HLA alleles, haplotypes frequencies, and their association with hematological disorders: a report from 1550 families whose patients underwent allogeneic bone marrow transplantation in Egypt.

HLA alleles are representative of ethnicities and may play important roles in predisposition to hematological disorders. We analyzed DNA samples for HLA-A, -B, -C, -DRB1, and -DQB1 loci, from 1550 patients and 4450 potential related donors by PCR-SSO (Polymerase chain reaction sequence-specific oligonucleotides) and estimated allele frequencies in donors and patients from 1550 families who underwent bone marrow transplantation (BMT) in Egypt. We also studied the association between HLA allele frequencies and incidence of acute myeloid leukemia, acute lymphoblastic leukemia, and severe aplastic anemia. The most frequently observed HLA class I alleles were HLA- A*01:01 (16.9%), A*02:01 (16.1%), B*41:01 (8.7%), B*49:01 (7.3%), C*06:02 (25.1%), and C*07:01 (25.1%), and the most frequently observed class II alleles were HLA-DRB1*11:01 (11.8%), DRB1*03:01 (11.6%), DQB1*03:01 (27.5%), and DQB1*05:01 (18.9%). The most frequently observed haplotypes were A*33:01~B*14:02 ~ DRB1*01:02 (2.35%) and A*01:01~B*52:01~DRB1*15:01 (2.11%). HLA-DRB1*07:01 was associated with higher AML odds (OR, 1.26; 95% CI, 1.02-1.55; p = 0.030). Only HLA-B38 antigen showed a trend towards increased odds of ALL (OR, 1.52; 95% CI, 1.00-2.30; p = 0.049) HLA-A*02:01, -B*14:02, and -DRB1*15:01 were associated with higher odds of SAA (A*02:01: OR, 1.35; 95% CI, 1.07-1.70; p = 0.010; B*14:02: OR, 1.43; 95% CI, 1.06-1.93; p = 0.020; DRB1*15:01: OR, 1.32; 95% CI, 1.07-1.64; p = 0.011). This study provides estimates of HLA allele and haplotype frequencies and their association with hematological disorders in an Egyptian population.

Photodynamic Therapy: Current Trends and Potential Future Role in the Treatment of Bladder Cancer.

Bladder cancer (BC) is the 10th most common cancer in the world. The therapeutic spectrum of BC is broad and is constantly expanding. Despite the wide clinical use of photodynamic diagnosis (PTD) for BC, PDT has not been sufficiently investigated in the treatment landscape of BC. We performed an online search of the PubMed database using these keywords: photodynamic therapy, bladder cancer, urothelial carcinoma, in vivo, in vitro, cell line, animal model. Reviews, case reports, and articles devoted to photodynamic diagnostics and the photodynamic therapy of tumors other than urothelial carcinoma were excluded. Of a total of 695 publications, we selected 20 articles with clinical data, 34 articles on in vivo PDT, and 106 articles on in vitro data. The results presented in animal models highlight the potential use of PDT in the neoadjuvant or adjuvant setting to reduce local recurrence in the bladder and upper urinary tracts. Possible regimens include the combination of PDT with intravesical chemotherapy for improved local tumor control or the integration of vascular-targeted PDT in combination with modern systemic drugs in order to boost local response. We summarize available evidence on the preclinical and clinical application of PDT for urothelial carcinoma in order to explain the current trends and future perspectives.

Practice change: No benefit of extended lymphadenectomy at radical cystectomy in patients with muscle invasive bladder cancer.

For many decades, extended pelvic lymph node dissection has been an integral part during radical cystectomy for patients with muscle invasive bladder cancer. This practice was based on large retrospective meta-analyses suggesting an oncologic benefit to an extended dissection. This mini review and meta-analysis includes the two available randomized trials in the current literature. Therefore, it can be considered as the strongest level of evidence regarding the prognostic benefit of an extended pelvic lymphadenectomy. Based on current randomized data, standard pelvic lymph node dissection up to the level of iliac bifurcation is sufficient, and extension of the dissection above this level does not provide any additional oncologic benefit.

Machine learning algorithms for prediction of entrapment efficiency in nanomaterials.

