Low-risk Status Research Articles

Multiparametric risk predictions for morbidity and mortality in patients with pulmonary arterial hypertension: insights from a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we aimed to evaluate risk predictions for morbidity and mortality. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). ESC/ERS 2022 risk scoring, COMPERA 2.0 and REVEAL lite 2 models were used for baseline risk predictions, and COMPERA 2.0 model was used for risk evaluation at follow-up. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age (mean +SD) was 51.27 + 21.37 years, and 72 % of patients were female. Incident cases were noted in 65.9 % of overall study group. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of overall patients, respectively. Background mono and dual targeted combinations, and sequential dual or triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. According to the ESC/ERS 2022 baseline risk scoring, low-, intermediate-, and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time was 867 (412-1667) days. Overall rates of mortality and CEP were 26 % and 39%, respectively. Prevalent versus incident cases were associated signifinatly lower mortality and CEP ( p=0.028 and p=0.024, respectively). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. Baseline high versus intermediate /low risk status were associated with a lower survival estimates for mortality and CEP in patients with PAH ( p=0.03 and p=0.003, respectively). Baseline COMPERA 2.0 risk status revealed significant differences in overall survival and CEP-free survival among risk groups ( p<0.0001 for both), but 1st year COMPERA 2.0 score did not (p=0.39 and p=0.06, respectively) . As compared to baseline, 1st year COMPERA 2.0 score decreased in 31 %, and remained unchanged in 34 % of patients. Baseline REVEAL lite 2.0 score was associated with mortality (hazard ratio (HR): 1.14;1.08-1.2, p<0.0001) and CEP (HR:1.17;1.1-1.25, p<0.0001) risks. Male sex (HR: 1.73; 1.2-2.51, p = 0.004), six-minute walk distance (p<0.001), functional class III/IV (HR: 2.52;1.47-4.32, p<0.001) and baseline low-risk status (HR:0.37;0.21-0.65, p<0.001) were independent predictors of mortality. Conclusions Our nation-wide data revealed current insights concerning the multiparametric risk predictions for morbidity and mortality in PAH.

Survival, mortality and epidemic risk status of COVID-19: a population-based Study in Golestan province, Iran

BackgroundAppreciating the various dimensions of the coronavirus disease 2019 (COVID-19) pandemic can improve health systems and prepare them to deal better with future pandemics and public health events. This study was conducted to investigate the association between the survival of hospitalized patients with COVID-19 and the epidemic risk stratification of the disease in Golestan province, Iran.MethodsIn this study, all patients with COVID-19 who were hospitalized in the hospitals of Golestan province of Iran from February 20, 2020, to December 19, 2022, and were registered in the Medical Care Monitoring Center (MCMC) system (85,885 individuals) were examined.The community's epidemic risk status (ERS) was determined based on the daily incidence statistics of COVID-19. The survival distribution and compare Survival in different subgroups was investigated using Kaplan–Meier and log-rank test and association between the survival and ERS by multiple Cox regression modeling.ResultsOut of 68,983 individuals whose data were correctly recorded, the mean age was 49 (SD = 23.98) years, and 52.8% were women. In total, 11.1% eventually died. The length of hospital stay was varying significantly with age, gender, ERS, underlying diseases, and COVID-19 severity (P < 0.001 for all). The adjusted hazard ratio of death for the ERS at medium, high, and very high-risk status compared to the low-risk status increased by 19%, 26%, and 56%, respectively (P < 0.001 for all).ConclusionsEnhancing preparedness, facilitating rapid rises in hospital capacities, and developing backup healthcare capacities can prevent excessive hospital referrals during health crises and further deaths.

A five-gene prognosis model based on lysine β-hydroxybutyrylation site genes to predict the survival and therapy response in pancreatic adenocarcinoma

