Oncological and Functional Outcomes for Men Undergoing Salvage Whole-gland Cryoablation for Radiation-resistant Prostate Cancer.

BACKGROUND: There is no consensus on the optimal approach for salvage local therapy in radiation-resistant/recurrent prostate cancer (RRPC). OBJECTIVE: To investigate oncological and functional outcomes for men treated with salvage whole-gland cryoablation (SWGC) of the prostate for RRPC. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed our prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with SWGC of the prostate at a tertiary referral center. INTERVENTION: SWGC of the prostate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was biochemical recurrence-free survival (BRFS) according to the Phoenix criterion. Secondary outcomes included metastasis-free survival, cancer-specific survival, and adverse events. RESULTS AND LIMITATIONS: A total of 110 men with biopsy-proven RRPC were included in the study. Median follow-up for patients without biochemical recurrence (BCR) after SWGC was 71 mo (interquartile range [IQR] 42.3-116). BRFS was 81% at 2 yr and 71% at 5 yr. A higher prostate-specific antigen (PSA) nadir after SWGC was associated with worse BRFS. The median International Index of Erectile Function-5 score was 5 (IQR 1-15.5) before SWGC and 1 (IQR 1-4) after SWGC. Stress urinary incontinence, strictly defined as the use of any pads after treatment, was 5% at 3 mo and 9% at 12 mo. Clavien-Dindo grade ≥3 adverse events occurred in three patients (2.7%). CONCLUSIONS: In patients with localized RPPC, SWGC achieved excellent oncological outcomes with a low rate of urinary incontinence, and represents an alternative to salvage radical prostatectomy. Patients with fewer positive cores and lower PSA tended to have better oncological outcomes following SWGC. PATIENT SUMMARY: For men with prostate cancer that persists after radiotherapy, a freezing treatment applied to the whole prostate gland can achieve excellent cancer control. Patients who did not have elevated prostate-specific antigen (PSA) at 6 years after this treatment appeared to be cured.

Oncological and functional outcomes of men undergoing primary whole gland cryoablation of the prostate: A 20-year experience.

BACKGROUND: This study reports the oncological and functional outcomes in men with localized prostate cancer (Pca) who were treated with primary whole gland cryoablation (WGC) of the prostate. METHODS: The authors retrospectively reviewed their prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with WGC of the prostate at a tertiary referral center. Primary outcome includes biochemical recurrence-free survival (BRFS). Secondary outcomes include failure-free survival (FFS), metastasis-free survival (MFS) and adverse events. RESULTS: A total of 260 men were included in the study. Men having had prior treatment for Pca were excluded. Median follow-up was 107 months (interquartile range [IQR], 68.3-132.5 months). BRFS, FFS, and MFS at 10 years were 84%, 66%, and 96%, respectively. High risk D'Amico classification was associated with a lower BRFS and FFS on multivariable analysis. No patient had any Pca-related death during follow-up. American Urological Association symptoms score and bother index were unchanged following cryoablation. Median International Index of Erectile Function score precryoablation and post-cryoablation was 7 (IQR, 3-11) and 1 (IQR, 1-5), respectively. Stress urinary incontinence, defined as requiring any protective pads only occurred in five patients (2%). No patient developed a fistula. Grade > 2 Clavien-Dindo adverse events occurred in six (2.3%) patients. CONCLUSION: WGC of the prostate can achieve excellent oncological and functional outcomes in men with localized Pca at the 10-year mark. Primary WGC may be a good option for men who desire to preserve urinary continence and have an excellent oncologic outcome. LAY SUMMARY: Primary whole gland cryoablation is an alternative treatment option to radical prostatectomy and radiotherapy for men with organ-confined prostate cancer. Patients had excellent cancer outcomes 1 years after whole gland cryoablation, and patients with PSA nadir 0.1 ng/ml or lower after treatment were less likely to have disease recurrence.

Factors Associated with Ophthalmology Referral and Adherence in a Teleretinal Screening Program: Insights from a Federally Qualified Health Center.

