The Ketone Bridge Between the Heart and the Bladder: How Fast Should We Go?

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) and central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism and sustain an inflammatory state, with serious implications for both the heart and bladder. Ketone bodies serve as an alternative energy source in this context. They are considered a "super-fuel" because they generate adenosine triphosphate with less oxygen consumption per molecule, thus enhancing metabolic efficiency. Ketone bodies have a positive impact on all components of MS. They aid in weight loss and glycemic control, lower blood pressure, improve lipid profiles, and enhance endothelial function. Additionally, they possess direct anti-inflammatory, antioxidant, and vasodilatory properties. A shared key player in dysfunction of both the heart and bladder dysfunction is the formation of the NLRP3 inflammasome, which ketone bodies inhibit. Interventions that elevate ketone body levels-such as fasting, a ketogenic diet, ketone supplements, and sodium-glucose cotransporter 2 inhibitors-have been shown to directly affect cardiovascular outcomes and improve lower urinary tract symptoms derived from MS. This review explores the pathophysiological basis of the benefits of ketone bodies in cardiac and bladder dysfunction.

Location of ureteral access sheath in the ureter. Does it affect the fluid flow in different calyces?

Introduction: The aim of this study was to evaluate outflow variation in different locations of the pyelocaliceal system with the use of different ureteral access sheath (UAS) sizes and different UAS positioning. Material and methods: The experimental setup included an anaesthetised porcine model, a 7.5-Fr ureteroscope with a 200-µm laser fibre inserted in the working channel, a hand-held pumping irrigating system, and UAS of different sizes, namely: 9.5/11.5 Fr, 12/14 Fr, and 14/16 Fr. Each UAS was placed just below the ureteropelvic junction (UPJ) or in the mid-ureter. The ureteroscope was placed in the renal pelvis, upper and lower calyces, and outflow measurements were obtained with 3-second interval pumping for one minute in every experimental setup. Results: The UAS positioning in the mid-ureter was associated with significantly higher outflow rates in the lower calyx (p = 0.041). While the UAS was below the UPJ, we observed a trend of lower outflow rate in the lower calyx, which was completely inverted when the UAS was in the mid-ureter. Increasing the UAS size from 9.5/11.5 Fr to 12/14 Fr led to a significant increase in outflow in the renal pelvis and upper calyx (p = 0.007), but not in the lower calyx. A further increase to 14/16 Fr did not produce increased flow. Conclusions: Different locations of the pyelocaliceal system have different fluid mechanics during fURS. In the renal pelvis and upper calyx increasing the diameter of the UAS improved the outflow, whereas in the lower calyx the position of the UAS seems to be the most relevant factor. These variables should be considered when performing fURS, especially with high-power laser lithotripsy.

Bladder Cancer during Pregnancy: A Review of the Literature.

Bladder malignancy represents the fourth most common cancer in men and the eighth in women in the western world. Women under 75 years of age have a risk of 0.5-1% of developing bladder cancer. The diagnosis usually occurs between 65 and 70 years of age, whereas the mortality rate for women varies from 0.5 to 4 per 100,000 every year. Nulliparous women present a greater risk than women who have given birth. The risk is further decreased when parity increases. Theoretically, hormonal changes occurring during pregnancy play a protective role. Smoking and occupational exposure to specific chemicals are the most common risk factors of bladder cancer. Other risk factors such as chronic urinary tract inflammation, cyclophosphamide, radiotherapy, and familial correlation have been reported. The aim of this review is to highlight a rare combination, which is the co-existence of bladder malignancy and pregnancy. We present thirteen different cases of women who were diagnosed with malignant bladder tumors during their pregnancy. A review of the literature was conducted, focusing on the unspecific symptoms, possible diagnostic tools, and suitable treatment modalities. The management of bladder cancer in pregnancy is a challenging process. The fragile balance between the possible complications of pregnancy and maternal health is yet to be discussed.

