Index Score Research Articles

Performance of risk scores in predicting major bleeding in left ventricular assist device recipients: a comparative external validation

BackgroundImplantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern. ObjectivesWe evaluated current risk scores’ predictive accuracy for MB in LVAD recipients. MethodsWe conducted an observational, single-center study of LVAD recipients (HeartWare or HeartMate-3, November 2010-December 2022) in the Netherlands. The primary outcome was the first post-LVAD MB (according to the International Society on Thrombosis and Haemostasis [ISTH] and Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and INTERMACS combined with intracranial bleeding [INTERMACS+] criteria). Mortality prior to MB was considered a competing event. Discrimination (C-statistic) and calibration were evaluated for the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke score, Anticoagulation and Risk Factors in Atrial Fibrillation score, Outpatient Bleeding Risk Index, venous thromboembolism score, atrial fibrillation score, and Utah Bleeding Risk Score (UBRS). ResultsOne hundred four patients were included (median age, 64 years; female, 20.2%; HeartWare, 90.4%; HeartMate-3, 9.6%). The cumulative MB incidence was 75.7% (95% CI 65.5%-85.9%) by ISTH and INTERMACS+ criteria and 67.0% (95% CI 56.0%-78.0%) per INTERMACS criteria over a median event-free follow-up time of 1916 days (range, 59-4521). All scores had poor discriminative ability on their intended prediction timeframe. Cumulative area under the receiving operator characteristic curve ranged from 0.49 (95% CI 0.35-0.63, venous thromboembolism-BLEED) to 0.56 (95% CI 0.47-0.65, UBRS) according to ISTH and INTERMACS+ criteria and from 0.48 (95% CI 0.40-0.56, Anticoagulation and Risk Factors in Atrial Fibrillation) to 0.56 (95% CI 0.47-0.65, UBRS) per INTERMACS criteria. All models showed poor calibration, largely underestimating MB risk. ConclusionCurrent bleeding risk scores exhibit inadequate predictive accuracy for LVAD recipients. There is a need for an accurate risk score to identify LVAD patients at high risk of MB who may benefit from patient-tailored antithrombotic therapy.

Effect of Colchicine Treatment on Clinical Course in Children with PFAPA Syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) is the most common periodic fever condition in children. There is no consensus on treatment to prevent attacks and reduce their frequency. In this study, we aimed to evaluate the effectiveness of colchicine treatment in PFAPA syndrome. In addition, we described the demographic and clinical features of PFAPA patients. We retrospectively analyzed 58 PFAPA patients who were started on colchicine treatment between January 2017 and January 2022. Demographic data, clinical features, laboratory tests, genetic analysis of MEditerranean FeVer (MEFV) mutations, and autoinflammatory disease activity index (AIDAI) scores of all patients were evaluated. In addition, patients were divided into two groups according to MEFV variants and compared. Attack frequency, duration, and AIDAI scores decreased in all patients after colchicine treatment. Duration of follow-up was 13.53±6.65 months. The median±IQR age at diagnosis was 3.2 (2-5) years. Thirty three (56.9%) patients had heterozygous mutations of MEFV. The most common MEFV variants were M694V (63.6%). There was no significant difference between the two groups in terms of colchicine responses. Colchicine treatment is effective and safe in patients with PFAPA who have frequent attacks. No association was established between the presence of heterozygous mutations of MEFV and colchicine response.

Identification of the immune repertoire of γδ T-cell receptors in psoriasis.

