Design and internal validation of S.I.C.K.: a novel nomogram predicting infectious and hemorrhagic events after percutaneous nephrolithotomy.

BACKGROUND: Hemorrhagic and infectious events represent severe complications after percutaneous nephrolithotomy (PCNLs). Existing nephrolithometric nomograms have been introduced but their reliability in predicting complications is debated. We present a newly designed nomogram with intention to predict hemorrhagic/infectious events after PCNLs. METHODS: We conducted a multicentric prospective study on adult patients undergoing standard (24 Fr) or mini (18 Fr) PCNL. Dataset was derived from previous RCT, where patients have been assigned to mini-PCNL or standard-PCNL to treat renal stones up to 40 mm. Aim of the study was to identify preoperative risk factors for early postoperative infectious/hemorrhagic complications including fever, septic shock, transfusion or angioembolization. RESULTS: A total of 1980 patients were finally included. 992 patients (50.1%) received mini-PCNL and 848 standard PCNL (49.9%). The overall SFR was 86.1% with a mean maximum stone diameter of 29 mm (SD 25.0-35.0). 178 patients (8.9%) had fever,14 (0.7%) urosepsis, 24 patients (1.2%) required transfusion and 18 (0.9%) angioembolization. The overall complication was (11.7%). After multivariable analysis, the included elements in the nomogram were age (P=0.041), BMI (P=0.018), maximum stone diameter (P<0.001), preoperative hemoglobin (P=0.005), type 1/2 diabetes (P=0.05), eGFR<30 (P=0.0032), hypertension (>135/85 mmHg, P=0.001), previous PCNL or pyelo/nephrolithotomy (P=0.0018), severe hydronephrosis (P=0.002). After internal validation, the AUC of the model was 0.73. CONCLUSIONS: This is the first nomogram predicting infections and bleedings after PCNLs, it shows a good accuracy and can support clinicians in their patients' peri-operative workout and management.

Reliability of nephrolithometric nomograms in patients treated with minimally invasive percutaneous nephrolithotomy: A precision study.

Objectives: The study aimed to evaluate quality of nephrolithometric nomograms to predict stone-free rates (SFRs) and complication rates (CRs) in case of minimally invasive percutaneous nephrolithotomy (PNL). In the last decade, nomograms have been introduced to estimate the SFRs and CRs of PNL. However, no data are available regarding their reliability in case of utilization of miniaturized devices. Herein we present a prospective multicentric study to evaluate reliability of Guy's stone score (GSS), the stone size, tract length, obstruction, number of involved calyces, and essence of stone (S.T.O.N.E.) nephrolithometry score and Clinical Research Office of the Endourological Society (CROES) score in patients treated with minimally invasive PNL. Methods: We evaluated SFRs and CRs of 222 adult patients treated with miniaturized PNL. Patients were considered stone-free if no residual fragments of any size at post-operative unenhanced computed tomography scan. Patients demographics, SFRs, and CRs were reported and analyzed. Performances of nomograms were evaluated with the area under the curve (AUC). Results: We included 222 patients, the AUCs of GSS, CROES score, and S.T.O.N.E. nephrolithometry score were 0.69 (95% confidence interval [CI] 0.61-0.78), 0.64 (95% CI 0.56-0.73), and 0.62 (95% CI 0.52-0.71), respectively. Regarding SFRs, at multivariate binomial logistic regression, only the GSS had significance with an odds ratio of 0.53 (95% CI 0.31-0.95, p=0.04). We did not find significant correlation with complications, with only a trend for GSS. Conclusion: This is the first study evaluating nomograms in miniaturized PNL. They still show good reliability; however, our data showed lower performances compared to standard PNL. We emphasize the need of further studies to confirm this trend. A dedicated nomogram for minimally invasive PNL may be necessary.

Introducing trifecta for percutaneous nephrolithotomies: a proposal for standard reporting outcomes after treatment for renal stones.

