Nevin Manimala

Aging Cell. 2022 Nov 3:e13730. doi: 10.1111/acel.13730. Online ahead of print.

ABSTRACT

Age-related diseases characteristic of post-reproductive life, aging, and life span are the examples of polygenic non-Mendelian traits with intricate genetic architectures. Polygenicity of these traits implies that multiple variants can impact their risks independently or jointly as combinations of specific variants. Here, we examined chances to live to older ages, 85 years and older, for carriers of compound genotypes comprised of combinations of genotypes of rs429358 (APOE ɛ4 encoding polymorphism), rs2075650 (TOMM40), and rs12721046 (APOC1) polymorphisms using data from four human studies. The choice of these polymorphisms was motivated by our prior results showing that the ɛ4 carriers having minor alleles of the other two polymorphisms were at exceptionally high risk of Alzheimer’s disease (AD), compared with non-carriers of the minor alleles. Consistent with our prior findings for AD, we show here that the adverse effect of the ɛ4 allele on survival to older ages is significantly higher in carriers of minor alleles of rs2075650 and/or rs12721046 polymorphisms compared with their non-carriers. The exclusion of AD cases made this effect stronger. Our results provide compelling evidence that AD does not mediate the associations of the same compound genotypes with chances to survive until older ages, indicating the existence of genetically heterogeneous mechanisms. The survival chances can be mainly associated with lipid- and immunity-related mechanisms, whereas the AD risk, can be driven by the AD-biomarker-related mechanism, among others. Targeting heterogeneous polygenic profiles of individuals at high risks of complex traits is promising for the translation of genetic discoveries to health care.

PMID:36330582 | DOI:10.1111/acel.13730

Arch Esp Urol. 2022 Oct;75(8):700-705. doi: 10.56434/j.arch.esp.urol.20227508.101.

ABSTRACT

OBJECTIVES: To evaluate the relationship between urine pH value and urodynamic parameters in patients with overactive bladder.

METHODS: The patients’ data whose underwent standard urodynamic study at two tertiary centers in our city. The period between January 2015-January 2021 was reviewed retrospectively. The inclusion criteria were the patients with overactive bladder, over 18 years of age, and with urine analysis before urodynamic study. Patients were divided into two groups as those with acidic urine pH (Group 1) and without (Group 2). The detrusor pressures obtained from filling cystometry were compared between the groups. In addition, the correlation between detrusor pressure and urine pH was examined.

RESULTS: The data from 211 patients (109 females, 102 males) were analyzed during the screening period. Eighty-two patients were in Group 1 and 129 patients in Group 2. The mean age was similar between the groups (p = 0.244). The bladder volume at first sensation of filling and urodynamic maximal bladder capacity was lower in Group 1 than Group 2 (p = 0.004; p < 0.001, respectively). The maximum detrusor pressure was higher in the acidic urine pH group (Group 1, 55.8 ± 20.6) than non-acidic urine pH group (Group 2, 14.5 ± 10.2), and it was statistically significant (p < 0.001). In addition, a significant negative correlation was observed between urine pH level and detrusor pressure (p < 0.001).

CONCLUSIONS: The presence of acidic urinalysis is associated with many urodynamic findings. Significantly, the patients with detrusor overactivity had more acidic urine than without detrusor overactivity. Therefore, for patients with high detrusor pressure, urinalysis should be evaluated carefully.

PMID:36330571 | DOI:10.56434/j.arch.esp.urol.20227508.101

Arch Esp Urol. 2022 Oct;75(8):693-699. doi: 10.56434/j.arch.esp.urol.20227508.100.

ABSTRACT

INTRODUCTION: Voiding urosonography (VUS) is a dynamic imaging technique which evaluates the lower urinary tract by introducing sonographic contrast into the bladder, preferably used in the diagnosis of vesicoureteral reflux (VUR). Our goals were to describe the clinical indications for performing a VUS for VUR’s diagnosis and analyse its diagnostic reliability.

MATERIAL AND METHODS: Cross-sectional study carried on patients under 15 years old with a VUS taken between November 2013-2020. Sex, age, indications (lower urinary tract infection-LUTI; dilatated lower urinary tract-DLUT; duplex collecting system-DCS), results (presence/absence of VUR, score and side) and complications were analysed. U Mann-Whitney and Chi-squared tests were used and 2 predictive capacity models for the indications used to detect VUR were employed (logistic binomial regression and multilayer perceptron neural network). Statistical significance p < 0.05.

