Bladder and Kidney Cancer Diagnosis and Survival Increase With Medicare Eligibility at Age 65.

INTRODUCTION: Medicare eligibility at 65 has been associated with increased diagnosis and survival for certain cancers due to greater health care utilization. We aim to assess for a similar "Medicare effect" for bladder and kidney cancers, which has not been previously established. METHODS: Patients diagnosed with bladder or kidney cancer from 2000-2018 at ages 60-69 years were identified with the Surveillance, Epidemiology, and End Results database. We used age-over-age percent change calculations to characterize trends in cancer diagnoses focusing on patients aged 65. Multivariable Cox models were used to compare cancer-specific mortality across ages at diagnosis. RESULTS: We identified 63,960 patients diagnosed with bladder cancer and 52,316 diagnosed with kidney cancer. Age-over-age change in diagnosis was highest for patients aged 65 compared to all other ages for both cancers (P < .01 for both). Stratified by stage, patients aged 65 had a higher age-over-age change than those aged 61-64 or 66-69 for in situ (P = .01, P < .01, respectively), localized (P = .03, P = .01), and regional (P = .02, P = .02) bladder cancer and localized (P = .01, P = .01) kidney cancer. Bladder cancer patients aged 65 had lower cancer-specific mortality than patients aged 66 (HR = 1.17, P = .01) and 69 (HR = 1.18, P = .01), while kidney cancer patients aged 65 had lower mortality than patients aged 64 (HR = 1.18, P < .01) and 66-69. CONCLUSIONS: The age of 65, marking the onset of Medicare eligibility, is associated with more diagnoses of bladder and kidney cancer. Patients diagnosed at age 65 demonstrate decreased bladder and kidney cancer-specific mortality.

Tauroursodeoxycholic Acid Protects Retinal and Visual Function in a Mouse Model of Type 1 Diabetes.

PURPOSE: Previous studies demonstrated that systemic treatment with tauroursodeoxycholic acid (TUDCA) is protective in in vivo mouse models of retinal degeneration and in culture models of hyperglycemia. This study tested the hypothesis that TUDCA will preserve visual and retinal function in a mouse model of early diabetic retinopathy (DR). METHODS: Adult C57BL/6J mice were treated with streptozotocin (STZ) and made diabetic at 8-10 weeks of age. Control and diabetic mice were treated with vehicle or TUDCA starting 1 or 3 weeks after induction of diabetes, and were assessed bimonthly for visual function via an optomotor response and monthly for retinal function via scotopic electroretinograms. RESULTS: Diabetic mice showed significantly reduced spatial frequency and contrast sensitivity thresholds compared to control mice, while diabetic mice treated early with TUDCA showed preservation at all timepoints. A-wave, b-wave, and oscillatory potential 2 (OP2) amplitudes decreased in diabetic mice. Diabetic mice also exhibited delays in a-wave and OP2-implicit times. Early TUDCA treatment ameliorated a-wave, b-wave, and OP2 deficits. Late TUDCA treatment showed reduced preservation effects compared to early treatment. CONCLUSIONS: Early TUDCA treatment preserved visual function in an STZ-mouse model of Type I diabetes. These data add to a growing body of preclinical research that may support testing whether TUDCA may be an effective early clinical intervention against declining visual function caused by diabetic retinopathy.

TrkB signalling pathway mediates the protective effects of exercise in the diabetic rat retina.

Diabetic retinopathy is a leading cause of vision loss. Treatment options for early retinopathy are sparse. Exercise protects dying photoreceptors in models of retinal degeneration, thereby preserving vision. We tested the protective effects of exercise on retinal and cognitive deficits in a type 1 diabetes model and determined whether the TrkB pathway mediates this effect. Hyperglycaemia was induced in Long Evans rats via streptozotocin injection (STZ; 100 mg/kg). Following confirmed hyperglycaemia, both control and diabetic rats underwent treadmill exercise for 30 min, 5 days/week at 0 m/min (inactive groups) or 15 m/min (active groups) for 8 weeks. A TrkB receptor antagonist (ANA-12), or vehicle, was injected 2.5 h before exercise training. We measured spatial frequency and contrast sensitivity using optokinetic tracking biweekly post-STZ; retinal function using electroretinography at 4 and 8 weeks; and cognitive function and exploratory behaviour using Y-maze at 8 weeks. Retinal neurotrophin-4 was measured using ELISA. Compared with non-diabetic controls, diabetic rats showed significantly reduced spatial frequency and contrast sensitivity, delayed electroretinogram oscillatory potential and flicker implicit times and reduced cognitive function and exploratory behaviour. Exercise interventions significantly delayed the appearance of all deficits, except for exploratory behaviour. Treatment with ANA-12 significantly reduced this protection, suggesting a TrkB-mediated mechanism. Despite this, no changes in retinal neurotrohin-4 were observed with diabetes or exercise. Exercise protected against early visual and cognitive dysfunction in diabetic rats, suggesting that exercise interventions started after hyperglycaemia diagnosis may be a beneficial treatment. The translational potential is high, given that exercise treatment is non-invasive, patient controlled and inexpensive.