The γδ Tcells are a subpopulation of Tcells that are abundantly found in the skin and mucous membranes. Their reactivity to self-antigens and ability to secrete various cytokines make them a key component in psoriasis development. Although the correlation between the immune repertoire (IR) of γδ T-cell receptors and the occurrence and severity of psoriasis remains incompletely explored, high-throughput sequencing of γδ Tcells has led to a deeper understanding of IR in psoriasis. This study investigated the differences between γδ Tcells in patients with psoriasis and healthy controls. The γδ Tcells were identified via immunofluorescence staining and a correlation analysis was performed according to the psoriasis area and severity index (PASI) scores. The IR sequencing method was used to detect IR in the γδ T-cell receptors. The findings demonstrated more skin γδ Tcells in patients with psoriasis, which were positively correlated with the PASI score. There were subtle differences in most variable (V), diversity (D) and joining (J) gene segments and VJ/VDJ combination segments between patients with psoriasis and healthy controls. However, a higher diversity of complementarity-determining region 3 (CDR3) was observed in patients with psoriasis. In summary, the IR of skin γδ Tcells was significantly altered in patients with psoriasis, and the diversity in the cell's CDR3 population is a promising biomarker for assessment of psoriasis severity.

Predictive Factors of Cloxacillin Susceptibility in Primary Bacterial Spinal Infection.

Prognostic study. The objective of this study is to identify predictive factors for cloxacillin susceptibility in spinal infections. A retrospective analysis was conducted using data from January 1, 1997, to December 31, 2021. The study included patients presenting with back pain and either a positive bacterial culture from the spine or radiological evidence of spinal infection (spondylodiscitis and/or epidural abscess) along with positive bacterial blood culture. Among 171 patients (127 males, 44 females), 53.2% had Staphylococcus isolates, with 40.4% showing cloxacillin resistance. Lower globulin levels (<33.5g/L), recent hospitalization within 90days, and residence in an old age home predicted gram-positive bacteria with cloxacillin resistance and gram-negative bacteria as causative organisms (P<.05). The 30-day and 1-year all-cause mortality rates were 0% and 8.2%, respectively. Higher red cell distribution width (RDW >16.1%) and Charlson comorbidity index (CCI) scores predicted 1-year all-cause mortality (P<.05). Intensive care unit admission was required for 9.9% of patients. This study identified predictive factors for spinal infection by gram-positive bacteria with cloxacillin resistance and gram-negative bacteria. Patients with lower globulin levels (<33.5g/L), recent hospitalization within 90days, or residency in an old age home upon admission should avoid standalone cloxacillin therapy and consider antibiotics with gram-negative coverage. Higher RDW (>16.1%) and CCI scores were associated with increased 1-year all-cause mortality. These findings contribute to treatment decision-making and improving patient outcomes in spinal infections.

Cognitive shadows in perimenopause: linking subjective cognitive decline (SCD) to menopausal symptom severity.

As women approach perimenopause, the incidence of Subjective Cognitive Decline (SCD) rises. This study aims to investigate the association between SCD and the severity of perimenopausal symptoms. Conducted at The Affiliated Hospital of Guizhou Medical University Menopause Clinic from November 2022 to June 2023. Participants, aged 40-55 years, were classified as perimenopausal using the STRAW + 10 criteria. SCD was assessed separately using the Chinese version of the SCD-Q9 scale and the SCD International Working Group (SCD-I) conceptual framework, while perimenopausal symptoms were evaluated with the Modified Kupperman Index (MKI). Linear relationships between MKI scores and SCD-Q9 scores were clarified using both univariate and multivariate linear regression analyses. Additionally, a multivariate Logistic regression analysis was conducted to examine the association between MKI scores and SCD classification based on SCD-I criteria. The primary outcomes were the Modified Kupperman Index scores, SCD-Q9 questionnaire scores, and the diagnosis of SCD based on SCD-I criteria. Among 101 participants, the average MKI score was 18.90 ± 9.74, and the average SCD-Q9 score was 4.57 ± 2.29. Both univariate and multivariate linear regressions demonstrated a positive correlation between these scores. A multivariate Logistic regression analysis, using MKI as the independent variable and SCD-I criteria classification as the dependent variable, revealed a significant positive association. A notable association exists between SCD and perimenopausal symptoms severity. This underscores the potential clinical importance of addressing perimenopausal symptoms to mitigate SCD risks in women. Further studies should focus on clarifying the causality between these factors.

The Glycemia Risk Index Predicts Performance of Diabetes Self-Management Habits in Youth With Type 1 Diabetes Mellitus.