Exploitation of machine learning in predicting performance of nanomaterials is a rapidly growing dynamic area of research. For instance, incorporation of therapeutic cargoes into nanovesicles (i.e., entrapment efficiency) is one of the critical parameters that ensures proper entrapment of drugs in the developed nanosystems. Several factors affect the entrapment efficiency of drugs and thus multiple assessments are required to ensure drug retention, and to reduce cost and time. Supervised machine learning can allow for the construction of algorithms that can mine data available from earlier studies to predict performance of specific types of nanoparticles. Comparative studies that utilize multiple regression algorithms to predict entrapment efficiency in nanomaterials are scarce. Herein, we report on a detailed methodology for prediction of entrapment efficiency in nanomaterials (e.g., niosomes) using different regression algorithms (i.e., CatBoost, linear regression, support vector regression and artificial neural network) to select the model that demonstrates the best performance for estimation of entrapment efficiency. The study concluded that CatBoost algorithm demonstrated the best performance with maximum R2 score (0.98) and mean square error (< 10-4). Among the various parameters that possess a role in entrapment efficiency of drugs into niosomes, the results obtained from CatBoost model revealed that the drug:lipid ratio is the major contributing factor affecting entrapment efficiency, followed by the lipid:surfactant molar ratio. Hence, supervised machine learning may be applied for future selection of the components of niosomes that achieve high entrapment efficiency of drugs while minimizing experimental procedures and cost.

Role of inguinal and pelvic lymph node dissection for primary urethral carcinoma: a systematic review.

PURPOSE OF REVIEW: Primary urethral carcinoma (PUC) is a rare urologic tumor. There is limited evidence on this entity. This review summarizes the existing evidence on lymph node dissection (LND) in patients with PUC. RECENT FINDINGS: We performed a systematic search of the PubMed, EMBASE, and Web of Science databases to evaluate the impact of inguinal and pelvic LND on the oncological outcomes of PUC and to identify indications for this procedure. RESULTS: Three studies met the inclusion criteria. The cancer detection rate in clinically nonpalpable inguinal lymph node (cN0) was 9% in men and 25% in women. In clinically palpable lymph node (cN+), the malignancy rate was 84% and 50% in men and women, respectively. Overall cancer detection rate in pelvic lymph nodes in patients with cN0 was 29%. Based on tumor stage, the detection rate was 11% in cT1-2 N0 and 37% in cT3-4 N0. Nodal disease was associated with higher recurrence and worse survival. Pelvic LND seems to improve overall survival for patients with LND regardless of the location or stage of lymph nodes. Inguinal LND improved overall survival only in patients with palpable lymph nodes. Inguinal LND had no survival benefit in patients with nonpalpable lymph nodes. SUMMARY: The available, albeit scarce, data suggest that inguinal LND derives the highest benefit in women and in patients with palpable inguinal nodes, whereas the benefit of pelvic LND seems to be more pronounced across all stages of invasive PUC. Prospective studies are urgently needed to further address the prognostic benefit of locoregional LND in PUC.

Low-Dose Initiation of Buprenorphine: A Narrative Review.

PURPOSE OF REVIEW: Opioid use disorder (OUD) is a chronic disorder in which a person loses control over the use of opioids, develops a compulsive behavior, and defends the use despite knowing the negative consequences. There are numerous treatments for OUD, including buprenorphine. Since it is displacing a full agonist opioid, precipitated withdrawal can occur with standard inductions involving buprenorphine. RECENT FINDINGS: Case reports have noted success with a low-dose initiation of buprenorphine, which is different from typical protocols, relatively limited by adverse effects when patients were recently administered full agonists. A cohort investigation studied the use of a transdermal patch as part of the protocol, which was fairly well tolerated. While ongoing research is being conducted on this topic, recent case studies and smaller cohort studies have demonstrated the feasibility of a trial to treat OUD with low-dose initiation of buprenorphine.

Complete Breast Cancer Detection and Monitoring System by Using Microwave Textile Based Antenna Sensors.