Comparative Perioperative Outcomes in Septuagenarians and Octogenarians Undergoing Radical Cystectomy for Bladder Cancer-Do Outcomes Differ?

BACKGROUND: Treatment choice for muscle invasive bladder cancer continues to be radical cystectomy. However, radical cystectomy carries a relatively high risk of morbidity and mortality compared with other urological procedures. OBJECTIVE: To compare surgical complications following radical cystectomy in septuagenarians and octogenarians. DESIGN, SETTING, AND PARTICIPANTS: The National Surgical Quality Improvement Program database (2009-2013) was used to identify patients who were 70 yr and older and underwent radical cystectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The data were analyzed for demographics and comorbidities, and compared for complications, including pulmonary, thromboembolic, wound, and cardiac complications. Patients who were 70-79 yr of age were compared with those 80 yr and older. Univariate and multivariate analyses were completed. RESULTS AND LIMITATIONS: A total of 1710 patients aged ≥70 yr met our inclusion criteria. Of them, 28.8% (n=493) were 80 yr and older, while 71.2% (n=1217) were between 70 and 79 yr old. Operative time (338.4 vs 307.2min, p=0.0001) and the length of stay (11.9 vs 10.4 d, p=0.0016) were higher in the octogenarian group. The intra- and postoperative transfusion rates, reoperative rates, wound dehiscence rates, and pneumonia, sepsis, and myocardial infarction rates were similar between the two groups. The wound infection rate (7.3% vs 4.1%, p=0.01) was higher in the septuagenarians and mortality rate (4.3% vs 2.3%, p=0.04) was higher in the octogenarian group. CONCLUSIONS: Radical cystectomy can safely be performed in octogenarians without increased cardiac, pulmonary, and thromboembolic complications when compared with septuagenarians. These patients need to be counseled that the mortality rate is slightly higher compared with that in septuagenarians. Chronological age alone should not be used to decide on offering radical cystectomy. PATIENT SUMMARY: We looked at complications following radical cystectomy in patients aged 80 yr and older. We found that there was no significant difference for wound, cardiac, or pulmonary complications, but there was an increased risk of mortality in this age group.

Laparoscopic Management of Penetrating Thoracoabdominal Trauma.

BACKGROUND: Traumatic thoracoabdominal injuries can involve multiple organs and multiple cavities, which increases the complexity of surgical management. Traditionally, these injuries required laparotomy and thoracotomy. However, minimally invasive intervention may be reasonable for stable patients. MATERIALS AND METHODS: We present a case of a thoracoabdominal gunshot wound resulting in multiorgan, multicavity injury to the lung, diaphragm, and liver. We performed hepatorrhaphy and diaphragm repair, and addressed a retained hemothorax through a transabdominal laparoscopic approach. RESULTS: The patient tolerated the procedure well. He required no further procedures, and had no evidence of retained hemothorax or bile leak from the liver injury. After a short stay in the hospital, the patient recovered uneventfully. CONCLUSIONS: In hemodynamically stable patients, the transabdominal laparoscopic approach is a feasible and effective approach to penetrating thoracoabdominal trauma.

Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve.

We investigated the effect of progesterone (P4) treatment on diabetes/hyperglycemia-induced pathological changes in brain, spinal cord and sciatic nerve tissue in male rats. Animals were rendered hyperglycemic by a single dose of streptozotocin (STZ). P4 treatment was started after hyperglycemia was confirmed and body weight and blood glucose levels were monitored once/week for 5weeks. Rats underwent behavioral testing at week 5 and were then euthanized for histology. We assessed the expression of markers of angiogenesis (vascular endothelial growth factor (VEGF)), inflammation (interleukin-6 (IL-6)) and tissue injury (CD11b, NG2, COX2 and matrix metalloproteinase-2 (MMP-2)) in the brain, spinal cord and sciatic nerve. We also examined the regenerative effect of P4 on pathological changes in intra-epidermal nerve fibers (IENF) of the footpads. Diabetes/hyperglycemia led to body weight loss over 5weeks and P4 treatment reduced this loss. At week 5, blood-glucose levels were significantly lower in the P4-treated diabetic group compared to vehicle. Compared to sham or P4-treated groups, the diabetic vehicle group showed hyperactivity on the spontaneous locomotor activity test. Western blot data revealed upregulation of VEGF, IL-6, CD11b, NG2, COX2 and MMP-2 levels in the vehicle group and P4 treatment normalized these expression levels. IENF densities were reduced in the vehicle group and normalized after P4 treatment. We conclude that P4 can reduce some of the chronic pathological responses to STZ-induced diabetes.

