Kaplan-Meier Survival Estimates Research Articles

MP56-04 CONTEMPORARY ONCOLOGIC, FUNCTIONAL, AND COMPLICATIONS OUTCOMES OF ROBOT-ASSISTED RADICAL CYSTECTOMY WITH TOTALLY INTRACORPOREAL NEOBLADDER DIVERSION

MP56-04 CONTEMPORARY ONCOLOGIC, FUNCTIONAL, AND COMPLICATIONS OUTCOMES OF ROBOT-ASSISTED RADICAL CYSTECTOMY WITH TOTALLY INTRACORPOREAL NEOBLADDER DIVERSION

PD27-11 COMPARISON OF PROSTATE BIOPSY GRADE OBTAINED BY HUMAN PATHOLOGISTS VERSUS AN ARTIFICIAL INTELLIGENCE ALGORITHM FOR PREDICTING BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023PD27-11 COMPARISON OF PROSTATE BIOPSY GRADE OBTAINED BY HUMAN PATHOLOGISTS VERSUS AN ARTIFICIAL INTELLIGENCE ALGORITHM FOR PREDICTING BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY Claire de la Calle, Thiago Vidotto, Eric Erak, Daniela Salles, Oluwademilade Dairo, Christian Pavlovich, Misop Han, Joonyoung Cho, In Hye Suh, Hye Yoon Chang, Sun Woo Kim, Michael Gorin, and Tamara Lotan Claire de la CalleClaire de la Calle More articles by this author , Thiago VidottoThiago Vidotto More articles by this author , Eric ErakEric Erak More articles by this author , Daniela SallesDaniela Salles More articles by this author , Oluwademilade DairoOluwademilade Dairo More articles by this author , Christian PavlovichChristian Pavlovich More articles by this author , Misop HanMisop Han More articles by this author , Joonyoung ChoJoonyoung Cho More articles by this author , In Hye SuhIn Hye Suh More articles by this author , Hye Yoon ChangHye Yoon Chang More articles by this author , Sun Woo KimSun Woo Kim More articles by this author , Michael GorinMichael Gorin More articles by this author , and Tamara LotanTamara Lotan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003305.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Several artificial intelligence (AI) algorithms have been developed to streamline biopsy Gleason grading, but most have not been challenged with predicting oncologic outcomes. In this study, we leveraged a cohort of patients with biopsy-detected Grade Group (GG) 2 prostate cancer (PCa) and examined the association of biopsy grade by contemporary pathologist consensus grade or AI algorithm with time to biochemical recurrence (BCR) after radical prostatectomy (RP). METHODS: We identified 286 patients originally diagnosed with GG2 PCa on biopsy who underwent RP at our institution from 2000 to 2014. All biopsies were re-graded by two expert genitourinary pathologists (pathologist 1 and 2). For cases with discrepant reads, a third expert genitourinary pathologist determined the consensus pathology read. GG was also obtained using a previously validated and published AI algorithm. Concordance between pathologist and AI GG was quantified using the quadratic kappa. BCR was defined as two consecutive PSAs ≥0.2 ng/mL. Kaplan-Meier BCR free survival estimates by GG were compared using the log-rank test. RESULTS: After RP median follow-up was 4 years (range 1-14). To date, 16% of the men have had BCR and median time to BCR was 2 years (range 1-10). Biopsy grading between pathologist 1 and 2 generated a kappa of 0.17. Grading between the consensus pathology read and the AI algorithm generated a kappa of 0.33. Grading by consensus pathology read was associated with time to BCR-free survival (log-rank p=0.003) as was the grading by the AI algorithm (log-rank p=0.004; Figure 1). CONCLUSIONS: The AI algorithm Gleason grading demonstrated poor agreement with the consensus contemporary pathology read, but the agreement was also poor between the two pathologists. Yet, our cohort was only comprised of men originally diagnosed with GG2 PCa, a GG usually associated with poor inter-pathologist agreement. Remarkably, both the consensus pathology and the AI algorithm grades on the biopsy stratified patients well for subsequent BCR after RP, suggesting that AI algorithms could be developed to stratify for oncologic outcomes instead of attempting to replicate somewhat subjective human grading. Source of Funding: Research funding from Deep Bio © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e746 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claire de la Calle More articles by this author Thiago Vidotto More articles by this author Eric Erak More articles by this author Daniela Salles More articles by this author Oluwademilade Dairo More articles by this author Christian Pavlovich More articles by this author Misop Han More articles by this author Joonyoung Cho More articles by this author In Hye Suh More articles by this author Hye Yoon Chang More articles by this author Sun Woo Kim More articles by this author Michael Gorin More articles by this author Tamara Lotan More articles by this author Expand All Advertisement PDF downloadLoading ...

