Role, Cost, and Availably of Urinary pH Monitoring for Kidney Stone Disease-A Systematic Review of the Literature.

PURPOSE OF REVIEW: Urinary pH is an important factor related to renal stone disease, and it plays an essential role in stone prevention. Monitoring of urinary pH by patients at home provides information that can help to assess the treatment needed by each patient. We conducted a systematic review is to assess the available evidence concerning urinary pH monitoring methods along with their accuracy, cost, and usefulness by patients with urolithiasis. RECENT FINDINGS: A total of 9 articles were included (1886 urinary pH measurements). They reported information about urinary dipsticks, portable electronic pH meters and electronic strip readers, amongst other methods. Accuracy was compared with a laboratory pH meter (gold standard). Urinary dipsticks were found to be not accurate enough to guide clinical decision making and portable electronic pH meters showed promising results. Urinary dipsticks are neither precise nor accurate enough. Portable electronic pH meters seem to be more accurate, easy to use, and cost-effective. They are a reliable source for patients to use at home in order to prevent future episodes of nephrolithiasis.

Thulium Fiber Laser Versus Holmium:Yttrium Aluminum Garnet for Lithotripsy: A Systematic Review and Meta-analysis.

CONTEXT: Thulium fiber laser (TFL) emerged as a competitor of holmium:yttrium aluminum garnet (Ho:YAG) laser for the treatment of urinary stones. OBJECTIVE: To compare the efficacy between Ho:YAG and TFL for laser lithotripsy of renal and ureteral stones. EVIDENCE ACQUISITION: A literature search was conducted using PubMed/Medline, Embase, and Web of Science databases to identify reports published until May 2023. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. The primary outcome was to compare the stone-free rate (SFR) between Ho:YAG and TFL for laser lithotripsy. EVIDENCE SYNTHESIS: Eleven studies met our inclusion criteria, and data from 1286 and 880 patients who underwent, respectively, Ho:YAG and TFL laser lithotripsy were reviewed. Most studies included ureteroscopy (URS) and retrograde intrarenal surgeries as procedures, two included percutaneous nephrolithotomy, and one included URS exclusively. Only two studies reported results in pediatric patients. TFL was associated with a higher SFR (odds ratio [OR] 1.84, 95% confidence interval [CI]: 1.06-3.20; p = 0.031) when no residual fragment is considered, but not when SFR refers to the presence of fragments <3 mm (OR 2.48, 95% CI: 0.98-6.29; p = 0.055) or when only Ho:YAG with MOSES is considered (p = 0.068). According to the stones' location, TFL was associated with higher SFRs than Ho:YAG for renal (OR 3.14, 95% CI: 1.69-5.86; p < 0.001) but not for ureteral (p = 0.8) stones. TFL was associated with a lower intraoperative complication rate (OR 0.34, 95% CI: 0.19-0.63; p < 0.001). No difference was found in major (p = 0.4) or overall (p = 0.4) complication rate, operative time (p = 0.051), and laser time (p = 0.9). CONCLUSIONS: TFL is a promising laser for the treatment of urinary stones with some advantages over Ho:YAG. Further high-quality studies are needed to confirm these findings and optimize the surgical settings. PATIENT SUMMARY: The use of thulium fiber laser rather than holmium:yttrium aluminum garnet permits to reach a higher stone-free rate in stones located in the kidney rather than in the ureter.

Bowel Perforation after Extracorporeal Wave Lithotripsy: A Review of the Literature.

