Nevin Manimala

J Urol. 2022 Nov 16:101097JU0000000000003069. doi: 10.1097/JU.0000000000003069. Online ahead of print.

ABSTRACT

BACKGROUND: The sentinel reference for antibiotic prophylaxis for radical cystectomy with ileal conduit (RCIC) in the AUA Guidelines reports data from 2003-2013 and has not been updated in the interim. Here, we assess adherence to antibiotic prophylaxis guidelines among patients undergoing radical cystectomy with ileal conduit for bladder cancer using a large national database. As a secondary objective, we assess the association between antimicrobial use and post-operative infection during the index admission following cystectomy.

METHODS: Premier Healthcare Database was queried for all patients undergoing cystectomy with ileal conduit with diagnosis of bladder cancer between 2015 and 2020. Antibiotics used and the duration of use was determined by charge codes and grouped as guidelines-based or not according to 2019 AUA Guidelines. Association with infectious complications was assessed by logistic mixed effects regression models.

RESULTS: Among 6,708 patients undergoing cystectomy with ileal conduit, only 28% (1843/6708) were given prophylaxis according to AUA guidelines. 1.8% (121/6708) of patients received an antifungal, and 37% (2482/6708) received extended duration prophylaxis beyond postoperative day 1. Patients who received guidelines-based prophylaxis were less likely to be diagnosed with a UTI (21% vs 24%, P = .04), pyelonephritis (5.1% vs 7.7%, P<.001), bacterial infection (24% vs 27%, P = .03), or pneumonia (12% vs 17%, P<.001). There was no statistically significant difference in clostridium difficile infection between guidelines-based and non-guidelines-based prophylaxis (3.2% vs 3.7%, P = .32). In a multivariable logistic regression adjusting for age, race, insurance, and hospital and provider characteristics, non-guideline antibiotic prophylaxis (OR 1.27 [1.12, 1.43], P<.001) was associated with an increased odds of infectious events, whereas a robotic approach (OR 0.82 [0.73, 0.92], P<.001) was associated with lower odds.

CONCLUSION: 73% of patients fail to receive guideline-based antibiotic prophylaxis when undergoing radical cystectomy with conduit, which was largely driven by extended duration antibiotic use. Despite the shorter duration of antibiotics, we found that guideline-based prophylaxis was associated with a 25% decrease in the odds of infectious complications. While residual confounding is possible, these data support current AUA guidelines and suggest a need for outreach to improve guideline adherence.

PMID:36383758 | DOI:10.1097/JU.0000000000003069

Clin Chem Lab Med. 2022 Nov 17. doi: 10.1515/cclm-2022-1006. Online ahead of print.

ABSTRACT

OBJECTIVES: Early recognition and timely intervention for urosepsis are key to reducing morbidity and mortality. Blood culture has low sensitivity, and a long turnaround time makes meeting the needs of clinical diagnosis difficult. This study aimed to use biomarkers to build a machine learning model for early prediction of urosepsis.

METHODS: Through retrospective analysis, we screened 157 patients with urosepsis and 417 patients with urinary tract infection. Laboratory data of the study participants were collected, including data on biomarkers, such as procalcitonin, D-dimer, and C-reactive protein. We split the data into training (80%) and validation datasets (20%) and determined the average model prediction accuracy through cross-validation.

RESULTS: In total, 26 variables were initially screened and 18 were statistically significant. The influence of the 18 variables was sorted using three ranking methods to further determine the best combination of variables. The Gini importance ranking method was found to be suitable for variable filtering. The accuracy rates of the six machine learning models in predicting urosepsis were all higher than 80%, and the performance of the artificial neural network (ANN) was the best among all. When the ANN included the eight biomarkers with the highest influence ranking, its model had the best prediction performance, with an accuracy rate of 92.9% and an area under the receiver operating characteristic curve of 0.946.

CONCLUSIONS: Urosepsis can be predicted using only the top eight biomarkers determined by the ranking method. This data-driven predictive model will enable clinicians to make quick and accurate diagnoses.

PMID:36383696 | DOI:10.1515/cclm-2022-1006

PLoS One. 2022 Nov 16;17(11):e0277785. doi: 10.1371/journal.pone.0277785. eCollection 2022.

