Energy Dose-Response in Selective Laser Trabeculoplasty: A Review.

PRCIS: A literature review of selective laser trabeculoplasty (SLT) energy dose-response found no definitive relationship between intraocular pressure (IOP) reduction with respect to total or pulse energy, race, pigmentation, or application pattern. PURPOSE: SLT is a safe and effective treatment for lowering IOP. Although evidence is mounting for the advantage of its use as a first-line treatment for IOP reduction, the SLT procedures in use vary widely. The purpose of this literature review was to investigate whether there were any relationships between SLT energy and efficacy for lowering IOP in the published literature. METHODS: A literature review was undertaken that included studies in which energy levels required for successful SLT treatment were investigated: in general, with respect to angle pigmentation, race or ethnicity, and treatment arc extent. RESULTS: There was no indication that higher (or lower) energy used in the treatment leads to greater (or less) IOP reduction. Similar results were obtained regarding the level of trabecular meshwork pigmentation. Race was not found to be associated with altered dose response in SLT. There were indications that treating the full 360 degrees, as opposed to smaller arcs, could be beneficial for more IOP reduction. IOP reduction from SLT was found to be similar to that provided by topical medications. CONCLUSIONS: The optimal energy level of SLT needed for IOP reduction has not yet been definitively established, with all reported pulse energies resulting in similar IOP reduction. Furthermore, similar lack of conclusive findings exists regarding optimal SLT energy dosage for use in different races and degrees of trabecular meshwork pigmentation. This parameter and each of the abovementioned factors requires further research.

Retinal Vascular Signs as Screening and Prognostic Factors for Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Current Evidence.

BACKGROUND: The substantial burden of kidney disease fosters interest in new ways of screening for early disease diagnosis, especially by non-invasive imaging. Increasing evidence for an association between retinal microvascular signs and kidney disease prompted us to investigate the relevant current literature on such an association systematically by performing a meta-analysis of our findings. METHODS: We scrutinized the current literature by searching PubMed and Embase databases from for clinical studies of the association between retinal microvascular signs and prevalent or incident kidney disease. After excluding cases that did not meet our criteria, we extracted relevant data from 42 published studies (9 prospective, 32 cross-sectional, and 1 retrospective). RESULTS: Our investigation yielded significant associations between retinal vascular changes (including retinopathy and retinal vascular diameter) and kidney dysfunction (including chronic kidney disease (CKD), end-stage renal disease (ESRD), albuminuria, and estimated glomerular filtration rate (eGFR) decline). According to our meta-analysis, retinopathy was associated with ESRD (hazard ratio (HR) 2.12 (95% confidence interval CI; 1.39-3.22)) and with CKD prevalence in the general population (odds ratio (OR) 1.31 (95% CI; 1.14-1.50)), and specifically in type 2 diabetic patients (OR 1.68 (95% CI; 1.68-2.16)). CRAE was associated with prevalent CKD (OR 1.41 (95% CI; 1.09-1.82)). CONCLUSIONS: Our findings suggest that the retinal microvasculature can provide essential data about concurrent kidney disease status and predict future risk for kidney disease development and progression.

Can Tonsillectomy Be Safely Performed by Residents? A Comparative Retrospective Study.