The Glycemia Risk Index (GRI) was developed in adults with diabetes and is a validated metric of quality of glycemia. Little is known about the relationship between GRI and type 1 diabetes (T1D) self-management habits, a validated assessment of youths' engagement in habits associated with glycemic outcomes. We retrospectively examined the relationship between GRI and T1D self-management habits in youth with T1D who received care from a Midwest pediatric diabetes clinic network. The GRI was calculated using seven days of continuous glucose monitor (CGM) data, and T1D self-management habits were assessed ±seven days from the GRI score. A mixed-effects Poisson regression model was used to evaluate the total number of habits youth engaged in with GRI, glycated hemoglobin A1c (HbA1c), age, race, ethnicity, and insurance type as fixed effects and participant ID as a random effect to account for multiple clinic visits per individual. The cohort included 1182 youth aged 2.5 to 18.0 years (mean = 13.8, SD = 3.5) comprising 50.8% male, 84.6% non-Hispanic White, and 64.8% commercial insurance users across a total of 6029 clinic visits. Glycemia Risk Index scores decreased as total number of habits performed increased, suggesting youth who performed more self-management habits achieved a higher quality of glycemia. In youth using CGMs, GRI may serve as an easily obtainable metric to help identify youth with above target glycemia, and engagement/disengagement in the T1D self-management habits may inform clinicians with suitable interventions for improving glycemic outcomes.

Abrocitinib may improve itch and quality of life in patients with itch‐dominant atopic dermatitis

AbstractBackgroundPatients with atopic dermatitis (AD) exhibit heterogeneous clinical phenotypes, reflecting different combinations of itch and lesional severity. AD with severe itch but clear‐moderate lesions, also known as itch‐dominant AD, is a common clinical phenotype.ObjectivesTo evaluate abrocitinib efficacy in patients with moderate‐to‐severe AD who have itch‐dominant AD.MethodsThis post hoc analysis includes pooled data from clinical trials of patients with moderate‐to‐severe AD receiving abrocitinib (100 or 200 mg) as monotherapy (phase 2b; phase 3 JADE MONO‐1 and JADE MONO‐2) or in combination with topical therapy (phase 3 JADE COMPARE). Data from the ongoing long‐term JADE EXTEND trial (data cutoff April 2020) were also evaluated. Itch‐dominant AD was defined as baseline Peak Pruritus Numerical Rating Scale (PP‐NRS) score of 7−10 and Investigator's Global Assessment of 0−3 or Eczema Area and Severity Index of 0‒21. Assessments included a ≥4‐point improvement in PP‐NRS (PP‐NRS4), PP‐NRS score of 0 (no itch) or 1 (little itch) in patients with PP‐NRS score ≥2 at baseline, ≥4‐point improvement from baseline in Patient‐Oriented Eczema Measure (POEM‐4), Patient Global Assessment (PtGA) of clear or almost clear, and Dermatology Life Quality Index (DLQI) score of 0 or 1 (no impact or little impact of AD on quality of life [QoL]).ResultsIn the pooled monotherapy trials, 37% of patients had itch‐dominant AD at baseline. As early as Week 2, more patients with itch‐dominant AD achieved PP‐NRS4 with abrocitinib 100 mg (35%) and abrocitinib 200 mg (57%) versus placebo (7%); 6% and 22% versus 0%, respectively, achieved PP‐NRS 0/1. More patients achieved a PtGA of clear/almost clear at Week 12 with abrocitinib 100 mg (28%) and abrocitinib 200 mg (45%) than placebo (9%). Additionally, abrocitinib led to clinically meaningful improvements in POEM and DLQI. Most patients with itch‐dominant AD experienced itch improvement over time with abrocitinib monotherapy or with concomitant topical therapy; 86%–87% and 62%–67% of patients had no itch‐moderate itch and clear‐moderate lesions by weeks 24 and 48, respectively.ConclusionsAbrocitinib is highly efficacious in patients with itch‐dominant AD, demonstrating rapid, deep, and sustained improvements in itch and clinically meaningful improvements in patients' QoL.Trial Registration NumbersNCT02780167; NCT03349060; NCT03575871; NCT03720470; NCT03422822.

