Category: Nevin Manimala

Eur Radiol. 2023 Jul 13. doi: 10.1007/s00330-023-09892-7. Online ahead of print.

ABSTRACT

OBJECTIVES: Adult solitary intra-axial cerebellar tumors are uncommon. Their presurgical differentiation based on neuroimaging is crucial, since management differs substantially. Comprehensive full assessment of MR dynamic-susceptibility-contrast perfusion-weighted imaging (DSC-PWI) may reveal key differences between entities. This study aims to provide new insights on perfusion patterns of these tumors and to explore the potential of DSC-PWI in their presurgical discrimination.

METHODS: Adult patients with a solitary cerebellar tumor on presurgical MR and confirmed histological diagnosis of metastasis, medulloblastoma, hemangioblastoma, or pilocytic astrocytoma were retrospectively retrieved (2008-2023). Volumetric segmentation of tumors and normal-appearing white matter (for normalization) was semi-automatically performed on CE-T1WI and coregistered with DSC-PWI. Mean normalized values per patient tumor-mask of relative cerebral blood volume (rCBV), percentage of signal recovery (PSR), peak height (PH), and normalized time-intensity curves (nTIC) were extracted. Statistical comparisons were done. Then, the dataset was split into training (75%) and test (25%) cohorts and a classifier was created considering nTIC, rCBV, PSR, and PH in the model.

RESULTS: Sixty-eight patients (31 metastases, 13 medulloblastomas, 13 hemangioblastomas, and 11 pilocytic astrocytomas) were included. Relevant differences between tumor types’ nTICs were demonstrated. Hemangioblastoma showed the highest rCBV and PH, pilocytic astrocytoma the highest PSR. All parameters showed significant differences on the Kruskal-Wallis tests (p < 0.001). The classifier yielded an accuracy of 98% (47/48) in the training and 85% (17/20) in the test sets.

CONCLUSIONS: Intra-axial cerebellar tumors in adults have singular and significantly different DSC-PWI signatures. The combination of perfusion metrics through data-analysis rendered excellent accuracies in discriminating these entities.

CLINICAL RELEVANCE STATEMENT: In this study, the authors constructed a classifier for the non-invasive imaging presurgical diagnosis of adult intra-axial cerebellar tumors. The resultant tool can be a support for decision-making in the clinical practice and enables optimal personalized patient management.

KEY POINTS: • Adult intra-axial cerebellar tumors exhibit specific, singular, and statistically significant different MR dynamic-susceptibility-contrast perfusion-weighted imaging (DSC-PWI) signatures. • Data-analysis, applied to MR DSC-PWI, could provide added value in the presurgical diagnosis of solitary cerebellar metastasis, medulloblastoma, hemangioblastoma, and pilocytic astrocytoma. • A classifier based on DSC-PWI metrics yields excellent accuracy rates and could be used as a support tool for radiologic diagnosis with clinician-friendly displays.

PMID:37439938 | DOI:10.1007/s00330-023-09892-7

J Geriatr Phys Ther. 2023 Jul 13. doi: 10.1519/JPT.0000000000000388. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Sarcopenia is a common muscle disease among the older population, posing an increased risk for functional decline and intervention for loss of independence in daily living. Early detection of sarcopenia among older people before functional decline would be beneficial in enhancing their quality of life. The Asian Working Group for Sarcopenia (AWGS) 2019 recommends the use of 3 screening methods for community-based sarcopenia detection: calf circumference (CC), or the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire, or the SARC-F in combination with CC (SARC-CalF) questionnaire. This study aims to compare the relative performance of these 3 methods as screening tools for sarcopenia within a community-dwelling older population.

METHODS: A total number of 700 community-dwelling older adults participated in the current study. Muscle mass, muscle strength, and physical performance were measured with bioelectrical impedance analysis, handgrip strength, and gait speed, respectively. The AWGS 2019 criteria were considered the criterion standard The sensitivity/specificity, receiver operating characteristic (ROC) curve, and area under the receiver operating characteristic curve (AUROC) analyses were determined for CC, SARC-F, and SARC-CalF to determine their relative diagnostic performance.