INTRODUCTION: Extracorporeal wave lithotripsy (ESWL) is considered a first-line treatment for renal and ureteral stones up to 10-20 mm in diameter. Complications are uncommon, with a reported rate of 0-6% in the literature. Bowel perforation has only been described in a few case reports but requires rapid diagnosis and treatment. METHODS: A review of the literature from PubMed/Medline, Embase, Cochrane, and Web of Science databases was performed including studies reporting bowel perforation secondary to ESWL between January 1990 and June 2022. RESULTS: We found 16 case reports of intestinal perforation in the literature. Although some patients had previously undergone abdominal surgery or had inflammatory intestinal disease, others were without comorbidities that could lead to complications. Abdominal pain was the main symptom and imaging was required to confirm the diagnosis, which usually necessitated a surgical intervention. As regards the ESWL technique, it appears that the combination of a high energy level and the prone position constitutes a risk factor for these rare complications. At the authors' centre, only one case has been reported among 24,000 ESWL procedures over 20 years: A 59-year-old female who underwent ESWL for a distal right ureteral stone presented acute abdominal pain and free intraperitoneal pelvic fluid on ultrasound. A CT scan revealed a small bowel perforation requiring open laparotomy with primary closure. CONCLUSIONS: In conclusion, although bowel perforation after ESWL is rare, progressive abdominal pain with tenderness at physical examination requires proper imaging evaluation to exclude bowel perforation and prompt intervention if required.

Use of Moses 2.0 with extended frequency and optimized Moses vs. high-power laser in MiniPCNL: a randomized controlled trial.

The aim of the study was to compare standard high-power laser (with < 80 Hz) to extended frequency (> 100 Hz) lithotripsy during miniPCNL. 40 patients were randomized in to two groups undergoing MiniPCNL. For both groups, the Holmium Pulse laser Moses 2.0 (Lumenis) was used. For group A, standard high-power laser with < 80 Hz, with Moses distance was set using up to 3 J. For Group B, extended frequency (100-120 Hz) was used allowing up to 0.6 J. All patients underwent MiniPCNL using an 18 Fr balloon access. Demographics were comparable between groups. Mean stone diameter was 19 mm (14-23) with no differences between groups (p = 0.14). Mean operative time was 91 and 87 min for group A and B (p = 0.71), mean laser time was similar in both groups, 6.5 min and 7.5 min, respectively (p = 0.52) as well as the number of laser activations during the surgery (p = 0.43). Mean Watts used was 18 and 16 respectively being similar in both groups (p = 0.54) as well as the total KJoules (p = 0.29). Endoscopic vision was good in all surgeries. The endoscopic and radiologic stone free rate was achieved in all patients expect for two in both groups (p = 0.72). Two Clavien I complications were seen, a small bleeding for group A and a small pelvic perforation in group B. The use of high-power holmium laser with extended frequency and optimized Moses was effective and safe being comparable to standard high-power laser for MiniPCNL allowing more versatility with the setting range.

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptosis by disruption of intracellular calcium homeostasis in human neuronal cell line SHSY5Y.

The persistent xenobiotic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces neurotoxic effects that alters neurodevelopment and behavior both during development and adulthood. There are many ongoing efforts to determine the molecular mechanisms of TCDD-mediated neurotoxicity, the signaling pathways involved and its molecular targets in neurons. In this work, we have used SHSY5Y human neuroblastoma cells to characterize the TCDD-induced toxicity. TCDD produces a loss of viability linked to an increased caspase-3 activity, PARP-1 fragmentation, DNA laddering, nuclear fragmentation and hypodiploid (apoptotic) DNA content, in a similar way than staurosporine, a prototypical molecule of apoptosis induction. In addition, TCDD produces a decrease of mitochondrial membrane potential and an increase of intracellular calcium concentration (P < 0.05). Finally, based on the high lipophilic properties of the dioxin, we test the TCDD effect on the membrane integrity using sarcoplasmic reticulum vesicles as a model. TCDD produces calcium efflux through the membrane and an anisotropy decrease (P < 0.05) that reflects an increase in membrane fluidity. Altogether these results support the hypothesis that TCDD toxicity in SHSY5Y neuroblastoma cells provokes the disruption of calcium homeostasis, probably affecting membrane structural integrity, leading to an apoptotic process.

New Generation Pulse Modulation in Holmium:YAG Lasers: A Systematic Review of the Literature and Meta-Analysis.

