Tag: pubmed

PLoS One. 2023 Jan 4;18(1):e0266985. doi: 10.1371/journal.pone.0266985. eCollection 2023.

ABSTRACT

PURPOSE: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.

METHODS: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.

RESULTS: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).

CONCLUSION: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

PMID:36598895 | DOI:10.1371/journal.pone.0266985

PLoS One. 2023 Jan 4;18(1):e0279163. doi: 10.1371/journal.pone.0279163. eCollection 2023.

ABSTRACT

OBJECTIVES: Understand the continuity and changes in headache not-otherwise-specified (NOS), migraine, and post-traumatic headache (PTH) diagnoses after the transition from ICD-9-CM to ICD-10-CM in the Veterans Health Administration (VHA).

BACKGROUND: Headache is one of the most commonly diagnosed chronic conditions managed within primary and specialty care clinics. The VHA transitioned from ICD-9-CM to ICD-10-CM on October-1-2015. The effect transitioning on coding of specific headache diagnoses is unknown. Accuracy of headache diagnosis is important since different headache types respond to different treatments.

METHODS: We mapped headache diagnoses from ICD-9-CM (FY 2014/2015) onto ICD-10-CM (FY 2016/2017) and computed coding proportions two years before/after the transition in VHA. We used queries to determine the change in transition pathways. We report the odds of ICD-10-CM coding associated with ICD-9-CM controlling for provider type, and patient age, sex, and race/ethnicity.

RESULTS: Only 37%, 58% and 34% of patients with ICD-9-CM coding of NOS, migraine, and PTH respectively had an ICD-10-CM headache diagnosis. Of those with an ICD-10-CM diagnosis, 73-79% had a single headache diagnosis. The odds ratios for receiving the same code in both ICD-9-CM and ICD-10-CM after adjustment for ICD-9-CM and ICD-10-CM headache comorbidities and sociodemographic factors were high (range 6-26) and statistically significant. Specifically, 75% of patients with headache NOS had received one headache diagnoses (Adjusted headache NOS-ICD-9-CM OR for headache NOS-ICD-10-CM = 6.1, 95% CI 5.89-6.32. 79% of migraineurs had one headache diagnoses, mostly migraine (Adjusted migraine-ICD-9-CM OR for migraine-ICD-10-CM = 26.43, 95% CI 25.51-27.38). The same held true for PTH (Adjusted PTH-ICD-9-CM OR for PTH-ICD-10-CM = 22.92, 95% CI: 18.97-27.68). These strong associations remained after adjustment for specialist care in ICD-10-CM follow-up period.

DISCUSSION: The majority of people with ICD-9-CM headache diagnoses did not have an ICD-10-CM headache diagnosis. However, a given diagnosis in ICD-9-CM by a primary care provider (PCP) was significantly predictive of its assignment in ICD-10-CM as was seeing either a neurologist or physiatrist (compared to a generalist) for an ICD-10-CM headache diagnosis.

CONCLUSION: When a veteran had a specific diagnosis in ICD-9-CM, the odds of being coded with the same diagnosis in ICD-10-CM were significantly higher. Specialist visit during the ICD-10-CM period was independently associated with all three ICD-10-CM headaches.

PMID:36598881 | DOI:10.1371/journal.pone.0279163

ACS Macro Lett. 2023 Jan 4:101-106. doi: 10.1021/acsmacrolett.2c00706. Online ahead of print.

ABSTRACT

A systematic investigation of the synthesis and characterization of a new class of amorphous atactic cis, trans poly(methylene-1,3-cyclopentane-stat-cyclohexane) statistical copolymers (I) is reported. Production of different grades of I that vary with respect to the ratio of 5- and 6-membered cycloalkane repeat units was achieved through the living coordinative chain transfer cyclopolymerization of different initial feed ratios of 1,5-hexadiene and 1,6-heptadiene comonomers. It was determined that the glass transition temperature, T_g, of I can be systematically increased from -16 to 100 °C as a function of increasing 6-membered ring content, although not in a strictly linear fashion. It was further determined that a small level of 6-membered ring content is sufficient to disrupt the crystallinity of the limiting atactic cis, trans poly(methylene-1,3-cyclopentane) (PMCP) homopolymer that possesses a melting temperature, T_m, of 98 °C. These results establish a foundation for future potential technological applications of this unique class of polyolefin copolymers.

