Nevin Manimala

Diagn Interv Radiol. 2022 May;28(3):200-207. doi: 10.5152/dir.2022.20872.

ABSTRACT

PURPOSE We aimed to investigate whether the texture analysis and functional magnetic resonance imaging (fMRI) could differentiate rectal cancer pathological stages T1-2 (pT1-2) and T3a (pT3a). METHODS Eighty-two rectal adenocarcinoma patients at stage pT1-2 and pT3a received T2 and fMRI examination before surgery. The latter included apparent diffusion coefficient (ADC) sequence, dynamic contrast enhancement (DCE) MRI, and intravoxel incoherent motion (IVIM) diffusion weighted imaging. Patients were grouped into early stage (pT1-2) and advanced stage (pT3a). The MRI accuracy in diagnosing rectal cancer before surgery was calculated. The differences in clinicopathological variables, quantitative parameters including ADC values, IVIM parameters (perfusion fraction [f], true diffusion coefficient [D], and pseudo- diffusion coefficient [D*]), DCE MRI parameters (transfer constant [Ktrans], reflux constant [Kep], and extravascular extracellular fractional volume [Ve]), and texture features were compared between the groups. Receiver operating characteristic (ROC) curves of texture features and fMRI parameters were generated to distinguish pT1-2 and pT3a tumors. The multivariate analysis was used to develop a predictive model and to find independent risk factors. Hosmer-Lemeshow test was used to see the fitness of the model. DeLong test was applied to compare the ROC curves of different features. Correlation of texture features and fMRI parameters with stage were calculated using r (Spearman’s rank correlation coefficient). RESULTS The preoperative accuracy in differentiating pT1-2 from pT3a rectal cancer using MRI was 74.39%. Kep, Ve, and ADC showed significant differences between the groups. Kep and ADC showed negative correlation with stage. Ve correlated positively with stage. Twenty-five texture features from T2 images showed significant differences between groups, and S(0,2)SumOfSqs and WavEnLH_s_2 among these showed better performance, showing negative correlation with stage. The area under the curve (AUC) values of S(0,2)SumOfSqs, WavEnLH_s_2, ADC, Kep, and Ve were 0.721, 0.699, 0.690, 0.666, and 0.653, respectively. The multivariate analysis showed that S(0,2) SumOfSqs, WavEnLH_s_2, and ADC are risk factors for advanced tumors, and the logistic model built by Kep, Ve, S(0,2)SumOfSqs, WavEnLH_s_2, and ADC has the AUC, sensitivity, and specificity of 0.833, 88.5%, and 73.3%, respectively. ROC curve of the model showed statistical significance between S(0,2)SumOfSqs, ADC, Kep, and Ve. The P value of the Hosmer-Lemeshow test was 0.65. CONCLUSION S(0,2)SumOfSqs, WavEnLH_s_2, and ADC are risk factors for advanced rectal cancer, and the model built by Kep, Ve, S(0,2)SumOfSqs, WavEnLH_s_2, and ADC has better performance than using a single method. The application of above combinations could be beneficial to patients’ accurate and individualized treatments.

PMID:35748201 | DOI:10.5152/dir.2022.20872

Pediatrics. 2022 Jun 24:e2021055641. doi: 10.1542/peds.2021-055641. Online ahead of print.

ABSTRACT

BACKGROUND: Several prediction models have been reported to identify patients with radiographic pneumonia, but none have been validated or broadly implemented into practice. We evaluated 5 prediction models for radiographic pneumonia in children.

METHODS: We evaluated 5 previously published prediction models for radiographic pneumonia (Neuman, Oostenbrink, Lynch, Mahabee-Gittens, and Lipsett) using data from a single-center prospective study of patients 3 months to 18 years with signs of lower respiratory tract infection. Our outcome was radiographic pneumonia. We compared each model’s area under the receiver operating characteristic curve (AUROC) and evaluated their diagnostic accuracy at statistically-derived cutpoints.

RESULTS: Radiographic pneumonia was identified in 253 (22.2%) of 1142 patients. When using model coefficients derived from the study dataset, AUROC ranged from 0.58 (95% confidence interval, 0.52-0.64) to 0.79 (95% confidence interval, 0.75-0.82). When using coefficients derived from original study models, 2 studies demonstrated an AUROC >0.70 (Neuman and Lipsett); this increased to 3 after deriving regression coefficients from the study cohort (Neuman, Lipsett, and Oostenbrink). Two models required historical and clinical data (Neuman and Lipsett), and the third additionally required C-reactive protein (Oostenbrink). At a statistically derived cutpoint of predicted risk from each model, sensitivity ranged from 51.2% to 70.4%, specificity 49.9% to 87.5%, positive predictive value 16.1% to 54.4%, and negative predictive value 83.9% to 90.7%.

