Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.

Background: Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression. Aim: To investigate the mechanistic pathways of high dose atorvastatin in MDD. Patients and methods: This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured. Results: The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively. Conclusion: These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05792540.

Bladder preservation by neoadjuvant chemotherapy followed by concurrent chemoradiation for muscle-invasive bladder cancer.

Introduction: In Egypt, bladder cancer (BC) represents about 8.7% of cancers in both sexes. In Egyptian men, it accounts for over 30% of all cancers, which makes it the second most frequent cancer. The standard curative treatment for patients with muscle-invasive bladder cancer (MIBC) has been radical cystectomy (RC) with urinary diversion and pelvic lymphadenectomy. Concomitant chemoradiation therapy (CCRT) in MIBC appears to produce results that are comparable to those of RC. Material and methods: Between January 2018 and March 2021, 34 BC- diagnosed patients, who refused RC, were enrolled. They received transurethral resection of the bladder tumour (TURBT) followed by 3 cycles of neoadjuvant chemotherapy (NACT) with gemcitabine, cisplatin, and CCRT. Concomitant chemoradiation therapy with cisplatin, as a chemosensitizer, was administered to patients who experienced a complete response (CR) and a partial response (PR) ≥ 50%. Results: Following NACT, CCRT was given to 27 patients (79.45%) who had either a PR > 50% or CR. Seven patients (20.5%) showed PR below 50%, stable disease, or progressive disease; 4 of them underwent RC followed by postoperative radiation. The average follow-up period was 46 months (range: 6-52 months). Twenty-three patients (67.6%) were still alive at the last check-up. Disease-free survival and 3-year overall survival were 70.8% and 65.1%, respectively. Conclusions: Bladder preservation provides survival rates comparable to those of MIBC patients, but with a higher quality of life. The findings show good survival rates without metastasis; nevertheless, more multicentre trials with larger sample sizes and longer follow-up periods are required to confirm these findings.

Outcome of docetaxel in treatment of metastatic hormone-sensitive prostate cancer and correlation with hemoglobin, albumin, lymphocyte and platelets score.

Introduction: We aimed to evaluate the outcome of treatment with docetaxel plus androgen deprivation therapy (ADT) in newly diagnosed patients with metastatic high tumor burden hormone-sensitive prostate cancer (mHSPC) and correlated the outcome with hemoglobin, albumin, lymphocyte and platelets (HALP) score. Material and methods: Six cycles of docetaxel plus ADT were given to 50 patients with high burden mHSPC. Baseline HALP score was calculated and disease outcome was tabulated; moreover, the prognostic impact of the HALP score in response to treatment and survival was calculated. Results: We found a significant association between high HALP score and response to treatment where a higher rate of complete response occurred in patients with a high HALP score than in patients with a low HALP score (53.8% vs. 5.4% respectively, p-value = 0.001). Patients with ≥ 12-month-duration castration-resistant prostate cancer (CRPC) had a significantly higher HALP score compared to patients with a lower HALP score (84.6% vs. 35.1% respectively, p-value = 0.002); 18-month-duration CRPC-free survival was significantly greater in patients with higher HALP score than patients with a lower HALP score (23.1% and 5.4% respectively, p-value < 0.001). Patients with a high HALP score had insignificantly higher mean overall survival than patients with a low HALP score (mean: 22.91 and 20.66 months respectively, p-value = 0.230). Conclusions: Our results confirmed the benefits of treatment with docetaxel plus ADT in high-burden mHSPC with accepted tolerance. HALP score was found to be an independent predictive factor for benefit from therapy; we can apply it as an easy way to stratify patients for appropriate selection of treatment for better tolerance and outcome.

Outcomes and clinical predictors of extracorporeal shock wave therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome: a prospective randomized double-blind placebo-controlled clinical trial.