High-power laser lithotripsy - do we treat or harm? Histological evaluation of temperature effects in an in vivo study with thulium fiber laser.

Introduction: The aim of this study was to evaluate the possible histopathological alterations that occur in the kidneys due to a continuous temperature increase above 43°C for one hour of lithotripsy using a newly introduced thulium fiber laser (TFL). Material and methods: Two female pigs were used. After the insertion of a 9.5/11.5 ureteral access sheath, flexible ureteroscopy and laser lithotripsy for one hour were conducted. A TFL laser with a 200-µm fiber was used. The power setting used was 8 W (0.5 J × 16 Hz). A K-type thermocouple was inserted and fixed in the upper calyx of the right porcine kidney to record the temperature in the pelvicalyceal system during the laser activation. Second-look flexible nephroscopy followed by nephrectomy and pathohistological evaluation of the operated kidney was performed one week after the procedure in the first pig and 2 weeks after the surgery in the second pig. Results: Flexible nephroscopy did not reveal significant differences between the 2 porcine kidneys. Nevertheless, the histopathological report demonstrated severe alterations in the kidney of the first pig. Mild changes were reported in the kidney of the second pig. A significant improvement in inflammation and haemorrhagic lesions was demonstrated when comparing the 2 kidneys. Conclusions: The difference demonstrated between the 2 kidneys based on the histopathological report shows that the healing process is capable of improving severe to mild alterations within a one-week time frame. Two weeks after the surgery, only minor changes were observed, suggesting that even temperature increases above the threshold can be tolerated regarding renal damage.

Endoscopic management of encrusted ureteral stents: outcomes and tips and tricks.

PURPOSE: To report our experience in the management of encrusted ureteral stents (EUS) and provide technical insight of our endourological approaches for difficult scenarios posed by this entity. MATERIALS AND METHODS: A retrospective evaluation of a longitudinally collected database of 58 patients with encrusted US between December 2012 and May 2022 was performed. The ureteral stents were initially inserted due to obstructive uropathy, pyelonephritis or after a successful endoscopic procedure for urolithiasis. A combination of antegrade/retrograde treatment in single or multiple sessions took place for the retrieval of the encrusted stents. Non-contrast enhanced computer tomography was used for the follow-up of the patients at 1-month after the removal of the encrusted stent. RESULTS: Overall 58 patients, 39 males and 19 females with a median age of 51 years old were included in the study. Indwelling time was < 6 months, 6-12 months and > 12 months in 22%, 57% and 21% of the cases, respectively. All US were successfully removed. Semi-rigid ureteroscopy (URS) and flexible ureteroscopy (fURS) were used in 90% of the cases. In 10% of the cases, a second-stage percutaneous nephrolithotomy (PCNL) or endoscopic combined intrarenal surgery (ECIRS) was performed. All US were successfully released. Stone-free rate was 84% at 1-month. Overall complication rate was 10.5% (mostly postoperative fevers, 5.4%). CONCLUSION: Removal of the encrusted US is a challenging procedure. Appropriate decision-making and knowledge of specific tricks may result in safe and successful management of significant EUS.

Determinants of outflow rate through the ureteral access sheath during flexible ureteroscopy: an experimental in vivo study in an anesthetized porcine model.

To evaluate the effect of different ureteroscope positions, saline pumping frequency, laser fiber diameter and ureteral access sheath (UAS) on outflow rate during flexible ureteroscopy (fURS). This study was performed in an anesthetized porcine model. The fURS setup included a manual pumping system, a 9.5 Fr single used-digital flexible ureteroscope and a ureteral access sheath (UAS). Outflow was collected and measured from the UAS during 1 min in all experimental settings. The evaluated variables were the position of the ureteroscope, the pumping frequency (2 s, 3 s or 5 s), the diameter of the used UAS (12/14 Fr or 14/16 Fr) and laser fiber (200 µm or a 272 µm). Ureteroscope position in the lower calyx was associated with significantly lower outflow rate (p < 0.05). The use of the 14/16 Fr UAS resulted in improved flow in the renal pelvis and upper calyx (p < 0.05) but not in the lower calyx. The use of a 200 µm laser fiber only improved flow in the upper calyx and when a 14/16 Fr UAS was being used. Pumping frequency did not show a significant correlation with outflow rate. The ureteroscope positioning and UAS size were important determinants of outflow rate through the UAS during fURS, while laser fiber diameter had a limited effect. In the lower calyx the outflow was minimal and was not improved by using a larger UAS.