98 Adding parasite resistance to the breeding objective in hair sheep

Abstract Economic selection indexes provide the best method to achieve genetic gain for multiple traits simultaneously. Hair sheep enterprises, particularly in environments with substantial gastrointestinal nematode challenge, may benefit from incorporating parasite resistance in a selection index. However, obtaining the relative economic value (REV) for parasite resistance is challenging; information on its impact on productivity is incomplete, as are the costs of treatment given anthelmintic resistance. The National Sheep Improvement Program (NSIP) currently provides producers with an index designed to increase total weight of lamb weaned per ewe lambing (TW). Our objective was to assess the effects of including fecal egg count, an indicator of parasite resistance, as an additional goal trait. Including the benchmark scenario with TW as its sole objective, 10 indexes were constructed using standard index theory. Post-weaning fecal egg count (PFEC) was added to this breeding objective with a REV of -1 and the REV for TW was varied from +1 to +5 at +0.5 increments. Weaning weight, number of lambs born and weaned, and PFEC were the selection criteria, modelled as either phenotypes or estimated breeding values (EBV). Phenotypes and EBV were simulated for 1,000 lambs by Cholesky decomposition and used to generate index scores. Ten replicates were run and the top 3% of males and 26% of females were retained on index scores. Annual responses in the goal traits were estimated. Responses in PFEC were expressed as a percentage, assuming a mean PFEC of 2,089 eggs/g as in NSIP. Concordances with those selected in the benchmark scenario were determined. Using EBV as selection criteria, TW increased by 1.7 kg/yr in the benchmark scenario (Table 1). However, unfavorably, PFEC increased by 2.3%/yr. When phenotypic criteria were used, TW increased by 0.5 kg/yr, and PFEC by 0.3%/yr. Once added to the breeding objective, PFEC decreased regardless of the REV of TW. However, response in TW also reduced, although less so as its REV increased. With EBV as the criteria, the REV of +3 for TW appeared preferable: PFEC reduced by 7.1%/yr with 98% of the response in TW retained. With phenotypic selection criteria, PFEC reduced by 5.2%/yr with 94% of the response in TW retained. With +3 REV for TW and EBV as the selection criteria, on average 65% and 82% of males and females, respectively, were chosen in common with the benchmark. When phenotypic criteria were used, those percentages were 60% and 80%, respectively. Implementing a more holistic index with REV of +3 for TW and -1 for PFEC would result in reasonable responses in both traits. However, producers will need to decide if reduced gains in TW is acceptable to improve parasite resistance in a hair sheep breeding program.

Diagnostic performances of Fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score in metabolic dysfunction-associated steatotic liver disease in Asian primary care clinics.

We aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB-4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort. This retrospective cross-sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n=6740). The prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n=80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB-4 (0.824 in NAFLD vs. 0.818 in MASLD, p=0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p=0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB-4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD. Most patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB-4 in the MASLD cohort demonstrated satisfactory results.

Cornuside alleviates psoriasis-like skin lesions in mice by relieving inflammatory effects

Psoriasis is a chronic inflammatory skin disease substantially affecting the quality of life, with no complete cure owing to its complex pathogenesis. Cornuside, a major bioactive compound present in Cornus officinalis Sieb. et Zucc., which is a well-known traditional Chinese medicine with a variety of biological and pharmacological activities, such as anti-apoptotic, antioxidant, and anti-inflammatory properties. However, its effects on psoriasis remain unclear. Our preliminary analysis of network pharmacology showed that cornuside may be involved in psoriasis by regulating the inflammatory response and IL-17 signaling pathway. Thus, we investigated the protective role and mechanism of cornuside in the pathogenesis of psoriasis in an imiquimod (IMQ)-induced psoriasis mouse model. In-vivo experiments demonstrated that cornuside-treated mice had reduced skin erythema, scales, thickness, and inflammatory infiltration. The Psoriasis Area Severity Index score was significantly lower than that of the IMQ group. Flow cytometry analysis indicated that cornuside effectively inhibited Th1- and Th17-cell infiltration and promoted aggregation of Th2 cells in skin tissues. Cornuside also inhibited the infiltration of macrophages to the skin. Furthermore, in-vitro experiments indicated that cornuside also decreased the polarization of M1 macrophages and reduced the levels of associated cytokines. Western blotting demonstrated that cornuside suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular receptor kinase (ERK) in bone marrow-derived macrophages. Our findings indicate that cornuside has a protective effect against IMQ-induced psoriasis by inhibiting M1 macrophage polarization through the ERK and JNK signaling pathways and modulating the infiltration of immune cells as well as the expression of inflammatory factors.

