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The mechanism of post-acute sequelae of SARS-CoV-2 (PASC) is unknown. Using optical coherence tomography angiography (OCT-A), we compared retinal foveal avascular zone (FAZ), vessel density (VD), and vessel length density (VLD) in non-hospitalized Neuro-PASC patients with those in healthy controls in an effort to elucidate the mechanism underlying this debilitating condition. Neuro-PASC patients with a positive SARS-CoV-2 test and neurological symptoms lasting ≥6 weeks were included. Those with prior COVID-19 hospitalization were excluded. Subjects underwent OCT-A with segmentation of the full retinal slab into the superficial (SCP) and deep (DCP) capillary plexus. The FAZ was manually delineated on the full slab in ImageJ. An ImageJ macro was used to measure VD and VLD. OCT-A variables were analyzed using linear mixed-effects models with fixed effects for Neuro-PASC, age, and sex, and a random effect for patient to account for measurements from both eyes. The coefficient of Neuro-PASC status was used to determine statistical significance; p-values were adjusted using the Benjamani–Hochberg procedure. Neuro-PASC patients (N = 30; 60 eyes) exhibited a statistically significant (p = 0.005) reduction in DCP VLD compared to healthy controls (N = 44; 80 eyes). The sole reduction in DCP VLD in Neuro-PASC may suggest preferential involvement of the smallest blood vessels.

Introduction The complete blood count (CBC) is the most commonly ordered blood test with a large range of reference values that do not consider time of day for interpretation. Clinicians are largely unfamiliar with the influence of time of day on CBC values. Our objective was to systematically review this topic to report on peak and trough timing of CBC values. Methods A systematic search of PubMed, Ovid, Scopus, CINAHL, Cochrane, Embase, and Web of Science was performed for studies evaluating any part of the CBC over 24 hours. The studies were screened for eligibility based on predetermined criteria including: measurement of a part of the CBC with at least 3 time points in 24 hours. In total, 164 full-text articles were screened and 32 were included in the final analysis. The aggregated data was analyzed with the Cosinor package of R statistical environment and Stata SE to create cosinor graphs and Forest plots for each component of the CBC, respectively. Results Of the 32 articles, a metalysis was performed on the following CBC subsets: leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Lymphocytes exhibited a statistically significant diurnal rhythm (p=0.014, n=10 articles) with a peak of 2280.10 cells/uL at 23:17 (CI: 1731.80, 2828.40) and trough of 1661.49 cells/uL at 08:53 (CI: 1242.64, 2080.33). Erythrocytes, hemoglobin, and hematocrit peaked in the morning; while platelets, neutrophils, monocytes, and basophils peaked in the late afternoon and early evening; and lymphocytes and eosinophils peaked late at night. High heterogeneity in the results across studies was noted, likely attributable to the difference in circadian factors controlled. Limitations include the small sample size for each component of the CBC, the limited samples included in the meta analysis, and the significant heterogeneity affecting the results. Conclusion There are significant time of day changes in CBC values that might be important to consider as we move towards precision medicine. Given the limited number of studies with small sample sizes, future work should evaluate large data sources to inform time-dependent interpretation of the CBC. Support (if any)

The complete blood count (CBC) is one of the most commonly ordered blood tests with a large range of reference values that does not consider time of day for interpretation. Our objective was to systematically review this topic to report on peak and trough timing of CBC values. A systematic search was performed for studies evaluating any component of the CBC with at least three collections over 24 hours. The studies were screened based on the predetermined eligibility criteria. Meta-analysis of aggregated data was analyzed with polynomial functions and forest plots. In total, 164 full-text articles were screened and 32 included in the final analysis with 548 total patients considering either leukocytes (  = 13), erythrocytes (  = 7), hemoglobin (  = 5), hematocrit (  = 5), platelets (  = 12), neutrophils (  = 11), lymphocytes (  = 13), monocytes (  = 8), eosinophils (  = 15), or basophils (  = 9). CBC components were analyzed by polynomial and forest plot analysis. Lymphocytes fitted best to a third-degree polynomial function (  = .010) with peak at 2264.87 cells/µL at 23:54 (CI: 1783.44 to 2746.31) with a trough of 1598.91 cells/µL at 10:47 (CI: 1230.12 to 1967.71). Lymphocytes and eosinophils peaked overnight, while erythrocytes, hemoglobin, and hematocrit peaked in the morning, and platelets, neutrophils, monocytes, and basophils peaked in late afternoon. Limitations include small sample size and significant study heterogeneity. We identified a limited scope of studies characterizing CBC component rhythms. However, we still noted significant differences, particularly with lymphocytes. Future work should evaluate larger datasets to inform time-dependent interpretation of the CBC as we move toward precision medicine.

