.51;1.92), were more variable in regard to duration between first caloric intake and average sleep offset (MD = 1.08, 95%CI = 0.07;2.08), and had more caloric episodes in a 24 h day (MD = 1.08, 95%CI = 0.26;1.90), in comparison to T2D controls. Secondary analyses showed similar patterns between T2D MT2 and non-diabetic controls. CONCLUSION This pilot study suggests that compared to diabetic controls, T2D MT2 patients display a number of adverse sleep, circadian, and caloric intake phenotypes, including more irregular behavioral timing. A prospective study is needed to determine the role of these behavioral phenotypes in T2D onset and severity, especially in view of rare MT2 mutations.
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Benign prostate hyperplasia and nutrition.
Das, K, Buchholz, N
Clinical nutrition ESPEN. 2019;:5-11
Abstract
BACKGROUND and aims: Benign Prostatic hyperplasia (BPH) is an important public health problem. Roughly half of all men will suffer from BPH related symptoms later in life. The prostate gland, a hormone dependent part of the male reproductive system, is susceptible to internal and external disruptions of regulatory systems. We attempt in this paper to collect available evidence on influence of lifestyle modifications, and naturally occurring substances, plants, micronutrients and supplements on BPH symptoms. METHODS Systematic review was performed within the MEDLINE database and Cochrane Library Central Search using a combination of Medical Subject Headings (MeSH) and keywords. RESULTS Moderate exercise and the type and amount of protein intake have a considerable influence on BPH symptoms. The intake of zinc and vitamin D also positively influence BPH symptoms, and so do certain supplements, such as saw palmetto, cemilton and pygeum extracts. CONCLUSIONS Lifestyle changes, diet modification and certain nutritional supplements can favorably influence BPH symptoms.
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National Profiles of Urinary Calculi: a Comparison Between Developing and Developed Worlds.
Alatab, S, Pourmand, G, El Howairis, Mel F, Buchholz, N, Najafi, I, Pourmand, MR, Mashhadi, R, Pourmand, N
Iranian journal of kidney diseases. 2016;(2):51-61
Abstract
INTRODUCTION The incidence of urolithiasis has increased in both the developed and the developing countries during the past decades. Economically, the increase of urolithiasis contributes to the rise of the healthcare burden everywhere. Moreover, this increase has been associated with a change in the epidemiology of urolithiasis in terms of age and sex distribution, and also the location and type of calculi. MATERIALS AND METHODS We searched the MEDLINE for relevant literature dating back to 1980. This review compared the trends in epidemiological factors affecting urolithiasis in the developed and the developing countries during the past decades. RESULTS People in the developing countries are more likely to contract kidney calculi at a younger age than in the developed countries. Although calculus disease is still more prevalent in men than in women, the latter are increasingly affected in both worlds. Uric acid calculi are more prevalent in the developing than in industrialized countries. There is a progressive increase in the frequency of calcium oxalate and calcium phosphate calculi in the developing countries where these used to be less frequent. CONCLUSIONS The incidence and prevalence of urinary calculi is increasing globally. Many factors including aging of the population, changes in diet, global warming, and employment of more accurate diagnostic tools seem to be involved in this increase. An increasing affluence and adaptation of Western diet habits in many developing countries seem likely to contribute to the changes.
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The current role of percutaneous chemolysis in the management of urolithiasis: review and results.
Kachrilas, S, Papatsoris, A, Bach, C, Bourdoumis, A, Zaman, F, Masood, J, Buchholz, N
Urolithiasis. 2013;(4):323-6
Abstract
The treatment of urolithiasis has changed dramatically over the past several decades. Novel technologies have led to new management protocols. Percutaneous chemolysis as a primary or adjuvant treatment for urinary tract stones has widely been neglected. We present our own experience with it and discuss it in the light of an extensive literature review. From a MEDLINE search on percutaneous chemolysis we evaluated the most important studies, a total of 58 articles, 43 case series and 15 review articles. In our unit between 2001 and 2011, 29 patients (mean age 62 years) with infectious staghorn calculi were treated with adjuvant percutaneous chemolysis post-percutaneous nephrolithotripsy. There were 17 women, with 10 complete and 14 partial staghorn stones (mean size 32 mm). Patients were generally deemed at high risk to undergo another procedure in the future. Suby G solution was used following an established protocol. Sixteen patients (55.1 %) were stone free after chemolysis, eight stones showed partial dissolution, half of them with so-called "insignificant" residual fragments <4 mm. Patients with residual stones underwent SWL. Mean follow-up was 5.25 years (1-11). One stone-free patient (6 %) and three of eight patients (37.5 %) with residual fragments post local chemolysis, developed new stones during follow-up. The often neglected percutaneous chemolysis represents a significant and effective.
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Inversion, hydration and diuresis during extracorporeal shock wave lithotripsy: does it improve the stone-free rate for lower pole stone clearance?
Albanis, S, Ather, HM, Papatsoris, AG, Masood, J, Staios, D, Sheikh, T, Akhtar, S, Buchholz, N
Urologia internationalis. 2009;(2):211-6
Abstract
OBJECTIVE It was the aim of this study to assess the efficacy and safety of combined forced hydration and diuresis with limited inversion during shock wave lithotripsy (SWL) by comparing this treatment modality with conventional SWL for lower calyceal nephrolithiasis. PATIENTS AND METHODS In this prospective, non-randomized study, we included 100 patients with lower calyceal calculi RESULTS Clinical outcomes were available in 90 patients. Follow-up at 3 months showed that 83.3% of the patients belonging to the study group were rendered stone free, whereas 71.5% were stone free in the control (p > 0.05). Complications were minimal and not statistically significant. CONCLUSIONS Forced diuresis and inversion therapy is very well tolerated; however, the stone-free rate was not significantly improved.