CONCLUSIONS: Prediction models for radiographic pneumonia had varying performance. The 3 models with higher performance may facilitate clinical management by predicting the risk of radiographic pneumonia among children with lower respiratory tract infection.

PMID:35748157 | DOI:10.1542/peds.2021-055641

Tijdschr Psychiatr. 2022;64(6):353-358.

ABSTRACT

Parenting with Love and Limits (PLL) is a family intervention aimed at reducing behavioral problems in adolescents up to the age of 18 by, among other things, improving communication between family members and the parenting skills of the parents.<br> AIM: This prospective study examined whether parental communication and parenting skills and youth externalizing problem behavior were positively changed after PLL. <br> METHOD: The study group consisted of 48 adolescents who had completed the PLL-intervention with their primary caregivers. Data from two measurements completed by the primary caregivers (44 mothers and 4 fathers) were used: prior to PLL (T0) and after PLL (T1).<br> RESULTS: Results of the paired t-test indicated strong positive changes in communication, parenting and aggressive behavior after nearly eight months of PLL. A statistically significant (reliable change) decrease in aggressive behavior was found in one third of the adolescents, but not in deviant behavior.<br> CONCLUSION: PLL improved functioning in some of the families, but further research is needed into the effective elements and for whom the intervention is effective under what circumstances.<br>.

PMID:35748146

ESC Heart Fail. 2022 Jun 24. doi: 10.1002/ehf2.13979. Online ahead of print.

ABSTRACT

AIMS: Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects.

METHODS AND RESULTS: We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise). The PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-seven studies were identified, providing data for 2180 HFpEF patients and 682 controls. At peak exercise, patients with HFpEF achieved higher PAWP (30 [29-31] vs. 16 [15-17] mmHg, P < 0.001) and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, and body position. However, peak PAWP values were highly heterogeneous among the cohorts (I² = 93%), with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls (3.75 [3.20-4.28] vs. 0.95 [0.30-1.59] mmHg/L/min, P value < 0.0001), even after adjustment for covariates (P = 0.007).

CONCLUSIONS: Despite methodological heterogeneity, as well as heterogeneity of pooled haemodynamic estimates, the exercise haemodynamic profile of HFpEF patients is consistent across studies and characterized by a steep PAWP rise during exercise. More standardization of exercise haemodynamics may be advisable for a wider application in clinical practice.

PMID:35748109 | DOI:10.1002/ehf2.13979

Yonsei Med J. 2022 Jul;63(7):665-674. doi: 10.3349/ymj.2022.63.7.665.

ABSTRACT

PURPOSE: This study was undertaken to identify factors that affect segmental lordosis (SL) after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) by comparing patients whose postoperative SL increased with those whose decreased.

MATERIALS AND METHODS: Fifty-five patients underwent MIS-TLIF at our institute from January 2018 to September 2019. Demographic, pre- and postoperative radiologic, and cage-related factors were included. Statistical analyses were designed to compare patients whose SL increased with decreased after surgery.

RESULTS: After surgery, SL increased in 34 patients (group I) and decreased in 21 patients (group D). The index level, disc lordosis, SL, lumbar lordosis, proximal lordosis (PL), and Y-axis position of the cage (Yc) differed significantly between groups I and D. The cage in group I was more anterior than that in group D (Yc: 55.84% vs. 51.24%). Multivariate analysis showed that SL decreased more significantly after MIS-TLIF when the index level was L3/4 rather than L4/5 [odds ratio (OR): 0.46, p=0.019], as preoperative SL (OR: 0.82, p=0.037) or PL (OR: 0.68, p=0.028) increased, and as the cage became more posterior (OR: 1.10, p=0.032).

CONCLUSION: Changes in SL after MIS-TLIF appear to be associated with preoperative SL and PL, index level, and Yc. An index level at L4/5 instead of L3/4, smaller preoperative SL or PL, and an anterior position of the cage are likely to result in increased SL after MIS-TLIF.

PMID:35748078 | DOI:10.3349/ymj.2022.63.7.665

Int J Lab Hematol. 2022 Jun 24. doi: 10.1111/ijlh.13917. Online ahead of print.