Moving Beyond Amyloid in Alzheimer's Therapeutics

Moving Beyond Amyloid in Alzheimer's Therapeutics

An investigation of the primary immunosuppressive therapy's influence on kidney transplant survival at one month after transplantation

Immunosuppressive therapy is complex and challenging to do correctly due to on-target and off-target side effects. However, it is vital to successful allotransplantation. In this article, we analyzed the critical classes of immunosuppressants used in renal transplantation, highlighting the mechanisms of action and typical clinical applications used to develop predictive models for the diagnosis of various diseases, including the prediction of survival after kidney transplantation. In patients, the authors used a dataset with two immunosuppressants (tacrolimus and cyclosporin). The primary task was investigating critical risk factors associated with early transplant rejection. For this, the censored Kaplan-Meier survival estimation method was used. Our study shows a pairwise correlation between taking and not using a particular immunosuppressant. Therefore, the correct choice of immunosuppressive drugs is necessary to improve the prognosis of transplant survival.

CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation.

Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1-99.7), 72.7% (95% CI 63.4-83.4), 48.0% (95% CI 41.2-56.0), and 16% (95% CI 11-23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0-2.8), III (HR 3.32; 95% CI 2.07-5.31), and IV (HR 7.44; 95% CI 4.61-12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant. The proposed independently validated staging system uses nonhistopathologic data to successfully stratify patients into 4 stages. This staging system has better prognostic accuracy compared with the TNM staging and can assist physicians and patients in treatment of iCCA.

Efficacy of Prolonged-release Tacrolimus After Conversion From Immediate-release Tacrolimus in Kidney Transplantation: A Retrospective Analysis of Long-term Outcomes From the ADMIRAD Study.

A retrospective, noninterventional chart review study examined long-term graft survival in adult kidney transplant participants in the Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograf to Advagraf (ADMIRAD) clinical trial at 4 Belgian sites. Patients were randomized to receive once-daily PRT or twice-daily IRT for 6 mo, followed by treatment as per real-world clinical practice. Data were collected retrospectively from randomization day until December 31, 2018. Primary endpoints included efficacy failure, defined as a composite endpoint of graft loss, biopsy-confirmed acute rejection, and graft dysfunction. Secondary endpoints included overall patient survival and course of kidney function. This analysis included 78.5% of patients from ADMIRAD (n = 108 PRT; n = 64 IRT). The Kaplan-Meier survival rate without efficacy failure from randomization to year 5 was 0.741 (95% confidence interval [CI]: 0.647, 0.813) for the PRT group (n = 80), and 0.667 (95% CI: 0.536, 0.768) for the IRT group (n = 42) and remained higher for PRT throughout 10 y follow-up (P = 0.041). The Kaplan-Meier estimate of overall survival from the time of last transplant was 0.981 (95% CI: 0.928, 0.995) and 0.880 (95% CI: 0.802, 0.928) at 5 and 10 y in the PRT group. Kidney function parameters and tacrolimus trough levels remained stable over the follow-up period. Patients in the ADMIRAD study who received PRT for up to 10 y had improved long-term outcomes compared with patients receiving IRT, with a consistent effect on both graft and patient survival.

