Tag: nevin manimala

Transl Psychiatry. 2022 Sep 17;12(1):392. doi: 10.1038/s41398-022-02153-z.

ABSTRACT

Structural differences in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), hippocampus, and amygdala were reported in adults who experienced childhood trauma; however, it is unknown whether metabolic differences accompany these structural differences. This multimodal imaging study examined structural and metabolic correlates of childhood trauma in adults with major depressive disorder (MDD). Participants with MDD completed the Childhood Trauma Questionnaire (CTQ, n = 83, n = 54 female (65.1%), age: 30.4 ± 14.1) and simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI). Structure (volume, n = 80, and cortical thickness, n = 81) was quantified from MRI using Freesurfer. Metabolism (metabolic rate of glucose uptake) was quantified from dynamic ¹⁸F-fluorodeoxyglucose (FDG)-PET images (n = 70) using Patlak graphical analysis. A linear mixed model was utilized to examine the association between structural/metabolic variables and continuous childhood trauma measures while controlling for confounding factors. Bonferroni correction was applied. Amygdala volumes were significantly inversely correlated with continuous CTQ scores. Specifically, volumes were lower by 7.44 mm³ (95% confidence interval [CI]: -12.19, -2.68) per point increase in CTQ. No significant relationship was found between thickness/metabolism and CTQ score. While longitudinal studies are required to establish causation, this study provides insight into potential consequences of, and therefore potential therapeutic targets for, childhood trauma in the prevention of MDD. This work aims to reduce heterogeneity in MDD studies by quantifying neurobiological correlates of trauma within MDD. It further provides biological targets for future interventions aimed at preventing MDD following trauma. To our knowledge, this is the first simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) study to assess both structure and metabolism associated with childhood trauma in adults with MDD.

PMID:36115855 | DOI:10.1038/s41398-022-02153-z

Pulmonology. 2022 Sep 15:S2531-0437(21)00152-5. doi: 10.1016/j.pulmoe.2021.07.004. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by limited airflow and is influenced by genetic and environmental factors. The purpose of this study was to investigate the effects of gene polymorphisms in MIR5708 and MIR1208 on COPD risk.

METHODS: Four single nucleotide polymorphisms (SNPs) in MIR5708 (rs6473227 and rs16907751) and MIR1208 (rs2608029 and rs13280095) were selected and genotyped among 315 COPD patients and 314 healthy controls using the Agena MassARRAY platform. SPSS 18.0 was used for statistical analysis and data processing. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between genetic variants of MIR1208 and MIR5708 and COPD risk.

RESULTS: The results suggested that rs16907751 variants in MIR5708 contributed to an increased susceptibility to COPD in the allelic (P = 0.001), co-dominant (homozygous) (P = 0.001), dominant (P = 0.017), recessive (P = 0.002), and additive (P = 0.002) models. The effects of MIR5708 and MIR1208 gene polymorphisms on the risk of COPD were age-, sex-, smoking status-, and BMI-related. Furthermore, the C-A and G-A haplotypes of rs2608029 and rs13280095 in MIR1208 were identified as risk factors for COPD in the population over 70 years (P = 0.029) and in women (P = 0.049), respectively. Finally, significant associations between rs16907751genotypes with pulse rate and forced expiratory volume in 1 s were found among COPD patients.

CONCLUSION: Genetic polymorphisms in MIR5708 and MIR1208 are associated with increased risk of COPD in China.

PMID:36115827 | DOI:10.1016/j.pulmoe.2021.07.004

Eur Urol Oncol. 2022 Sep 14:S2588-9311(22)00142-0. doi: 10.1016/j.euo.2022.08.003. Online ahead of print.

ABSTRACT

BACKGROUND: Most patients diagnosed with renal cancer today present with small renal masses (SRMs). Although these patients have a low risk of dying from their disease and many are followed with active surveillance protocols, a small subset of renal cell carcinomas (RCCs) behave aggressively. Knowledge regarding features of aggressive behavior would enable better adoption of active surveillance strategies among these patients.

OBJECTIVE: We sought to improve prognostic models to predict metastasis-free survival after nephrectomy through focused analyses of clinicopathologic characteristics of SRMs associated with adverse outcomes.

DESIGN, SETTING, AND PARTICIPANTS: We identified consecutive patients with surgically resected SRMs (≤4 cm) at the University of Texas Southwestern Kidney Cancer Program between 1998 and 2020. In addition, we evaluated the ability of SRMs to form tumors when implanted in mice, an indicator of tumor aggressiveness.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined the clinicopathologic factors associated with metastasis including prospectively performed BAP1 immunohistochemistry at our Clinical Laboratory Improvement Amendments laboratory. Multivariable Cox proportional hazard regression was used to predict metastasis-free survival.