PMID:36598863 | DOI:10.1021/acsmacrolett.2c00706

Mol Biol Cell. 2023 Jan 4:mbcE21030099. doi: 10.1091/mbc.E21-03-0099. Online ahead of print.

ABSTRACT

Rho GTPases regulate cell morphogenesis and motility under the tight control of guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). However, the underlying mechanism(s) that coordinate their spatiotemporal activities, whether separately or together, remain unclear. We show that a pro-metastatic RhoGAP, ARHGAP8/BPGAP1, binds to inactive Rac1 and localizes to lamellipodia. BPGAP1 recruits the RacGEF Vav1 under EGF stimulation and activates Rac1, leading to polarized cell motility, spreading, invadopodium formation, cell extravasation and promotes cancer cell migration. Importantly, BPGAP1 downregulates local RhoA activity which influences Rac1 binding to BPGAP1 and its subsequent activation by Vav1. Our results highlight the importance of BPGAP1 in recruiting Vav1 and Rac1 to promote Rac1 activation for cell motility. BPGAP1 also serves to control the timing of Rac1 activation with RhoA inactivation via its RhoGAP activity. BPGAP1, therefore, acts as a dual-function scaffold that recruits Vav1 to activate Rac1 while inactivating RhoA to synchronize both Rho and Rac signalling in cell motility. As EGFR, Vav1, RhoA, Rac1 and BPGAP1 are all associated with cancer metastasis, BPGAP1 could provide a crucial checkpoint for the EGFR-BPGAP1-Vav1-Rac1-RhoA signalling axis for cancer intervention. [Media: see text] [Media: see text] [Media: see text].

PMID:36598812 | DOI:10.1091/mbc.E21-03-0099

J Med Internet Res. 2023 Jan 4;25:e42040. doi: 10.2196/42040.

ABSTRACT

BACKGROUND: The novel concept of immersive 3D augmented reality (AR) surgical navigation has recently been introduced in the medical field. This method allows surgeons to directly focus on the surgical objective without having to look at a separate monitor. In the dental field, the recently developed AR-assisted dental implant navigation system (AR navigation), which uses innovative image technology to directly visualize and track a presurgical plan over an actual surgical site, has attracted great interest.

OBJECTIVE: This study is the first systematic review and meta-analysis study that aimed to assess the accuracy of dental implants placed by AR navigation and compare it with that of the widely used implant placement methods, including the freehand method (FH), template-based static guidance (TG), and conventional navigation (CN).

METHODS: Individual search strategies were used in PubMed (MEDLINE), Scopus, ScienceDirect, Cochrane Library, and Google Scholar to search for articles published until March 21, 2022. This study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database. Peer-reviewed journal articles evaluating the positional deviations of dental implants placed using AR-assisted implant navigation systems were included. Cohen d statistical power analysis was used to investigate the effect size estimate and CIs of standardized mean differences (SMDs) between data sets.

RESULTS: Among the 425 articles retrieved, 15 articles were considered eligible for narrative review, 8 articles were considered for single-arm meta-analysis, and 4 were included in a 2-arm meta-analysis. The mean lateral, global, depth, and angular deviations of the dental implant placed using AR navigation were 0.90 (95% CI 0.78-1.02) mm, 1.18 (95% CI 0.95-1.41) mm, 0.78 (95% CI 0.48-1.08) mm, and 3.96° (95% CI 3.45°-4.48°), respectively. The accuracy of AR navigation was significantly higher than that of the FH method (SMD=-1.01; 95% CI -1.47 to -0.55; P<.001) and CN method (SMD=-0.46; 95% CI -0.64 to -0.29; P<.001). However, the accuracies of the AR navigation and TG methods were similar (SMD=0.06; 95% CI -0.62 to 0.74; P=.73).

CONCLUSIONS: The positional deviations of AR-navigated implant placements were within the safety zone, suggesting clinically acceptable accuracy of the AR navigation method. Moreover, the accuracy of AR implant navigation was comparable with that of the highly recommended dental implant-guided surgery method, TG, and superior to that of the conventional FH and CN methods. This review highlights the possibility of using AR navigation as an effective and accurate immersive surgical guide for dental implant placement.