ABSTRACT

BACKGROUND: In many of the risk estimation algorithms for patients with ST-elevation myocardial infarction (STEMI), heart rate and systolic blood pressure are key predictors. Yet, these parameters may also be altered by the applied medical treatment / circulatory support without concomitant improvement in microcirculation. Therefore, we aimed to investigate whether venous lactate level, a well-known marker of microcirculatory failure, may have an added prognostic value on top of the conventional variables of the “Global Registry of Acute Coronary Events” (GRACE) 2.0 model for predicting 30-day all-cause mortality of STEMI patients treated with primary percutaneous coronary intervention (PCI).

METHODS: In a prospective single-center registry study conducted from May 2020 through April 2021, we analyzed data of 323 cases. Venous blood gas analysis was performed in all patients at admission. Nested logistic regression models were built using the GRACE 2.0 score alone (base model) and with the addition of venous lactate level (expanded model) with 30-day all-cause mortality as primary outcome measure. Difference in model performance was analyzed by the likelihood ratio (LR) test and the integrated discrimination improvement (IDI). Independence of the predictors was evaluated by the variance inflation factor (VIF). Discrimination and calibration was characterized by the c-statistic and calibration intercept / slope, respectively.

RESULTS: Addition of lactate level to the GRACE 2.0 score improved the predictions of 30-day mortality significantly as assessed by both LR test (LR Chi-square = 8.7967, p = 0.0030) and IDI (IDI = 0.0685, p = 0.0402), suggesting that the expanded model may have better predictive ability than the GRACE 2.0 score. Furthermore, the VIF was 1.1203, indicating that the measured lactate values were independent of the calculated GRACE 2.0 scores.

CONCLUSIONS: Our results suggest that admission venous lactate level and the GRACE 2.0 score may be independent and additive predictors of 30-day all-cause mortality of STEMI patients treated with primary PCI.

PMID:36383629 | DOI:10.1371/journal.pone.0277785

PLoS Genet. 2022 Nov 16;18(11):e1010464. doi: 10.1371/journal.pgen.1010464. eCollection 2022 Nov.

ABSTRACT

The identification and understanding of gene-environment interactions can provide insights into the pathways and mechanisms underlying complex diseases. However, testing for gene-environment interaction remains a challenge since a.) statistical power is often limited and b.) modeling of environmental effects is nontrivial and such model misspecifications can lead to false positive interaction findings. To address the lack of statistical power, recent methods aim to identify interactions on an aggregated level using, for example, polygenic risk scores. While this strategy can increase the power to detect interactions, identifying contributing genes and pathways is difficult based on these relatively global results. Here, we propose RITSS (Robust Interaction Testing using Sample Splitting), a gene-environment interaction testing framework for quantitative traits that is based on sample splitting and robust test statistics. RITSS can incorporate sets of genetic variants and/or multiple environmental factors. Based on the user’s choice of statistical/machine learning approaches, a screening step selects and combines potential interactions into scores with improved interpretability. In the testing step, the application of robust statistics minimizes the susceptibility to main effect misspecifications. Using extensive simulation studies, we demonstrate that RITSS controls the type 1 error rate in a wide range of scenarios, and we show how the screening strategy influences statistical power. In an application to lung function phenotypes and human height in the UK Biobank, RITSS identified highly significant interactions based on subcomponents of genetic risk scores. While the contributing single variant interaction signals are weak, our results indicate interaction patterns that result in strong aggregated effects, providing potential insights into underlying gene-environment interaction mechanisms.

PMID:36383614 | DOI:10.1371/journal.pgen.1010464

JAMA Netw Open. 2022 Nov 1;5(11):e2242240. doi: 10.1001/jamanetworkopen.2022.42240.

ABSTRACT

IMPORTANCE: Herpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk.

OBJECTIVE: To assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the early pandemic period (March 1, 2020, to November 30, 2020). Data were obtained from Optum Labs Data Warehouse, a US national deidentified claims-based database. A total of 2 039 854 individuals who received any dose of a COVID-19 vaccine with emergency use authorization (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], or Ad26.COV2.S [Johnson & Johnson]) from December 11, 2020, through June 30, 2021, were eligible for inclusion. Individuals included in the SCRI analysis were a subset of the COVID-19-vaccinated cohort who had herpes zoster during either a risk or control interval.

EXPOSURES: Any dose of a COVID-19 vaccine.

MAIN OUTCOMES AND MEASURES: Incident herpes zoster, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and a prescription of a new antiviral medication or a dose increase in antiviral medication within 5 days of diagnosis.