ABSTRACT

OBJECTIVE: This study analysed the relationships between the main thromboelastography (TEG) parameters, the platelet (PLT) count and clinical bleeding in patients with blood diseases. We explored the threshold of the relevant parameters in the pathological condition of bleeding, aiming to scientifically guide clinical prophylactic PLT transfusion.

METHODS: In total, 268 patients with clear diagnoses of blood diseases and thrombocytopenia were enrolled and divided into five groups, A, B, C, D and E, corresponding to PLT counts of 0-10 × 10⁹ /L, 11-20 × 10⁹ /L, 21-30 × 10⁹ /L, 31-50 × 10⁹ /L and 51-100 × 10⁹ /L, respectively. TEG and routine blood testing were performed simultaneously, the main TEG parameters and the PLT count were analysed, and the thresholds of the main TEG parameters in each group when the patient had bleeding were obtained.

RESULTS: The maximum amplitude (MA) in groups A, B and C increased gradually, with a significant difference between each pair of these groups (P < 0.05). In groups A, B, C, D and E, the corresponding MA at the time of bleeding was 43.5 mm, 39.6 mm, 38.0 mm, 35.2 mm and 50.5 mm, respectively, with statistically significant differences (P < 0.05).

CONCLUSIONS: The MA can be used as a reference indicator for preventive PLT transfusion to a certain extent. When the PLT count is within different ranges, the MA threshold for preventive PLT transfusion also differs. It is recommended that different PLT counts be correlated with different MA thresholds to guide clinical prophylactic PLT transfusion.

PMID:35748054 | DOI:10.1111/ijlh.13917

Cancer Med. 2022 Jun 23. doi: 10.1002/cam4.4971. Online ahead of print.

ABSTRACT

INTRODUCTION: New treatment strategies for advanced non-small-cell lung carcinoma (NSCLC) include synthetic lethality targets focused on protein arginine methyl transferases such as PRMT5 that exploit the impact of genomic loss of methylthioadenosine phosphorylase (MTAP).

METHODS: Twenty nine thousand three hundred seventy nine advanced NSCLC cases underwent hybrid-capture based comprehensive genomic profiling between June 1, 2018 and May 31, 2020. PD-L1 expression was determined by immunohistochemistry (Dako 22C3 PharmDx assay).

RESULTS: 13.4% (3928/29,379) NSCLC cases exhibited MTAP loss distributed in adenocarcinoma (59%), squamous cell carcinoma (22%), NSCLC not otherwise specified (16%), and 1% each for large-cell neuroendocrine, sarcomatoid, and adenosquamous carcinoma. Statistically significant differences in mitogenic driver alterations included more KRAS G12C mutations in MTAP-intact versus MTAP-lost (12% vs. 10%, p = 0.0003) and fewer EGFR short variant mutations in MTAP-intact versus MTAP-lost NSCLC (10% vs. 13%, p < 0.0001). Statistically significant differences in currently unforgettable genomic alterations included higher frequencies of TP53 (70% vs. 63%, p < 0.0001) and RB1 inactivation (10% vs. 2%, p < 0.0001) in MTAP-intact compared to MTAP-lost NSCLC. SMARCA4 inactivation (7% vs. 10%, p < 0.0001) was less frequent in MTAP-intact versus MTAP-lost NSCLC. Alterations in ERBB2, MET, ALK, ROS1, and NTRK1 did not significantly differ between the two groups. Predictors of immunotherapy efficacy were higher in MTAP-intact versus MTAP-lost NSCLC including tumor mutational burden (9.4 vs. 8.6 mut/Mb, p = 0.001) and low (30% vs. 28%, p = 0.01) and high PD-L1 (32% vs. 30%, p = 0.01) expression. Alterations in biomarkers potentially predictive of immune checkpoint inhibitor resistance (STK11, KEAP1, and MDM2) were similar in the two groups.

CONCLUSIONS: MTAP loss occurs in 13% of NSCLC, supporting the development of targeted therapies to exploit PRMT5 hyper-dependence. MTAP loss is accompanied by small differences in targeted and immunotherapy options which may impact future combination strategies.

PMID:35747993 | DOI:10.1002/cam4.4971

Curr Pharm Des. 2022 Jun 23. doi: 10.2174/1381612828666220623102537. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Cardio-cerebrovascular disease is an important public health challenge worldwide, and its complex etiology has not been elucidated fully. The study was to investigate the relationship between two common polymorphisms C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, baseline lipids and the lipid-lowering efficacy of simvastatin in a Chinese hyperlipidemic population.