197 Effects of dietary zinc supplementation strategy on immune response, bacterial load and disease severity in growing gilts infected with Mycoplasma hyopneumoniae.

Abstract The objective of this study was to assess impacts of dietary zinc (Zn) supplementation strategy on immune response, bacterial clearance, and disease severity in growing gilts infected with Mycoplasma hyopneumoniae. Weaned gilts [n = 96; 21-d old; initial body weight (BW) = 6.94 kg], were used in a 63-d experiment which consisted of a pre- (d 0-35) and post- (d 35-63) M. hyopneumoniae challenge. On d 0 (-35 d post-inoculation; dpi), gilts were confirmed negative for M. hyopneumoniae and PRRSv and assigned randomly to 1 of 2 dietary treatments with 8 pens/treatment and 6 gilts/pen. Treatments were: 1) Control; 125 mg/kg Zn from ZnSO4, and 2) Zn-blend; 125 mg/kg Zn with 50 mg/kg Zn from Zn-amino acid complex (ZnAA) and 75 mg/kg Zn from ZnSO4. Dietary treatments were fed in 4-phases with pharmacological levels of zinc oxide included in the first 2 phases. Phase 1 (d 0) control and Zn-blend diets contained 3,121 and 3,256 mg/kg total Zn, respectively. Phase 2 (d 0-14) control and Zn-blend diets contained 3,657 and 3,593 mg/kg total Zn, respectively. Phases 3 (d 14-35) and 4 (d 35-63) control and Zn-blend diets contained 213 and 193 mg/kg and 229 and 212 mg/kg total Zn, respectively. At 0 and 1 dpi, all gilts were inoculated intratracheally with 10 mL of a lung homogenate containing 1×105 CCU/mL of M. hyopneumoniae strain 232. Blood and tracheal secretions were collected on -35, 0, 7, 14, 21, 28 dpi. Blood samples were evaluated for antibody detection, and tracheal secretions were analyzed by PCR. Number of coughs were recorded daily from 7 to 28 dpi. At 28 dpi, gilts were humanely euthanized, and bronchoalveolar lavage fluid (BALF) and macroscopic lung lesion observations were collected. Gross lung lesions were scored, and lung tissues were fixed for histopathology. Normally distributed data were analyzed in a generalized linear model with the fixed effect of diet and repeated measures for days post-inoculation. Non-normal data were analyzed using a Mann Whitney U Test using the NPAR1WAY procedure of SAS with a fixed effect of diet or a Chi-square test. Gilts consuming control diets tended (21.68 vs. 20.90 Ct, P = 0.08) to have less relative bacterial load than those consuming Zn-blend diets, over time. No differences in mean sample-to-positive ratio or proportion of gilt seroconversion (P &amp;gt; 0.05) were detected between treatments. There were no differences in mean concentrations of IL-1α, IL-1β, IL-6, IL-8, IL-10 (P &amp;gt; 0.05) in BALF for gilts consuming control or Zn-blend diets. There were no differences in mean macroscopic (P = 0.73) or microscopic (P = 0.67) lung scores, and coughing index score (P = 0.25) over the entire period between gilts consuming the different dietary Zn supplementation strategies. In conclusion, growing gilts consuming diets containing different Zn sources exhibited similar signs of infection during the acute phase of a M. hyopneumoniae infection.

Dapagliflozin and quality of life measured using the EuroQol 5-dimension questionnaire in patients with heart failure with reduced and mildly reduced/preserved ejection fraction.