(1) Background: New pulse modulation (PM) technologies in Holmium:YAG lasers are available for urinary stone treatment, but little is known about them. We aim to systematically evaluate the published evidence in terms of their lithotripsy performance. (2) Methods: A systematic electronic search was performed (MEDLINE, Scopus, and Cochrane databases). We included all relevant publications, including randomized controlled trials, non-randomized comparative and non-comparative studies, and in-vitro studies investigating Holmium:YAG lithotripsy performance employing any new PM. (3) Results: Initial search yielded 203 studies; 24 studies were included after selection: 15 in-vitro, 9 in-vivo. 10 In-vitro compared Moses with regular PM, 1 compared Quanta's, 1 Dornier MedTech's, 2 Moses with super Thulium Fiber Laser, and 1 compared Moses with Quanta PMs. Six out of seven comparative studies found a statistically significant difference in favor of new-generation PM technologies in terms of operative time and five out of six in fragmentation time; two studies evaluated retropulsion, both in favor of new-generation PM. There were no statistically significant differences regarding stone-free rate, lasing and operative time, and complications between Moses and regular PM when data were meta-analyzed. (4) Conclusions: Moses PM seems to have better lithotripsy performance than regular modes in in-vitro studies, but there are still some doubts about its in-vivo results. Little is known about the other PMs. Although some results favor Quanta PMs, further studies are needed.

mTOR Inhibition and T-DM1 in HER2-Positive Breast Cancer.

In patients with trastuzumab-resistant HER2-positive breast cancer, the combination of everolimus (mTORC1 inhibitor) with trastuzumab failed to show a clinically significant benefit. However, the combination of mTOR inhibition and the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) remains unexplored. We tested T-DM1 plus everolimus in a broad panel of HER2-positive breast cancer cell lines. The combination was superior to T-DM1 alone in four cell lines (HCC1954, SKBR3, EFM192A, and MDA-MB-36) and in two cultures from primary tumor cells derived from HER2-positive patient-derived xenografts (PDX), but not in BT474 cells. In the trastuzumab-resistant HCC1954 cell line, we characterized the effects of the combination using TAK-228 (mTORC1 and -2 inhibitor) and knockdown of the different mTOR complex components. T-DM1 did not affect mTOR downstream signaling nor induct autophagy. Importantly, mTOR inhibition increased intracellular T-DM1 levels, leading to increased lysosomal accumulation of the compound. The increased efficacy of mTOR inhibition plus T-DM1 was abrogated by lysosome inhibitors (chloroquine and bafilomycin A1). Our experiments suggest that BT474 are less sensitive to T-DM1 due to lack of optimal lysosomal processing and intrinsic resistance to the DM1 moiety. Finally, we performed several in vivo experiments that corroborated the superior activity of T-DM1 and everolimus in HCC1954 and PDX-derived mouse models. In summary, everolimus in combination with T-DM1 showed strong antitumor effects in HER2-positive breast cancer, both in vitro and in vivo. This effect might be related, at least partially, to mTOR-dependent lysosomal processing of T-DM1, a finding that might apply to other ADCs that require lysosomal processing. IMPLICATIONS: Inhibition of mTOR increases the antitumor activity of T-DM1, supporting that the combination of mTOR inhibitors and antibody-drug conjugates warrants clinical evaluation in patients with HER2-positive breast cancer.