Transcatheter Aortic Valve Replacement Outcomes in End-Stage Renal Disease Patients on Hemodialysis Requiring Midodrine

BackgroundPatients with dialysis-dependent end-stage renal disease (ESRD) taking midodrine may be at high risk for poor outcomes following transcatheter aortic valve replacement (TAVR). We evaluated dialysis-dependent ESRD patients taking midodrine. MethodsWe conducted a retrospective analysis of non-clinical trial TAVR patients from February 2012 to December 2020 from 11 facilities in a Western US health system. Patient groups included ESRD patients on midodrine before TAVR (ESRD [+M]), ESRD patients without midodrine (ESRD [−M]), and non-ESRD patients. The endpoints of 30-day and 1-year mortality were represented by Kaplan–Meier survival estimator and compared by log-rank test. ResultsForty-five ESRD (+M), 216 ESRD (−M), and 6898 non-ESRD patients were included. ESRD patients had more comorbid conditions, despite no significant difference in predicted Society of Thoracic Surgeons mortality risk between ESRD (+M) and ESRD (−M) (8.7% vs. 9.2%, p = 0.491). Thirty-day mortality was significantly higher for ESRD (+M) patients vs. ESRD (−M) patients (20.1% vs. 5.6%, p = 0.001) and for ESRD (+M) vs. non-ESRD patients (2.5%, p < 0.001). One-year mortality trended higher for ESRD (+M) vs. ESRD (−M) patients (41.9% vs. 29.8%, p = 0.07), and was significantly higher for ESRD (+M) vs. non-ESRD patients (10.7%, p < 0.001). Compared to ESRD (−M), ESRD (+M) patients had a higher incidence of 30-day stroke (6.7% vs. 1.4%, p = 0.033), 30-day vascular complications (6.7% vs. 0.9%, p = 0.011), and a lower rate of discharge to home (62.2% vs. 84.7%, p < 0.001). In contrast, ESRD (−M) patients had no significant differences from non-ESRD patients for these outcomes. ConclusionsOur experience suggests ESRD patients on midodrine are a higher acuity population with worse survival after TAVR, compared to ESRD patients not on midodrine. These findings may help with risk stratification for ESRD patients undergoing TAVR.

Does care fragmentation in patients with bladder cancer lead to worse outcomes?

Care fragmentation may influence oncologic outcomes. The impact of care fragmentation on the outcomes of patients receiving neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is not well defined. We aimed to compare outcomes between patients who received fragmented care (FC) versus non-fragmented care (NFC). The National Cancer Database was queried for adult (≥18 years old) patients with cT2-T4aN0M0 urothelial carcinoma of the bladder receiving NAC followed by RC between 2004 and 2017. Patients were dichotomized based on whether they received FC (defined as receiving NAC at a different facility from where RC was performed) or NFC (defined as receiving NAC and RC at a single facility). The main outcome of interest was overall survival (OS). Secondary outcomes included time from diagnosis to treatment (NAC and RC) and perioperative outcomes. Kaplan-Meier survival estimates were calculated after stratifying by type of care received. Multivariable Cox regression analysis was performed to evaluate the association between FC and OS in the context of other clinically relevant covariates. A total of 2223 patients were included: 1035 (46.6%) received FC whereas 1188 (53.4%) received NFC. Factors associated with FC included greater travel distance, higher comorbidity burden, and surgical treatment at a high-volume facility. Patients who received FC had a slightly longer median time to RC (160 vs. 154 days, P = 0.001). However, on Kaplan-Meier analysis no differences in median OS were found between the two groups. On multivariable Cox regression analysis, factors associated with worse OS included age, advanced TNM stage, lymphovascular invasion, and positive surgical margins; yet FC was not associated with worse OS (hazard ratio [HR] 1.02; 95% confidence interval [CI] 0.88-1.17). On subgroup analysis, we found that FC received at academic facilities (HR 0.76; 95% CI 0.58-0.99), as well as NFC received at high-volume centers (HR 0.65; 95% CI 0.43-0.98), were associated with a decrease in overall mortality. Fragmented care is not associated with worse survival outcomes in patients with MIBC receiving NAC followed by RC.