Although much is known about the usefulness of heart failure (HF)-specific instruments for assessing patient well-being, less is known about the value of generic instruments for the measurement of health-related quality of life (HRQL) in HF. The aim of this study was to assess the relationship between the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analogue scale (VAS) and index scores, clinical characteristics, and outcomes in patients with HF and the effect of dapagliflozin on these scores. We performed a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which investigated the effectiveness and safety of dapagliflozin in patients with HF and reduced ejection fraction (HFrEF) and mildly reduced/preserved ejection fraction (HFmrEF/HFpEF), respectively. Patients reporting higher (better) EQ-5D-5L VAS and index scores had a lower prevalence of comorbidities, including atrial fibrillation and hypertension, than patients with a worse score. They were also more likely to have better investigator-reported (New York Heart Association class) and patient-self-reported (Kansas City Cardiomyopathy Questionnaire) health status and lower median N-terminal pro-B-type natriuretic peptide levels. Compared to patients with the lowest scores (Q1), those with higher EQ-5D-5L VAS scores had better outcomes: the hazard ratio for the composite of cardiovascular death or worsening HF was 0.81 (95% confidence interval 0.72-0.91) in Q2, 0.74 (0.65-0.84) in Q3, and 0.62 (0.54-0.72) in Q4. The risk of each component of the composite outcome, and all-cause death, was also lower in patients with better scores. Similar findings were observed for the index score. Treatment with dapagliflozin improved both EQ-5D-5L VAS and index scores across the range of ejection fraction. Both higher (better) EQ-5D-5L VAS and index scores were associated with better outcomes. Dapagliflozin treatment improved EQ-5D-5L VAS and index scores, irrespective of ejection fraction.

Associations Among Tremor Amplitude, Activities of Daily Living, and Quality of Life in Patients with Essential Tremor.

Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = -0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = -0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.

Comparison of post-COVID-19 symptoms in patients infected with the SARS-CoV-2 variants delta and omicron-results of the Cross-Sectoral Platform of the German National Pandemic Cohort Network (NAPKON-SUEP).

The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).

Hepatocellular carcinoma in hepatitis C virus patients treated with direct acting antivirals (DAAs) and patients not exposed to DAAs: a large center comparative study

BackgroundHepatocellular carcinoma (HCC) is the first cause of cancer in Egypt. Recently, HCC developed post direct-acting antivirals (DAAs) differ in some characteristics from those developed without DAAs exposure regarding the biological features and behavior of HCC. We aimed to assess the epidemiological, clinical, laboratory, and radiological findings besides the biological behavior of HCC patients post DAAs in comparison to HCC not exposed to DAAs. An analytic cross-sectional research was performed at the National Liver Institute which is a tertiary multidisciplinary HCC center. Subjects included hepatitis C virus patients and were allocated into two groups: group I included 2036 HCC cases post-DAA treatment and group II included 6338 HCC cases who did not receive DAAs. Subjects were examined to evaluate clinical, laboratory, and radiological findings. Tumor staging was done using the BCLC staging system.ResultsGroup II showed a more advanced Child–Pugh score, FIB-4 index, and MELD score than Group I (P = 0.001). The multiplicity of hepatic focal lesions was elevated in group I than in group II (P = 0.033). AFP level was significantly elevated in group I than in group II (p = 0.012). Portal vein invasion was significantly elevated in group I than in group II patients (P = 0.001). Extrahepatic spread of HCC was significantly elevated in group I than in group II (P = 0.001). Infiltrative lesions were significantly elevated in group I than in group II (P = 0.002).ConclusionOur study detected that the behavior in HCC post DAAs treatment is more aggressive in respect of the number of lesions, PV invasion; local and distant metastasis, and serum AFP level than in patients unexposed to DAAs. Strict surveillance in cirrhotic patients treated with DAA should be followed according to the international guidelines for early diagnosis and treatment of HCC.

Excess Weight, Polygenic Risk Score, and Findings of Colorectal Neoplasms at Screening Colonoscopy.