BACKGROUND: In literature, the reports of outcomes after percutaneous nephrolithotomies are rather heterogeneous. This may influence studies comparison, it may also render difficult to evaluate surgical adequacy, perioperative morbidity, and patient's Quality of Life between studies. For this reason, we propose to introduce PNL-Trifecta as composite measure to standardize data reporting outcomes after percutaneous nephrolithotomies. METHODS: We performed a prospective multicentric study on consecutive patients undergone PNL to treat renal stones between 2018 and 2020. Successful PNL-trifecta was considered achieved when procedures obtained the three following results: no residual fragments >2 mm at unenhanced CT scan at 3 months postop, no complications (defined as Clavien-Dindo Score 0) and operation carried out without placing a nephrostomy tube (tubeless or totally tubeless). We compared results of standard versus mini-PNL and between stones of different complexity (evaluated with Guy's Stone Score and S.T.O.N.E. Nephrolithometry Score). Univariate analysis was utilized to identify other factors influencing achievement of PNL-Trifecta. RESULTS: Two hundred forty-five patients fulfilled inclusion/exclusion criteria and have been enrolled in the study (median age: 56, IQR 48-57). The overall PNL-Trifecta achievement rate was 22.85% (28.66% in the mini-PNL group and 13.68% in the standard-PNL group, P=0.010). The stone free rate, CD 0 rate and tubeless/totally tubeless rate in the mini-PNL group were 60.66%, 89.33% and 51.33% respectively. In the standard-PNL group they were 44.21%, 40.00% and 15.78% respectively. At the univariate analysis, differences between Guy's Stone Score groups in achieving PNL-Trifecta were significant (P=0.001). Also, the level of upper puncture (P=0.010) and utilization of device with active suction (P=0.002) showed statistically significant differences. Furthermore, the length of stay in the patient's group achieving Trifecta was 2.28 versus a mean length of stay of 4.64 days in the group of patients not achieving Trifecta (P=0.046). CONCLUSIONS: We present Trifecta for PNLs as a potential tool to evaluate quality of percutaneous nephrolithotomies and to provide an instrument for an adequate standard data reporting. It can represent a valid way to assess and monitor surgeon's learning curves. It will require further external validation and studies to evaluate its correlation with mid- and long-term results and patient's health related Quality of Life outcomes.

European Association of Urology Section of Urolithiasis and International Alliance of Urolithiasis Joint Consensus on Retrograde Intrarenal Surgery for the Management of Renal Stones.

BACKGROUND: Retrograde intrarenal surgery (RIRS) has become the preferred treatment modality for nephrolithiasis. However, because of ongoing uncertainties regarding the optimal perioperative management, operative technique, and postoperative follow-up, as well as a lack of standardization for outcome reporting, consensus is needed to achieve more uniform clinical practice worldwide. OBJECTIVE: To develop recommendations for RIRS on the basis of existing data and expert consensus. DESIGN, SETTING, AND PARTICIPANTS: A protocol-driven, three-phase study was conducted by the European Association of Urology Section of Urolithiasis (EULIS) and the International Alliance of Urolithiasis (IAU). The process included: (1) a nonsystematic review of the literature to define domains for discussion; (2) a two-round modified Delphi survey involving experts in this field; and (3) an additional group meeting and third-round survey involving 64 senior representative members to formulate the final conclusions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The results from each previous round were returned to the participants for re-evaluation of their decisions during the next round. The agreement threshold was set at 70%. RESULTS AND LIMITATIONS: The panel included 209 participants who developed 29 consensus statements on the following topics of interest: (1) perioperative infection management; (2) perioperative antithrombotic therapy; (3) fundamentals of the operative technique; and (4) standardized outcome reporting. Although this consensus can be considered as a useful reference for more clinically oriented daily practice, we also acknowledge that a higher level of evidence from further clinical trials is needed. CONCLUSIONS: The consensus statements aim to guide and standardize clinical practice and research on RIRS and to recommend standardized outcome reporting. PATIENT SUMMARY: An international consensus on the best practice for minimally invasive surgery for kidney stones was organized and developed by two international societies. It is anticipated that this consensus will provide further guidance to urologists and may help to improve clinical outcomes for patients.

Characterization of the m6A-Associated Tumor Immune Microenvironment in Prostate Cancer to Aid Immunotherapy.

The aim of this study was to elucidate the correlation between m6A modification and the tumor immune microenvironment (TIME) in prostate cancer (PCa) and to identify the m6A regulation patterns suitable for immune checkpoint inhibitors (ICIs) therapy. We evaluated the m6A regulation patterns of PCa based on 24 m6A regulators and correlated these modification patterns with TIME characteristics. Three distinct m6A regulation patterns were determined in PCa. The m6A regulators cluster with the best prognosis had significantly increased METTL14 and ZC3H13 expression and was characterized by low mutation rate, tumor heterogeneity, and neoantigens. The m6A regulators cluster with a poor prognosis had markedly high KIAA1429 and HNRNPA2B1 expression and was characterized by high intratumor heterogeneity and Th2 cell infiltration, while low Th17 cell infiltration and Macrophages M1/M2. The m6Ascore was constructed to quantify the m6A modification pattern of individual PCa patients based on m6A-associated genes. We found that the low-m6Ascore group with poor prognosis had a higher immunotherapeutic response rate than the high-m6Ascore group. The low-m6Ascore group was more likely to benefit from ICIs therapy. This study was determined that immunotherapy is more effective in low-m6Ascore PCa patients with poor prognosis.

