Extracorporeal shock wave lithotripsy for treatment of large pediatric renal pelvic stone burden more than 2 cm.

BACKGROUND: The high recurrence rates in pediatric urolithiasis indicate the need for none invasive or a minimally invasive treatment such as SWL. Therefore, EAU, ESPU and AUA recommend SWL as a first line treatment for renal calculi ≤ 2, and RIRS or PCNL for renal calculi > 2 cm. SWL is superior to RIRS and PCNL as it is inexpensive, outpatient procedure, and it has a high SFR in well selected cases specially pediatrics. On the other hand, SWL therapy has a limited efficacy with a lower SFR, and high retreatment rate and/or additional interventions for treatment of larger and harder renal calculi. OBJECTIVE: We carried out this study to evaluate the efficacy and safety of SWL for treatment of renal stones > 2 cm to extend its indications for pediatric renal calculi. METHODS: Between January 2016 and April 2022, we reviewed the records of patients with renal calculi treated by SWL, mini-PCNL, RIRS and open surgery in our institution. Forty-nine eligible children aged 1-5 years old, presented with renal pelvic and/or calyceal calculi measuring 2-3.9 cm and underwent SWL therapy were picked up and participated in the study. The data of an additional eligible 79 children with the same age and had renal pelvic and/or calyceal calculi > 2 cm up to stag horn calculi and underwent mini-PCNL, RIRS and open renal surgery were also picked up and participated in the study. We retrieved the following preoperative data from the records of the eligible patients; age, gender, weight, length, radiological findings (stone size, side, site, number and radio-density), renal function tests, routine laboratory findings, and urine analysis. The outcomes data in the form of; operative time, fluoroscopy time, hospital stay, SFRs, retreatment rates and complication rates were also retrieved from the records of patients treated with SWL and other techniques. Also, we collected the SWL characteristics in terms of; position, number and frequency of shocks, voltage, time of the session and U/S monitoring to assess stone fragmentation. All SWL procedures were performed according to the institution's standards. RESULTS: The mean age of patients treated with SWL was 3.23 ± 1.19 years old, the mean size of the treated calculi was 2.31 ± 0.49 and the mean length of the SSD was 8.2 ± 1.4 cm. All patients had NCCT scan and the mean radio-density of the treated calculi was 572 ± 169.08 HUs based on NCCT scans Table (1). Single- and two-session SFRs of SWL therapy were 75.5% (37/49 patients) and 93.9% (46/49 patients), respectively. The overall success rate was 95.9% (47/49 patients) after three-session of SWL. Complications experienced by 7 patients (14.3%) in the form of fever (4.1%), vomiting (4.1%), abdominal pain (4/1%), and hematuria (2%). All complications were managed in outpatient settings. Our results were obtained on the basis of preoperative NCCT scans for all patients and postoperative plain KUB films and real-time abdominal U/S. Furthermore, single-session SFRs for SWL, mini-PCNL, RIRS and open surgery were 75.5%, 82.1%, 73.7% and 90.6%, respectively. Two-session SFRs by the same technique were 93.9%, 92.8%, and 89.5% for SWL, mini-PCNL and RIRS, respectively. A lower overall complication rate and higher overall SFR were found with SWL therapy compared to other techniques, Fig. (1). DISCUSSION: Being a non-invasive outpatient procedure with a low complication rate and good spontaneous passage of stone fragments is the main advantage of SWL. In this study, the overall SFR is 93.9% where 46 out of 49 patients were completely rendered stone free after three session of SWL with overall success rate 95.9%. Badawy et al. reported overall success rates of 83.4% for renal stones with a mean stone size of 12.5 ± 7.2 mm. In children with renal stones measuring 18.2 mm, Ramakrishnan et al. reported a 97% SFR in accordance with our results. The high overall success rate (95.9%) and SFR (93.9%) in our research were attributed to the regular use of ramping procedure, low shock wave rate, percussion diuretics inversion (PDI) approach and alpha blocker therapy in all participants and short SSD. The limitations of our study are small sample of patients and its retrospective nature. CONCLUSION: The non-invasive nature and replicability of the SWL procedure, along with the high success and low complication rates, give us a new insight to consider its application for treating pediatric renal calculi > 2 cm over the other more invasive techniques. Short SSD, the use of ramping procedure, low shock wave rate, 2 min break, PDI approach and alpha blockers therapy help better success of SWL. LEVEL OF EVIDENCE: IV.

MALAT-1/p53/miR-155/miR-146a ceRNA circuit tuned by methoxylated quercitin glycoside alters immunogenic and oncogenic profiles of breast cancer.

Triple-Negative Breast Cancer (TNBC) is one of the most aggressive and hot BC subtypes. Our research group has recently shed the light on the utility of natural compounds as effective immunotherapeutic agents. The aim of this study is to investigate the role of a methoxylated quercetin glycoside (MQG) isolated from Cleome droserifolia in harnessing TNBC progression and tuning the tumor microenvironment and natural killer cells cytotoxicity. Results showed that MQG showed the highest potency (IC50 = 12 µM) in repressing cellular proliferation, colony-forming ability, migration, and invasion capacities. Mechanistically, MQG was found to modulate a circuit of competing endogenous RNAs where it was found to reduce the oncogenic MALAT-1 lncRNA and induce TP53 and its downstream miRNAs; miR-155 and miR-146a. Accordingly, this leads to alteration in several downstream signaling pathways such as nitric oxide synthesizing machinery, natural killer cells' cytotoxicity through inducing the expression of its activating ligands such as MICA/B, ULBP2, CD155, and ICAM-1 and trimming of the immune-suppressive cytokines such as TNF-α and IL-10. In conclusion, this study shows that MQG act as a compelling anti-cancer agent repressing TNBC hallmarks, activating immune cell recognition, and alleviating the immune-suppressive tumor microenvironment experienced by TNBC patients.

Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial.

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2-day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2-10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.

Single session vs two sessions of flexible ureterosopy (FURS) for dusting of renal pelvic stones 2-3 cm in diameter: Does stone size or hardness play a role in number of sessions to be applied?"

OBJECTIVE: To evaluate the stone hardness in predicting the need for single or two sessions of retrograde intrarenal surgery (RIRS) for renal pelvis stones of 2-3 cm in size. MATERIAL AND METHODS: Ninety-six patients (64 male and 32 female) with only renal stones (2.5±0.3 cm) underwent RIRS using flexible 7.5 Fr ureteroscope (FURS). The stone hardness was evaluated by preoperative non-contrast computed tomography (NCCT). The patients were divided into two groups based on stone hardness: Group I (n=54) (hard stones - Hounsfield Unit (HU) >1000) and group II (n=42) (not hard stone - HU <1000). The stone-free rate, the operative time, any intra or postoperative complications and the need for second sessions of RIRS were evaluated. RESULTS: All stones were successfully accessed. Intraoperative complications were not reported. The initial stone-free rate was 40% in Group I and 95% in Group II after a single session (p=0.01). A second session FURS was needed in 32 cases of Group I (40%) where postoperative CT showed significant residual stone fragments of 6±2 mm, and stone-free rate up to 100 percent. On the contrary only 2 cases from Group II underwent second session FURS (p=0.01). The operative times were 75±15 minutes in Group I and 55±13 minutes in Group II (p<0.01). Six patients (4 in group I and 2 in group II) had postoperative high-grade fever (Clavien Grade II). CONCLUSION: Stone hardness had a significant impact on the decision of performing single versus two sessions of FURS for renal pelvic stones of 2-3 cm rather than the stone size alone.

Surgical outcomes and complications of Tube® (Promedon) malleable penile prostheses in diabetic versus non-diabetic patients with erectile dysfunction.

OBJECTIVE: To evaluate surgical outcome, complications, and patients satisfaction with the Tube® (Promedon, Cordoba, Argentina) malleable penile prosthesis in diabetic and non-diabetic patients with refractory erectile dysfunction (ED). PATIENTS AND METHODS: The records of 128 eligible patients who received Tube malleable penile prostheses at our institute between September 2008 and October 2015 were reviewed. RESULTS: Of the 128 patients, who received Tube penile prostheses at our institute, 53 were diabetics and 75 were non-diabetics. Both groups of patients were comparable for mean age, education level, marital status, hospital stay, time to commencing sexual intercourse, and median follow-up. Complications included: inter-corporeal septal perforation (2.3%), glanular urethral injury (1.5%), acute urinary retention (3.9%), superficial wound infection (7%), penile discomfort (9.4%), and penile prostheses infection (5.5%). Moreover, 3.9% developed atrophy of the cavernosal tissue, 5.5% experienced bad cosmesis, 6.3% experienced ejaculatory disorders, and 2.3% developed bladder calculi. In all, 13 prostheses (9.4%) were removed, seven of them due to infection, three on the patients' demand and three due to mechanical failure. The satisfaction rates with the prostheses were 77.3% and 79.4% in the diabetic and non-diabetic patients, respectively; with an overall satisfaction rate of 78.5%. There was no significant difference in the complication rate or prostheses infection between diabetic and non-diabetic patients. CONCLUSION: Tube malleable penile prostheses are associated with low complication and high satisfaction rates. There was no significant difference in the complication rate or prostheses infection between diabetic and non-diabetic patients. A prospective comparative study with a large number of patients is recommended.

Spectrofluorimetric determination of drugs containing active methylene group using N1-methyl nicotinamide chloride as a fluorigenic agent.

A spectrofluorimetric method was described for the determination of drugs containing active methylene groups adjacent to carbonyl groups. The method was applied successfully to the determination of three life saving cardiovascular drugs, with narrow therapeutic indices: pentoxifylline (I), propafenone hydrochloride (II) and acebutolol hydrochloride (III), in laboratory-prepared mixtures, in commercial tablets and in plasma samples. The method involved the reaction of each of the tested drugs with N1-methyl nicotinamide chloride (NMNCl) in the presence of alkali, followed by addition of formic acid, where highly fluorescent reaction products were produced. The produced fluorescence were measured quantitatively at 472 nm (lambdaex 352 nm), 409 nm (lambdaex 310 nm) and 451 nm (lambdaex 266 nm) for (I), (II), and (III) respectively. The method was linear over concentration ranges of 10-1000 microg/ml , 0.2-12 microg/ml and 0.08-10 microg/ml in standard solutions for (I), (II), and (III) respectively. In spiked human plasma samples, calibration graphs were linear over concentration ranges of 20-1000 microg/ml, 0.2-15 microg/ml and 0.08-10 microg/ml for (I), (II), and (III) respectively. The method showed good accuracy, specificity and precision in both laboratory-prepared mixtures and spiked human plasma samples. The proposed method is simple, with low instrumentation requirements, suitable for quality control application, bioavailability and bioequivalency studies.