RESULTS: 415 VUS were completed correctly (male 51.8%, median age 7.3 (3.1-15.3) months). Indications were: LUTI (67.5%), DLUT (33.5%) and DCS (10.2%); presenting 1, 2 and 3 indications in 86.5%, 12.8% and 0.7% respectively. VUR was diagnosed in 34.7% cases. A tendency towards statistically significance was showed related to male sex (p = 0.052) and the only significative clinical indication for VUR was DCS (p = 0.007). Patients with 2 simultaneous indications had higher probability of VUR (p = 0.012). DCS presence or male sex were the only predictive variables of VUR: DCS = OR 1.89 (1.54-6.52) (p = 0.006) and male sex = OR 1.56 (1.03-2.35) (p = 0.035).

CONCLUSIONS: VUS is a thriving technique, radiation free and with a low complications rate. Presence of DCS, male sex or 2 simultaneous indications for VUS increase the probability of presenting VUR.

PMID:36330570 | DOI:10.56434/j.arch.esp.urol.20227508.100

Front Oncol. 2022 Oct 18;12:931592. doi: 10.3389/fonc.2022.931592. eCollection 2022.

ABSTRACT

PURPOSE: To systematically assess the diagnostic performance of the Bosniak classification, version 2019 for risk stratification of cystic renal masses.

METHODS: We conducted an electronic literature search on Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar to identify relevant articles between June 1, 2019 and March 31, 2022 that used the Bosniak classification, version 2019 for risk stratification of cystic renal masses. Summary estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were pooled with the bivariate model and hierarchical summary receiver operating characteristic (HSROC) model. The quality of the included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

RESULTS: A total of eight studies comprising 720 patients were included. The pooled sensitivity and specificity were 0.85 (95% CI 0.79-0.90) and 0.68 (95% CI 0.58-0.76), respectively, for the class III/IV threshold, with a calculated area under the HSROC curve of 0.84 (95% CI 0.81-0.87). The pooled LR+, LR-, and DOR were 2.62 (95% CI 2.0-3.44), 0.22 (95% CI 0.16-0.32), and 11.7 (95% CI 6.8-20.0), respectively. The Higgins I ² statistics demonstrated substantial heterogeneity across studies, with an I ² of 57.8% for sensitivity and an I ² of 74.6% for specificity. In subgroup analyses, the pooled sensitivity and specificity for CT were 0.86 and 0.71, respectively, and those for MRI were 0.87 and 0.67, respectively. In five studies providing a head-to-head comparison between the two versions of the Bosniak classification, the 2019 version demonstrated significantly higher specificity (0.62 vs. 0.41, p < 0.001); however, it came at the cost of a significant decrease in sensitivity (0.88 vs. 0.94, p = 0.001).

CONCLUSIONS: The Bosniak classification, version 2019 demonstrated moderate sensitivity and specificity, and there was no difference in diagnostic accuracy between CT and MRI. Compared to version 2005, the Bosniak classification, version 2019 has the potential to significantly reduce overtreatment, but at the cost of a substantial decline in sensitivity.

PMID:36330503 | PMC:PMC9623069 | DOI:10.3389/fonc.2022.931592

Front Oncol. 2022 Oct 18;12:924961. doi: 10.3389/fonc.2022.924961. eCollection 2022.

ABSTRACT

We evaluated the impact of respiratory motion on the lung dose during linac-based intensity-modulated total marrow irradiation (IMTMI) using two different approaches: (1) measurement of doses within the lungs of an anthropomorphic phantom using thermoluminescent detectors (TLDs) and (2) treatment delivery measurements using ArcCHECK where gamma passing rates (GPRs) and the mean lung doses were calculated and compared with and without motion. In the first approach, respiratory motions were simulated using a programmable motion platform by using typical published peak-to-peak motion amplitudes of 5, 8, and 12 mm in the craniocaudal (CC) direction, denoted here as M1, M2, and M3, respectively, with 2 mm in both anteroposterior (AP) and lateral (LAT) directions. TLDs were placed in five selected locations in the lungs of a RANDO phantom. Average TLD measurements obtained with motion were normalized to those obtained with static phantom delivery. The mean dose ratios were 1.01 (0.98-1.03), 1.04 (1.01-1.09), and 1.08 (1.04-1.12) for respiratory motions M1, M2, and M3, respectively. To determine the impact of directional respiratory motion, we repeated the experiment with 5-, 8-, and 12-mm motion in the CC direction only. The differences in average TLD doses were less than 1% when compared with the M1, M2, and M3 motions indicating a minimal impact from CC motion on lung dose during IMTMI. In the second experimental approach, we evaluated extreme respiratory motion 15 mm excursion in only the CC direction. We placed an ArcCHECK device on a commercial motion platform and delivered the clinical IMTMI plans of five patients. We compared, with and without motion, the dose volume histograms (DVHs) and mean lung dose calculated with the ArcCHECK-3DVH tool as well as GPR with 3%, 5%, and 10% dose agreements and a 3-mm constant distance to agreement (DTA). GPR differed by 11.1 ± 2.1%, 3.8 ± 1.5%, and 0.1 ± 0.2% with dose agreement criteria of 3%, 5%, and 10%, respectively. This indicates that respiratory motion impacts dose distribution in small and isolated parts of the lungs. More importantly, the impact of respiratory motion on the mean lung dose, a critical indicator for toxicity in IMTMI, was not statistically significant (p > 0.05) based on the Student’s t-test. We conclude that most patients treated with IMTMI will have negligible dose uncertainty due to respiratory motion. This is particularly reassuring as lung toxicity is the main concern for future IMTMI dose escalation studies.