This paper presents the development of a new complete wearable system for detecting breast tumors based on fully textile antenna-based sensors. The proposed sensor is compact and fully made of textiles so that it fits conformably and comfortably on the breasts with dimensions of 24 × 45 × 0.17 mm3 on a cotton substrate. The proposed antenna sensor is fed with a coplanar waveguide feed for easy integration with other systems. It realizes impedance bandwidth from 1.6 GHz up to 10 GHz at |S11| ≤ -6 dB (VSWR ≤ 3) and from 1.8 to 2.4 GHz and from 4 up to 10 GHz at |S11| ≤ -10 dB (VSWR ≤ 2). The proposed sensor acquires a low specific absorption rate (SAR) of 0.55 W/kg and 0.25 W/kg at 1g and 10 g, respectively, at 25 dBm power level over the operating band. Furthermore, the proposed system utilizes machine-learning algorithms (MLA) to differentiate between malignant tumor and benign breast tissues. Simulation examples have been recorded to verify and validate machine-learning algorithms in detecting tumors at different sizes of 10 mm and 20 mm, respectively. The classification accuracy reached 100% on the tested dataset when considering |S21| parameter features. The proposed system is vision as a "Smart Bra" that is capable of providing an easy interface for women who require continuous breast monitoring in the comfort of their homes.

New Intravesical Agents for BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer.

BACKGROUND: With the exception of the FDA-approved valrubicin and pembrolizumab, there are no standard second-line treaments for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC). OBJECTIVES: To provide a systematic review of the novel intravesically administered therapeutic agents for the salvage treatment of BCG-unresponsive NMIBC. METHODS: Online search of the PubMed, EMBASE and Web of Science databases was performed. The endpoints of this review were to evaluate the efficacy of the agents in terms of complete response rates (CR) and durability of CR, overall survival, recurrence-free survival and cancer-specific survival and to report on their toxicity profile. A search on Clinicaltrials.gov was performed to identify ongoing clinical trials. RESULTS: 14 studies were included in this review. The critical clinical need for the development of an effective, safe and durable intravesical drug for the salvage treatment of high-risk NMIBC seems to be met mainly by intravesical gene therapy; in fact, data support the FDA-approved nadofaragene firadenovec as a potentially important therapeutic advancement in this context. Promising results are also being obtained by the combination of N-803/BCG and by innovative drug delivery systems. CONCLUSIONS: Considering the plethora of novel intravesical treatments that have completed phase II evaluation, one can reasonably expect that clinicians will soon have at their disposal new agents and treatment options for BCG-unresponsive NMIBC. In the near future, it will be up to the urologist to identify, for each specific patient, the right agent to use, based on safety, results and cost-effectiveness.

Comparison of Renal Function before and after Autologous Stem Cell Transplantation in Egyptian Patients with Multiple Myeloma and Renal Insufficiency: A Retrospective Study.

Renal failure is a common feature of multiple myeloma (MM) that occurs in 20%-40% of newly diagnosed patients with MM and is the result of monoclonal immunoglobulin light chains. Many studies have examined the effect of autologous stem cell transplantation (ASCT) in MM patients with renal impairment and the safety of performing the transplantation in patients with renal failure. This study aimed to compare renal function before and after ASCT in Egyptian MM patients with renal insufficiency to evaluate the effect of ASCT on renal recovery. Our study included 31 MM patients with renal impairment out of 400 patients who met the criteria of the International Myeloma Working Group for symptomatic MM. The estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease formula was compared before and after the transplant. Only four patients (12.9%) were dependent on dialysis. Six of those with a history of hemodialysis (HD) who were either dependent on dialysis or dialyzed according to need achieved independence from HD. There was no significant correlation between the degree of renal impairment and the disease's status at the time of transplantation (P = 0.86). The study showed significant improvements in serum creatinine levels compared with its value before the transplant (P = 0.016) and in eGFR (P = 0.004). In total, 45% of patients achieved renal improvement, shown by a 25% increase in GFR above the baseline. There was a significant improvement of renal function after ASCT in MM patients with renal impairment.

Guillain-Barré Syndrome following intravesical Bacillus Calmette-Guérin therapy for bladder cancer: a rare and intriguing case report.

Intravesical Bacillus Calmette-Guérin (BCG) therapy is a standard treatment for non-muscle invasive bladder cancer, but some patients experience side effects that lead to treatment discontinuation. Local side effects are typically mild, while systemic side effects can be severe and life-threatening. BCG therapy has immunotherapy effects on bladder cancer, but the mechanism is not fully understood. Due to its effect on the immune system, patients may also develop rare autoimmune complications, such as neuropathy. This case report suggests a potential association between BCG therapy and Guillain-Barré Syndrome (GBS), as a patient developed GBS after receiving intravesical BCG therapy for invasive bladder cancer.