Assessing the risk of rapid fibroid growth in patients with asymptomatic solitary uterine myoma using a multivariate prediction model.

BACKGROUND: Long-term conservative approaches are effective management options for asymptomatic uterine fibroids, but not for uterine myomas with excessive growth. In this investigation, a regression model was constructed to evaluate the clinical characteristics related to uterine fibroids' growth. METHODS: In this retrospective study, 19,840 patients with ultrasound-diagnosed uterine fibroids were identified from six centers between 2013 and 2019. In total, 739 patients were followed up for more than 1 year with B-ultrasound test results and clinical test results and had no acute events or surgical treatments. The endpoint was changed in the size of the uterine fibroids. Multivariate stepwise logistic regression analysis was used to identify predictors of uterine fibroid growth, and these were used to build a prediction model. The prediction model's discrimination, calibration, and clinical efficacy were assessed using the area under the curve (AUC)/index of concordance (C-index), calibration plot, decision curve analysis, and clinical impact curve. Internal validation was performed using bootstrapping validation. A linear regression model was constructed to predict uterine fibroids' growth rate without the occurrence of acute events. RESULTS: A total of 513 patients presented with significant growth of uterine fibroids, with an average follow-up time of 927 days, and 267 patients showed negative growth, with an average follow-up time of 960 days. Age, follicle-stimulating hormone (FSH), low-density lipoprotein (LDL), luteinizing hormone (LH), total cholesterol (TCHO), and neutrophil to lymphocyte ratio (NLR) were the main influential factors that predicted the uterine fibroid growth state, and these were used to develop a nomogram with predictive accuracy (AUC: 0.825). A linear regression prediction model was built based on the following factors: FSH, high-density lipoprotein (HDL), LH, triglyceride (TRIG), TCHO, and lymphocyte to monocyte ratio (LMR). The mean square error (MSE) was 0.32. CONCLUSIONS: This study directly measured the growth rate of uterine fibroids. A prediction model assessing the growth rate of asymptomatic uterine fibroids was established. This model is useful for the early detection of potentially rapidly growing uterine fibroids in patients.

m6A modification patterns and tumor immune landscape in clear cell renal carcinoma.

BACKGROUND: Recent studies have focused on the correlation between N6-methyladenosine (m6A) modification and specific tumor-infiltrating immune cells. However, the potential roles of m6A modification in the tumor immune landscape remain elusive. METHODS: We comprehensively evaluated the m6A modification patterns and tumor immune landscape of 513 clear cell renal cell carcinoma (ccRCC) patients, and correlated the m6A modification patterns with the immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore. RESULTS: We identified three m6Aclusters-characterized by differences in Th17 signature, extent of intratumor heterogeneity, overall cell proliferation, aneuploidy, expression of immunomodulatory genes, overall somatic copy number alterations, and prognosis. The m6Ascore was established to quantify the m6A modification pattern of individual ccRCC patients. Further analyses revealed that the m6Ascore was an independent prognostic factor of ccRCC. Finally, we verified the prognostic value of the m6Ascore in the programmed cell death protein 1 (PD-1) blockade therapy of patients with advanced ccRCC. CONCLUSIONS: This study demonstrated the correlation between m6A modification and the tumor immune landscape in ccRCC. The comprehensive evaluation of m6A modification patterns in individual ccRCC patients enhances our understanding of the tumor immune landscape and provides a new approach toward new and improved immunotherapeutic strategies for ccRCC patients.

Immune-related biomarker risk score predicts prognosis in prostate cancer.

In this study, we constructed a model using a Cox proportional hazards model based on the expression of eight immune-related genes that were associated with prognosis in prostate cancer: EDNRB, ANGPTL2, TNFSF15, TNFRSF10D, EDN2, BMP2, NLRP14, and PLK1. We then identified associations between risk scores calculated with the model, tumor microenvironment characteristics, and immune cell infiltration. Prostate cancer patients in the high score group had poorer prognoses, and validation with the external GSE54460 dataset confirmed that the scoring model predicted biochemical recurrence with AUC values of 0.749 at 1 year, 0.804 at 3 years, and 0.774 at 5 years. Proportions of infiltrated M2 macrophages and regulatory T cells were increased in the high risk group, while CD8+ T cells were increased in the low risk group. Network analysis revealed that PLK1 may be a key regulator of the immune-suppressive microenvironment in prostate cancer. Double immunofluorescence labeling of a prostate cancer tissue microarray indicated that PLK1 expression correlated positively with numbers of infiltrating macrophages. These results indicate that an immune- related, gene-based risk score effectively reflects immune microenvironment characteristics and predicts prognosis in prostate cancer.

Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis.

BACKGROUND: Inflammation may play an important role in cancer progression, and a higher systemic immune-inflammation index (SII) has been reported to be a poor prognostic marker in several malignancies. However, the results of published studies are inconsistent. MATERIALS AND METHODS: A systematic review of databases was conducted to search for publications regarding the association between blood SII and clinical outcome in solid tumors with a date up to February 12, 2017. The primary outcome was overall survival (OS) and the secondary outcomes were progression-free survival (PFS) and cancer-specific survival (CSS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the strength of the association between blood SII and clinical outcome in solid tumors. RESULTS: A total of 15 articles were included in the analysis. Overall, systemic immune-inflammation index greater than the cutoff predicted poor overall survival (HR = 1.55, 95% CI = 1.27-1.88; P < 0.001). Subgroup analyses revealed that high systemic immune-inflammation index indicated a worse overall survival in hepatocellular carcinoma (P < 0.001), urinary cancers (P < 0.001), gastrointestinal tract cancers (P = 0.02), small cell lung cancer (P < 0.05) and acral melanoma (P < 0.001). Hazard ratio for systemic immune-inflammation index greater than the cutoff for cancer-specific survival was 1.44 (P < 0.05). CONCLUSIONS: Elevated systemic immune-inflammation index is associated with a worse overall survival in many solid tumors. The systemic-inflammation index can act as a powerful prognostic indicator of poor outcome in patients with solid tumors.

Association between APE1 Asp148Glu polymorphism and the risk of urinary cancers: a meta-analysis of 18 case-control studies.

BACKGROUND: Several observational studies suggested that APE1 Asp148Glu was significantly associated with urinary cancers; however, the results of published studies are inconsistent. MATERIALS AND METHODS: The PubMed and EMBASE were searched for case-control studies regarding the association between Asp148Glu and the risk of urinary cancers with a time limit of September 12, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between Asp148Glu and the risk of developing prostate cancer, kidney cancer, bladder cancer, as well as all urinary cancers combined. RESULTS: A total of 18 case-control studies were included in the analysis. Our meta-analysis revealed that the inheritance of at least one APE1 148Glu among Asian men was associated with a 1.26-fold increase in the risk of developing urinary cancers. Meanwhile, APE1 Asp148Glu was significantly associated with the risk of prostate cancer. However, there were no significant relationships between the APE1 SNP (single nucleotide polymorphism) and all urinary cancers combined and bladder cancer and kidney cancer among the men of Caucasian/Asian/African descent or all racial/ethnic groups combined. When stratified by the quality score, no significant association was found in high-quality studies (score ≥7), but a significant increased risk of urinary cancers was observed in lower quality studies (score <7) (dominant model: OR=1.27, 95% CI=1.11-1.45). CONCLUSION: Our meta-analysis suggests that APE1 Asp148Glu was not associated with the risk of urinary cancers but might increase the risk of urinary cancers among Asians. Stratification by cancer type identified a significant association of Asp148Glu with prostate cancer.

Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis.

To date, the results of studies exploring the relation between exonuclease 1 (Exo1) polymorphisms and cancer risks have differed. In this study, we performed a meta-analysis to investigate the effect of the three most extensively studied Exo1 polymorphisms (Pro757Leu, Glu589Lys, and Glu670Gly) on cancer susceptibility. The related studies published before August 5, 2015, were collected by searching the PubMed and EMBASE databases. We found 16 publications containing studies that were eligible for our study, including 10 studies for Pro757Leu polymorphism (4,093 cases and 3,834 controls), 12 studies for Glu589Lys polymorphism (6,479 cases and 6,550 controls), and 7 studies for Glu670Gly polymorphism (3,700 cases and 3,496 controls). Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations, and all the statistical analyses were calculated using the software program STATA version 12.0. Our results revealed that the Pro757Leu polymorphism was significantly associated with a reduced cancer risk, whereas an inverse association was found for the Glu589Lys polymorphism. Furthermore, subgroup analysis of smoking status indicated that the Glu589Lys polymorphism was significantly associated with an increased cancer risk in smokers, but not in nonsmokers. However, no evidence was found for an association between the Glu670Gly polymorphism and cancer risk. In conclusion, this meta-analysis suggests that the Pro757Leu polymorphism may provide protective effects against cancer, while the Glu589Lys polymorphism may be a risk factor for cancer. Moreover, the Glu670Gly polymorphism may have no influence on cancer susceptibility. In the future, large-scaled and well-designed studies are needed to achieve a more precise and comprehensive result.