Aryl hydrocarbon receptor-dependent induction of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in cerebellar granule cells from mouse.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a prototypical environmental contaminant with neurotoxic properties that alters neurodevelopment and behavior. TCDD is a ligand of the aryl hydrocarbon receptor (AhR), which is a key signaling molecule to fully understand the toxic and carcinogenic properties of dioxin. Much effort is underway to unravel the molecular mechanisms and the signaling pathways involved in TCDD-induced neurotoxicity, and to define its molecular targets in neurons. We have used cerebellar granule cells (CGC) from wild-type (AhR+/+) and AhR-null (AhR-/-) mice to characterize the cell death that takes place in neurons after TCDD toxicity. TCDD induced cell death in CGC cultures from wild-type mice with an EC(50) of 127±21 nM. On the contrary, when CGC neurons from AhR-null mice were treated with TCDD no significant cell death was observed. The role of AhR in TCDD-induced death was further assessed by using the antagonists resveratrol and α-naphtoflavone, which readily protected against TCDD toxicity in AhR+/+ CGC cultures. AhR+/+ CGC cultures treated with TCDD showed nuclear fragmentation, DNA laddering, and increased caspase 3 activity, similarly to what was found by the use of staurosporine, a well-established inducer of apoptosis. Finally, the AhR pathway was active in CGC because TCDD could induce the expression of the target gene cytochrome P450 1A2 in AhR+/+ CGC cultures. All together these results support the hypothesis that TCDD toxicity in CGC neurons involves the AhR and that it takes place mainly through an apoptotic process. AhR could be then considered a novel target in neurotoxicity and neurodegeneration whose down-modulation could block certain xenobiotic-related adverse effects in CNS.

Systematic Review and Meta-Analysis Comparing Fluoroless Ureteroscopy and Conventional Ureteroscopy in the Management of Ureteral and Renal Stones.

Context: Stone recurrence is frequent in stone formers, and repeated diagnostic and therapeutic procedures in recurrent stone formers place patients and urologists at a significant risk of radiation-related effects. Objective: To assess the efficacy and safety of fluoroless ureteroscopy (fURS) compared with conventional ureteroscopy (cURS) in the management of ureteral and renal stones. Evidence Acquisition: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies providing data on the stone-free rate (SFR), secondary procedures, operative time (OT), and complication rate for fURS and cURS were included. An overall analysis and a subgroup analysis based on the stone target (ureteral stones, renal stones, or a combination thereof) were performed. Evidence Synthesis: A total of 23 studies were included, recruiting 4029 patients. Pooled data showed that in comparison with cURS, fURS exhibited a similar SFR (odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.92 to 1.06; p = 0.709), without significant differences in overall intraoperative complication rate (OR: 0.73; 95% CI: 0.33 to 1.63; p = 0.446), overall postoperative complication rate (OR: 0.98; 95% CI: 0.59 to 1.63; p = 0.949), major postoperative complication rate (Clavien ≥3; OR: 0.46; 95% CI: 0.14 to 1.53; p = 0.205), OT (standardized mean difference [SMD]: 0.07; 95% CI: -0.15 to 0.29; p = 0.537), hospital stay (SMD: -0.12; 95% CI: -0.26 to 0.02; p = 0.084), or secondary procedures (OR: 1.20; 95% CI: 0.58 to 2.49; p = 0.616). The subgroup analysis revealed no differences in outcomes according to the stone target. We also identified a rate of conversion to the conventional technique of 5% (95% CI: 3% to 7%). Conclusions: The available data suggest that for the treatment of ureteral and renal stones, fURS offers a similar SFR to that provided by the cURS without any increase in complication rate, OT, hospital stay, or secondary procedures. Critical review of the dogmatic routine use of fluoroscopy during ureteroscopy may be warranted.

The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls.

Introduction: In colorectal cancer, anti-VEGF agents have demonstrated a survival benefit when combined with chemotherapy. However, development of resistance is very common. One of the mechanisms is due not to a failure in the VEGFR blockade, but rather to development of compensatory mechanisms of resistance, such as hypoxia-triggered upregulation of other proangiogenic factors, like placental growth factor (PlGF).Areas covered: This article summarizes the fundamental role of PlGF in the development of resistance to antiangiogenic treatment as well as the efficacy of aflibercept, ramucirumab, and regorafenib.Expert opinion: Aflibercept functions as a soluble decoy receptor precluding VEGFs and PlGF from binding to native VEGFR, and therefore preventing the emergence of resistance. Bevacizumab limits its function to preventing the interaction between VEGF-A and VEGFR. In combination with FOLFIRI (VELOUR trial), aflibercept improves survival in patients with metastatic CRC who are resistant or have progressed to oxaliplatin-based chemotherapy. Ramucirumab, a fully humanized immunoglobulin G1 (IgG-1) monoclonal antibody and regorafenib, a multikinase inhibitor, have significant improvement for overall survival as well as for progression-free survival in chemotherapy refractory settings.

