Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change.

Objective: This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP). Design: Retrospective cohort study. Subjects Participants and/or Controls: 1247 glaucoma surgery and treatment naïve eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment naïve eyes of 547 patients who were initiated on other oral antidiabetics. Methods Intervention or Testing: The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ΔIOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings. Main Outcome Measures: Primary outcome measure was ΔIOP after exposure to the medication. Results: The median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ΔIOP was -0.4±2.8 mmHg (paired t-test p<0.001) and -0.2±3.3 mmHg (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results. Conclusions: Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.

Evaluation and Optimization of Diabetic Retinopathy Screenings for Uninsured Latinx Patients in a Resource-Limited Student-Run Free Clinic.

Background: Diabetic retinopathy (DR) is a sight-threatening condition that causes progressive retina damage. Student-run free clinics represent a valuable opportunity to provide DR screenings to high-risk populations. We characterized the patient population, evaluated the performance, and conducted a needs assessment of DR screenings at the University of California, San Diego Student-Run Ophthalmology Free Clinic, which provides care to predominantly uninsured, Latino patients. Methods: Retrospective chart review was conducted of all patients seen at the free clinic since 2019 with a diagnosis of type II diabetes. Date and outcome of all DR-related screenings or visits from 2015 onward, demographics information, and DR risk factors such as A1c and insulin dependence were recorded. Predictors of diabetic retinopathy and frequency of DR screenings for each patient were analyzed using multiple logistic regression, t-test for equality of means, and Pearson's correlation. Results: Of 179 uninsured diabetic patients receiving care at the free clinic, 71% were female and average age was 59. 83% had hypertension, 93% had hyperlipidemia, and 79% had metabolic syndrome. Prevalence of non-proliferative DR was 34% and that of proliferative DR was 15% in diabetic patients. The free clinic capacity in recent years plateaued at just under 50% of patients seen for DR screening or visit per year, though average wait time was over 2 years between visits. Patients with higher no-show rates had less frequent DR screenings. Chronic kidney disease and poor glycemic control were the strongest predictors of DR. Conclusion: The student-run free ophthalmology clinic has been effective in providing screening and follow-up care for DR patients. Creation of a protocol to identify which patients are at highest risk of DR and should be seen more urgently, addressing no-shows, and implementation of a tele-retina program are potential avenues for improving clinic efficiency in a resource-limited setting for vulnerable populations.

Impact of COVID-19 on the Delivery of Eye Care to Uninsured Diabetic Patients at a Student-Run Free Clinic: A Comprehensive Evaluation of Eye Clinic Performance.

Background: Diabetic retinopathy is the leading cause of blindness among working-age adults in the United States and requires timely screening and management. This study evaluates the impact of the coronavirus disease 2019 (COVID-19) pandemic on diabetic retinopathy screening (DRS) for uninsured, predominantly Latino patients at the University of California San Diego Student-Run Free Clinic Project (SRFCP). Methods: A retrospective chart review was conducted of all living diabetic patients at SRFCP who were seen in 2019 (n=196), 2020 (n=183), and 2021 (n=178). Ophthalmology clinic referrals, scheduled patient visits, and visit outcomes were analyzed longitudinally to determine the impact of the pandemic on screening patterns. Results: The study population was 92.1% Latino, 69.5% female, with a mean age of 58.7 years. The distribution of patients seen (p<0.001), referred (p=0.012), and scheduled (p<0.001) in 2020 and 2021 significantly differed from 2019. In 2019, 50.5% of 196 patients eligible for DRS were referred, 49.5% were scheduled, and 45.4% were seen. In 2020, 41.5% of 183 eligible patients were referred, but only 20.2% were scheduled and 11.4% were seen. In 2021, there was a rebound: 63.5% of 178 patients were referred, 56.2% scheduled and 46.1% seen. No shows and cancellations represented 12.4% and 6.2% of the 97 encounters scheduled in 2019, but were markedly higher (10.8% and 40.5% respectively) for the 37 encounters scheduled in 2020. Conclusions: The COVID-19 pandemic significantly impacted the delivery of eye care at SRFCP. The need for annual DRS exceeded the capacity of the ophthalmology clinic in all years studied, but the difference was especially pronounced with more stringent COVID-19 restrictions in 2020. SRFCP patients could benefit from telemedicine DRS programs to improve screening capacity.