PMID:36598798 | DOI:10.2196/42040

JAMA Netw Open. 2023 Jan 3;6(1):e2248685. doi: 10.1001/jamanetworkopen.2022.48685.

ABSTRACT

IMPORTANCE: Fetal ultrasonography is essential for confirmation of gestational age (GA), and accurate GA assessment is important for providing appropriate care throughout pregnancy and for identifying complications, including fetal growth disorders. Derivation of GA from manual fetal biometry measurements (ie, head, abdomen, and femur) is operator dependent and time-consuming.

OBJECTIVE: To develop artificial intelligence (AI) models to estimate GA with higher accuracy and reliability, leveraging standard biometry images and fly-to ultrasonography videos.

DESIGN, SETTING, AND PARTICIPANTS: To improve GA estimates, this diagnostic study used AI to interpret standard plane ultrasonography images and fly-to ultrasonography videos, which are 5- to 10-second videos that can be automatically recorded as part of the standard of care before the still image is captured. Three AI models were developed and validated: (1) an image model using standard plane images, (2) a video model using fly-to videos, and (3) an ensemble model (combining both image and video models). The models were trained and evaluated on data from the Fetal Age Machine Learning Initiative (FAMLI) cohort, which included participants from 2 study sites at Chapel Hill, North Carolina (US), and Lusaka, Zambia. Participants were eligible to be part of this study if they received routine antenatal care at 1 of these sites, were aged 18 years or older, had a viable intrauterine singleton pregnancy, and could provide written consent. They were not eligible if they had known uterine or fetal abnormality, or had any other conditions that would make participation unsafe or complicate interpretation. Data analysis was performed from January to July 2022.

MAIN OUTCOMES AND MEASURES: The primary analysis outcome for GA was the mean difference in absolute error between the GA model estimate and the clinical standard estimate, with the ground truth GA extrapolated from the initial GA estimated at an initial examination.

RESULTS: Of the total cohort of 3842 participants, data were calculated for a test set of 404 participants with a mean (SD) age of 28.8 (5.6) years at enrollment. All models were statistically superior to standard fetal biometry-based GA estimates derived from images captured by expert sonographers. The ensemble model had the lowest mean absolute error compared with the clinical standard fetal biometry (mean [SD] difference, -1.51 [3.96] days; 95% CI, -1.90 to -1.10 days). All 3 models outperformed standard biometry by a more substantial margin on fetuses that were predicted to be small for their GA.

CONCLUSIONS AND RELEVANCE: These findings suggest that AI models have the potential to empower trained operators to estimate GA with higher accuracy.

PMID:36598790 | DOI:10.1001/jamanetworkopen.2022.48685

JAMA Netw Open. 2023 Jan 3;6(1):e2249370. doi: 10.1001/jamanetworkopen.2022.49370.

ABSTRACT

IMPORTANCE: Prevalent use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, previous studies were limited by inclusion of individuals with prevalent hypertension and a history of antihypertensive use prior to the start of the study, which can introduce bias.

OBJECTIVE: To examine the association of new use of antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors with Alzheimer disease and related dementias (ADRD) among Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among 57 773 Medicare fee-for-service beneficiaries (January 1, 2006, through December 31, 2018) aged 65 years or older with incident hypertension. Data analysis was conducted from January 1 through June 30, 2022.

EXPOSURES: Initiation of antihypertensive medication regimens that stimulate or inhibit type 2 and 4 angiotensin II receptors, or mixed regimens (both stimulating and inhibiting), with the time-dependent measure being each 30-day interval.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to first occurrence of ADRD (Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse definition). Cox proportional hazards regression modeling with time-dependent variables was performed to estimate the association between time-dependent treatment groups and time to ADRD, after adjusting for sociodemographic and clinical characteristics.