Association Between Obesity and Outcomes Following Endovascular Aneurysm Repair

Obesity is prevalent in patients with abdominal aortic aneurysms (AAA). There is an association between increasing body mass index (BMI) and increased overall cardiovascular mortality and morbidity. This study aims to assess the difference in mortality and complication rates between normal weight (NW), overweight (OW), and obese patients undergoing endovascular aneurysm repair (EVAR) for infrarenal AAA. This is a retrospective analysis of consecutive patients undergoing EVAR for AAA between January 1998 and December 2019. Weight classes were defined as: BMI<18.5kg/m2, underweight; BMI 18.5-24.9kg/m2, NW; BMI 25.0-29.9kg/m2, OW; BMI 30.0-39.9kg/m2, obese; BMI>39.9kg/m2 morbidly obese. Primary outcomes were long-term all-cause mortality and freedom from reintervention. Secondary outcome was aneurysm sac regression (defined as a reduction in sac diameter of 5mm or more). Kaplan-Meier survival estimates and mixed model analysis of variance were used. The study included 515 patients (83% males, mean age 77±8years) with a mean follow-up of 3.8±2.8years. In terms of weight class, 2.1% (n=11) were underweight, 32.4% (167) were NW, 41.6% (n=214) were OW, 21.2% (n=109) were obese, and 2.7% (n=14) were morbidly obese. Obese patients were younger (mean difference -5.0years) but had a higher prevalence of diabetes mellitus (33.3% vs. 10.6% for NW) and dyslipidemia (82.4% vs. 60.9% for NW). Obese patients had similar freedom from all-cause mortality (88%) compared to OW (78%) and NW (81%) patients. The same findings were evident for freedom from reintervention where obese (79%) was similar to OW (76%) and NW (79%). At a mean follow-up of 5.1±0.4years, sac regression was observed similarly across weight classes at 49.6%, 50.6%, and 51.8% for NW, OW, and obese, respectively (P=0.501). There was a significant difference in mean AAA diameter pre- and post-EVAR [F(2,318)=24.37, P<0.001] across weight classes. NW [mean reduction 4.8mm (2.0-7.6mm, P<0.001)], OW [mean reduction 3.9mm (1.5-6.3mm, P<0.001)], and obese [mean reduction 5.7mm (2.3-9.1mm, P<0.001)] achieved similar reductions. Obesity was not associated with increased mortality or reintervention in patients undergoing EVAR. Obese patients achieved similar rates of sac regression on imaging follow-up.

Repetition of Paclitaxel-Coated Devices for the Treatment of Lower Extremity Artery Disease: Mortality Outcomes and Predictors.

A recent meta-analysis reported late excess mortality in patients treated with paclitaxel-coated devices (PCDs) for symptomatic femoropopliteal disease. However, this finding is controversial. To investigate the impact on mortality and predictors of repeat exposure to PCDs in patients with lower extremity peripheral arterial disease (LE-PAD). We analyzed registry patient-level data from two centers. A total of 214 patients were enrolled, and stratified based on terciles of cumulative dose of paclitaxel. We treated 134 patients with a single PCD exposure and 80 with multiple PCD exposures. We used the follow-up index (FUI) in Kaplan-Meier survival estimates to minimize potential selection bias. We used Cox proportional hazard and splines models to determine the predictors of mortality and assess their relationships with mortality. The mean cumulative dose of paclitaxel was significantly different among groups (6.40 mg vs. 15.06 mg vs. 38.57 mg, p < 0.001). The 5-year FUI (0.93 ± 0.19 vs. 0.94 ± 0.18 vs. 0.95 ± 0.15, p = 0.836) and survival rates were not different (65.4% vs. 51.9% vs. 72.0%, p = 0.148). There was no dose-response association between paclitaxel dosage and death (p = 0.297). The predictors of death were congestive heart failure, stroke, dialysis dependence, neutrophil-lymphocyte ratio (NLR) > 3, age > 71 years, and body mass index (BMI) < 20 kg/m2. Spline model analysis validated the non-linear associations between mortality, age, BMI, and NLR. Repeated PCD exposure for LE-PAD did not result in excess late mortality. Predictors of mortality might change over time, and continuous variables had non-linear relationships with death.

'Get Data Out' Skin: national cancer registry incidence and survival rates for all registered skin tumour groups for2013-2019 in England.