METHODS: All participants were recruited from Anhui, China. By the extreme sampling method, we selected subjects with low response (n=108) and high response (n=106) based on their adjusted lipid-lowering response to simvastatin administrated for 8 consecutive weeks. Both MTHFR C677T and A1298C loci were genotyped by MALDI-TOF MS platform. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured at baseline and after 8 weeks of oral 20 mg/d tablet of simvastatin.

RESULTS: Patients with the 677TT genotype had significantly higher baseline TC, HDL-C, and change in HDL-C (ΔHDL-C) levels after treatment than those with 677CC+CT genotypes (β = 0.207, P = 0.045; β = 0.182, P = 0.026; and β = 0.16, P = 0.002, respectively). Patients with 1298AC+CC genotypes had significantly higher baseline LDL-C and change in LDL-C (ΔLDL-C) levels (β = 0.276, P =0.043; β = 0.359, P = 0.025, respectively) than those with 1298AA genotype. We found statistical interactions between the two SNPs in association with baseline HDL-C (P for interaction = 0.034), TC (P for interaction = 0.069), and TG (P for interaction = 0.034). Baseline TC (P = 0.027) and HDL-C (P = 0.046) and change in HDL-C (P = 0.019) were different among those with the MTHFR A-T haplotype compared with A-C.

CONCLUSIONS: Our major findings suggest that both MTHFR C677T and A1298C polymorphisms could be important genetic determinants of lipid traits and drug efficacy of simvastatin. This will contribute to a better understanding of strategies for personalized medication in Chinese patients with dyslipidemia.

PMID:35747958 | DOI:10.2174/1381612828666220623102537

Rejuvenation Res. 2022 Jun 23. doi: 10.1089/rej.2022.0029. Online ahead of print.

ABSTRACT

Our previous study showed that the exchange of blood between heterochronic parabionts for 3 months did not rejuvenate the immune system of the old partners. Moreover, the young immune system became more aged and began to function according to the “old” principle. Does this “forced aging” affect all organism’s systems in this model? We checked the levels of corticosterone, testosterone, IGF-1, insulin, thyroxine in the blood of heterochronic parabionts but did not find significant changes compared to the age-related controls. Since numerous data support the possibility of rejuvenation of the brain, muscles, and other tissues using the model of heterochronic parabiosis, as well as opposite data, we planned to assess the overall effect of this long-term blood exchange on the rate of organism aging. We measured the lifespan of animals that exchanged with blood for 3 months and then were disconnected. Median and maximum life expectancy decreased in young heterochronic parabionts compared with the isochronic control. Old heterochronic parabionts showed only a small trend towards an increase in the median lifespan but it was not statistically significant, and the maximum lifespan did not change compared to the isochronic parabionts. These data support our assumption that old blood contains factors capable of inducing aging in young animals. Finding and selective suppression of aging factor production in the organism could be the key research field for life extension.

PMID:35747947 | DOI:10.1089/rej.2022.0029

Prostate. 2022 Jun 23. doi: 10.1002/pros.24402. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate the prognostic value and potential therapeutic target of the baseline serum hormones in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone.

METHODS: This retrospective study was performed in patients with mCRPC receiving abiraterone acetate (AA) from July 2016 to September 2020. Patients who had serum hormone tests within 2 weeks before AA treatment were included. Univariate analysis and Cox regression were performed to evaluate the correlation of sex hormones with progression-free survival (PFS) and overall survival (OS). Prolactin (PRL) expression in the clinical specimens was evaluated by immunohistochemistry. Bone metastases were quantified by automated Bone Scan Index (aBSI).

RESULTS: The study included 61 patients with a median follow-up of 19.0 months. Patients with lower baseline PRL levels (median) responded better to AA than those with higher baseline PRL levels as indicated by prostate-specific antigen (PSA) reduction (PSA90, 66.7% vs. 25.8%, p = 0.001), PFS (19.6 vs. 7.9 months), and OS (52.8 vs. 19.2 months). Cox regression adjusted for clinical factors also confirmed that baseline PRL level was an independent predictive factor for PFS (hazard ratio = 1.096, p = 0.007). Prostatic PRL expression increased as the disease progressed. PRL expression was also detected in biopsy samples from bone metastasis but not in normal bone tissue, and the serum PRL levels were positively correlated with aBSIs (r = 0.28, p = 0.037).

CONCLUSIONS: Serum PRL levels are predictive of response to AA in patients with mCRPC. Serum PRL levels are positively correlated with the volume of metastatic bone disease.

PMID:35747943 | DOI:10.1002/pros.24402