Advancing science and technology via 3D culture on basement membrane matrix.

Many cells in tissues are in contact with a highly specialized extracellular matrix, termed the basement membrane. Basement membranes have certain common components, including collagen IV, laminins, heparan sulfate proteoglycans, and growth factors which have a wide variety of biological activities. Extracts of basement membrane-rich tissue have yielded material suitable for studying cell-basement membrane interactions. Cells cultured in a 3D basement membrane matrix allow the in vitro modeling of cell behavior, including differentiation, apoptosis, steps in capillary formation, cancer growth, invasion, etc. It has also led to the development of widely used assays for invasion and angiogenesis and more recently for tumor cell dormancy. Importantly, stem cell culture in 3D basement membrane matrices has provided important advances that allow for expansion of these cells in feeder layer-free cultures and for studying their differentiation. 3D basement membrane culture has allowed the molecular dissection of pathways and genes important in differentiation, aided in the identification of progenitor cells, and led to the development of tissue constructs which may be models for regenerative medicine. This review will outline how this technology has led to important research assays and findings that have advanced our understanding of tissue development and disease and aided in the preclinical development of various therapeutics.

ACS NSQIP Risk Calculator: An Accurate Predictor of Complications in Major Head and Neck Surgery?

The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator is meant to provide an estimation of perioperative risk. Our goal was to determine the clinical applicability of the calculator in major head and neck surgery. A retrospective chart review was completed for major head and neck operations performed at 1 institution from 2013 to 2014. The calculated perioperative complication risks from the ACS NSQIP calculator were compared with observed complication rates. Overall, the ACS NSQIP calculator had little predictive value for pneumonia, surgical site infection, 30-day return to operating room, or length of stay within this cohort (P > .05). The calculator appears to have some value predicting total numbers of complications but has poor performance predicting an individual's risk of suffering a perioperative complication. In conclusion, in our small cohort of patients, the ACS NSQIP calculator was a poor predictor of perioperative complications following major head and neck operations.

Ability of the National Surgical Quality Improvement Program Risk Calculator to Predict Complications Following Total Laryngectomy.

Importance: The accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator has been assessed in multiple surgical subspecialties; however, there have been no publications doing the same in the head and neck surgery literature. Objective: To evaluate the accuracy of the calculator's predictions in a single institution's total laryngectomy (TL) population. Design, Setting, and Participants: Total laryngectomies performed between 2013 and 2014 at a tertiary referral academic center were evaluated using the risk calculator. Predicted 30-day outcomes were compared with observed outcomes for return to operating room, surgical site infection, postoperative pneumonia, length of stay, and venous thromboembolism. Main Outcomes and Measures: Comparison of the NSQIP risk calculator's predicted postoperative complication rates and length of stay to what occurred in this patient cohort using percent error, Brier scores, area under the receiver operating characteristic curve, and Pearson correlation analysis. Results: Of 49 patients undergoing TL, the mean (SD) age at operation was 59 (9.3) years, with 67% male. The risk calculator had limited efficacy predicting perioperative complications in this group of patients undergoing TL with or without free tissue reconstruction or preoperative chemoradiation or radiation therapy with a few exceptions. The calculator overestimated the occurrence of pneumonia by 165%, but underestimated surgical site infection by 7%, return to operating room by 24%, and length of stay by 13%. The calculator had good sensitivity and specificity of predicting surgical site infection for patients undergoing TL with free flap reconstruction (area under the curve, 0.83). For all other subgroups, however, the calculator had poor sensitivity and specificity for predicting complications. Conclusions and Relevance: The risk calculator has limited utility for predicting perioperative complications in patients undergoing TL. This is likely due to the complexity of the treatment of patients with head and neck cancer and factors not taken into account when calculating a patient's risk.

Effects of dynamic cardiomyoplasty on left ventricular performance and myocardial mechanics in dilated cardiomyopathy.