PurposeTo develop nomograms that predict the detection of clinically significant prostate cancer (csPCa, defined as ≥GG2 [Grade Group 2]) at diagnostic biopsy based on multiparametric prostate MRI (mpMRI), serum biomarkers, and patient clinicodemographic features.Materials and methodsNomograms were developed from a cohort of biopsy-naïve men presenting to our 11-hospital system with prostate specific antigen (PSA) of 2–20 ng/mL who underwent pre-biopsy mpMRI from March 2018-June 2021 (n = 1494). The outcomes were the presence of csPCa and high-grade prostate cancer (defined as ≥GG3 prostate cancer). Using significant variables on multivariable logistic regression, individual nomograms were developed for men with total PSA, % free PSA, or prostate health index (PHI) when available. The nomograms were both internally validated and evaluated in an independent cohort of 366 men presenting to our hospital system from July 2021-February 2022.Results1031 of 1494 men (69%) underwent biopsy after initial evaluation with mpMRI, 493 (47.8%) of whom were found to have ≥GG2 PCa, and 271 (26.3%) were found to have ≥GG3 PCa. Age, race, highest PIRADS score, prostate health index when available, % free PSA when available, and PSA density were significant predictors of ≥GG2 and ≥GG3 PCa on multivariable analysis and were used for nomogram generation. Accuracy of nomograms in both the training cohort and independent cohort were high, with areas under the curves (AUC) of ≥0.885 in the training cohort and ≥0.896 in the independent validation cohort. In our independent validation cohort, our model for ≥GG2 prostate cancer with PHI saved 39.1% of biopsies (143/366) while only missing 0.8% of csPCa (1/124) with a biopsy threshold of 20% probability of csPCa.ConclusionsHere we developed nomograms combining serum testing and mpMRI to help clinicians risk stratify patients with elevated PSA of 2–20 ng/mL who are being considered for biopsy. Our nomograms are available at https://rossnm1.shinyapps.io/MynMRIskCalculator/ to aid with biopsy decisions.

ObjectivesYouth are at high risk of sexually transmitted infections (STIs) in Africa. We aimed to determine the risk factors for curable STIs in youth in Zimbabwe.MethodsA population-based survey was conducted among randomly selected 18–24 year-olds in 16 communities across two provinces in Zimbabwe to ascertain outcomes for a cluster randomised trial investigating the impact of community-based STI screening for youth on population prevalence of STIs. Participants underwent an interviewer-administered questionnaire, HIV testing and screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Risk factors for curable STIs were explored through multivariable logistic regression.ResultsOf the 5601 participants, 62.5% (n=3500) were female, and the median age was 20 (IQR 19–22) years. HIV prevalence was 6.3% (351/5556), and 55.4% (1939/3501) reported condomless sex at last intercourse. Only 7.2% (401/5599) reported STI symptoms, but CT/NG/TV prevalence was 19.8% (1107/5601). On multivariable analysis, factors associated with STI diagnosis included being aged 21–24 years (adjusted OR (aOR) 1.37, 95% CI 1.17 to 1.61); female sex (aOR 2.11, 95% CI 1.76 to 2.53); being unemployed/informally employed (compared with in education/formal employment) (aOR 1.35, 95% CI 1.13 to 1.61); increasing number of sexual partners in the preceding 12 months (one partner: aOR 2.23, 95% CI 1.73 to 2.88; two partners: aOR 2.39, 95% CI 1.69 to 3.39); living with HIV (aOR 1.44, 95% CI 1.07 to 1.94); and previous attempted suicide (aOR 1.58, 95% CI 1.08 to 2.32).ConclusionsThe prevalence of STIs among youth in Zimbabwe is high, particularly among those with HIV. In addition to moving away from syndromic STI management and strengthening implementation of existing prevention tools, there is a need for a more holistic focus on broader risk factors such as mental health and employment opportunities, and of integration of HIV and STI programming.Trial registration number ISRCTN15013425, NCT03719521.