BackgroundPancreatic adenocarcinoma (PAAD) is one of the most malignancy diseases. Lysine β-hydroxybutyrylation (Kbhb) has been reported to involve various metabolism and cancer progression. MethodsData from online databases (TCGA and GEO) were retrieved for the selection of differential expressed Kbhb site genes (DTRGs). Univariate cox and LASSO analysis were performed to identify the prognostic DTRGs. Based on the optimal DTRGs, a prognostic risk score model was established. Kaplan-Meier and Receiver operator characteristic analysis were conducted to evaluate the predicting ability of the prognosis model. Generated with clinical data, independent analysis and nomogram model were performed. Finally, the differences of survival, immune cell levels, immunotherapy response, drug sensitivity between high- and low-risk groups were explored. ResultsA total of 63 DTRGs were identified in PAAD, and these genes were related to cell division and apoptosis biological functions. Through univariate cox regression and LASSO analysis, 30 DTRGs were selected to be related to prognosis and five (KRT18, ANLN, ECT2, RBM5, and RBM6) were identified as the optimal DTRGs in PAAD. Based on the five optimal DTRGs, a prognostic risk score model was constructed, with promising predictive ability in PAAD survival (AUC >0.70). High-risk group showed lower survival rate (P < 0.05). Moreover, based on the risk score, a nomogram model was also established, which possessed perfect stability. Finally, lower risk score was related to higher immune cell levels, indicating an immune activation in low-risk status, which maybe the reason for the better survival in low-risk group. Furthermore, the immunotherapy response and drug sensitivity were all higher than that in low-risk groups (P < 0.05). ConclusionA five-gene prognosis risk model which exhibit promising predictive ability in survival is constructed for patients with PAAD.

Polyserositis as an Initial Manifestation of Chronic Lymphocytic Lymphoma

Abstract Chronic lymphocytic lymphoma (CLL) is a lymphoproliferative malignancy characterized by the generation and accumulation of CD5+ monoclonal B-cell lymphocytes, which are physically mature lymphocytes with aberrant immunological activity. The common presenting features are lymphadenopathy and leukocytosis. Because of its asymptomatic and indolent appearance, CLL requires a high index of suspicion to be diagnosed. Our patient presented with unusual symptoms of malignant polyserositis without substantial lymphadenopathy or hepatosplenomegaly. Ascitic fluid cytology and flow cytometry were done to confirm the diagnosis. The patient was staged modified Rai 0 and Binet A and categorized as low-risk status. Treatment is usually advised at Rai stage II and Binet stage B and higher. Although there is no mention of ascites or pleural effusion in the staging disease or deciding therapy, malignant polyserositis carries a poor prognosis and the decision to treat should be individualized. Our patient was offered chemotherapy but the patient denied it. He was on regular follow-ups receiving palliative therapy.

Association of risk assessment at diagnosis with healthcare resource utilization and health-related quality of life outcomes in pulmonary arterial hypertension.

We aimed to describe the clinical characteristics, healthcare resource utilization (HCRU) and costs, health-related quality of life (HRQoL), and survival for patients with pulmonary arterial hypertension (PAH), stratified by 1-year mortality risk at diagnosis. Adults diagnosed with PAH at the Sheffield Pulmonary Vascular Disease Unit between 2012 and 2019 were included. Patients were categorized as low, intermediate, or high risk for 1-year mortality at diagnosis. Demographics, clinical characteristics, comorbidities, HCRU, costs, HRQoL, and survival were analyzed. Overall, 1717 patients were included: 72 (5%) at low risk, 941 (62%) at intermediate risk, and 496 (33%) at high risk. Low-risk patients had lower HCRU prediagnosis and 1-year postdiagnosis than intermediate- or high-risk patients. Postdiagnosis, there were significant changes in HCRU, particularly inpatient hospitalizations and accident and emergency (A&E) visits among high-risk patients. At 3 years postdiagnosis, HCRU for all measures was similar across risk groups. Low-risk patients had lower EmPHasis-10 scores (indicating better HRQoL) at diagnosis and at 1-year follow-up compared with intermediate- and high-risk patients; only the score in the high-risk group improved. Median overall survival decreased as risk category increased in analyzed subgroups. Low-risk status was associated with better 1-year survival and HRQoL compared with intermediate- and high-risk patients. HCRU decreased in high-risk patients postdiagnosis, with the most marked reduction in A&E admissions. The pattern of decreased per-patient inpatient hospitalizations and A&E visits at 3 years postdiagnosis suggests that a diagnosis of PAH helps to decrease HCRU in areas that are key drivers of costs.