Excess weight is an established risk factor of colorectal cancer (CRC). However, evidence is lacking on how its impact varies by polygenic risk at different stages of colorectal carcinogenesis. We assessed the individual and joint associations of body mass index (BMI) and polygenic risk scores (PRSs) with findings of colorectal neoplasms among 4,784 participants of screening colonoscopy. Adjusted odds ratios (aORs) for excess weight derived by multiple logistic regression were converted to genetic risk equivalents (GREs) to quantify the impact of excess weight compared with genetic predisposition. Overweight and obesity (BMI 25-<30 and ≥30 kg/m 2 ) were associated with increased risk of any colorectal neoplasm (aOR [95% confidence interval, CI] 1.26 [1.09-1.45] and 1.47 [1.24-1.75]). Obesity was associated with increased risk of advanced colorectal neoplasm (aOR [95% CI] 1.46 [1.16-1.84]). Dose-response relationships were seen for the PRS (stronger for advanced neoplasms than any neoplasms), with no interaction with BMI, suggesting multiplicative effects of both factors. Obese participants with a PRS in the highest tertile had a 2.3-fold (95% CI 1.7-3.1) and 2.9-fold (95% CI 1.9-4.3) increased risk of any colorectal neoplasm and advanced colorectal neoplasm, respectively. The aOR of obesity translated into a GRE of 38, meaning that its impact was estimated to be equivalent to the risk caused by 38 percentiles higher PRS for colorectal neoplasm. Excess weight and polygenic risk are associated with increased risk of colorectal neoplasms in a multiplicative manner. Maintaining normal weight is estimated to have an equivalent effect as having 38 percentiles lower PRS.

Temporal relationships between pain, functioning, and human assumed central sensitization in patients with chronic low back pain; a single-case design

BackgroundInterdisciplinary pain rehabilitation (IPR) aims to improve functioning in people with chronic low back pain (CLBP), and is not primary aimed at pain reduction. Many patients however also report a decrease in pain. An explanation could be that IPR results in a decrease in Central Sensitization (CS). As CS is not directly assessable in humans the term Human Assumed Central Sensitization (HACS) is used in this study. It is unknown whether a decrease in HACS precedes a decrease in pain and improved functioning or vice versa. ObjectivesThis study aimed to gain understanding into the temporal relationships between changes in pain, functioning, and HACS in patients with CLBP during IPR. DesignLongitudinal observational small-N-study. MethodTwelve patients filled in frequently repeated self-reports 1 week before, during the 12-week IPR program, and 2 weeks after IPR. Pain was assessed by Visual Analogue Scale for pain (daily), functioning by Pain Disability Index (weekly) and Work Ability Score (daily), and HACS by Central Sensitization Inventory part A (bi-weekly). Analyses were performed by visual inspection and time series cross-correlation analyses. ResultsVisual inspection showed large fluctuations within and between individual participants in patterns over time. Cross-correlation analyses showed that in most participants, relationships between pain, functioning, and HACS were strongest when analyzed at the same time (55% of comparisons). Strength and direction of (strongest) correlations showed high interindividual variability (neg: 0.33–0.97; pos: 0.22–0.99). ConclusionOverall, relationships between pain, functioning, and HACS did not show consistent temporality in patients with CLBP.

-A machine learning model to predict surgical site infection after surgery of lower extremity fractures.

This study aimed to develop machine learning algorithms for identifying predictive factors associated with the risk of postoperative surgical site infection in patients with lower extremity fractures. A machine learning analysis was conducted on a dataset comprising 1,579 patients who underwent surgical fixation for lower extremity fractures to create a predictive model for risk stratification of postoperative surgical site infection. We evaluated different clinical and demographic variables to train four machine learning models (neural networks, boosted generalised linear model, naïve bayes, and penalised discriminant analysis). Performance was measured by the area under the curve score, Youdon's index and Brier score. A multivariate adaptive regression splines (MARS) was used to optimise predictor selection. The final model consisted of five predictors. (1) Operating room time, (2) ankle region, (3) open injury, (4) body mass index, and (5) age. The best-performing machine learning algorithm demonstrated a promising predictive performance, with an area under the ROC curve, Youdon's index, and Brier score of 77.8%, 62.5%, and 5.1%-5.6%, respectively. The proposed predictive model not only assists surgeons in determining high-risk factors for surgical site infections but also empowers patients to closely monitor these factors and take proactive measures to prevent complications. Furthermore, by considering the identified predictors, this model can serve as a reference for implementing preventive measures and reducing postoperative complications, ultimately enhancing patient outcomes. However, further investigations involving larger datasets and external validations are required to confirm the reliability and applicability of our model.