RESULTS: Sarcopenia was identified in 21.4% of participants according to the AWGS2019 criteria. The overall prevalence of sarcopenia was 56.6%, 14.7%, and 22.9% according to CC, SARC-F, and SARC-CalF, respectively. Calf circumference showed the highest sensitivity but lowest specificity based on AWGS 2019 as the criterion standard regardless of age, gender, and body mass index. The SARC-CalF showed better sensitivity but similar specificity than the SARC-F. The AUROC of CC was significantly better than that of SARC-F and SARC-CalF. The AUROCs of CC, SARC-F, and SARC-CalF were statistically significant in all populations, as well as in the categories of age, gender, and body mass index (P < .05).

CONCLUSIONS: Calf circumference is useful in ruling out the presence of sarcopenia while the SARC-F is more effective in ruling in sarcopenia, especially in the context of population-based screening. Future studies should be carried out to investigate the value of population-based sarcopenia detection using these screening tools.

PMID:37439875 | DOI:10.1519/JPT.0000000000000388

J Exp Biol. 2023 Jul 13:jeb.245256. doi: 10.1242/jeb.245256. Online ahead of print.

ABSTRACT

In general, sustained high rates of physical activity require a high maximal aerobic capacity (VO2max), which may also necessitate a high basal aerobic metabolism (BMR), given that the two metabolic states are linked via shared organ systems, cellular properties, and metabolic pathways. We tested the hypotheses that (a) selective breeding for high voluntary exercise in mice would elevate both VO2max and BMR, and (b) these increases are accompanied by increases in the sizes of some internal organs (ventricle, triceps surae muscle, liver, kidney, spleen, lung, brain). We measured 72 females from generations 88 and 96 of an ongoing artificial selection experiment comprising 4 replicate High Runner (HR) lines bred for voluntary daily wheel-running distance and 4 non-selected Control (C) lines. With body mass as a covariate, HR lines as a group had significantly higher VO2max (+13.6%, P<0.0001), consistent with previous studies, but BMR did not significantly differ between HR and C lines (+6.5%, P=0.181). Additionally, HR mice did not statistically differ from C mice for whole-body lean or fat mass, or for the mass of any organ collected (with body mass as a covariate). Finally, mass-independent VO2max and BMR were uncorrelated (r=0.073, P=0.552) and the only statistically significant correlation with an organ mass was for VO2max and ventricle mass (r=0.285, P=0.015). Overall, our results indicate that selection for a behavioral trait can yield large changes in behavior without proportional modifications to underlying morphological or physiological traits.

PMID:37439323 | DOI:10.1242/jeb.245256

Pharm Stat. 2023 Jul 13. doi: 10.1002/pst.2321. Online ahead of print.

ABSTRACT

In oncology/hematology early phase clinical trials, efficacies were often observed in terms of response rate, depth, timing, and duration. However, the true clinical benefits that eventually support registrational purpose are progression-free survival (PFS) and/or overall survival (OS), the follow-up of which are typically not long enough in early phase trials. This gap imposes challenges in strategies for late phase drug development. In this article, we tackle the question by leveraging published study to establish a quantitative link between early efficacy outcomes and late phase efficacy endpoints. We used solid tumor cancer as disease model. We modeled the disease course of a RECISTv1.1 assessed solid tumor with a continuous Markov chain (CMC) model. We parameterize the transition intensity matrix of a CMC model based on published aggregate-level summary statistics, and then simulate subject-level time-to-event data. The simulated data is shown to have good approximation to published studies. PFS and/or OS could be predicted with the transition intensity matrix modified given clinical knowledge to reflect various assumptions on response rate, depth, timing, and duration. The authors have built a R shiny application named PubPredict, the tool implements the algorithm described above and allows customized features including multiple response levels, treatment crossover and varying follow-up duration. This toolset has been applied to advise phase 3 trial design when only early efficacy data are available from phase 1 or 2 studies.

PMID:37439295 | DOI:10.1002/pst.2321

Int J Cancer. 2023 Jul 13. doi: 10.1002/ijc.34637. Online ahead of print.