Hybrid nanoparticulate system of Fluvastatin loaded phospholipid, alpha lipoic acid and melittin for the management of colon cancer.

As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-ß1 and p-ERK1/2 Axis.

The immunosuppressant cyclosporine A (CSA) has been linked to serious renal toxic effects. Although 2-methoxyestradiol (2ME) possesses a wide range of pharmacological abilities, it suffers poor bioavailability after oral administration. The purpose of this study was to evaluate the potential of 2ME loaded D-ɑ-tocopheryl polyethylene glycol succinate (TPGS) micelles to prevent CSA-induced nephrotoxicity in rats. A 2ME-TPGS was prepared and showed particle size of 44.3 ± 3.5 nm with good entrapment efficiency and spherical structures. Male Wistar rats were divided into 5 groups, namely: Control, Vehicle, CSA, CSA + 2ME-Raw, and CSA + 2ME-Nano. CSA was injected daily at a SC dose of 20 mg/kg. Both 2ME-Raw and 2ME-Nano were given daily at oral doses of 5 mg/kg. Treatments continued for three successive weeks. 2ME-TPGS exerted significant protective effects against CSA nephrotoxicity. This was evidenced in ameliorating deterioration of renal functions, attenuation of pathological changes in kidney tissues, exerting significant anti-fibrotic, antioxidant, and anti-inflammatory effects together with significant anti-apoptotic effects. Western blot analyses showed both 2ME-Raw and 2ME-Nano significantly inhibited protein expression of TGF-ß1 and phospho-ERK (p-ERK). It was observed that 2ME-TPGS, in almost all experiments, exerted superior protective effects as compared with 2ME-Raw. In conclusion, 2ME loaded in a TPGS nanocarrier possesses significant protective activities against CSA-induced kidney injury in rats. This is attributable to 2ME anti-fibrotic, antioxidant, anti-inflammatory, and anti-apoptotic activities which are mediated at least partly by inhibition of TGF-ß1/p-ERK axis.

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis.

Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. Methods: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. Results: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p < 0.00001; RR = 1.91), rash incidence was equal to 11.1% (160/1441) vs. 6.5% (86/1320) (Z = 4.35; p <0.0001; RR = 1.75), pruritis was 13.6% (201/1473) vs. 7.7% (104/1352) (Z = 5.35; p < 0.00001; RR = 1.83), fever was 10.5% (42/399) vs. 6.6% (22/330) (Z = 2.27; p = 0.02; RR = 1.77), discontinuation rate was 18% (91/504) vs. 3% (36/434) (Z = 4.78; p < 0.00001; RR = 2.41), and death rate was 2.6% (13/504) vs. 0.7% (3/434) (Z = 1.90; p = 0.06; RR = 2.77). Conclusions: It was observed that the combined (durvalumab and tremelimumab) vs. monotherapy (durvalumab) is associated with a higher risk of treatment discontinuation, mortality, fever, diarrhea, rash, pruritis, and reduced appetite. This information is relevant and should be disclosed, especially to patients that are currently enrolled in clinical trials considering this combined therapy.

Electrocardiographic Features and Outcome: Correlations in 124 Hospitalized Patients With COVID-19 and Cardiovascular Events.

OBJECTIVES: Electrocardiographic (ECG) changes have been associated with coronavirus disease 2019 (COVID-19) severity. However, the progression of ECG findings in patients with COVID-19 has not been studied. The purpose of this study was to describe ECG features at different stages of COVID-19 cardiovascular (CV) events and to examine the effects of specific ECG parameters and cardiac-related biomarkers on clinical outcomes in COVID-19. DESIGN: Retrospective, cohort study. SETTING: Major tertiary-care medical centers and community hospitals in Louisville, KY. PARTICIPANTS: A total of 124 patients with COVID-19 and CV events during hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twelve-lead ECG parameters, biomarkers of cardiac injuries, and clinical outcomes were analyzed with Spearman correlation coefficients and Kruskal-Wallis 1-way analysis of variance. Atrial fibrillation/atrial flutter was more frequent on the ECG obtained at the time of the CV event when compared with admission ECG (9.5% v 26.9%; p = 0.007). Sinus tachycardia was higher in the last available hospital ECG than the CV event ECG (37.5% v 20.4%; p = 0.031). Admission ECG-corrected QT interval was significantly associated with admission troponin levels (R = 0.52; p < 0.001). The last available hospital ECG showed nonsurvivors had longer QRS duration than survivors (114.6 v 91.2 ms; p = 0.026), and higher heart rate was associated with longer intensive care unit length of stay (Spearman ρ = 0.339; p = 0.032). CONCLUSIONS: In hospitalized patients with COVID-19 and CV events, ECGs at various stages of COVID-19 hospitalization showed significantly different features with dissimilar clinical outcome correlations.