OBJECTIVES: To report the one-year results of ESWT on CPPS patients and the possible clinical characteristics that may affect its efficacy. PATIENTS & METHODS: A prospective randomized clinical study between January 2017 and January 2021 on 155 adult patients with chronic pelvic pain syndrome. All patients were initially evaluated with a thorough history and physical examination. Baseline symptoms evaluation of each participant was assessed using NIH-CPSI score, IPSS, VAS, and IIEF-5 score. Patients were randomized into two groups: a verum treatment group and a placebo treatment group. Patients of verum group in the lithotomy position received a perineally applied ESWT treatment once a week for four weeks with 3000 impulses each. Patients of placebo group received the same therapy head of the same device with a layer of air-filled microspheres to absorb the shock waves. The previously mentioned validated scores were reassessed on regular follow-up visits at one, three, six, and 12 months after the completion of ESWT. RESULTS: A statistically significant improvement was noticed in the mean values of NIH-CPSI, IPSS, VAS, and IIEF-5 of the patients of verum group over the follow-up period with also statistically significant difference between both groups. At the first visit of follow-up after ESWT, 63 (82.8%) patients had ≥6 points decrease in the NIH-CPSI total score, while 13 (17.2%) patients did not. Univariate and multivariate analyses of the clinical characteristics between the responders and non-responders showed that those patients with history of psychological disorders or had higher initial NIH-CPSI score had a significantly lower response rate to ESWT (p = 0.005, 0.02 & p = 0.002, 0.004 respectively). ROC curve of NIH-CPSI score showed that a score of 32 was the cut-off point above which the response to ESWT decreased. CONCLUSION: ESWT is an effective treatment option for CPPS. Its efficacy remained throughout long-term follow up. High initial NIH-CPSI score and history of psychological problems are significant predictors for it.

Fracture resistance of primary molars restored with endocrowns versus zirconia crowns (an in vitro study) / Resistência à fratura de molares decíduos restaurados com endocrowns versus coras de zircônia (um estudo in vitro)

Objective: This study aimed to assess the fracture resistance of primary molars restored with endocrowns compared to prefabricated zirconia crowns. Material and Methods: Twelve sound, defect-free primary second molars were selected and divided into two groups: group I included 6 molars restored with zirconia crowns, while group II included 6 teeth restored with endocrowns. For both groups access cavity was prepared for the teeth to open pulp chamber. Fracture resistance of both groups was tested using a universal testing machine. Results: Zirconia crown showed statistically significantly higher mean fracture resistance than Endocrown (P-value = 0.001, Effect size = 2.72). Conclusion: Pulpotomized primary molars restored with Zirconia crowns showed significantly higher mean fracture resistance compared to primary molars restored with endocrowns, meanwhile both restorations have shown higher mean fracture resistance than the maximum biting force in children. (AU)

Objetivo: Este estudo teve como objetivo avaliar a resistência à fratura de molares decíduos restaurados com endocrowns em comparação com coroas de zircônia pré-fabricadas. Material e Métodos: Doze segundos molares decíduos hígidos e livres de defeitos foram selecionados e divididos em dois grupos: o grupo l incluiu 6 molares restaurados com coroas de zircônia, enquanto o grupo ll incluiu 6 dentes restaurados com edocrowns. Para ambos os grupos, foi preparada uma cavidade de acesso à câmara pulpar. A resistência à fratura de ambos os grupos foi testada em uma máquina de ensaio universal. Resultados: A coroa de zircônia apresentou resistência média à fratura estatisticamente significativa maior do que endocrown (p=0,001, Tamanho do efeito = 2,72). Conclusão: Molares decíduos pulpotomizados restaurados com coroas de zircônia apresentam resistência média à fratura significativamente maior em comparação aos molares decíduos restaurados com endocrowns, entretanto, ambas as restaurações mostraram maior média à fratura do que a força máxima de mordida em crianças (AU)

Minimally invasive percutaneous nephrolithotomy vs standard PCNL for management of renal stones in the flank-free modified supine position: single-center experience.

To assess the safety and efficacy of minimally invasive percutaneous nephrolithotomy (mPCNL) as compared to standard PCNL (sPCNL) for management of 2-3-cm renal stones in the flank-free modified supine position. Between September 2010 and December 2013, 150 patients (168 renal units) with 2-3-cm renal stones were prospectively randomized into two treatment groups; Group A (75 patients/87 renal units) treated by mPCNL and Group B (75 patients/81 renal units) treated by sPCNL. In both groups, the patients were placed in the flank-free modified supine position. In mPCNL group, the tract was dilated up to 16.5 F whereas in sPCNL group the tract was dilated up to 30 F. Both groups were compared regarding several perioperative parameters. No significant difference was recorded among both groups regarding fluoroscopy time (4.3 ± 1.3 vs 4.8 ± 2.1 min, p = 0.06), operative time (83.2 ± 17.3 vs 78.6 ± 24.4 min, p = 0.16), hospital stay (4.3 vs 4.5 days, p = 0.76), VAS score (3.2 ± 0.6 vs 3.3 ± 0.8, p = 0.36) and need for analgesia. The mean drop in hemoglobin level and the incidence of bleeding that necessitated blood transfusion were significantly lower in the mPCNL group (0.6 ± 0.1 vs 1.9 ± 1.1 g/dl, p < 0.0001 and 1.2 vs 9.8%, p = 0.03, respectively). Although the stone-free rate was higher in the sPCNL group, but this was statistically insignificant (97.1 vs 95.4%, p = 0.86). Mini-PCNL is effective for managing renal calculi with comparable operative time and stone-free rate to standard PCNL with the merit of higher safety due to lower incidence of bleeding that necessitates blood transfusion.