Self-reported dyspnoea and shortness of breathing deterioration in long-term survivors after segmentectomy or lobectomy for early-stage lung cancer.

The aim of this study was to assess the self-reported current dyspnoea and perioperative changes of dyspnoea in long-term survivors after minimally invasive segmentectomy or lobectomy for early-stage lung cancer. Cross-sectional telephonic survey of patients alive and disease-free as of March 2023, with pathologic stage IA1-2, non-small-cell lung cancer, assessed 1-5 years after minimally invasive segmentectomy or lobectomy (performed from January 2018 to January 2022). Current dyspnoea level: Baseline Dyspnoea Index score <10. Perioperative changes of dyspnoea were assessed using the Transition Dyspnoea Index. A negative Transition Dyspnoea Index focal score indicates perioperative deterioration in dyspnoea. Mixed effect models were used to examine demographic, medical and health-related correlates of current dyspnoea and changes in dyspnoea level. A total of 152 of 236 eligible patients consented or were available to respond to the telephonic interview(67% response rate): 90 lobectomies and 62 segmentectomies. The Baseline Dyspnoea Index score was lower (greater dyspnoea) in lobectomy patients (median 7, interquartile range 6-10) compared to segmentectomy (median 9, interquartile range 6-11), P = 0.034. 70% of lobectomy patients declared to have a current dyspnoea vs 53% after segmentectomy, P = 0.035. 82% of patients after lobectomy reported a perioperative deterioration in their dyspnoea compared to 57% after segmentectomy, P = 0.002. Mixed effect logistic regression analysis adjusting for patient-related factors and time elapsed from operation showed that segmentectomy was associated with a reduced risk of perioperative dyspnoea deterioration (as opposed to lobectomy) (Odds ratio (OR) 0.31, P = 0.004). Our findings may be valuable to inform the shared decision-making process by complementing objective data on perioperative changes of pulmonary function.

Eosinophilia is a favorable marker for pneumonia in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) expressing eosinophilia experience slightly fewer episodes of community-acquired pneumonia (CAP) than those without eosinophilia. However, the severity and burden of hospitalized pneumonia patients with COPD concerning eosinophilia have not been assessed. We evaluated the differences in clinical characteristics between patients with CAP and COPD with or without eosinophilia by a post-hoc analysis of a prospective, multi-center, cohort study data. Of 349 CAP patients with COPD, 45 (12.9%) had eosinophilia (blood eosinophil ≥ 300 cells/µL). Patients with eosinophilia had a lower sputum culture percentile (8.1% vs. 23.4%, P < 0.05), a lower percentile of neutrophils (70.3% vs 80.2%, P<0.05), reduced C-reactive protein levels (30.6 mg/L vs 86.6 mg/L, P<0.05), and a lower pneumonia severity index score (82.5 vs. 90.0, P < 0.05) than those without eosinophilia. The duration of antibiotic treatment (8.0 days vs. 10.0 days, P < 0.05) and hospitalization (7.0 days vs. 9.0 days, P < 0.05) were shorter in eosinophilic patients. The cost of medical care per day (256.4 US$ vs. 291.0 US$, P < 0.05), cost for the medication (276.4 US$ vs. 349.9 US$, P < 0.05), and cost for examination (685.5 US$ vs 958.1 US$, P<0.05) were lower in patients with eosinophilia than those without eosinophilia. Eosinophilia serves as a favorable marker for severity of pneumonia, health-care consumption, and cost of medical care in patients with CAP and COPD.