Preparation of Liposomal Raloxifene-Graphene Nanosheet and Evaluation of Its In Vitro Anticancer Effects.

BACKGROUND: In current years, researchers have shown their prime interest in developing multifunctional drug delivery systems, especially against cancers, for effective anticancer outcomes. METHODOLOGY: Raloxifene (RLX) loaded liposomal-graphene nanosheet (GNS) was developed. The novelty of this work was to enhance the solubilization of RLX and improvement of its bioavailability in the disease area. So, the selection of optimized formula design of experiment was implemented which produced the desired formula with the particle size of 156.333 nm. Further, encapsulation efficiency, in vitro release, and thermodynamic stability of optimized formulation were evaluated. The optimized formulation exhibited prolonged release of RLX for a longer period of 24 h, which can minimize the dose-related toxicity of the drug. Furthermore, optimized formulation demonstrated remarkable thermodynamic stability in terms of phase separation, creaming, and cracking. RESULTS: The cytotoxicity study on the A549 cell line exhibited significant (P < .05) results in favor of optimized formulation than the free drug. The apoptotic activity was carried out by Annexin V staining and Caspase 3 analysis, which demonstrated remarkable promising results for optimized liposomal formulation. CONCLUSION: From the findings of the study, it can be concluded that the novel optimized liposomal formulation could be pondered as a novel approach for the treatment of lung cancer.

Impact of Preoperative Stenting on the Outcome of Flexible Ureterorenoscopy for Upper Urinary Tract Urolithiasis: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to investigate the effect of preoperative stenting (POS) on the perioperative outcomes of flexible ureterorenoscopy (fURS). MATERIALS AND METHODS: A systematic review and meta-analysis was conducted based on the PRISMA statement. From the initially retrieved 609 reports, we excluded the ineligible studies at 2 stages. We only included studies that contained fURS patients with and without POS in the same report. Data of patients who underwent semirigid ureteroscope only were excluded from the analysis. The Newcastle-Ottawa Scale (NOS) system was applied for risk of bias assessment. RESULTS: A total of 20 studies including 5,852 patients were involved. 48.5% of the patients had preoperative stent. Stone-free rate was significantly higher with prestenting; odds ratio (OR) was 1.98 (95% CI: 1.51-2.58) (Z = 5.02; p = 0.00001). It also displayed tendency toward lower complications; OR was 0.74 (95% CI: 0.52-1.05) (Z = 1.67; p = 0.09). POS significantly increased the use of ureteral access sheath; OR was 1.49 (95% CI: 1.05-2.13) (Z = 2.22; p = 0.03). Risk of bias assessment showed 13 and 7 studies with low and moderate risk, respectively. CONCLUSIONS: POS clearly improves the stone-free rates after fURS. It might reduce the complications, especially ureteral injury. These findings might help solve the current debate and can be useful for urologists during patient counselling for a proper decision-making.

Retrograde intrarenal surgery versus percutaneous nephrolithotomy for treatment of renal pelvic stone more than 2 centimeters: a prospective randomized controlled trial.