The prognostic significance of p53, p63 and her2 expression in non-muscle-invasive bladder cancer in relation to treatment with bacille Calmette-Guerin.

OBJECTIVE: To investigate whether the immunohistochemical expression of p53, p63 and her2/neu is correlated with the prognosis of tumour recurrence and progression in patients with non-muscle invasive (NMI) bladder cancer. PATIENTS AND METHODS: In all, 88 patients diagnosed with NMI transitional cell carcinoma of the bladder in a Urology Department from May 2009 to April 2014 were included in the study. Paraffin-embedded specimens were obtained by transurethral resection of the bladder tumours. Sections on haematoxylin and eosin-stained slides were examined histologically and tumour grade was classified according to the World Health Organisation system (2004) Mostofi classification. The sections were evaluated using p63, p53 and her2/neu immunohistochemical staining before and after immunotherapy with bacille Calmette-Guerin (BCG), and patients were followed up for 36 months in the Urology Department. RESULTS: For tumour grade there was a significant relationship with the overexpression of p53 (P = 0.010), her2 (P = 0.025) and negativity of p63 (P = 0.025). There was no significant relationship between p53 or her2/neu overexpression and tumour stage. However, there was a significant correlation (P = 0.005) between p63 negativity and tumour stage. There was a significant relationship between p53 (P = 0.01), her2/neu (P = 0.025) overexpression and p63 negativity (P = 0.005) and tumour recurrence and progression. CONCLUSION: Patients with transitional cell carcinoma who are selected for BCG treatment should preferably be positively immunoreactive for p63, but negative for both p53 and her2/neu. These patients were less susceptible to recurrence and/or progression after BCG adjuvant therapy. Further studies are needed to investigate the relationship between these three markers and treatment with anti-her2/neu therapies.

Laparo endoscopic single site balloon vaginoplasty (LESS-BV).

OBJECTIVE: To evaluate feasibility, advantages, and disadvantages of the laparo-endoscopic single site surgery (LESS) technique for balloon vaginoplasty (BV). STUDY DESIGN: Cohort study. SETTING: Tertiary care facility. RESULTS: LESS-BV was successfully performed in 6 patients with Mullerian aplasia and one with androgen insensitivity syndrome (AIS). Patients presented with failure of intravaginal intercourse and/or dyspareunia. The procedure was performed successfully in conjunction with gonadectomy for the AIS case. The total operative time was 50-75 minutes. No operative complications were reported. Postoperative pain scores ranged from 0 to 2 points at rest and from 20 to 60 points during dressing change, increasing distension, and traction. The depths of the constructed neovaginas measured up to 12.8 cm. Sexual intercourse was initiated on the day of catheter removal. Penetrations and satisfactions scores increased to up 90 points for both partners. CONCLUSIONS: LESS-BV is technically feasible. LESS-BV allows better, stronger midline and long traction pass along the anatomic longitudinal axis of the hypoplastic vagina. Surgical outcomes should be compared prospectively to conventional laparoscopic BV.

Evaluation of transvaginal slings using different materials in the management of female stress urinary incontinence.