Background: Early detection of ophthalmic conditions such as diabetic retinopathy (DR) and glaucoma is crucial to preventing vision loss. Previous studies have evaluated teleretinal screening programs for DR in well-insured populations. The purpose of this retrospective study was to evaluate a teleretinal screening program in a population of uninsured and underinsured patients seen in a Federally Qualified Health Center (FQHC). Methods: We conducted a retrospective chart review of patients (age ≥18) who underwent teleretinal imaging (TRI) at a FQHC between January 2015 and September 2019. TRI gradings and patient demographic and clinical information were abstracted. Factors associated with referral for a dilated eye exam by an ophthalmologist, adherence to recommended follow-up dilated eye exam, and ophthalmology visit attendance were examined. Results: 3130 TRIs were graded in 2216 eyes (1107 patients). 65.2% (N = 722) self-identified as Hispanic and 56.3% (N = 623) required interpreter services. Follow-up dilated fundus examination (DFE) was recommended for 388 TRIs, 49% (N = 190) of which were completed within 1 year. Adherence to the recommended ophthalmology exam was not associated with any baseline clinical or demographic characteristics (p > 0.05). Older age, male sex, hypertension, proteinuria, and higher A1c were significantly associated with greater odds of ophthalmology referral based on TRI (all p < 0.05), after adjusting for covariates. Less severe diabetic retinopathy, no insurance coverage, and Hispanic ethnicity were associated with lower odds of attending an ophthalmology visit, regardless of follow-up recommendations based on TRI (all p < 0.05). Conclusion: In an FQHC serving predominantly uninsured and underinsured patients, only 49% of recommended DFE were completed within one year. Less severe diabetic retinopathy, lack of insurance coverage, and Hispanic ethnicity were associated with a lower likelihood of having a DFE regardless of recommendation. These results suggest that greater system-level efforts are needed to increase adherence to follow-up eye exams after TRI to ensure sight-saving care for underserved populations.

Optical Coherence Tomography in Patients with Alzheimer's Disease: What Can It Tell Us?

PURPOSE: Although Alzheimer's disease (AD) is a leading cause of dementia worldwide, its clinical diagnosis remains a challenge. Optical coherence tomography (OCT) and OCT with angiography (OCTA) are non-invasive ophthalmic imaging tools with the potential to detect retinal structural and microvascular changes in patients with AD, which may serve as biomarkers for the disease. In this systematic review, we evaluate whether certain OCT and OCTA parameters are significantly associated with AD and mild cognitive impairment (MCI). METHODS: PubMed database was searched using a combination of MeSH terms to identify studies for review. Studies were organized by participant diagnostic groups, type of imaging modality, and OCT/OCTA parameters of interest. Participant demographic data was also collected and baseline descriptive statistics were calculated for the included studies. RESULTS: Seventy-one studies were included for review, representing a total of 6757 patients (2350 AD, 793 MCI, 2902 healthy controls (HC), and 841 others with a range of other neurodegenerative diagnoses). The mean baseline ages were 72.78±3.69, 71.52±2.88, 70.55±3.85 years for AD, MCI and HC groups, respectively. The majority of studies noted significant structural and functional decline in AD patients when compared to HC. Although analysis of MCI groups yielded more mixed results, a similar pattern of decline was often noted amongst patients with MCI relative to HC. OCT and OCTA measurements were also shown to correlate with established measures of AD such as neuropsychological testing or neuroimaging. CONCLUSION: OCT and OCTA show great potential as non-invasive technologies for the diagnosis of AD. However, further research is needed to determine whether there are AD-specific patterns of structural or microvascular change in the retina and optic nerve that distinguish AD from other neurodegenerative diseases. Development of sensitive and specific OCT/OCTA parameters will be necessary before they can be used to detect AD in clinical settings.