Providing detailed skin cancer statistics, including incidence and survival, by tumour type and patient characteristics is important for up-to-date epidemiological information. To create a new clinically relevant consensus-based classification for registered skin tumours using tumour type and patient characteristics and to describe its application to all registered tumours in England between 2013 and 2019. Tumours with skin topographical codes (ICD-10) and morphology and behaviour (ICD-O3) were grouped together in an iterative process creating a hierarchical tree structure. The primary-level grouping partitioned skin tumours into skin cancer, melanoma in situ, extramammary Paget disease (EMPD) and tumours of uncertain malignant potential. Second-level groups splitskin cancer into keratinocyte cancer (KC), melanoma and rare cancers. The third-level group splitKC into basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC). Further groups were split intogenital or non-genital, first or subsequent tumour, age, gender, stage, orNational Health Service(NHS)region. Incidence counts, Kaplan-Meier and net survival estimates and referral routes [two-week wait (TWW), general practitioner (GP), outpatient] categorisations were calculated for each grouping across all years. A total of 1 445 377 skin cancers and 49 123 precancerous lesions and undefined entities were registered in England between 2013 and 2019. Skin tumours and skin cancer incidence rates are increasing for most tumour types. The most common type of skin cancer was BCC with an incidence rate of 282.36 per 100 000 person-years (PYs) [n = 158 934, 95% confidence interval (CI) 280.98-283.76] in 2019, followed by cSCC with an incidence rate of 85.24 per 100 000 PYs (n = 47 977, 95% CI 84.48-86.00) and melanoma with 27.24 (n = 15 332, 95% CI 26.81-27.67) per 100 000 PYs. Each year approximately 1800 rare skin cancers, 1500 genital cSCCs and 100 cases of EMPD are registered. Of 15 000 melanoma cases, 120 cases of melanoma occur in individuals aged < 25 years annually. One-year and five-year overall net survival varies by tumour type. cSCC 5-year net survival (89.8%, 95% CI 88.8-90.9) was comparable to the net survival of all melanomas (89.6%, 95% CI 88.7-90.6). BCC had excellent survival (overall net survival > 100%). Patients with late-stage melanoma, Merkel cell carcinoma and genital cSCC have a 5-year net survival < 60%. Older patients received fewer TWW referrals than their younger counterparts with the same tumour type at the same location. Patients with acral lentiginous melanoma had fewer TWW referrals and more standard GP referrals than patients with common melanomas. 'Get Data Out' Skin provides detailed and up-to-date statistics on all registrable skin tumours in England, including for the first time precancerous lesions and rare subtypes of common cancers. These data can be used by clinicians, researchers and commissioners to better understand skin cancer and improve resource allocation.

Incidence and Risk Factor of Implant Dislocation After Cervical Disk Arthroplasty: A Retrospective Cohort Analysis of 756 Patients.

Implant dislocation after cervical disk arthroplasty (CDA) is obviously a critical complication, but no information about the incidence and associated risk factor has been reported. To investigate the incidence and risk factor of implant dislocation after CDA by a retrospective cohort analysis. A retrospective review of a consecutive series of CDA performed between January 2009 and March 2021 at a single institution was conducted. Analyses of chart records and radiological data established the incidence and associated risk factor of implant dislocation after CDA. A Kaplan-Meier survival estimation of implant survival was performed. A total of 756 consecutive patients were included in this analysis. Five patients (0.7%) had a migration and even dropout of the artificial disk. The overall cumulative survival rate of the implant reached approximately 99.3% of the 756 patients. Preoperative kyphosis was significantly related to implant dislocation ( P = .016), with an odds ratio of 15.013. The incidence of implant dislocation after CDA is as low as 0.7% or 5/756 patients. Preoperative kyphosis significantly increases the risk of postoperative implant dislocation by a factor of 15. The migrating implants could be revealed on radiographs as early as 0.9 to 1.4 months postoperatively and were revised to anterior cervical diskectomy and fusion within half a year. No new event of implant dislocation occurred half a year postoperatively. The overall cumulative survival rate of the implant reached 99.3% of the 756 patients. In conclusion, CDA remains a safe and reliable procedure.