Abstract PO3-02-04: Comparison of OncotypeDX Recurrence Scores (RS) and MammaPrint (MP) scores, and chemotherapy indications in early-stage Estrogen Receptor positive/HER2 negative (ER-/HER2-) breast cancer

Abstract Background: Both RS and MP are endorsed by ASCO and NCCN practice guidelines to estimate prognosis of early-stage ER+/HER2- breast cancers and results guide adjuvant chemotherapy treatment recommendations. Earlier studies reported around 30% discordance in risk assignments by different genomic assays, but these comparisons were complicated by the 3-way (low, intermediate, high) versus 2-way (low, high) risk assignment by RS and MP respectively. More recently, RS thresholds were re-evaluated in the context of the TAILORx and RxPONDER randomized clinical trials and RS &amp;gt;25 is now considered indication for adjuvant chemotherapy. MP results are now also reported as continuous scores similar to RS, and MP high risk patients can be subdivided into MP1 (high) and MP2 (ultra-high) risk groups. The goal of this analysis was to assess correlation between RS and MP scores as continuous variables and examine concordance in chemotherapy eligibility and risk category assignments. Methods: 168 patients treated at the West Cancer Center and Research Institute had patients with both MP and RS results available for the same patient generated by Agendia as a research activity and Exact Sciences in the context of routine care. Molecular class was assigned by the MammaPrint Blueprint assay. Results and clinical information were retrieved from the medical records. Median age was 64 years (range 25-92), 77% were postmenopausal, 59% White, 37% Black and 4% other. 78% had histologic grade 1 or 2 cancers, 53%, 38%, and 8% were stage I, II, and III, respectively. 84% were invasive ductal carcinoma, 13% invasive lobular carcinoma, the rest mixed or other rare histologies. Patients were considered high-risk and chemotherapy eligible if the RS was &amp;gt;25 or the MP score was &amp;lt; 0 (i.e. any negative value), MP high-risk patients were further categorized into MP1 (MP score between 0 to -0.5699) and MP2 (MPs score -0.57 or less). Correlation between scores were assessed using Pearson correlation. Results: There was statistically significant correlation between RS and MP scores with a Pearson correlation coefficient of -0.61, (p&amp;lt; 0.0001). 51 (30%) cancers were MP low-risk (Luminal A), and 122 (73%) were RS low risk (RS≤25). Among the MP low-risk cancers, 47 (92%) had concordant low risk assignment by RS. Based on RS, 46 (27%) patients were high-risk chemotherapy eligible and 42 of these (91%) were concordantly classified as MP high-risk. MP high-risk cancers included 115 Luminal B and 1 Basal-like cancers, and 64% of these (n=74) had low-risk status by RS. When the MP high category was subdivided into MP 1 (n=105) and MP2 (n=11) subgroups, (35/105) 33% and (7/11) 64% of cases were RS &amp;gt;25, respectively. Black patients had a statistically higher mean index MP score of -0.191 compared to -0.082 for White patients (p=0.02). No statistical difference was noted by race for RS. Conclusions: There was strong concordance (92%) between low-risk MP and low-risk RS. Similar concordance was not identified when comparing chemotherapy eligible high-risk MP (MP1 and MP2) to high-risk ( &amp;gt;25) recurrence scores. Only 36% of chemotherapy eligible MP patients (MP1 and MP2) would be chemotherapy eligible by RS. Higher concordance (58%) for chemotherapy eligibility was seen when limited to the ultra-high (MP2) scores. By contrast most (92%) of chemotherapy eligible patients by RS (&amp;gt;25) were considered high risk by MP (MP1 or MP2). Table1. RS and MP risk categories Citation Format: Rishika Singh, William Barlow, Nupur Singh, James Elliott, Richard Fine, Michael Berry, Erin Cobain, Lajos Pusztai, Gregory Vidal. Comparison of OncotypeDX Recurrence Scores (RS) and MammaPrint (MP) scores, and chemotherapy indications in early-stage Estrogen Receptor positive/HER2 negative (ER-/HER2-) breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-04.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time. We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score. At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up. The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines.

Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. TheCOMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Assessing quality of life in pulmonary arterial hypertension: An independent prognostic marker.