RESULTS: The sample included 57 773 Medicare beneficiaries (36 348 women [62.9%]; mean [SD] age, 73.8 [6.3] years; 2954 [5.1%] Black, 1545 [2.7%] Hispanic; 50 184 [86.9%] White, and 3090 [5.4%] Other individuals [the Other category included individuals of American Indian, Asian, other, or unknown race and ethnicity]). During a median of 6.9 years (IQR, 4.7-9.3 years) of follow-up, the unadjusted incidence density rate of ADRD was 2.2 cases per 100 person-years (95% CI, 2.1-2.4 cases per 100 person-years) for the group receiving regimens that stimulate type 2 and 4 angiotensin II receptors compared with 3.1 cases per 100 person-years (95% CI, 3.0-3.2 cases per 100 person-years) for the group receiving regimens that inhibit type 2 and 4 angiotensin II receptors and 2.7 cases per 100 person-years (95% CI, 2.6-2.9 cases per 100 person-years) for the group receiving mixed treatment regimens. In adjusted Cox proportional hazards regression modeling, stimulating treatment was associated with a statistically significant 16% reduction in the hazard of ADRD compared with inhibiting treatment (hazard ratio, 0.84; 95% CI, 0.79-0.90). Mixed regimen use was also associated with reduced hazards of ADRD compared with the inhibiting group (hazard ratio, 0.90; 95% CI, 0.84-0.96).

CONCLUSIONS AND RELEVANCE: This cohort study of Medicare beneficiaries suggests that use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors was associated with lower risk of ADRD compared with antihypertensive medications that inhibit these receptors. Confirmation is needed in a randomized trial.

PMID:36598787 | DOI:10.1001/jamanetworkopen.2022.49370

JAMA Dermatol. 2023 Jan 4. doi: 10.1001/jamadermatol.2022.5607. Online ahead of print.

ABSTRACT

IMPORTANCE: Keloids and hypertrophic scars (excessive scarring) are relatively understudied disfiguring chronic skin conditions with high treatment resistance.

OBJECTIVE: To evaluate established comorbidities of excessive scarring in European individuals, with comparisons across ethnic groups, and to identify novel comorbidities via a phenome-wide association study (PheWAS).

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cross-sectional population-based cohort study used UK Biobank (UKB) data and fitted logistic regression models for testing associations between excessive scarring and a variety of outcomes, including previously studied comorbidities and 1518 systematically defined disease categories. Additional modeling was performed within subgroups of participants defined by self-reported ethnicity (as defined in UK Biobank). Of 502 701 UKB participants, analyses were restricted to 230078 individuals with linked primary care records.

EXPOSURES: Keloid or hypertrophic scar diagnoses.

MAIN OUTCOMES AND MEASURES: Previously studied disease associations (hypertension, uterine leiomyoma, vitamin D deficiency, atopic eczema) and phenotypes defined in the PheWAS Catalog.

RESULTS: Of the 972 people with excessive scarring, there was a higher proportion of female participants compared with the 229 106 controls (65% vs 55%) and a lower proportion of White ethnicity (86% vs 95%); mean (SD) age of the total cohort was 64 (8) years. Associations were identified with hypertension and atopic eczema in models accounting for age, sex, and ethnicity, and the association with atopic eczema (odds ratio [OR], 1.68; 95% CI, 1.36-2.07; P < .001) remained statistically significant after accounting for additional potential confounders. Fully adjusted analyses within ethnic groups revealed associations with hypertension in Black participants (OR, 2.05; 95% CI, 1.13-3.72; P = .02) and with vitamin D deficiency in Asian participants (OR, 2.24; 95% CI, 1.26-3.97; P = .006). The association with uterine leiomyoma was borderline significant in Black women (OR, 1.93; 95% CI, 1.00-3.71; P = .05), whereas the association with atopic eczema was significant in White participants (OR, 1.68; 95% CI, 1.34-2.12; P < .001) and showed a similar trend in Asian (OR, 2.17; 95% CI, 1.01-4.67; P = .048) and Black participants (OR, 1.89; 95% CI, 0.83-4.28; P = .13). The PheWAS identified 110 significant associations across disease systems; of the nondermatological, musculoskeletal disease and pain symptoms were prominent.

CONCLUSIONS AND RELEVANCE: This cross-sectional study validated comorbidities of excessive scarring in UKB with comprehensive coverage of health outcomes. It also documented additional phenome-wide associations that will serve as a reference for future studies to investigate common underlying pathophysiologic mechanisms.