Early Reduction in C-Reactive Protein Following Treatment for Spinal Epidural Abscess: A Potential Treatment Guide.

Retrospective Cohort Study. To assess the predictive value of early C-reactive protein (CRP) trends following diagnosis of spinal epidural abscess (SEA). Non-operative management with intravenous antibiotics has not demonstrated equivalent outcomes with regard to mortality and morbidity. Knowledge of specific patient and disease factors associated with worse outcomes may predict treatment failure. All patients treated for spontaneous SEA in a tertiary centre in New Zealand over a 10-year period were followed for at least 2years. CRP at diagnosis and day 4-5 following treatment initiation was analyzed to determine predictors of CRP reduction of at least 50%. Proportional Cox hazards regression investigated mortality over 2years. 94 patients met inclusion criteria and with CRP values available for analysis. Median age was 62years (+/- 17.7) and 59 (63%) were treated operatively. Kaplan-Meier analysis estimate of 2-year survival was .81 (95% CI .72-.88). CRP reduction by 50% was seen in 34 patients. Patients who did not experience a 50% reduction were more likely to have thoracic infection (27 vs 8, P = .02) or multifocal sepsis (41 vs 13, P = .002). Failure to achieve a 50% reduction by day 4-5 was associated with worse post-treatment Karnofsky scores (70 vs 90, P = .03) and longer hospital stay (25days vs 17.5days, P = .04). Cox regression model showed mortality predicted by Charlson Comorbidity Index, thoracic location of infection, pre-treatment Karnofsky score, and failure to achieve a 50% CRP reduction by day 4-5. Patients who fail to reduce CRP values by 50% at day 4-5 following treatment initiation are more likely to experience prolonged hospital stay, have poorer functional outcome and have greater mortality risk at 2years. This group has severe illness regardless of treatment type. Failure to achieve a biochemical response to treatment should prompt reassessment.

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

BackgroundDomesticated animals play a role in maintaining residual transmission of Plasmodium parasites of humans, by offering alternative blood meal sources for malaria vectors to survive on. However, the blood of animals treated with veterinary formulations of the anti-helminthic drug ivermectin can have an insecticidal effect on adult malaria vector mosquitoes. This study therefore assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure.MethodsEight head of a local breed of cattle were randomly assigned to either one of two treatment arms (2 × 2 cattle injected with one of two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg), or one of two control arms (2 × 2 cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3–5-day-old Anopheles coluzzii mosquitoes through direct skin-feeding assays, from 1 to 210 days after treatment. The efficacy of each formulation was evaluated and compared using Cox proportional hazards survival models, Kaplan–Meier survival estimates, and log-logistic regression on cumulative mortality.ResultsBoth formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (hazard ratio > 1). The treatments significantly reduced mosquito survival, with average median survival time of 4–5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC50) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations.ConclusionsThis long-lasting formulation of ivermectin injected in cattle could complement insecticide-treated nets by suppressing field populations of zoophagic mosquitoes that are responsible, at least in part, for residual malaria transmission. The impact of this approach will of course depend on the field epidemiological context. Complementary studies will be necessary to characterize ivermectin withdrawal times and potential environmental toxicity.Graphical

Outcomes of Transcatheter Aortic Valve Replacement in Patients With Concomitant Aortic Regurgitation