PURPOSE: To evaluate tailored polypropylene (prolene) mesh, anterior rectus sheath, and vaginal wall slings positioned under the mid-urethra, to treat stress urinary incontinence (SUI) in women, as SUI is a common pathological condition causing considerable distress and compromising social, physical, psychological, and sexual health, and for which surgical treatment remains controversial. PATIENTS AND METHODS: This prospective randomised study included 32 patients with SUI, evaluated by SEAPI (Stress, Emptying, Anatomy, Protection, and Instability) symptom score and urodynamics. According to sling material, 12 patients had tailored prolene mesh, 12 had anterior rectus sheath and eight had anterior vaginal wall slings. Operative variables (intraoperative bleeding, duration, complications and hospital stay) were documented, and postoperative complications and continence status were assessed. The follow-up was 12-18 months. RESULTS: Patients who received tailored prolene mesh slings had a lower operative duration and hospital stay, and less intraoperative bleeding. Postoperative complications, e.g. urinary retention and urgency, were <12%, with no significant differences. There was no significant difference among the three studied groups in the success rate (75%, 67% and 75%). CONCLUSIONS: Tailored prolene mesh, anterior rectus sheath and the vaginal wall sling are good alternatives to treat SUI in women, with comparable results in a short-term follow up. The surgeon's experience and the patient's clinical circumstances should be considered when choosing a sling material, as success rates are comparable, being slightly better for the prolene sling in operative duration, bleeding and hospital stay.

Protective effect of trapidil and l-arginine against renal and hepatic toxicity induced by cyclosporine in rats.

RATIONALE: Cyclosporine A (CsA) leads to renal and liver injury, production of free radicals and nitric oxide (NO) deficiency. This study investigates the possible protective effects of trapidil and L-arginine against CsA-induced tissue injury. OBJECTIVES: Forty adult male Wistar rats (180 +/- 20 g) were divided into five groups, eight animals in each. The first group served as control, second group served as CsA group, third group served as CsA + trapidil group, fourth group served as CsA + L-arginine group, and fifth group served as CsA + trapidil + L-arginine group. Kidney and liver functions, inflammatory mediators, cytokines, oxidant and antioxidant parameters as well as histopathological studies of renal and liver tissue were assessed in all groups. MAIN FINDINGS: CsA induced renal and hepatic dysfunction, which was confirmed by laboratory and histopathological examination. Administration of trapidil diminished the renal and liver injury and significantly attenuated the levels of serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and oxidative stress, while it significantly elevated the level of serum nitric oxide and the activity of antioxidative stress. L-Arginine gave the same trend as trapidil, but trapidil effect was more pronounced. Coadministration of trapidil + L-arginine significantly ameliorated the toxic effect of CsA, but did not differ significantly from the effect of trapidil alone. CONCLUSIONS: Treatment with trapidil or L-arginine diminished the renal and hepatic CsA-induced toxicity. However, the effect of trapidil was more pronounced. Therefore, treatment with trapidil alone may be the most economic and effective as a potential therapeutic agent in CsA injury.

Open eye injuries in the pediatric population in Kuwait.

OBJECTIVE: To report the epidemiological characteristics of pediatric open globe injuries and to discuss treatment, management and outcomes of such injuries. MATERIALS AND METHOD: The hospital records and operative notes of 95 patients 16 years old and younger who were treated for open eye injury at Ibn Sina Hospital, Kuwait between September 1995 and January 1999 were reviewed. The average age of patients was 6.6 years. Patients were divided into three groups according to their final visual acuity (FVA): group 1, FVA of 20/40 or better; group 2, 20/40-20/200, and group 3, 20/400 or worse. The FVA of each group was compared to initial visual acuity (IVA), wound entry site, injury-to-presentation interval, injury-to-surgery interval, time of surgery, duration of surgery, associated injuries and medical treatment. RESULTS: Injury was most common in children 3-6 years old. Most injuries occurred during play at home (46%), between the months of July and November (58%), and evening time (42%). The most common causes were glass, pencil, stick, soft drink bottle, metal bar, and stone. The cornea was the most common entry site (59 cases). Seventy-three patients presented on the day of injury, and 38 of them had surgical repair that same day. The follow-up period ranged from 2 weeks to 58 months. Thirty-eight patients (40%) had an FVA of 20/40 or better (group 1), 23 (24%) between 20/40 and 20/200 (group 2), 12 (13%) 20/400 or worse (group 3), and 22 (23%) had no record of FVA. The difference between IVA and FVA of wound entry site was statistically significant (p < 0.005). Differences due to injury-to-presentation interval, injury-to-surgery interval, time of surgery, duration of surgery, associated injuries, and the use of systemic antibiotics were found not to be statistically significant (p > 0.2). CONCLUSION: The prevalence of open globe injury among the pediatric population in Kuwait was high. Most injuries were due to household objects and occurred at home in the evening during the summer and autumn. IVA and anatomical location of the wound impacted on final outcome.