Pulmonary arterial hypertension (PAH, or PH Group 1), a disease of aberrant pulmonary vascular remodeling, causing progressive right heart failure (RHF) due to elevation of pulmonary vascular resistance (PVR). Patient mortality risk stratification guides choice and intensity of pharmacological intervention and is assessed by haemodynamics (especially PVR) as well as noninvasive tools including WHO functional class (FC), 6-min walk distance (6MWD), and NT-proBNP levels. Quality of life (QOL) assessment is acknowledged as a central aspect of patient-centered care, but our study sought to extend QOL's role as an additional noninvasive risk marker that could further refine risk stratification and hence therapeutic choices within a "treatment to target" paradigm (aiming to achieve low-risk status). This study found that QOL assessment using the PAH-SYMPACT© physical activity tool provided enhanced, independent mortality risk information, with one unit rise in this score associated with a 41% increase in likelihood risk (odds ratio 1.41, 95% confidence interval: 1.01-1.98 (p < 0.05)) of falling within intermediate versus low-group category. We therefore found further support for additional prognostic value being conferred by measurement of QOL as part of routine PAH evaluation, reinforcing its critical role.

CD74 is expressed in a subset of pediatric acute myeloid leukemia patients and is a promising target for therapy: a report from the Children's Oncology Group.

As curative therapies for pediatric acute myleoid leukemia (AML) remain elusive, identifying potential new treatment targets is vital. We assessed the cell surface expression of CD74, also known as the major histocompatibility complex-II invariant chain, by multidimensional flow cytometry in 973 patients enrolled in the Children's Oncology Group AAML1031 clinical trial (clinicaltrials gov. Identifier: NCT01371981). Thirty-eight percent of pediatric AML patients expressed CD74 at any level and a comparison to normal hematopoietic cells revealed a subset with increased expression relative to normal myeloid progenitor cells. Pediatric AML patients expressing high intensity CD74 typically had an immature immunophenotype and an increased frequency of lymphoid antigen expression. Increased CD74 expression was associated with older patients with lower white blood cells and peripheral blood blast counts, and was enriched for t(8;21), trisomy 8, and CEBPA mutations. Overall, high CD74 expression was associated with low-risk status, however 26% of patients were allocated to high-risk protocol status and 5-year event-free survival was 53%, indicating that a significant number of high expressing patients had poor outcomes. In vitro preclinical studies indicate that anti-CD74 therapy demonstrates efficacy against AML cells but has little impact on normal CD34+ cells. Together, we demonstrate that CD74 is expressed on a subset of pediatric AML at increased levels compared to normal hematopoietic cells and is a promising target for therapy in expressing patients. Given that nearly half of patients expressing CD74 at high levels experience an adverse event within 5 years, and the availability of CD74 targeting drugs, this represents a promising line of therapy worthy of additional investigation.

Higher Molecular Injury at Diagnosis of Acute Cellular Rejection Increases the Risk of Lung Allograft Failure: A Clinical Trial.

Rationale: The association of acute cellular rejection (ACR) with chronic lung allograft dysfunction (CLAD) in lung transplant recipients has primarily been described before consensus recommendations incorporating restrictive phenotypes. Furthermore, the association of the degree of molecular allograft injury during ACR with CLAD or death remains undefined. Objectives: To investigate the association of ACR with the risk of CLAD or death and to further investigate if this risk depends on the degree of molecular allograft injury. Methods: This multicenter, prospective cohort study included 188 lung transplant recipients. Subjects underwent serial plasma collections for donor-derived cell-free DNA (dd-cfDNA) at prespecified time points and bronchoscopy. Multivariable Cox proportional-hazards analysis was conducted to analyze the association of ACR with subsequent CLAD or death as well as the association of dd-cfDNA during ACR with risk of CLAD or death. Additional outcomes analyses were performed with episodes of ACR categorized as "high risk" (dd-cfDNA ⩾ 1%) and "low risk" (dd-cfDNA < 1%). Measurements and Main Results: In multivariable analysis, ACR was associated with the composite outcome of CLAD or death (hazard ratio [HR], 2.07 [95% confidence interval (CI), 1.05-4.10]; P = 0.036). Elevated dd-cfDNA ⩾ 1% at ACR diagnosis was independently associated with increased risk of CLAD or death (HR, 3.32; 95% CI, 1.31-8.40; P = 0.012). Patients with high-risk ACR were at increased risk of CLAD or death (HR, 3.13; 95% CI, 1.41-6.93; P = 0.005), whereas patients with low-risk status ACR were not. Conclusions: Patients with ACR are at higher risk of CLAD or death, but this may depend on the degree of underlying allograft injury at the molecular level. Clinical trial registered with www.clinicaltrials.gov (NCT02423070).

Factors Influencing Omega-3 Index Status in Active-Duty Military Personnel.