ABSTRACT

Metabolic dysfunction-associated fatty liver disease (MAFLD) can coexist with chronic viral hepatitis. MAFLD is a heterogeneous disease because the diagnostic criteria include various metabolic traits. We aimed to identify patients at high risk of poor long-term outcomes based on MAFLD subgroups in chronic viral hepatitis patients. We evaluated 63 273 chronic hepatitis B and C patients. Patient with a fatty liver index ≥30 was defined to have hepatic steatosis. MAFLD was defined as the presence of hepatic steatosis with any one of the following three conditions, overweight/obesity, type 2 diabetes or ≥2 metabolic risk factors. The prevalence of MAFLD was 38.4% (n = 24 290). During a median 8.8-year follow-up, 1839 HCCs and 2258 deaths were documented in MAFLD patients. Among MAFLD patients, diabetes could identify patients at high risk of HCC and mortality, whereas overweight/obesity and metabolic risk factors did not. Compared with non-MAFLD patients, risk of HCC and mortality was significantly higher in diabetic MAFLD patients (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] = 1.26-1.43 for HCC; aHR = 1.15, 95% CI = 1.08-1.22 for mortality). Risk of HCC and mortality was significantly higher in diabetic MAFLD patients (aHR = 1.40, 95% CI = 1.26-1.55 for HCC; aHR = 1.77, 95% CI = 1.63-1.93 for mortality) compared with non-diabetic MAFLD patients. Diabetic MAFLD is associated with increased risk of HCC and mortality among chronic viral hepatitis patients. Our findings highlight the need for close surveillance and effective treatment for these high-risk patients to reduce HCC and mortality in patients with chronic viral hepatitis.

PMID:37439276 | DOI:10.1002/ijc.34637

J Exp Biol. 2023 Jul 13:jeb.245973. doi: 10.1242/jeb.245973. Online ahead of print.

ABSTRACT

Auditory sensitivity measurements have been published for only 12 of the more than 1,150 extant species of elasmobranchs (sharks, skates, and rays). As a result, there is the need to further understand sound perception in more species from different ecological niches. In this study the auditory evoked potential (AEP) technique was used to compare hearing abilities of the bottom-dwelling New Zealand carpet shark Cephaloscyllium isabellum, and two benthopelagic houndsharks (Triakidae), rig Mustelus lenticulatus, and school shark Galeorhinus galeus. AEPs were measured in response to tone bursts (frequencies: 80, 100, 150, 200, 300, 450, 600, 800, and 1200Hz) from an underwater speaker positioned 55cm in front of the shark in an experimental tank. AEP-detection thresholds were derived visually and statistically, with statistical measures slightly more sensitive (average∼4dB) than visual methodology. Hearing abilities differed between species, mainly with respect to bandwidth rather than sensitivity. Hearing was least developed in the benthic C. isabellum [upper limit: 300Hz, best hearing: 100Hz (82.3+1.5 dB re:1µms-2)]. Hearing was superior in the benthopelagic rig and school sharks [upper limit: 800Hz, best hearing: 100Hz (79.2+1.6 dB re:1µms-2) for G. galeus, and 150Hz (74.8+1.8 dB re:1µms-2) for M. lenticulatus]. The data are consistent with those known for ‘hearing non-specialist’ teleost fishes that only detect particle motion, not pressure. Further, our results provide evidence that benthopelagic sharks exploit higher frequencies (max.800Hz) than some of the bottom-dwelling sharks (max.300Hz). Further behavioural and morphological studies are needed to identify what ecological factors drive differences in upper frequency limits of hearing in elasmobranchs.

PMID:37439272 | DOI:10.1242/jeb.245973

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2023 Jul 10. doi: 10.5507/bp.2023.029. Online ahead of print.

ABSTRACT

AIMS: Mepolizumab, a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5, has shown improved asthma control and lung function in randomised controlled trials. The aim of this study was to evaluate real-world clinical experience in patients with severe eosinophilic asthma treated with mepolizumab in Slovakia.

METHODS: A retrospective, non-interventional study based on medical records of all adult asthma patients initiating mepolizumab between November 1, 2017 and January 31, 2019, completing 12 months of treatment. At baseline, general and clinical profile data were recorded 12 months prior to treatment. Primary and secondary endpoints described the results of mepolizumab use at 2, 6, and 12 months after the initiation and compared to baseline. Statistical testing of individual change (in each patient) in selected parameters was performed.

RESULTS: The cohort included 17 patients with particularly severe asthma at baseline, with frequent severe exacerbations (SE, median 5 [IQR 4-6]/patient/year), high blood eosinophil counts (median 0.6×10⁹/L), frequent oral corticosteroid (OCS) dependence (82.35%), median dose 15 (IQR 7.5-20) mg/day, impaired lung function, and a spectrum of comorbidities. In a one-year follow-up, the data showed reductions in median SE (0 [IQR 0-1] patient/year, eosinophilia (median 0.175×10⁹/L) and OCS maintenance dose (median 6.25 [IQR 2.5-20] mg/day), all statistically significant after 12 months on mepolizumab. Improved and stabilised lung functions throughout the cohort and a reduced incidence of nasal polyposis were observed.