Oral Acidification with l-Methionine as a Noninvasive Treatment for Encrusted Uropathy.

Background: Encrusted uropathy (EU) is a rare disease caused by urea-splitting bacteria, most commonly Corynebacterium urealyticum, whose incidence is increasing. Standard treatment is based on pathogen-directed antibiotic therapy, urinary diversion, bladder instillations, and surgical resection of urinary calcifications. Case Presentation: We present the case of a 60-year-old man with symptomatic bilateral encrusted pyelitis and cystitis with acute renal failure. We initially treated the patient with antibiotic therapy, urinary diversion, and oral acidification with acetohydroxamic acid, achieving negative urinary cultures. Because of the persistence of encrusted pyelitis, the patient was discharged on oral l-methionine 500 mg bid and 12 months later the encrustations had almost disappeared. Finally, we performed right retrograde intrarenal surgery to remove a persistent small calcification. Conclusion: Oral urinary acidification with l-methionine is a valid treatment for urinary encrustations in EU, with no complications reported. Complete resolution of the calcifications may be achieved without the need for invasive processes and unnecessary manipulation of the urinary system.

The relationship between calcium oxalate lithiasis and chronic proinflammatory intestinal dysbiosis pattern: a prospective study.

The objective is to establish whether a pattern of intestinal dysbiosis exists in calcium oxalate (CaOx) lithiasis and, if so, to identify its characteristics and explore whether there are differences in the pattern between CaOx dihydrate (COD) and monohydrate (COM) lithiasis. With this aim 24 patients diagnosed with CaOx lithiasis by means of optical microscopy and spectrometry were prospectively recruited. Faecal analysis was carried out by means of RT-PCR 16S rRNA assay and agar plate culture according to the methodology proposed by the Institute of Microecology (Herborn, Germany). The total number of bacteria was depleted due to COD lithiasis (p = 0.036). The mean values of immunoregulating microbiota were normal, but the percentage of normal values was lower in the COD group (30%) than in the COM group (69.2%) (p = 0.062). The total mean values of protective microbiota were normal in both groups. There was a large decrease in the mean values of the muconutritive microbiota Akkermansia muciniphila and Faecalibacterium prausnitzii, the most intense decline being observed in the COD group (p = 0.019). Levels of proteolytic microbiota were elevated in both groups, without differences between them. We conclude that patients with CaOx lithiasis have a chronic pro-inflammatory intestinal dysbiosis pattern characterised by a reduction in the total number of bacteria, a reduction in immunoregulating microbiota and a large reduction in muconutritive microbiota that is significantly more intense in COD lithiasis than in COM lithiasis.

[The Open Access Initiative (OAI) in the scientific literature]. / La Iniciativa Open Access (OAI) en la literatura científica.

According to the declaration of the Budapest Open Access Initiative (OAI) is defined as a editorial model in which access to scientific journal literature and his use are free. Free flow of information allowed by Internet has been the basis of this initiative. The Bethesda and the Berlin declarations, supported by some international agencies, proposes to require researchers to deposit copies of all articles published in a self-archive or an Open Access repository, and encourage researchers to publish their research papers in journals Open Access. This paper reviews the keys of the OAI, with their strengths and controversial aspects; and it discusses the position of databases, search engines and repositories of biomedical information, as well as the attitude of the scientists, publishers and journals. So far the journal Actas Urológicas Españolas (Act Urol Esp) offer their contents on Open Access as On Line in Spanish and English.

[Robotic radical cystoprostatectomy: oncological and functional analysis]. / Cistoprostatectomía radical robótica: análisis oncológico y funcional.

