Citations

ABSTRACT The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022. Two reviewers independently extracted data and assessed the risk of bias. We defined patients' important outcomes and used grading of recommendations, assessment, development, and evaluation (GRADE) to provide the structure for quantifying absolute effects and rating the quality of evidence. Seven randomized trials of 12 publications that enrolled a total of 386 patients proved eligible. The follow-up duration ranged from 1 to 36 months. Compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life (mean difference [MD] 3.4, 95% confidence interval [CI] 1.5–5.3, minimally important difference 3.0, moderate certainty). PTH therapy results in more patients reaching 50% or greater reduction in the dose of active vitamin D and calcium (relative risk [RR] = 6.5, 95% CI 2.5–16.4, 385 more per 1000 patients, high certainty). PTH therapy may increase hypercalcemia (RR =2.4, 95% CI 1.2–5.04, low certainty). The findings may support the use of PTH therapy in patients with chronic hypoparathyroidism. Because of limitations of short duration and small sample size, evidence from randomized trials is limited regarding important benefits of PTH therapy compared with conventional therapy. Establishing such benefits will require further studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

ABSTRACT The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II). We searched Medline, Medline In-Process, EMBASE, and Cochrane CENTRAL to identify complications and symptoms associated with chronic hypoparathyroidism. We used two predefined criteria (at least three studies reported the complication and symptom and had statistically significantly greater pooled relative estimates). To estimate prevalence, we used the median and interquartile range (IQR) of the studies reporting complications and symptoms. For testing the predictive values of early postoperative measurements of PTH and calcium, we used a bivariate model to perform diagnostic test meta-analysis. In Part I, the 93 eligible studies enrolled a total of 18,973 patients and reported on 170 complications and symptoms. We identified nine most common complications or symptoms probably associated with chronic hypoparathyroidism. The complications or symptoms and the prevalence are as follows: nephrocalcinosis/nephrolithiasis (median prevalence among all studies 15%), renal insufficiency (12%), cataract (17%), seizures (11%), arrhythmia (7%), ischemic heart disease (7%), depression (9%), infection (11%), and all-cause mortality (6%). In Part II, 18 studies with 4325 patients proved eligible. For PTH measurement, regarding the posttest probability, PTH values above 10 pg/mL 12–24 hours postsurgery virtually exclude chronic hypoparathyroidism irrespective of pretest probability (100%). When PTH values are below 10 pg/mL, posttest probabilities range from 3% to 64%. Nine complications and symptoms are probably associated with chronic hypoparathyroidism. A PTH value above a threshold of 10 pg/mL 12–24 hours after total thyroidectomy is a strong predictor that the patients will not develop chronic hypoparathyroidism. Patients with PTH values below the threshold need careful monitoring as some will develop chronic hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

Abstract Activation of innate immunity in the brain is a prominent feature of Alzheimer's disease (AD). The present study investigated the regulation of innate immunity by young serum in a transgenic AD mouse model. We found that young serum significantly reduced the number of neutrophils and microglial reactivity in the brains of APP/PS1 mice. Neutrophil depletion via Ly6G neutralizing antibodies mimicked the benefits of young serum on AD brain functions. Serum proteomic analysis of young serum revealed significant enrichment of the factors VEGF-A and CXCL1, which are crucial for neutrophil migration and chemotaxis, leukocyte migration, and cell chemotaxis. Intravenously injected VEGF-A reversed Aβ-induced decreases in Cdk5 and increases in CXCL1 in vitro and blocked neutrophil infiltration into the AD brain. Endothelial Cdk5 overexpression conferred an inhibitory effect on CXCL1 and neutrophil infiltration and thereby restored memory in APP/PS1 mice. Our data uncover a previously unknown link between blood-derived VEGF signaling and neutrophil infiltration and provide a rationale for targeting endothelial Cdk5 signaling as a potential therapeutic strategy for AD.

Abstract Rapid point-of-care (POC) diagnosis of bacterial infection diseases provides clinical benefits of prompt initiation of antimicrobial therapy and reduction of the overuse/misuse of unnecessary antibiotics for nonbacterial infections. We present here a POC compatible method for rapid bacterial infection detection in 10 min. We use a large-volume solution scattering imaging (LVSi) system with low magnifications (1–2×) to visualize bacteria in clinical samples, thus eliminating the need for culture-based isolation and enrichment. We tracked multiple intrinsic phenotypic features of individual cells in a short video. By clustering these features with a simple machine learning algorithm, we can differentiate Escherichia coli from similar-sized polystyrene beads, distinguish bacteria with different shapes, and distinguish E. coli from urine particles. We applied the method to detect urinary tract infections in 104 patient urine samples with a 30 s LVSi video, and the results showed 92.3% accuracy compared with the clinical culture results. This technology provides opportunities for rapid bacterial infection diagnosis at POC settings.