CONCLUSIONS: The results provide clinical evidence of mepolizumab efficacy in a real sample of patients with severe asthma when administered in routine care settings in Slovakia.

PMID:37439266 | DOI:10.5507/bp.2023.029

J Appl Physiol (1985). 2023 Jul 13. doi: 10.1152/japplphysiol.00631.2022. Online ahead of print.

ABSTRACT

Sliding between lung lobes along lobar fissures is a poorly understood aspect of lung mechanics. The objective of this study was to test the hypothesis that lobar sliding helps reduce distortion in the lung parenchyma during breathing. Finite element models of left lungs with geometries and boundary conditions derived from medical images of human subjects were developed. Effect of lobar sliding was studied by comparing nonlinear finite elastic contact mechanics simulations that allowed and disallowed lobar sliding. Lung parenchymal distortion during simulated breath holds and tidal breathing was quantified with the model’s spatial mean anisotropic deformation index (ADI), a measure of directional preference in volume change that varies spatially in the lung. Models that allowed lobar sliding had significantly lower mean ADI (i.e. lesser parenchymal distortion) than models that disallowed lobar sliding under both simulations of tidal breathing (5.3% median difference, p = 0.008, n = 8) and simulations of lung deformation between breath holds at total lung capacity and functional residual capacity (3.2% median difference, p = 0.03, n = 6). This effect was most pronounced in the lower lobe where lobar sliding reduced parenchymal distortion with statistical significance, but not in the upper. Additionally, more lobar sliding was correlated with greater reduction in distortion between sliding and non-sliding models in our study cohorts (Pearson’s correlation coefficient of 0.95 for tidal breathing, 0.87 for breath holds, and 0.91 for the combined data set). These findings are consistent with the hypothesis that lung lobar sliding reduces parenchymal distortion during breathing.

PMID:37439240 | DOI:10.1152/japplphysiol.00631.2022

Circulation. 2023 Jul 13. doi: 10.1161/CIRCULATIONAHA.123.064521. Online ahead of print.

ABSTRACT

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown.

METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding.

RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%).

CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT02777580.

PMID:37439219 | DOI:10.1161/CIRCULATIONAHA.123.064521

Public Health Nutr. 2023 Jul 13:1-30. doi: 10.1017/S136898002300126X. Online ahead of print.

ABSTRACT

OBJECTIVE: Government policy guidance in Victoria, Australia, encourages schools to provide affordable, healthy foods in canteens. This study analysed the healthiness and price of items available in canteens in Victorian primary schools; and associations with school characteristics.

DESIGN: Dietitians classified menu items (main, snack, beverage) using the red, amber, green traffic light system defined in the Victorian government’s school canteens and other school food services policy. This system also included a black category for confectionary and high sugar content soft drinks which should not be supplied. Descriptive statistics, and regressions were used to analyse differences in the healthiness and price of main meals, snacks and beverages offered, according to school remoteness, sector (government, Catholic/independent), size, and socio-economic position.

SETTING: State of Victoria, Australia.

PARTICIPANTS: A convenience sample of canteen menus drawn from three previous obesity prevention studies in 48 primary schools between 2016-2019.

RESULTS: On average, school canteen menus were 21% ‘green’ (most healthy – ‘everyday’), 53% ‘amber’ (‘select carefully’), 25% ‘red’ (‘occasional’) and 2% ‘black’ (banned) items, demonstrating low adherence with government guidelines. ‘Black’ items were more common in schools in regional population centres. ‘Red’ main meal items were cheaper than ‘green’ (mean difference -$0.48 (95%CI -0.85, -0.10)) and ‘amber’ -$0.91 (-1.27, -0.57)) main meal items. In ∼50% of schools, the mean price of ‘red’ main meal, beverages and snack items were cheaper than ‘green’ items; or no ‘green’ alternative items were offered.

CONCLUSION: In this sample of Victorian canteen menus, there was no evidence of associations of healthiness and pricing by school characteristics except for regional centres having the highest proportion of ‘black’ (banned) items compared to all other remoteness categories examined. There was low adherence with state canteen menu guidelines. Many schools offered a high proportion of ‘red’ food options, and ‘black’ (banned) options, particularly in regional centres. Unhealthier options were cheaper than healthy options. More needs to be done to bring Victorian primary school canteen menus in line with guidelines.

PMID:37439210 | DOI:10.1017/S136898002300126X