PMID:36598763 | DOI:10.1001/jamadermatol.2022.5607

J Trauma Acute Care Surg. 2023 Jan 5. doi: 10.1097/TA.0000000000003858. Online ahead of print.

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality in the pediatric population. Microglia and infiltrating monocyte-derived macrophages (MDMs) are crucial immune cells that modulate the neuroinflammatory response following TBI. Using C34, a novel pharmacologic TLR4 inhibitor, we investigated the intricate interactions between these cells in a murine TBI model.

METHODS: A murine controlled cortical impact (CCI) model was utilized, and the results were analyzed on post-injury days (PID) 1, 7, 28 and 35. The experimental groups are (1) Sham C57BL/6 wild-type (WT), (2) TBI WT, (3) Sham WT + C34 and (4) TBI WT + C34. Real-time PCR (qRT-PCR) was used to quantify gene expression associated with microglial activation, apoptotic pathways and type 1 interferon pathway. Flow cytometry was used to isolate microglia and infiltrating monocytes. Brain lesion volumes were assessed using MRI. Last, neurocognitive outcomes were evaluated using the Morris Water Maze (MWM) test. Student’s T-test and One-way ANOVA were used for statistical analysis with significance achieved when p < 0.05.

RESULTS: TLR4 inhibition leads to improved neurological sequela post-TBI, possibly due to an increase in infiltrating anti-inflammatory monocytes and a decrease in IRF7 during acute inflammation, followed by a reduction in apoptosis and M2 microglial expression during chronic inflammation.

CONCLUSIONS: TLR4 inhibition with C34 skews infiltrating monocytes towards an anti-inflammatory phenotype leading to enhanced neurocognitive outcomes. Moreover, although M2 microglia have been consistently shown as inducers of neuroprotection, our results clearly demonstrate their detrimental role during the chronic phases of healing post-TBI.Study type: Original Research (Basic Science).

PMID:36598757 | DOI:10.1097/TA.0000000000003858

Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320221149849. doi: 10.1177/03946320221149849.

ABSTRACT

OBJECTIVE: Airway inflammation is a prominent feature of asthma and may play an important role in disease pathophysiology. Despite the increasing incidence of asthma worldwide, reliable diagnostic biomarkers are lacking and widely lead to asthma misdiagnosis. Neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation, in addition to NLR-alanine aminotransferase ratio (NAR) and NLR-albumin ratio (NBR). The aim of this study was to evaluate associations of NLR, NAR, and NBR with diagnosis of childhood asthma to determine if they can aid clinical childhood asthma diagnosis.

METHODS: This retrospective case-control study included 89 children with asthma and 53 healthy children from the Wuxi Children’s Hospital affiliated with Nanjing Medical University. We applied various statistical tests to the dataset: Mann-Whitney U test to compare characteristics of the case and control groups; chi-squared test to compare categorical variables; Kruskal-Wallis test to compare statistical differences of asthma indicators among groups; receiver operating characteristic (ROC) curves to assess the diagnostic value of indices; and Spearman correlation analysis to evaluate relationships between NLR and lactate dehydrogenase, albumin, aspartate transaminase, and alanine transaminase levels.

RESULTS: Compared with controls, the asthma case group had significantly higher white blood cell (p < 0.01), neutrophil, lactate dehydrogenase, C-reactive protein, and NLR levels (p < 0.01) and significantly lower lymphocyte (p = 0.001), platelet (p = 0.039), and albumin levels (p = 0.04). We determined optimal cutoff levels for several metrics: 1.723 for NLR, with sensitivity of 0.73 and specificity of 0.906; 0.135 for NAR, with sensitivity of 0.685 and specificity of 0.887; and 0.045 for NBR, with sensitivity of 0.674 and specificity of 0.906. The areas under the curve (AUCs) were 0.824 for NLR, 0.788 for NAR, 0.818 for NBR, and 0.83 for the combination of NLR + NAR + NBR.

CONCLUSION: The combination of NLR, NAR, and NBR biomarkers distinguished asthmatic ones suffering from exacerbation of the condition from healthy children. Thus, our results indicate NLR + NAR + NBR could be used as a clinical biomarker for asthma in children.

PMID:36598755 | DOI:10.1177/03946320221149849