Association of Body Length with Ocular Parameters in Mice.

PURPOSE: To determine the association between changes in body length with ocular refraction, corneal radii, axial length, and lens thickness in two different mouse strains. METHODS: Body length, ocular refraction, corneal radii, axial length, and lens thickness were measured for two inbred mouse strains: 129S1/SvJ (n = 7) and C57BL/6 J (n = 10) from 4 to 12 weeks of age. Body length, from tip of nose to base of tail, was obtained using a digital camera. Biometric parameters, corneal radii, and refractions were measured using spectral-domain optical coherence tomography, automated keratometry, and infrared photorefraction, respectively. A mixed-model ANOVA was performed to examine the changes in ocular parameters as a function of body length and strain in mice controlling for age, gender, and weight over time. RESULTS: C57BL/6J mice had significantly longer body length (average body length at 10 weeks, 8.60 ± 0.06 cm) compared to 129S1/SvJ mice (8.31 ± 0.05 cm) during development (P < .001). C57BL/6J mice had significantly hyperopic refractions compared to 129S1/SvJ mice across age (mean refraction at 10 weeks, 129S1/SvJ: +0.99 ± 0.44D vs. C57BL/6J: +6.24 ± 0.38D, P < .001). Corneal radius of curvature, axial length, and lens thickness (except 10 weeks lens thickness) were similar between the two strains throughout the measurement. In the mixed-model ANOVA, changes in body length showed an independent and significant association with the changes in refraction (P = .002) and corneal radii (P = .016) for each mouse strain. No significant association was found between the changes in axial length (P = .925) or lens thickness (P = .973) as a function of body length and strain. CONCLUSIONS: Changes in body length are significantly associated with the changes in ocular refraction and corneal radii in different mouse strains. Future studies are needed to determine if the association between body length and ocular refraction are related to changes in corneal curvature in mice.

In Vivo Imaging of Retinal Oxidative Stress Using a Reactive Oxygen Species-Activated Fluorescent Probe.

PURPOSE: In vivo methods for detecting oxidative stress in the eye would improve screening and monitoring of the leading causes of blindness: diabetic retinopathy, glaucoma, and age-related macular degeneration. METHODS: To develop an in vivo biomarker for oxidative stress in the eye, we tested the efficacy of a reactive oxygen species (ROS)-activated, near-infrared hydrocyanine-800CW (H-800CW) fluorescent probe in light-induced retinal degeneration (LIRD) mouse models. After intravitreal delivery in LIRD rats, fluorescent microscopy was used to confirm that the oxidized H-800CW appeared in the same retinal layers as an established ROS marker (dichlorofluorescein). RESULTS: Dose-response curves of increasing concentrations of intravenously injected H-800CW demonstrated linear increases in both intensity and total area of fundus hyperfluorescence in LIRD mice, as detected by scanning laser ophthalmoscopy. Fundus hyperfluorescence also correlated with the duration of light damage and functional deficits in vision after LIRD. In LIRD rats with intravitreal injections of H-800CW, fluorescent labeling was localized to photoreceptor inner segments, similar to dichlorofluorescein. CONCLUSIONS: Hydrocyanine-800CW detects retinal ROS in vivo and shows potential as a novel biomarker for ROS levels in ophthalmic diseases.

TAK-242, an antagonist for Toll-like receptor 4, protects against acute cerebral ischemia/reperfusion injury in mice.

Toll-like receptor 4 (TLR4) contributes to cerebral ischemia/reperfusion (I/R) injury and is a potential target for the treatment of ischemic stroke. This experiment is to evaluate the effect of an exogenous TLR4 antagonist, TAK-242, against acute cerebral I/R injury. A mouse model of cerebral I/R was induced by transient middle cerebral artery occlusion. TAK-242 (3 mg/kg body weight) was injected intraperitoneally 1 hour after ischemia. Our results showed that the concentration of TAK-242 in plasma increased to 52.0 ng/mL 3 hours after injection, was maintained at 54.1 ng/mL 8 hours after injection, and decreased to 22.6 ng/mL 24 hours after injection. The concentration of TAK-242 in brain tissue increased to 26.1 ng/mL in ischemic hemisphere and 14.2 ng/mL in nonischemic hemisphere 3 hours after injection, and was maintained at the similar levels 24 hours after injection. We found that TAK-242 significantly reduced cerebral infarction compared with vehicle control, improved neurologic function, inhibited the phosphorylation of downstream protein kinases in TLR4 signaling pathway, and downregulated the expression of inflammatory cytokines. We conclude that TAK-242 is able to cross blood-brain barrier, blocks TLR4 signaling, mediates the expression of inflammatory cytokines, and protects the brain from acute damage induced by I/R.