INTRODUCTION: The da Vinci robotic laparoscopic surgery, has been shown in radical prostatectomy, optimal functional and oncological results with a lower learning curve, greater comfort and vision for the surgeon, and proper preservation of the neurovascular bundles. This has led to begin the experience with robotic radical cystectomy (RRC). OBJECTIVES: Review our initial experience in CRR, evaluating surgical and functional results obtained, and also immediate and short-term complications. MATERIAL AND METHODS: Between December 2007 and January 2009 we performed nine robotic radical cystoprostatectomy and in seven patients robotic lymphadenectomy (LDN). Five patients had a muscle-invasive disease and 4 non-muscle invasive bladder cancer. The median age was 57 years (range 34-81). Urinary diversion was performed extracorporeally in all cases, 3 cases an ileal conduit and 6 an Studer neobladder in 3 of these 6 cases, the urethra-neobladder anastomosis was performed intracorporeally. RESULTS: The average time of surgery was 300 minutes (range 280-420) in the ileal conduit and 360 (range 330-540) in the Studer. No cases required conversion or blood transfusion. The median number of nodes removed by LDN robotics was 10 (range 6-18). The pathology revealed 3 pT0. 2 CIS, 3 pT3, 1 pT4b (positive margins). With a median follow up of 7 months there have been no peritoneal implant and only one ureteral stenosis. Oral diet was initiated in 5 cases at 48 hours. Of the 6 patients with preserved sexual function preoperatively and followup of more than 3 months, 2 had full erection at 1 month, 2 at 3 and 6 months, and the remaining 2 presented with a full erection with 5 PD inhibitors at 3 and 9 months. All patients with neobladder presented correct daytime continence. The average hospital stay was 8.5 days (range 7-19). CONCLUSIONS: The radical robotic cystectomy with extracorporeal reconstruction of the urinary diversion offers good early functional and surgical outcomes. The careful preservation of the neurovascular bundles in radical pelvic surgery provides excellent results in urinary and sexual function.

[Spanish bottled and tap water analysis and their relation with urinary lithiasis]. / Análisis de las aguas embotelladas y de grifo españolas y de las implicaciones de su consumo en la litiasis urinaria.

OBJECTIVE: To perform a chemical analysis of all the available waters in Spain with the idea of offering consume recommendations to lithiasic patients. MATERIAL AND METHODS: Information research of the chemical composition of Spanish tap and bottled water in publications, supermarkets and Internet. A descriptive study, and a correlation study between water components by means of Pearson test were performed. RESULTS: Information about composition from tap water of most of the main Spanish cities and 85 bottled water brands was found. A significant correlation between calcium and magnesium concentration (p = 0.0001) and high correlation between bicarbonate and sodium concentration (p = 0.0001, Pearson coefficient 0.958) was found. It is also offered water classifications according to calcium, bicarbonate, sodium and magnesium concentrations. CONCLUSION: A guideline about water election for lithiasic patients is offered according to their geographical origin and dietetic preferences, mainly lactic consume.

HER-Family Ligands Promote Acquired Resistance to Trastuzumab in Gastric Cancer.

Despite the clinical benefit of trastuzumab, eventually all HER2-amplified gastric cancer tumors develop drug resistance. We aimed to identify molecular mechanisms of acquired resistance to trastuzumab in gastric cancer by using well-established cell line-based preclinical models, as well as samples from patients with HER2-positive gastric cancer treated with trastuzumab. We studied trastuzumab resistance in NCI-N87 and OE19, two gastric cancer cell lines that overexpress HER2 receptor and are trastuzumab sensitive. Differences at protein, DNA, and RNA levels between the parental and resistant cells were characterized and functional studies were performed. Paired pre- and post-trastuzumab blood and tissue samples from patients with gastric cancer treated with trastuzumab were analyzed. We found that resistant cells were associated with increased activation of MAPK/ERK and PI3K/mTOR pathways driven by SRC activation. Upstream, resistant cells showed increased coexpression of multiple HER-family ligands that allowed for compensatory activation of alternative HER receptors upon HER2 blockade. Simultaneous inhibition of EGFR, HER2, and HER3 by the novel antibody mixture, Pan-HER, effectively reverted trastuzumab resistance in vitro and in vivo Similarly, an increase in HER-family ligands was observed in serum and tumor from patients with gastric cancer after trastuzumab therapy. We propose that trastuzumab resistance in gastric cancer is mediated by HER-family ligand upregulation that allows a compensatory activation of HER receptors and maintains downstream signaling activation despite trastuzumab therapy. Resistance is reverted by simultaneous inhibition of EGFR, HER2, and HER3, thereby revealing a potential therapeutic strategy to overcome trastuzumab resistance in patients with gastric cancer.