This study assessed omega-3 fatty acid (O3FA) status, previous brain injury risk exposures, and associations between O3FA status and risk exposures among active-duty military personnel. O3FA status was measured by a Holman omega-3 blood test. A survey was conducted to assess brain injury risk history and dietary O3FA factors. More than 50% of the participants had high-risk status, based on an omega-3 index (O3I) <4%, while less than 2% of the participants recorded low-risk O3I (>8%). O3FA supplementation (p<.001, Cramer's V=0.342) and fish consumption (p<.001, Cramer's V=0.210) were positively correlated with O3FA status. Only 5 O3FA supplement users (n=97 [5.2%]) had a low-risk O3I status, while all nonusers (n=223) had moderateto high-risk O3I status. Supplementing with O3FA was associated with better O3I status in this population. However, only a few participants achieved optimal O3I status even when taking an O3FA supplement. Participants who ate fish and did not supplement were in the moderateor high-risk O3I groups.

Analysis of urinary tobacco-specific nitrosamine 4- (methylnitrosamino)1-(3-pyridyl)-1- butanol (NNAL) and HPV infection in American women: National health and nutrition examination survey.

Tobacco-specific nitrosamines (TSNAs) are a group of toxic substances specific to tobacco. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. We aimed to examine the association between urinary tobacco-specific NNAL and HPV infection among American women. We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014 to collect details on their urinary NNAL, HPV infection status, and other essential variables. The association between dietary urinary NNAL and HPV infection status was analyzed by using a weighted multivariate logistic regression model, and stratified subgroup analysis. In total, 5197 participants aged 18-59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 22.0% and 19.1%, respectively. The highest quartile of NNAL(Q4) was more positively associated with low-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 1.83 (1.35,2.50), p<0.001). the highest quartile of NNAL(Q4) was more positively associated with high-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 2.20 (1.57,3.08), p < 0.001). In subgroup analyses, the positive correlation between urinary NNAL levels and low-risk HPV infection status was inconsistent in marital status and BMI (interaction p < 0.05). The positive association of urinary NNAL levels with high-risk HPV infection status was inconsistent in smoking and BMI. (interaction p < 0.05). Tobacco-specific NNAL levels positively correlate with high- and low-risk HPV. Future well-designed longitudinal studies are still needed to validate the effect of tobacco exposure on HPV infection by NNAL.

Clinical characteristics, treatment, and outcome of low-risk non-HIV-associated cryptococcal meningitis: A retrospective cohort study.

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P=.012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP<250-mm H2O, 60.0% vs. 32.4%, P=.001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P<.001), higher baseline CSF white blood cell (median, 130 vs. 90, P=.029) and CSF protein (median, 0.87 vs. 0.73, P=.011). Multivariate analysis showed that baseline CSF OP<250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P=.019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P<.001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P<.001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP< 250-mm H2O were prone to the low-risk status.

Predictive validity of the reduced Cariogram model for caries increment in non-cavitated and cavitated lesions: cohort study

BackgroundThe aim of this study is to assess the caries prediction of the reduced Cariogram by comparing baseline caries risk profiles with non-cavitated and cavitated lesions over periods of six, twelve, and 18 months.MethodsFrom May 2016 to October 2017, seven schools in Bhakkar, Pakistan, participated in a cohort study. First base line examination was conducted followed by examinations at 6, 12 and 18 months. Children intraoral examinations were performed on portable dental chair with in school premises by a trained examiner. A modified ICDAS index was used to measure caries at baseline and at follow-up examinations after 6, 12, and 18-months. A receiver operating curve (ROC) analysis was performed to evaluate its effectiveness for predicting dental caries increment.ResultsAbout 40% of children had a low-risk status, 30.5% medium risk, and 29.7% high risk, at baseline risk assessment. At 18 months, 73% of high-risk children, 59% of medium-risk children, and 41% of low-risk children showed a caries increment. For the reduced Cariogram model, the area under the curve on the 6, 12 and 18 months follow-up was 0.63, 0.65 and 0.70 respectively.ConclusionsOur findings indicates that a reduced Cariogram can predict the progression of caries in both cavitated and non-cavitated lesions and model exhibits a level of discriminatory ability. While it might not achieve a very high accuracy, it suggests that the model is able to predict caries increment effectively than random guessing.

Are changes in mothers’ representations of their infants related to changes in observed mother–infant interaction quality?