Nonpapillary prone endoscopic combined intrarenal surgery: effectiveness, safety and tips, and tricks.

PURPOSE: To evaluate the effectiveness and safety of nonpapillary prone endoscopic combined intrarenal surgery (ECIRS) and provide practical tips and tricks for the successful accomplishment of the procedure respecting the anatomical particularities. MATERIAL AND METHODS: This study is an analysis of a prospectively collected database including all cases of ECIRS performed between January 2019 and December 2021 in a high-volume tertiary center. All patients underwent the procedure in prone-split leg position. A nonpapillary renal puncture was performed. The used access sheaths were 22Fr or 30Fr. Lithotripsy was performed anterogradely with a dual-energy lithotripter with incorporated suction and retrogradely with holmium Yttrium-Aluminum-Garnet laser. RESULTS: A total of 33 patients were included. The initial stone-free rate (SFR) was 84.8% and the final SFR was 90.9%. The median stone size was 35 mm and 60% of patients had staghorn calculi. The prevalence of renal abnormalities was 21.3%, including 3 cases of horseshoe kidney, 2 cases of malrotation and 2 cases with complete duplicated systems. The median operative time was 47 min. The median hospital stay was 3 days and median hemoglobin loss was 1.2 gr/dL. Overall, the complication rate was 9.1%, all being Grade II complications (n = 2 fever and n = 1 transient bleeding). CONCLUSIONS: Nonpapillary prone ECIRS is an effective and safe procedure. Standardization of the procedure is critical to achieve good outcomes. Patients who benefit the most are probably the ones where additional punctures can be avoided using this technique, namely patients with renal abnormalities, incrusted ureteral stents and staghorn stones.

Myogenic Underactive Bladder and Heart Failure Resemblance: A Novel Role for SGLT2 Inhibition?

The heart and bladder share physiological biomechanical determinants of contraction. Heart failure (HF) and myogenic underactive bladder (mUAB) also share similarities in their pathophysiology. In both cases there is muscle injury that is directly linked to disease stage. In the final stage, both myocardium and detrusor show marked fibrosis and lower contractility. While HF has an established pharmacological treatment, there are still no effective drugs for mUAB. This mini-review explores the similarities between HF and mUAB and suggests that, as in HF, SGLT2 inhibitors may also have a beneficial role in mUAB. PATIENT SUMMARY: To date, there is no treatment for underactive bladder caused by problems with the bladder muscle (mUAB). We review similarities between this condition and heart failure and hypothesize that a recent drug class with striking results in heart failure might also have a beneficial role in mUAB.

Effects of chronic moderate alcohol consumption on right ventricle and pulmonary remodelling.