RESULTS: Among 2 039 854 individuals who received any dose of a COVID-19 vaccine during the study period, the mean (SD) age was 43.2 (16.3) years; 1 031 149 individuals (50.6%) were female, and 1 344 318 (65.9%) were White. Of those, 1451 patients (mean [SD] age, 51.6 [12.6] years; 845 [58.2%] female) with a herpes zoster diagnosis were included in the primary SCRI analysis. In the SCRI analysis, COVID-19 vaccination was not associated with an increased risk of herpes zoster after adjustment (incidence rate ratio, 0.91; 95% CI, 0.82-1.01; P = .08). In the supplementary cohort analysis, COVID-19 vaccination was not associated with a higher risk of herpes zoster compared with influenza vaccination in the prepandemic period (first dose of COVID-19 vaccine: hazard ratio [HR], 0.78 [95% CI, 0.70-0.86; P < .001]; second dose of COVID-19 vaccine: HR, 0.79 [95% CI, 0.71-0.88; P < .001]) or the early pandemic period (first dose of COVID-19 vaccine: HR, 0.89 [95% CI, 0.80-1.00; P = .05]; second dose: HR, 0.91 [95% CI, 0.81-1.02; P = .09]).

CONCLUSIONS AND RELEVANCE: In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.

PMID:36383382 | DOI:10.1001/jamanetworkopen.2022.42240

JAMA Netw Open. 2022 Nov 1;5(11):e2242378. doi: 10.1001/jamanetworkopen.2022.42378.

ABSTRACT

IMPORTANCE: Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches.

OBJECTIVE: To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020.

EXPOSURES: Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy.

MAIN OUTCOMES AND MEASURES: MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio.

RESULTS: Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44).

CONCLUSIONS AND RELEVANCE: Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

PMID:36383379 | DOI:10.1001/jamanetworkopen.2022.42378

Shock. 2022 Nov 17. doi: 10.1097/SHK.0000000000002035. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate and compare the clinical features and prognosis of chronic critical illness (CCI)/ persistent inflammation immunosuppression and catabolism (PICS).

METHODS: This is a prospective observational clinical study. During this study period, we collect ICU patients’ data from Suzhou Municipal Hospital and Suzhou Ninth People’s Hospital. All patients older than 18 years of age were included and according to the corresponding exclusion and diagnostic criteria, they were divided into four groups: PICS group, CCI group, CCI and PICS group (CCI + PICS), nor CCI and nor PICS group (NCCI+NPICS), collected and recorded age, sex, hospital time, hospital diagnosis, acute physiological and chronic health status score II (APACHEII), sequential organ failure detection score(SOFA), c-reactive protein (CRP), absolute value lymphocyte count (L), serum albumin (Alb), white cells count (WBC), absolute value neutrophils count (N), secondary infection and 28-day case fatality rate separately.

RESULTS: A total of 687 patients were admitted to the ICU during the study period. The hospitalization time less than 14 days were excluded, and 168 patients were eventually included. There are 17 in the PICS group, 71 in the CCI group, 50 in the CCI + PICS group, and 30 in the NCCI+NPICS group. Baseline characteristics showed statistically significant differences in SOFA, length of hospital stay, 28-day mortality among four groups. Baseline main indicator, and multiple comparisons showed that the CCI + PICS group had longer hospital stay, worse prognosis and more adverse outcomes. Multivariate analysis showed that final age, CRP on day 14 and 21, serum albumin on day 1 and 21 had an impact on the prognosis (P<0.05).

CONCLUSION: The clinical prognosis of the four groups decreased in order of NCCI+NPICS, CCI, PICS, CCI + PICS. Our finding of clinically isolated PICS may indicate that PICS acts as a inducement or independent factor to worsen the prognosis of CCI.

PMID:36383370 | DOI:10.1097/SHK.0000000000002035

Clin Oral Investig. 2022 Nov 16. doi: 10.1007/s00784-022-04779-1. Online ahead of print.

ABSTRACT

OBJECTIVES: Large part of the tooth is required to be removed during crown preparation. A minimally invasive method for preparing single crowns is required to increase the durability of teeth. The aim of this study was to evaluate the clinical performance of two ceramic systems fabricated with minimally invasive vertical preparation.

MATERIALS AND METHODS: Forty endodontically treated maxillary premolars were prepared with vertical preparation and received temporary crowns for a period of 21 days. Twenty zirconia-reinforced lithium silicate (Celtra Duo HT, Dentsply Sirona, Germany) and 20 monolithic high translucency zirconia (Katana HT, Kuarary Noritake, Japan) crowns were fabricated by CAD/CAM and cemented with dual-polymerizing luting resin. The crowns were evaluated clinically and radiographically for 36 months following modified FDI criteria. Statistical analysis was conducted with t Student test (Cochran Q).