Infant mental health clinicians aiming to improve mother–infant dyads at risk typically target mothers’ representations of their infant or mother–infant interactions, assuming that one port of entry leads to change in the other. However, little is known about the relation between changes in mothers’ representations and in mother–infant interactions. Therefore, the current study aimed to investigate this in a low- to moderate-risk community sample of 152 mothers (M = 29.7 years) of infants aged 0–2 years (M = 11.5 months) recruited from rural and urban cities in Norway. The mothers’ representations were measured using the Working Model of the Child Interview, and the quality of the mother–infant interactions was measured with the Emotional Availability Scales. We found no evidence of a relation between mothers’ changed representations and changed quality of mother–infant interactions. Several explanations concerning the low-risk status of the sample, the observation situation, the time between assessment points, and the homogeneous scores from the instruments used are discussed, as are the implications for clinical practice and future research.

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterised by remodelling of the pulmonary arteries and progressive narrowing of the pulmonary vasculature. This leads to a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure and, if left untreated, to right ventricular failure and death. A correct diagnosis requires a complete work-up including right heart catheterisation performed in a specialised centre.Although our knowledge of the epidemiology, pathology and pathophysiology of the disease, as well as the development of innovative therapies, has progressed in recent decades, PAH remains a serious clinical condition. Current treatments for the disease target the three specific pathways of endothelial dysfunction that characterise PAH: the endothelin, nitric oxide and prostacyclin pathways.The current treatment algorithm is based on the assessment of severity using a multiparametric risk stratification approach at the time of diagnosis (baseline) and at regular follow-up visits. It recommends the initiation of combination therapy in PAH patients without cardiopulmonary comorbidities. The choice of therapy (dual or triple) depends on the initial severity of the condition. The main treatment goal is to achieve low-risk status. Further escalation of treatment is required if low-risk status is not achieved at subsequent follow-up assessments. In the most severe patients, who are already on maximal medical therapy, lung transplantation may be indicated.Recent advances in understanding the pathophysiology of the disease have led to the development of promising emerging therapies targeting dysfunctional pathways beyond endothelial dysfunction, including the TGF-β and PDGF pathways.

Predictive Role of a Novel Ferroptosis-Related lncRNA Pairs Model in the Prognosis of Papillary Thyroid Carcinoma.

This study aimed to evaluate the potential prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid carcinoma (PTC). Based on The TCGA database, lncRNAs and ferroptosis-related genes with differential expression levels in PTC tumors vs. normal tissues were screened. After the co-expression network construction, ferroptosis-related lncRNAs (FRLs) were screened. Kaplan-Meier analysis was conducted to compare the survival performance of patients with PTC in the high- and low-risk groups. Furthermore, a nomogram was created to enhance PTC prognosis. CIBERSORT was used to investigate the infiltration of various immune cells in high- and low-risk groups. In total, 10 lncRNA pairs with differential expression levels were obtained. There were significant differences in the histological subtype and pathological stage between the high- and low-risk groups, and age (P = 7.39E-13) and FRLM model status (P = 1.09E-04) were identified as independent prognostic factors. Subsequently, the nomogram survival model showed that the predicted one-, three-, and five-year survival rates were similar to the actual one- (c-index = 0.8475), three- (c-index = 0.7964), and five-year (c-index = 0.7555) survival rates. Subjects in the low-risk group had significantly more CD4 + memory T cells and resting myeloid dendritic cells, and subjects in the high-risk group had more plasma B cells and monocytes. The risk assessment model constructed using FRLs showed good predictive value for the prognosis of patients with PTC.

Risk Stratification in Pulmonary Arterial Hypertension, Update and Perspectives

Risk stratification in pulmonary arterial hypertension (PAH) is crucial in assessing patient prognosis. It serves a prominent role in everyday patient care and can be determined using several validated risk assessment scores worldwide. The recently published 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines underline the importance of risk stratification not only at baseline but also during follow-up. Achieving a low-risk status has now become the therapeutic goal, emphasising the importance of personalised therapy. The application of these guidelines is also important in determining the timing for lung transplantation referral. In this review, we summarise the most relevant prognostic factors of PAH as well as the parameters used in PAH risk scores and their evolution in the guidelines over the last decade. Finally, we describe the central role that risk stratification plays in the current guidelines not only in European countries but also in Asian countries.