Levator muscle resection for simple congenital ptosis: its impact on preoperative levator function and dose-response ratio.

OBJECTIVE: The primary aim of this study is to calculate the dose-response ratio in patients with different levels of levator function following levator resection in simple congenital ptosis. The secondary outcome is to evaluate the success rate and effect of levator resection on postoperative levator function. METHODS: In a retrospective study, the medical records of patients were reviewed for age, gender, laterality, preoperative and postoperative measurements (palpebral fissure height, marginal reflex distance 1, and levator function), magnitude of levator resection, follow-up time, and postoperative complications. RESULTS: Of 154 patients with a mean age of 17.12 ± 11.14 years, 54 patients had excellent levator function, 41 had good function, and 59 had fair function. Following surgery, the mean levator function increased from 8.81 ± 3.40 mm to 11.29 ± 3.25 mm. The magnitude of increase in the 3 groups of excellent, good, and fair was 3.18 ± 2.63, 2.53 ± 2.24 and 1.92 ± 1.80 mm, respectively. The rate of success was 81.8% with no statistically significant difference in the 3 groups. In a multivariate logistic regression, older age, local anaesthesia, and milder ptosis were predictors of success. A table of dose-response ratios was calculated that determined the amounts of levator muscle resection for 1 mm of marginal reflex distance 1 and levator function increase. CONCLUSIONS: Levator resection has high success rate in patients with simple congenital ptosis. The function of levator muscle improved significantly following surgery, and the rate of improvement was higher in patients with better preoperative levator function.

Pharmacists' role in detection and evaluation of adverse drug reactions: Developing proactive systems for pharmacosurveillance.

PURPOSE: To identify current challenges in detection of medication-related symptoms, and review technology-based opportunities to increase the patient-centeredness of postmarketing pharmacosurveillance to promote more accountable, safer, patient-friendly, and equitable medication prescribing. SUMMARY: Pharmacists have an important role to play in detection and evaluation of adverse drug reactions (ADRs). The pharmacist's role in medication management should extend beyond simply dispensing drugs, and this article delineates the rationale and proactive approaches for pharmacist detection and assessment of ADRs. We describe a stepwise approach for assessment, best practices, and lessons learned from a pharmacist-led randomized trial, the CEDAR (Calling for Detection of Adverse Drug Reactions) project. CONCLUSION: Health systems need to be redesigned to more fully utilize health information technologies and pharmacists in detecting and responding to ADRs.

The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment.

Macrophages are among the most common cells in the colorectal cancer microenvironment, but their prognostic significance is incompletely understood. Using multiplexed immunofluorescence for CD68, CD86, IRF5, MAF, MRC1 (CD206), and KRT (cytokeratins) combined with digital image analysis and machine learning, we assessed the polarization spectrum of tumor-associated macrophages in 931 colorectal carcinomas. We then applied Cox proportional hazards regression to assess prognostic survival associations of intraepithelial and stromal densities of M1-like and M2-like macrophages while controlling for potential confounders, including stage and microsatellite instability status. We found that high tumor stromal density of M2-like macrophages was associated with worse cancer-specific survival, whereas tumor stromal density of M1-like macrophages was not significantly associated with better cancer-specific survival. High M1:M2 density ratio in tumor stroma was associated with better cancer-specific survival. Overall macrophage densities in tumor intraepithelial or stromal regions were not prognostic. These findings suggested that macrophage polarization state, rather than their overall density, was associated with cancer-specific survival, with M1- and M2-like macrophage phenotypes exhibiting distinct prognostic roles. These results highlight the utility of a multimarker strategy to assess the macrophage polarization at single-cell resolution within the tumor microenvironment.

Prognostic Significance of Immune Cell Populations Identified by Machine Learning in Colorectal Cancer Using Routine Hematoxylin and Eosin-Stained Sections.

PURPOSE: Although high T-cell density is a well-established favorable prognostic factor in colorectal cancer, the prognostic significance of tumor-associated plasma cells, neutrophils, and eosinophils is less well-defined. EXPERIMENTAL DESIGN: We computationally processed digital images of hematoxylin and eosin (H&E)-stained sections to identify lymphocytes, plasma cells, neutrophils, and eosinophils in tumor intraepithelial and stromal areas of 934 colorectal cancers in two prospective cohort studies. Multivariable Cox proportional hazards regression was used to compute mortality HR according to cell density quartiles. The spatial patterns of immune cell infiltration were studied using the GTumor:Immune cell function, which estimates the likelihood of any tumor cell in a sample having at least one neighboring immune cell of the specified type within a certain radius. Validation studies were performed on an independent cohort of 570 colorectal cancers. RESULTS: Immune cell densities measured by the automated classifier demonstrated high correlation with densities both from manual counts and those obtained from an independently trained automated classifier (Spearman's ρ 0.71-0.96). High densities of stromal lymphocytes and eosinophils were associated with better cancer-specific survival [P trend < 0.001; multivariable HR (4th vs 1st quartile of eosinophils), 0.49; 95% confidence interval, 0.34-0.71]. High GTumor:Lymphocyte area under the curve (AUC0,20µm; P trend = 0.002) and high GTumor:Eosinophil AUC0,20µm (P trend < 0.001) also showed associations with better cancer-specific survival. High stromal eosinophil density was also associated with better cancer-specific survival in the validation cohort (P trend < 0.001). CONCLUSIONS: These findings highlight the potential for machine learning assessment of H&E-stained sections to provide robust, quantitative tumor-immune biomarkers for precision medicine.

Association of Vitamin D Deficiency and Thyroid Function in Postmenopausal Women.

Pupose: Although there are reports of vitamin D (VitD) insufficiency in immune-mediated hypothyroidism, an association between VitD and thyroid-stimulating hormone (TSH) levels has yet to be shown. We aim to examine VitD and TSH levels among postmenopausal women, as both conditions are more prevalent in elderly women. Methods: The clinic records of postmenopausal women during their routine maintenance visits were reviewed. All patients were examined for the symptoms related to thyroid function and osteoporosis. Participants were divided into three subgroups according to their TSH levels (below <0.5 mIU/L, 0.51-4.0 mIU/L and >4.0 mIU/L). Patient characteristics and VitD levels were compared between these subgroups. Multivariate linear regression model was constructed using serum VitD and serum TSH as the dependent variables to identify factors independently associated with these laboratory values. Results: Two-hundred and nighty nine postmenopausal women were included. Average age was 62.2±7.5 years old. VitD was insufficient (10-30 ng/mL) in 12.0% and deficient (<10 ng/mL) in 60.9% of the participants. In 11.3%, TSH was low and in 7.6% of women, TSH was high, while the remaining 80.1%, had normal TSH levels. Subjects with low TSH had significantly higher VitD concentrations (34.2±29.1 ng/mL) compared to the other two groups (P-value: 0.039). In multivariate regression analysis, TSH was not a contributing factor, as age was the only significant predictor of VitD levels. Meanwhile, no predictor (including age and VitD) was identified for TSH levels in linear regression analysis. Conclusion: Age was the only independent predictor of serum VitD in this study population. Though suppressed TSH was associated with higher VitD levels, the association was not linear between TSH and VitD in postmenopausal women.