Tissues Harvested Using an Automated Surgical Approach Confirm Molecular Heterogeneity of Glioblastoma and Enhance Specimen's Translational Research Value.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Designing effective individualized therapies for GBM requires quality fresh tissue specimens, and a comprehensive molecular profile of this highly heterogenous neoplasm. Novel neuro-surgical approaches, such as the automated resection NICO Myriad™ system, are increasingly used by neurosurgeons to better reach the invasive front of tumors. However, no information exists on how harvesting GBM tissue using this approach may impact the translational research value of the sample. Here, we set out to characterize matched specimens from 15 patients, where one tissue sample was obtained using traditional tumor de-bulking (herein referred to as "en bloc" sample), and the other sample was obtained using the MyriadTM System (herein referred to as "Myriad" sample). We investigated the fidelity of patient derived xenografts (PDXs) for each sample type to the corresponding human tissues and evaluated the added value of sequencing both samples for each patient. Matched en bloc and Myriad samples processed in parallel, were subjected to the following assays: cell viability, self-renewal, in vivo tumorigenicity using an orthotopic model of glioma, genomic sequencing, and pharmacological testing using PI3K-MTOR pathway inhibitors. Our results demonstrate that primary GBM cultures derived from matched specimens grew at similar rates (correlation coefficient R = 0.72), generated equivalent number of neurospheres, and had equivalent tumorigenic potential in vivo (mouse survival correlation coefficient R = 0.93). DNA Sequencing using the Illumina tumor panel amplicons revealed over 70% concordance in non-synonymous mutations between matched human GBM specimens. PDX genomic profiles were also highly concordant with the corresponding patient tissues (>70%). RNA sequencing of paired GBM samples revealed unique genomic variants and differential gene expression between the en bloc and Myriad specimens, with the former molecularly resembling the "tumor core" and the latter resembling the "invasive tumor front" signature. Functionally, we show that primary-derived GBM cells-obtained after fresh specimen's dissociation-are more effectively growth-inhibited by co-targeting non-overlapping mutations enriched in each sample type, suggesting that profiling both specimens more adequately capture the molecular heterogeneity of GBM and may enhance the design accuracy and efficacy of individualized therapies.

Hyper-Crosslinked Carbohydrate Polymer for Repair of Critical-Sized Bone Defects.

This study evaluated the safety and efficacy of a novel hyper-crosslinked carbohydrate polymer (HCCP) for the repair of critical-sized bone defects in comparison to two alternative treatments: autologous bone and poly(lactide-co-glycolide) with hyaluronic acid (PLGA/HA). Bilateral critical-sized defects were created in the lateral femoral condyles of skeletally mature New Zealand White rabbits, and they were subsequently implanted with HCCP, PLGA/HA, or autologous bone in a randomized manner. Clinical and behavioral observations were made daily, and radiological and histopathological evaluations were performed at 4, 10, and 16 weeks postimplantation. Defects implanted with HCCP showed progressive bone regeneration and bridging of the defect without adverse histological events. No signs of infection or inflammation associated with the implant material were observed in all animals that received HCCP implantation. A radiographic assessment performed at 16 weeks post-implantation showed significantly higher bone density and volume in defects implanted with HCCP compared to PLGA/HA. No statistically significant difference was observed in bone density and volume between HCCP and autologous bone. These findings demonstrate that HCCP is biocompatible, osteoconductive, and capable of promoting bone regeneration in vivo; therefore, it is suitable for both tissue engineering and the repair of critical-sized bone defects.

Blood and Blood Product Conservation: Results of Strategies to Improve Clinical Outcomes in Open Heart Surgery Patients at a Tertiary Hospital.

Blood product usage is a quality outcome for patients undergoing cardiac surgery. To address an increase in blood product usage since the discontinuation of aprotinin, blood conservation strategies were initiated at a tertiary hospital in Oakland, CA. Improving transfusion rates for open heart surgery patients requiring Cardiopulmonary bypass (CPB) involved multiple departments in coordination. Specific changes to conserve blood product usage included advanced CPB technology upgrades, and precise individualized heparin dose response titration assay for heparin and protamine management. Retrospective analysis of blood product usage pre-implementation, post-CPB changes and post-Hemostasis Management System (HMS) implementation was done to determine the effectiveness of the blood conservation strategies. Statistically significant decrease in packed red blood cells, fresh frozen plasma, cryoprecipitate, and platelet usage over the stepped implementation of both technologies was observed. New oxygenator and centrifugal pump technologies reduced active circuitry volume and caused less damage to blood cells. Individualizing heparin and protamine dosing to a patient using the HMS led to transfusion reductions as well. Overall trends toward reductions in hospital length of stay and intensive care unit stay, and as a result, blood product cost and total hospitalization cost are positive over the period of implementation of both CPB circuit changes and HMS implementation. Although they are multifactorial in nature, these trends provide positive enforcement to the changes implemented.