NEW FINDINGS: What is the central question of this study? Does the consumption of a moderate amount of alcohol differentially impact the heart ventricles and pulmonary vasculature. What is the main finding and its importance? Moderate alcohol consumption for a short period of time impaired pulmonary vascular cellular renewal through an apoptosis resistance pattern that ultimately affected the right ventricular function and structure. These findings support the need for a deeper understanding of effects of moderate alcohol consumption on the overall cardiovascular and pulmonary systems. ABSTRACT: Over the past decades, observational studies have supported an association between moderate alcohol consumption and a lower risk of cardiovascular disease and mortality. However, recent and more robust meta-analyses have raised concerns around the robustness of the evidence for the cardioprotective effects of alcohol. Also, studies of the functional, structural and molecular changes promoted by alcohol have focused primarily on the left ventricle, ignoring the fact that the right ventricle could adapt differently. The aim of this study was to evaluate the bi-ventricular impact of daily moderate alcohol intake, during a 4-week period, in a rodent model. Male Wistar rats were allowed to drink water (Control) or a 5.2% ethanol mixture (ETOH) for 4 weeks. At the end of the protocol bi-ventricular haemodynamic recordings were performed and samples collected for further histological and molecular analysis. ETOH ingestion did not impact cardiac function. However, it caused right ventricle hypertrophy, paralleled by an activation of molecular pathways responsible for cell growth (ERK1/2, AKT), proteolysis (MURF-1) and oxidative stress (NOX4, SOD2). Furthermore, ETOH animals also presented remodelling of the pulmonary vasculature with an increase in pulmonary arteries' medial thickness, which was characterized by increased expression of apoptosis-related proteins expression (BCL-XL, BAX and caspases). Moderate alcohol consumption for a short period of time impaired the lungs and the right ventricle early, before any change could be detected on the left ventricle. Right ventricular changes might be secondary to alcohol-induced pulmonary vasculature remodelling.

Anti-Remodeling Effects of Xanthohumol-Fortified Beer in Pulmonary Arterial Hypertension Mediated by ERK and AKT Inhibition.

Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.

Assessment in pediatrics clerkships: impact of strategies to solve item-sharing problems.

INTRODUCTION: Reusing multiple-choice questions in different examinations may lead to item sharing between students. Our aim was to analyze and solve an item-sharing problem during assessment of medical students in pediatrics clerkship. METHODS: This is a 3 years prospective analysis of 5th year medical students, submitted to an examination at the end of their Pediatrics' clerkship. In 2012, questions were reused across different clerkships. In 2013, no questions were reused in different clerkships. In 2014, no questions were reused and the review of the test was postponed to the end of the year, after all clerkships ended. RESULTS: In 2012, the mean score increased 1.36 points (in a scale of 0-20) per clerkship rotation, with the last clerkship having a difference of 9.5 points regarding the first one (P < .001). Fifty percent of this variation was due to the repetition of questions. In 2013, with a new question bank, the mean score increased 0.8 points per clerkship rotation, with a difference of 5.6 points between the last and the first rotations (P < .024). Finally, in 2014 there was no significant variation between clerkships.Tests' scores had a significant moderate correlation with students' average course grade (r = 0.39, r = 0.30, r = 0.48, for 2012, 2013, and 2014, respectively). The students' average course grade, however, did not confound the increase in tests' scores across different clerkships. CONCLUSION: The present work demonstrated an item-sharing problem among students during pediatric clerkships. An effective approach to correct this bias assessment was achieved by restricting the reuse of questions, by changing the time-point of test revision and by progressively adapting equating strategies.

Cardiovascular effects of the angiotensin type 2 receptor.

The angiotensin type 2 receptor, AT2R, has been described as having opposite effects to the angiotensin type 1 receptor, AT1R. Although the quantities of the AT2R found in the adult are low, its expression rises in pathological situations. The AT2R has three major signaling pathways: activation of serine/threonine phosphatases (promoting apoptosis and antioxidant effects), activation of the bradykinin/NO/cGMP pathway (promoting vasodilation), and activation of phospholipase A2 (associated with regulation of potassium currents). The AT2R appears to have effects in vascular remodeling, atherosclerosis prevention and blood pressure lowering (when associated with an AT1R inhibitor). After myocardial infarction, the AT2R appears to decrease infarct size, cardiac hypertrophy and fibrosis, and to improve cardiac function. However, its role in the heart is controversial. In the kidney, the AT2R promotes natriuresis. Until now, treatment directed at the renin-angiotensin-aldosterone system has been based on angiotensin-converting enzyme inhibitors or angiotensin type 1 receptor blockers. The study of the AT2R has been revolutionized by the discovery of a direct agonist, C21, which promises to become part of the treatment of cardiovascular disease.