Simultaneous and synchronous bilateral endoscopic treatment of urolithiasis: a multicentric study.

INTRODUCTION: The general prevalence of bilateral urolithiasis has risen to 15% and bilateral non-simultaneous treatment has been reported to have good outcomes. The objective of this study was to evaluate the effectiveness and safety of simultaneous bilateral endoscopic surgery (SBES). MATERIAL AND METHODS: An international multicenter analysis was performed between May 2015 and December 2017. All patients with bilateral stone disease that underwent SBES were included. Patients were treated under general anesthesia in either the supine or lithotomy position. Demographic, clinical, intraoperative and postoperative data were analyzed. RESULTS: A total of 47 patients were included. Mean age was 53.8 years and 70% of the patients were males. The mean American Society of Anesthesiology (ASA) score was 2. The mean diameter of right- and left-sided stones was 29.43 mm (2-83 mm) and 31.15 (4-102 mm), respectively. Staghorn stones were treated in 18 cases (8 right-sided and 10 left-sided), four of them were defined as complete staghorn. The procedures performed were 42 cases of bilateral URS and PCNL and ureteroscopy. Additionally, 5 bilateral flexible ureteroscopy (fURS) cases were described. Intraoperative complications occurred in five patients: four of them were classified as Clavien-Dindo (CD) I and one as CD II. Postoperatively, there were two cases with CD I, 6 with CD II and one CD IIIa.The stone-free status was 70%. Residual stones (30%) were detected only on the side treated for high-volume (complete) staghorn calculi. CONCLUSIONS: SBES is a feasible, effective and safe procedure. It may potentially avoid repeated anesthetic sessions as needed for staged procedures and reduce the length of patients' hospital stay.

NMDA-induced neuroprotection in hippocampal neurons is mediated through the protein kinase A and CREB (cAMP-response element-binding protein) pathway.

N-Methyl-d-aspartate (NMDA) receptors play a critical role in the brain stimulating synaptic plasticity and mediating neurodegeneration; a neuroprotective role has also been described, but its molecular mechanisms in hippocampus are under study. Here, we report that in primary cultures of rat hippocampal neurons exposure to low micromolar NMDA concentrations are neuroprotective against excitotoxic insults, while high micromolar NMDA concentrations provoke neuronal death. Molecular analysis reveals that a toxic concentration of NMDA induced a transient phosphorylation of cAMP-response element-binding protein (pCREB) in 2 min that rapidly decreased below basal levels. In contrast, a nontoxic NMDA concentration gave up to longer (20 min) rise of pCREB, suggesting that neuroprotection could be associated to a relatively prolonged presence of pCREB in the neurons. In support of this tenet, rolipram, an inhibitor of phosphodiesterase IV that increases the levels of cAMP and pCREB, protected against NMDA-induced neuronal death. Similar results were obtained with dibutyrate-cAMP (a cAMP analogue with membrane permeability) that also abrogated NMDA excitotoxicity. Conversely, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide (H89), an inhibitor of protein kinase A (PKA), that prevents the formation of pCREB induced by nontoxic NMDA concentrations, reverted the neuroprotection achieved by preincubation of low micromolar NMDA concentrations. These results substantiate the notion that induction of pCREB via PKA plays an important role in NMDA-mediated neuroprotection.