We tested the hypothesis that dynamic cardiomyoplasty produces beneficial changes in the functional mechanics of the dilated, failing left ventricle. Chronic dilated cardiomyopathy was induced in seven mongrel dogs by rapid ventricular pacing (260 beats/min) for 3 to 4 weeks. After completion of the induction period, dynamic cardiomyoplasty was performed with the left latissimus dorsi muscle, paced synchronously with the R waves of the electrocardiogram (Medtronic SP1005). Instruments included an aortic flow probe, a left ventricular Millar pressure catheter, and piezoelectric sonomicrometric crystals on the left ventricle for measurements of wall thickness and minor and major axis dimensions. Data were obtained with the stimulator off and on. Statistical comparisons were made with Student's t test for paired data. Dynamic cardiomyoplasty increased the cardiac output of the failing heart (966 +/- 124 versus 1166 +/- 112 ml/min; p less than 0.01). Systolic shortening of both minor and major axis dimensions increased (3.1 +/- 0.3 versus 4.7 +/- 0.3 mm, p less than 0.01, and 4.6 +/- 0.3 versus 7.3 +/- 0.9 mm, p less than 0.05, respectively). Left ventricular end-diastolic pressure decreased by 16% (18 +/- 1 versus 15 +/- 1 mm Hg, p less than 0.01). Although skeletal muscle contraction increased the pressure development in the left ventricular chamber, mean systolic wall stress was diminished by concomitant changes in left ventricular dimensions (116,144 +/- 11,530 versus 101,268 +/- 7464 dynes/cm2, p less than 0.05). At end-systole, wall thickness increased (11.8 +/- 1.1 versus 12.7 +/- 1.1 mm, p less than 0.01), minor axis dimension decreased (51.3 +/- 1.4 versus 49.2 +/- 1.8 mm, p less than 0.01), and major axis dimension also decreased (85.6 +/- 3.3 versus 79.0 +/- 2.3 mm, p less than 0.05). Our detailed evaluation of left ventricular chamber mechanics suggests that dynamic cardiomyoplasty may have a role in ameliorating the functional and mechanical derangements associated with progression of dilated cardiomyopathy both by augmenting cardiac performance and by diminishing determinants of myocardial oxygen consumption. (All values are expressed as mean +/- standard error of the mean.)

Cost effectiveness of early digit amputation in the patient with diabetes.

Osteomyelitis in the digit of the diabetic patient is best managed by antibiotics and amputation. Antibiotics alone are not effective or cost-effective as demonstrated in a retrospective study of 22 such patients diagnosed clinically and confirmed roentgenographically. Definitive operation allows the patient to return to work within two weeks of amputation.

Characteristics of magnesium-adenosine triphosphate-dependent inactivators of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The inhibition of homogeneous 3-hydroxy-3-methyl-glutaryl coenzyme A reductase by MgATP-dependent inactivators isolated from rat liver cytosol and microsomes was examined. The inhibition was independent of incubation time. The inhibition was readily reversed by dilution or dialysis, by the addition of EDTA, and by incubating the inhibited enzyme with glycerol and glycerol kinase to convert the ATP to ADP. The inactivated enzyme was not reactivated by various phosphatases. When inactivated in the presence of [gamma-32P]ATP, no radioactivity was incorporated into the reductase. These observations indicate that the inactivators do not exert their effects through covalent modification of the reductase.

Experience with a metered-dose inhaler with a spacer in the pediatric emergency department.

Studies of adults suggest that metered-dose inhalers with spacers are as effective as hand-held nebulizers for bronchodilator delivery. We studied 13 children with acute asthma. They received two puffs every 2 minutes from metered-dose inhalers with spacers (range, 4 to 14 puffs) titrated until improvement stopped. Peak expiratory flow increased 34% for metered-dose inhalers with spacers after the first 2 puffs and increased 87% for metered-dose inhalers with spacers after dose titration. After titration, respiratory rate decreased by 12%, heart rate increased by 2%, and breath sounds improved in 92% of the patients. We concluded that the metered-dose inhalers with spacers are an effective device for the treatment of asthma in the pediatric emergency department and that the use of metered-dose inhalers with spacers with titration can achieve significant bronchodilation in the treatment of patients with acute asthma.