BackgroundThis study sought to evaluate outcomes of transcatheter aortic valve replacement (TAVR) in patients with moderate or greater aortic regurgitation (AR). MethodsThis was an observational study using an institutional database of TAVRs from November 2012 to April 2022. The study compared outcomes of TAVR in patients with isolated aortic stenosis (AS) vs patients with AS and concomitant AR (moderate or greater). Those patients with trace or mild AR were excluded. Clinical and echocardiographic outcomes were compared, with end points established by the Valve Academic Research Consortium 3. Kaplan-Meier survival estimation and Cox regression for mortality were performed. Competing-risk cumulative incidence estimates for heart failure readmissions were also compared. ResultsOf 3295 patients, 605 (53.4%) had severe AS with no AR and 529 (46.6%) had severe AS with moderate or severe AR. There were no significant differences in in-hospital mortality, length of stay, stroke, myocardial infarction, permanent pacemaker requirement, transfusion requirement, minor or major vascular complications, or 30-day readmissions between the 2 groups (P > .05). There were also no significant differences in annular dissection or rupture, coronary obstruction, or device embolization. Mean gradient and paravalvular leak rates at 30 days and 1 year were similar between the groups. Survival estimates were comparable, and, on multivariable Cox regression, mixed aortic valvular disease was not associated with an increased hazard of death as compared with isolated AS (hazard ratio, 1.01; 95% CI, 0.81-1.25; P = .962). Cumulative incidence estimates for heart failure readmissions were comparable between groups. ConclusionsTAVR can be safely performed in patients with mixed valvular disease, with outcomes comparable to those in isolated AS.

Long-Term Survival and Predictors of Failure of Opening Wedge High Tibial Osteotomy.

High tibial valgus osteotomy (HTO) is a widely accepted procedure indicated for varus knee with symptomatic osteoarthritis of the medial compartment. However, there is a lack of studies evaluating long term results of this procedure. The primary aim of this study was to evaluate the long-term survival of opening wedge high tibial osteotomy (HTO) for isolated osteoarthritis in the medial compartment of the knee. The secondary objective was to identify independent predictors of conversion to total knee arthroplasty (TKA). This is a long term retrospective study of 296 cases of open wedge HTOs performed at a single center (level of evidence IV) between January 2005 and August 2015. Opening wedge medial HTO was always performed after diagnostic arthroscopy. Eighty-three percent of the population (233 patients, 247 procedures) was followed up at a mean 11.6 years (6-17) by telephone interview, to evaluate the possible conversion to TKA. Mean age at the index operation was 42.8 years (range 15-70) and most patients were male (70%). Associated procedures (e.g., platelet rich plasma supplementation, microfractures, meniscectomy, etc.) were carried out at the time of the HTO in 80 (32%) cases. Survival of HTO and its association with age, sex, body mass index, smoking habit, preoperative severity of varus deformity, cartilage status at surgery, and associated procedures were evaluated. Kaplan-Meier and Cox regression analyses were performed. Thirty-three of the 247 HTOs (13.4%) were converted to knee replacement, with 86.6% of the original procedures surviving at a mean 12-year follow-up. Kaplan-Meier survival estimates at 17 years for HTO were 75.5% (95% confidence interval [CI] 66.7-84.3). There was significant difference (P < 0.001) in the 17-year survival rate between obese (55.5%; 95% CI 35.3-75.6) and non-obese (79.7%; 95% CI 70.1-89.2) patients. The determinants of conversion to knee arthroplasty detected at multivariate Cox regression analysis were body mass index, severity of cartilage degeneration in the medial compartment (Outerbridge grade), and age. The long-term survival of open wedge HTO for osteoarthritis in the medial compartment of the knee is satisfactory. The risk of conversion to TKA is significantly increased in obese patients. Advanced age and severity of pre-existing cartilage damage may also contribute to the risk of conversion to TKA.

Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial

PurposeThe natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. Methods1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. ResultsMedian follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77). ConclusionsThe risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer.

Hematopoietic stem cell transplantation for inborn errors of immunity: 30-year single-center experience.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an effective treatment for a variety of inborn errors of immunity (IEI). We report the experience of children affected by IEI who received allo-HSCT over a period of 32 years at IRCCS Istituto Giannina Gaslini, Genoa, Italy. HSCTs were performed in 67 children with IEI. Kaplan-Meier estimates of overall survival (OS) rate at 5 years in the whole group of patients was 83.4% after a median follow-up of 4 years. Median age at transplant was 2.5 years. Eight allo-HSCTs were complicated by either primary or secondary graft failure (GF), the overall incidence of this complication being 10.9%. Incidence of grade 3-4 acute GvHD (aGvHD) was 18.7%, significantly lower in the haploidentical transplant cohort (p = 0.005). Year of transplant (≤2006 vs. >2006) was the main factor influencing the outcome. In fact, a significant improvement in 5-year OS was demonstrated (92.5% >2006 vs. 65% ≤2006, p = 0.049). Frequency of severe aGvHD was significantly reduced in recent years (≤2006 61.5%, vs. >2006 20%, p = 0.027). A significant progress has been the introduction of the TCR αβ/CD19-depleted haploidentical platform, which was associated with the absence of severe aGvHD. However, it was associated with 23.5% incidence of GF. All but one patient experiencing GF in the this specific cohort were successfully retransplanted. In summary, allo-HSCT is confirmed to be an effective treatment for children with IEI, even in the absence of an HLA-matched donor.