RESULTS: Over the follow-up period, there was no need to replace any of the study’s crowns. The overall survival rate of the 40 crowns was 100% according to the Kaplan-Meier survival method. The clinical quality of all crowns and the patient’s satisfaction were high. No caries was detected and no adverse soft tissue reactions around the crowns were observed. Periodontal probing depth was reported to be increased at mesial and distal sites more than the facial one in the 36-month follow-up with no statistically significant difference between both materials (P = 0.186).

CONCLUSIONS: Zirconia and zirconia-reinforced lithium silicate could be used as a material for restoration of teeth prepared with vertical preparation technique. Both ceramic materials achieved good esthetic results, promotes healthy and stable soft tissues with no mechanical complications after 3 years of clinical evaluation.

CLINICAL RELEVANCE: Monolithic high translucency zirconia and zirconia-reinforced lithium silicate ceramics can be used for the restorations of minimal invasive vertical preparation in premolar area with 0.5 mm margin thickness.

PMID:36383297 | DOI:10.1007/s00784-022-04779-1

Eur J Pediatr. 2022 Nov 16. doi: 10.1007/s00431-022-04710-6. Online ahead of print.

ABSTRACT

The purpose of this study is to compare group B Streptococcus (GBS) infection incidence in HIV-exposed uninfected (HEU) and HIV-unexposed (HU) infants in a Spanish cohort. We conducted a retrospective study in 5 hospitals in Madrid (Spain). Infants ≤ 90 days of life with a GBS infection were included from January 2008 to December 2017. Incidence of GBS infection in HEU and HU children was compared. HEU infants presented a sevenfold greater risk of GBS infection and a 29-fold greater risk of GBS meningitis compared to HU, with statistical significance. Early-onset infection was tenfold more frequent in HEU children, with statistical significance, and late-onset infection was almost fivefold more frequent in the HUE infants’ group, without statistical significance.

CONCLUSION: HEU infants presented an increased risk of GBS sepsis and meningitis. One in each 500 HEU infants of our cohort had a central nervous system infection and 1 in each 200, a GBS infection. Although etiological causes are not well understood, this should be taken into account by physicians when attending this population.

WHAT IS KNOWN: • HIV-exposed uninfected infants are at higher risk of severe infections. • An increased susceptibility of these infants to group B Streptococcus infections has been described in low- and high-income countries, including a higher risk of meningitis in a South African cohort.

WHAT IS NEW: • Group B Streptococcal meningitis is more frequent in HIV-exposed uninfected infants also in high-income countries. • Physicians should be aware of this increased risk when attending these infants.

PMID:36383285 | DOI:10.1007/s00431-022-04710-6

J Robot Surg. 2022 Nov 16. doi: 10.1007/s11701-022-01482-x. Online ahead of print.

ABSTRACT

Robotic-assisted perineal prostatactomy(RAPP) is a new alternative surgical technique, in prostate cancer patients especially with a history of intra-abdominal surgery. The aim of this study is to examine the effects of the challenging patient position and CO₂ insufflation in perineal space during RAPP on both hemodynamic parameters and respiratory mechanics. Hemodynamic and respiratory parameters of 30 patients who underwent RAPP and 31 patients who underwent Robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer between 2017 and 2019 were retrospectively evaluated. Comparison between RAPP and RALP patients showed that anesthesia, surgery and insufflation times were shorter in RAPP patients (p < 0.05). Blood pCO₂ level was higher, and the pH decrease was more prominent in the RAPP patients 30 and 60 min after perineal CO₂ insufflation (p < 0.05). The mean arterial pressures, driving pressure, Ppeak and Pplato values were statistically higher in the RALP patients and 60 min after insufflation while static and dynamic lung compliance values were found to be lower. Our results showed that blood pCO₂ level may severely increase after perineal CO₂ insufflation. The fact that respiratory mechanics are less affected despite the difficult patient position for lungs in RAPP patients, the presence of higher CO₂ level supports that the perineal CO₂ insufflation plays a more important role in increased CO₂ level. Considering these changes, especially the sudden increase in the risk of CO₂ level, close follow-up and timely intervention by anesthesiology can ensure all changes remain in a clinically safe range.

PMID:36383279 | DOI:10.1007/s11701-022-01482-x