PMID:36330489 | PMC:PMC9622752 | DOI:10.3389/fonc.2022.924961

Front Oncol. 2022 Oct 18;12:975444. doi: 10.3389/fonc.2022.975444. eCollection 2022.

ABSTRACT

OBJECTIVE: To analyze the learning curve for robot- assisted radical cystectomy (RARC) with total intracorporeal urinary diversion (ICUD) in terms of both time efficiency and quality of surgery based on radical cystectomy (RC)-pentafecta.

PATIENTS AND METHODS: We identified 203 consecutive patients who underwent RARC with ICUD of the ileal conduit (IC, 85) and orthotopic neobladder (ONB, 118) performed by a single surgeon between 2011 and 2021. We grouped ten consecutive patients into time-associated blocks according to the operation order. Process efficiency and operation quality were measured based on the surgeon’s console time and attainment/score sum of RC-pentafecta. The overcoming point of the learning curve was defined graphically and statistically.

RESULTS: The mean follow-up period was 44.5 ± 30.7 months. Of the 203 patients, 109 (53.7%) attained the five criteria of RC-pentafecta (ONB vs IC, 50.6% vs. 55.9%, p = 0.35). The attainment rate and sum of the RC-pentafecta score of the third group were not significantly different from those of all patients (40.0% vs. 53.7%, p = 0.369, 4.00 ± 1.05 vs. 4.41 ± 0.75, p = 0.137, respectively), and the proficiency in operation quality was satisfactory in the third group. The console times continually improved and stabilized after the 140^th case (IC, 60; ONB, 80), and the attainment rate and sum of the RC-pentafecta were significantly different between before and after the 140^th case (p<0.001).

CONCLUSION: A single surgeon’s learning curve for RARC with ICUD and pelvic lymph node dissection (PLND) showed an acceptable level of proficiency after 30 consecutive cases in terms of the operation quality. However, for an expert surgeon, 140 cases were required to reach a plateau in time efficiency and second leap with the RC-pentafecta. RARC with ICUD and PLND can be performed safely without compromising functional outcomes and complications through sharing and transmission of standardized techniques.

PMID:36330475 | PMC:PMC9623051 | DOI:10.3389/fonc.2022.975444

Front Oncol. 2022 Oct 18;12:998159. doi: 10.3389/fonc.2022.998159. eCollection 2022.

ABSTRACT

BACKGROUND: Indocyanine green (ICG) imaging-guided lymphadenectomy has been introduced in gastric cancer (GC) surgery and its clinical value remains controversial. The aim of this study is to evaluate the efficacy of ICG fluorescence imaging-guided lymphadenectomy in radical gastrectomy for GC.

METHODS: Studies comparing lymphadenectomy in radical gastrectomy between use and non-use of ICG fluorescence imaging up to July 2022 were systematically searched from PubMed, Web of Science, Embase and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, the number of retrieved lymph nodes (LNs), the number of metastatic LNs and surgical outcomes as well as oncological outcomes. RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted.

RESULTS: 17 studies with a total of 2274 patients (1186 in the ICG group and 1088 in the control group) undergoing radical gastrectomy and lymphadenectomy were included. In the pooled analysis, the baseline features were basically comparable. However, the number of retrieved LNs in the ICG group was significantly more than that in the control group (MD = 7.41, 95% CI = 5.44 to 9.37, P < 0.00001). No significant difference was found between the ICG and control groups in terms of metastatic LNs (MD = -0.05, 95% CI = -0.25 to 0.16, P = 0.65). In addition, the use of ICG could reduce intraoperative blood loss (MD = -17.96, 95% CI = -27.89 to -8.04, P = 0.0004) without increasing operative time (P = 0.14) and overall complications (P = 0.10). In terms of oncological outcomes, the use of ICG could reduce the overall recurrence rate (OR = 0.50; 95% CI 0.28-0.89; P = 0.02) but could not increase the 2-year overall survival rate (OR = 1.25; 95% CI 0.72-2.18; P = 0.43).