This study aimed at investigating the efficacy and safety of retrograde intrarenal surgery (RIRS) in treatment of renal pelvic stone larger than 2 cm against the percutaneous nephrolithotomy (PCNL). Between March 2018 and December 2020, 121 patients were randomized to undergo PCNL (60 patients), or RIRS (61 patients). Both groups were compared in terms of operative time, intraoperative complications. Postoperative complications were assessed based on Clavien-Dindo grading system. Stone-free rates were evaluated by CT scan 6 weeks after surgery. No significant difference were observed between both groups in perioperative criteria. The main operative time was slightly longer in PCNL group (105 vs 95 min, p = 0.49). Stone clearance was higher in PCNL, yet the difference was not significant. (53 patients in PCNL group had either complete clearance or residual fragments < 4 mm, compared to 49 in RIRS group (p = 0.22). Blood transfusion rate was 8.3% in PCNL compared to 1.6% in RIRS group, with a trend towards significance (p = 0.08). Post-operative fever was higher in RIRS, yet it fell just short of statistical significance (13.1% vs 5.0%, p = 0.12). Compared to PCNL, RIRS displayed acceptable efficacy with less risk of bleeding requiring transfusion. It can be applied to patients with large renal pelvic stone as an alternative to PCNL.

Systematic Review and Meta-Analysis on the Role of Perioperative Blood Transfusion in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma.

BACKGROUND: Radical cystectomy (RC) is the standard of care in patients with muscle-invasive bladder cancer. The impact of perioperative red blood cell (RBC) transfusion on oncological outcomes after RC is not clearly established as the existing publications show conflicting results. OBJECTIVES: The aim of this systematic review and meta-analysis was to investigate the prognostic role of perioperative RBC transfusion on oncological outcomes after RC. METHODS: Systematic online search on PubMed was conducted, based on PRISMA criteria for publications reporting on RBC transfusion during RC. Publications with the following criteria were included: (I) reported data on perioperative blood transfusion; (II) Reported Hazard ratio (HR) and 95% -confidence interval (CI) for the impact of transfusion on survival outcomes. Primary outcome was the impact of perioperative RBC transfusion on recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Risk of bias assessment was performed using Newcastle-Ottawa Scale. Statistical analysis was performed using Revman 5.4 software. RESULTS: From 27 primarily identified publications, 19 eligible articles including 22897 patients were selected. Perioperative RBC transfusion showed no impact on RFS (Z = 1.34; p = 0,18) and significant negative impact on CSS (Z = 2.67; p = 0.008) and OS (Z = 3.22; p = 0.001). Intraoperative RBC transfusion showed no impact on RFS (Z = 0.58; p = 0.56) and CSS (Z = 1.06; p = 0.29) and OS (Z = 1.47; p = 0.14).Postoperative RBC transfusion showed non-significant trend towards improved RFS (Z = 1.89; p = 0.06) and no impact on CSS (Z = 1.56; p = 0.12) and OS (Z = 0.53 p = 0.60). CONCLUSION: In this meta-analysis, we found perioperative blood transfusion to be a significant predictor only for worse CSS and OS but not for RFS. This effect may be determined by differences in tumor stages and patient comorbidities for which this meta-analysis cannot control due to lack of respective raw data.

Impact of Prostate Size on the Outcomes of Radical Prostatectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: The impact of prostate size on the radical prostatectomy outcome is not clear. Several published reports have shown conflicting results. OBJECTIVES: To investigate the effect of prostate size on the surgical, functional and oncological results of radical prostatectomy. METHODS: A systematic review and meta-analysis were carried out in accordance with the PRISMA criteria. Finally, we investigated the research that reported on the impact of prostate size on radical prostatectomy outcome. The Review Manager (RevMan) software version 5.4 was utilized for statistical analysis. RESULTS: Eighteen studies including 12,242 patients were included. Estimated blood loss was significantly less with smaller prostates (Z = 3.01; p = 0.003). The complications rate was 17% with larger prostates, compared to 10% for smaller prostates (Z = 5.73; p < 0.00001). Seventy-three percent of patients with a smaller prostate were continent within one month, compared to 64% with a larger prostate (Z = 1.59; p = 0.11). The rate of positive surgical margins was significantly higher with smaller prostates (20.2% vs. 17.8%). (Z = 2.52; p = 0.01). The incidence of biochemical recurrence was higher with smaller prostates (7.8% vs. 4.9%) (Z = 1.87; p = 0.06). CONCLUSION: Larger prostate size is associated with more blood loss and a higher rate of complications. However, the oncological outcome is better, compared to that in patients with smaller prostates. The impact of the size on the functional outcome is not clear.