The Long-Term Impact of Diastolic Dysfunction After Routine Cardiac Surgery

To determine the impact of diastolic dysfunction (DD) on survival after routine cardiac surgery. This was an observational study of consecutive cardiac surgeries from 2010 to 2021. At a single institution. Patients undergoing isolated coronary, isolated valvular, and concomitant coronary and valvular surgery were included. Patients with a transthoracic echocardiogram (TTE) longer than 6 months prior to their index surgery were excluded from the analysis. Patients were categorized via preoperative TTE as having no DD, grade I DD, grade II DD, or grade III DD. A total of 8,682 patients undergoing a coronary and/or valvular surgery were identified, of whom 4,375 (50.4%) had no DD, 3,034 (34.9%) had grade I DD, 1,066 (12.3%) had grade II DD, and 207 (2.4%) had grade III DD. The median (IQR) time of the TTE prior to the index surgery was 6 (2-29) days. Operative mortality was 5.8% in the grade III DD group v 2.4% for grade II DD, 1.9% for grade I DD, and 2.1% for no DD (p=0.001). Atrial fibrillation, prolonged mechanical ventilation (>24 hours), acute kidney injury, any packed red blood cell transfusion, reexploration for bleeding, and length of stay were higher in the grade III DD group compared to the rest of the cohort. The median follow-up was 4.0 (IQR: 1.7-6.5) years. Kaplan-Meier survival estimates were lower in the grade III DD group than in the rest of the cohort. These findings suggested that DD may be associated with poor short-term and long-term outcomes.

THE EFFECT OF SURGEON VOLUME AND RISK OF REVISION FOLLOWING TOTAL KNEE ARTHROPLASTIES WITH AND WITHOUT PATELLAR RESURFACING: A STUDY FROM THE AUSTRALIAN ORTHOPAEDIC ASSOCIATION NATIONAL JOINT REPLACEMENT REGISTRY

Strategy regarding patella resurfacing in total knee replacement (TKR) remains controversial. TKR revision rates are reportedly influenced by surgeon procedure volume. The study aim was to compare revision outcomes of TKR with and without patella resurfacing in different surgeon volume groups using data from the AOANJRR.The study population included 571,149 primary TKRs for osteoarthritis. Surgeons were classified as low, medium, or high-volume based on the quartiles of mean primary TKR volume between 2011 and 2020. Cumulative percent revision (CPR) using Kaplan-Meier estimates of survivorship were calculated for the three surgeon volume groups with and without patella resurfacing. Cox proportional hazards models, adjusted for age and sex, were used to compare revision risks.High-volume surgeons who did not resurface the patella had the highest all-cause CPR (20-year CPR 10.9%, 95% CI [10.0%, 12.0%]). When the patella was resurfaced, high-volume surgeons had the lowest revision rate (7.3%, 95% CI [6.4%, 8.4%]). When the high-volume groups were compared there was a higher rate of revision for the non-resurfaced group after 6 months. When the medium-volume surgeon groups were compared, not resurfacing the patella also was associated with a higher rate of revision after 3 months. The low-volume comparisons showed an initial higher rate of revision with patella resurfacing, but there was no difference after 3 months. When only patella revisions were considered, there were higher rates of revision in all three volume groups where the patella was not resurfaced.TKR performed by high and medium-volume surgeons without patella resurfacing had higher revision rates compared to when the patella was resurfaced. Resurfacing the patella in the primary procedure protected against revision for patella reasons in all surgeon volume groups.Level of evidence: III (National registry analysis)