PURPOSEThe advancement of natural language processing (NLP) has promoted the use of detailed textual data in electronic health records (EHRs) to support cancer research and to facilitate patient care. In this review, we aim to assess EHR for cancer research and patient care by using the Minimal Common Oncology Data Elements (mCODE), which is a community-driven effort to define a minimal set of data elements for cancer research and practice. Specifically, we aim to assess the alignment of NLP-extracted data elements with mCODE and review existing NLP methodologies for extracting said data elements.METHODSPublished literature studies were searched to retrieve cancer-related NLP articles that were written in English and published between January 2010 and September 2020 from main literature databases. After the retrieval, articles with EHRs as the data source were manually identified. A charting form was developed for relevant study analysis and used to categorize data including four main topics: metadata, EHR data and targeted cancer types, NLP methodology, and oncology data elements and standards.RESULTSA total of 123 publications were selected finally and included in our analysis. We found that cancer research and patient care require some data elements beyond mCODE as expected. Transparency and reproductivity are not sufficient in NLP methods, and inconsistency in NLP evaluation exists.CONCLUSIONWe conducted a comprehensive review of cancer NLP for research and patient care using EHRs data. Issues and barriers for wide adoption of cancer NLP were identified and discussed.

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.

Abstract Background and purpose: Poor ST-segment resolution (STR) is strongly associated with poor prognosis in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). previous studies suggested higher HCY level in the people who live in high altitudes, so a retrospective analysis is conducted to examine the potential relationship between elevated serum HCY and poor STR after PPCI at high altitudes. Methods: This retrospective analysis included 308 high-altitude dwelling patients (1800-2200 meters elevation from the sea level) undergoing PPCI for STEMI during a period from September 2021 to March 2022. Clinical data were collected and statistically analyzed. Results: In comparison to the patients with normal plasma homocysteine (≤15 mmol/L; n = 155), patients with elevated homocysteine (>15 mmol/L) had higher percentage of men (92.81% vs. 80.00%; p = 0.001) and smoker (79.08% vs. 63.87%; p = 0.003), but no difference in other key baseline characteristics. The rate of complete ST-segment resolution after PPCI (≥ 70%) was 83.23% in the control group and 49.67% in the elevated HCY group (p ≤ 0.001). In multivariable regression analysis, poor ST-segment resolution (<70%) was independently associated with longer pain-to-balloon time (OR 0.832; 95%CI: 0.775–0.894), lower uric acid (OR 1.003; 95%CI: 1.000-1.005), and elevated HCY (OR 0.957 vs. normal HCY; 95%CI: 0.937–0.977). Conclusion: Elevated plasma HCY level was associated with poor ST segment resolution in patients undergoing PPCI STEMI at high altitude.

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P<0.001). Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

Background: Black adults experience a disproportionately higher burden of cardiovascular risk factors and disease in comparison with White adults in the United States. Less is known about how sex-based disparities in cardiovascular mortality between these groups have changed on a national scale over the past 20 years, particularly across geographic determinants of health and residential racial segregation. Methods: We used CDC WONDER (Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research) to identify Black and White adults age ≥25 years in the United States from 1999 to 2019. We calculated annual age-adjusted cardiovascular mortality rates (per 100 000) for Black and White women and men, as well as absolute rate differences and rate ratios to compare the mortality gap between these groups. We also examined patterns by US census region, rural versus urban residence, and degree of neighborhood segregation. Results: From 1999 to 2019, age-adjusted mortality rates declined overall for both Black and White adults. There was a decline in age-adjusted cardiovascular mortality among Black (602.1 to 351.8 per 100 000 population) and White women (447.0 to 267.5), and the absolute rate difference (ARD) between these groups decreased over time (1999: ARD, 155.1 [95% CI, 149.9–160.3]; 2019: ARD, 84.3 [95% CI, 81.2–87.4]). These patterns were similar for Black (824.1 to 526.3 per 100 000) and White men (637.5 to 396.0; 1999: ARD, 186.6 [95% CI, 178.6–194.6]; 2019: ARD, 130.3 [95% CI, 125.6–135.0]). Despite this progress, cardiovascular mortality in 2019 was higher for Black women (rate ratio, 1.32 [95% CI, 1.30–1.33])— especially in the younger (age <65 years) subgroup (rate ratio, 2.28 [95% CI, 2.23–2.32])—as well as for Black men (rate ratio, 1.33 [95% CI, 1.32–1.34]), compared with their respective White counterparts. There was regional variation in cardiovascular mortality patterns, and the Black-White gap differed across rural and urban areas. Cardiovascular mortality rates among Black women and men were consistently higher in communities with high levels of racial segregation compared with those with low to moderate levels. Conclusions: During the past 2 decades, age-adjusted cardiovascular mortality declined significantly for Black and White adults in the United States, as did the absolute difference in death rates between these groups. Despite this progress, Black women and men continue to experience higher cardiovascular mortality rates than their White counterparts.