OBJECTIVE: To assess whether a surgeon's level of training is associated with outcomes in pediatric tonsillectomy. DESIGN: A retrospective cohort study of the outcomes of pediatric tonsillectomies performed between 2006 and 2016 by senior surgeons versus resident surgeons under the supervision of senior surgeons. SETTING: An otolaryngology department in a tertiary academic hospital. PATIENTS: Children younger than 18 years who underwent bilateral tonsillectomy with or without adenoidectomy. MAIN OUTCOME MEASURES: Intraoperative bleeding, initiation of oral intake, and intraoperative and postoperative complications. RESULTS: Of 785 children, 397 (50.5%) were operated on by a resident surgeon and 388 (49.5%) by a senior surgeon. Patient demographics and surgical techniques were similar between the groups. The mean surgical time was 33.2 minutes in the residents' group and 27.1 minutes in the seniors' group (P = .032). The groups were similar in intraoperative bleeding, while same-day initiation of oral intake was 71% for children in the residents' group versus 61% in the seniors' group (P = .28). Reports of postoperative bleeding necessitating readmission and revised operations were similar for both groups (3.0% and 0.7%, respectively, in the residents' group; and 2.5% and 1.0%, respectively, in the seniors' group). CONCLUSION: Children undergoing tonsillectomy showed similar short-term outcomes, whether the operations were performed by a senior surgeon or a resident surgeon supervised by an attending surgeon. This study demonstrates the safety of pediatric tonsillectomy performed by resident surgeons supervised by attending physicians.

Retinal Microvascular Signs as Screening and Prognostic Factors for Cardiac Disease: A Systematic Review of Current Evidence.

The substantial burden of heart disease promotes an interest in new ways of screening for early disease diagnosis, especially by means of noninvasive imaging. Increasing evidence for association between retinal microvascular signs and heart disease prompted us to systematically investigate the relevant current literature on the subject. We scrutinized the current literature by searching PubMed and Embase databases from 2000 to 2020 for clinical studies of the association between retinal microvascular signs and prevalent or incident heart disease in humans. Following exclusions, we extracted the relevant data from 42 publications (comprising 14 prospective, 26 cross-sectional, and 2 retrospective studies). Our search yielded significant associations between retinal vascular changes, including diameter, tortuosity, and branching, and various cardiac diseases, including acute coronary syndrome, coronary artery disease, heart failure, and conduction abnormalities. The findings of our research suggest that the retinal microvasculature can provide essential data about concurrent cardiac disease status and predict future risk of cardiac-related events.

Metabolic Control of Plasma Cell Differentiation- What We Know and What We Don't Know.

Antibody secretion is executed by plasma cells that are generated in the periphery and migrate to the bone marrow to establish a long lived pool. The terminal differentiation of B lymphocytes into plasma cells is executed by a network of transcription factors that cross-regulate each other in order to irreversibly promote this transition. While major progress has been made in the understanding the transcriptional activity of the underlying master regulators, much less is known on the metabolic regulation of plasma cell differentiation that is required to support antibody synthesis, folding and secretion at high levels and allow their long-lasting survival. In this review we will address the known cross talks between the transcription and metabolic control of plasma cells and elaborate on the gaps of knowledge in the field.

CHO cells knocked out for TSC2 display an improved productivity of antibodies under fed batch conditions.

The kinase mTOR operates in two cellular complexes, mTORC1 and mTORC2. mTORC1 adjusts metabolic activity according to external growth conditions and nutrients availability. When conditions are prosperous, mTOR facilitates protein and lipid biosyntheses and inhibits autophagy, while under metabolic constraints, however, its attenuation induces a catabolic program, energy preservation and autophagy. CHO is a key cell line for manufacturing of biologics owing to its remarkable ability to grow to high densities and maintain protein production and secretion for extended times. While high mTOR activity has been associated with high productivity in CHO cells, its inhibition by rapamycin has also been documented to augment productivity via promotion of viability. Here using CRISPR/Cas9 editing we engineered CHO cells to enforce high mTORC1 activity by knocking-out TSC2, a major mTOR inhibitory protein, or PTEN, a phosphatase that attenuates the PI3K/AKT/mTOR pathway. Only TSC2-deleted cells exhibited a constitutive activation of mTORC1 under fed batch conditions. Cells grew larger in size, synthesized more proteins and displayed an over twofold elevation in their specific productivity. While peak viable cell density was compromised, overall titers increased to an extent dependent upon the parental clone. Our data underscore manipulation of TSC as a strategy to improve performance of CHO cell in bioreactors. Biotechnol. Bioeng. 2016;113: 1942-1952. © 2016 Wiley Periodicals, Inc.