CONCLUSIONS: ICG imaging-guided lymphadenectomy is valuable for complete LNs dissection in radical gastrectomy for GC. However, more high-quality randomized controlled trials are needed to confirm this benefit.

PMID:36330471 | PMC:PMC9623049 | DOI:10.3389/fonc.2022.998159

Kidney Res Clin Pract. 2022 Sep 14. doi: 10.23876/j.krcp.21.254. Online ahead of print.

ABSTRACT

BACKGROUND: The diagnosis of peritonitis among peritoneal dialysis (PD) patients is based on clinical presentation, dialysis effluent white blood cell (WBC) count, and dialysis effluent culture. Peritoneal fluid WBC count is very important in the initial diagnosis of peritonitis. The purpose of this work was to determine the optimal number of peritoneal WBCs with different clinical presentations at admission to define PD-related peritonitis.

METHODS: Medical records of chronic PD patients who underwent work-up for suspected peritonitis between 2008 and 2019 were reviewed retrospectively. Results of all peritoneal WBC count tests during this period were collected. Clinical manifestations and follow-up analysis of each peritoneal WBC count were performed.

RESULTS: The peritoneal WBC count cutoff of 100/μL recommended by International Society for Peritoneal Dialysis provided specificity of only 35%. Increasing peritoneal WBC count cutoff to 150, 200, and 250/μL provided sensitivity around 98% and gradually increasing specificity. The chi-square automatic interaction detector model of statistical analysis determined that peritoneal WBC count below 230/μL combined with absence of inflammatory markers (fever, increased C-reactive protein) ruled out peritonitis with 99.8% sensitivity. Peritoneal fluid WBC count cutoff of 230/μL provided specificity of 89% and good positive and negative likelihood scores of 8.3 and 0.03, respectively. Peritoneal fluid polymorphonuclear count has lower discriminating ability for peritonitis compared to peritoneal fluid WBC count.

CONCLUSION: Increasing peritoneal fluid WBC count cutoff to 230/μL in suspected PD-related peritonitis could improve specificity without compromising the sensitivity of the test.

PMID:36328997 | DOI:10.23876/j.krcp.21.254

Kidney Res Clin Pract. 2022 Sep 13. doi: 10.23876/j.krcp.22.039. Online ahead of print.

ABSTRACT

BACKGROUND: Many countries have their own hemodialysis (HD) quality assurance programs and star rating systems for HD facilities. However, the effects of HD quality assurance programs on patient mortality are not well understood. Therefore, in the present study, the effects of the Korean HD facility star rating on patient mortality in maintenance HD patients were evaluated.

METHODS: This longitudinal, observational cohort study included 35,271 patients receiving HD treatment from 741 facilities. The fivestar ratings of HD facilities were determined based on HD quality assessment data from 2015, which includes 12 quality measures in structural, procedural, and outcome domains. The patients were grouped into high (three to five stars) and low (one or two stars) groups based on HD facility star rating. Cox proportional hazards model was used to evaluate the effects of star rating on patient mortality during the mean follow-up duration of 3 years.

RESULTS: The patient ratio between high and low HD facility star rating groups was 82.0% vs. 18.0%. The patients in the low star rating group showed lower single-pool Kt/V and higher calcium and phosphorus levels compared with subjects in the high star rating group. After adjusting for sociodemographic and clinical parameters, the HD facility star rating independently increased the mortality risk (hazard ratio, 1.11; 95% confidence interval, 1.04-1.18; p = 0.002).

CONCLUSION: The HD facilities with low star rating showed higher patient mortality.

PMID:36328993 | DOI:10.23876/j.krcp.22.039

Kidney Res Clin Pract. 2022 Sep 8. doi: 10.23876/j.krcp.21.294. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have reported that depression is prevalent in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD).

METHODS: From the Korean National Health Insurance Service database, we selected 67,866 patients with DKD and body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. Weight change over 2 years was categorized into five groups: ≥-10%, <-10% to ≥-5%, <-5% to <5%, ≥5% to <10%, and ≥10%. The occurrence of depression was monitored via the codes of International Statistical Classification of Diseases, 10th revision through the end of 2018.

RESULTS: During the 5.24-year follow-up, 17,023 patients with DKD developed depression. Weight change and the risk of depression had a U-shaped relationship: patients with ≥-10% weight change (hazard ratio [HR], 1.12) and those with ≥10% weight change (HR, 1.11) showed higher HRs for depression than those with <-5% to <5% weight change, even after adjusting for several confounding factors. In the subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups.

CONCLUSION: Both weight loss and weight gain increased the risk of depression in patients with DKD.

PMID:36328992 | DOI:10.23876/j.krcp.21.294