RESULTS AND LIMITATIONS: A total of 3900 evaluable nephrectomies (from 3674 ethnically diverse patients) were identified, of which 1984 (51%) were SRMs including 1720 RCC. Of these patients with RCC (SRM^RCC), 1576 did not have synchronous or metachronous larger RCCs and among these, 37 (2%) developed metastases. SRM^RCC that metastasized were significantly enriched for aggressive morphologic phenotypes and engrafted in mice at comparable rates as larger metastatic tumors. BAP1 loss remained significantly associated with metastasis-free survival after accounting for TNM (tumor-node-metastasis) stage and SSIGN (stage, size, grade, and necrosis) score in multivariable analysis.

CONCLUSIONS: We identified clinicopathologic features that influence metastasis-free survival for patients with SRM^RCC. If validated independently, these data should assist with patient prognosis and help with active surveillance strategies.

PATIENT SUMMARY: We report the identification of features of aggressiveness in small renal tumors that influence the likelihood of metastases after surgery.

PMID:36115820 | DOI:10.1016/j.euo.2022.08.003

Cardiovasc Revasc Med. 2022 Sep 12:S1553-8389(22)00773-4. doi: 10.1016/j.carrev.2022.09.005. Online ahead of print.

ABSTRACT

INTRODUCTION: In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of therapeutic hypothermia (TH). However, results from previous studies are contradictory.

METHOD: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcomes were the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door-to-balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95 % confidence intervals (CIs) were calculated using the random-effects model.

RESULTS: A total of 10 RCTs, including 706 patients were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door-to-balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation.

CONCLUSIONS: According to our meta-analysis of published RCTs, TH is not beneficial in awake patients with STEMI and has a marginal safety profile with potential for care delays. Larger-scale RCTs are needed to further clarify our results.

PMID:36115819 | DOI:10.1016/j.carrev.2022.09.005

Clin Neurophysiol. 2022 Aug 30:S1388-2457(22)00867-7. doi: 10.1016/j.clinph.2022.08.014. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare scalp-EEG recorded physiological ripples co-occurring with vertex waves to pathological ripples co-occurring with interictal epileptiform discharges (IEDs).

METHODS: We marked ripples in sleep EEGs of children. We compared the start of ripples to vertex wave- or IED-start, and duration, frequency, and root mean square (RMS) amplitude of physiological and pathological ripples using multilevel modeling. Ripples were classified as physiological or pathological using linear discriminant analysis.

RESULTS: We included 40 children with and without epilepsy. Ripples started (χ²(1) = 38.59, p < 0.001) later if they co-occurred with vertex waves (108.2 ms after vertex wave-start) than if they co-occurred with IEDs (4.3 ms after IED-start). Physiological ripples had longer durations (75.7 ms vs 53.0 ms), lower frequencies (98.3 Hz vs 130.6 Hz), and lower RMS amplitudes (0.9 μV vs 1.8 μV, all p < 0.001) than pathological ripples. Ripples could be classified as physiological or pathological with 98 % accuracy. Ripples recorded in children with idiopathic or symptomatic epilepsy seemed to form two subgroups of pathological ripples.

CONCLUSIONS: Ripples co-occurring with vertex waves or IEDs have different characteristics and can be differentiated as physiological or pathological with high accuracy.

SIGNIFICANCE: This is the first study that compares physiological and pathological ripples recorded with scalp EEG.

PMID:36115810 | DOI:10.1016/j.clinph.2022.08.014

Explore (NY). 2022 Aug 29:S1550-8307(22)00160-4. doi: 10.1016/j.explore.2022.08.017. Online ahead of print.

ABSTRACT

BACKGROUND: Hemiparesis is a serious motor impairment following stroke and affecting around 65% of stroke patients. This trial attempts to study the efficacy of individualized homeopathic medicines (IHMs) in comparison with identical-looking placebos in treatment of post-stroke hemiparesis (PSH) in the mutual context of standard physiotherapy (SP).

METHODS: A 3-months, open-label, randomized, placebo-controlled trial (n = 60) was conducted at the Organon of Medicine outpatient departments of National Institute of Homoeopathy, West Bengal, India. Patients were randomized to receive IHMs plus SP (n = 30) or identical-looking placebos plus SP (n = 30). Primary outcome measure was Medical Research Council (MRC) muscle strength grading scale; secondary outcomes were Stroke Impact Scale (SIS) version 2.0, Modified Ashworth Scale (MAS), and stroke recovery 0-100 visual analogue scale (VAS) scores; all measured at baseline and 3 months after intervention. Group differences and effect sizes (Cohen’s d) were calculated on intention-to-treat sample.

RESULTS: Although overall improvements were higher in the IHMs group than placebos with small to medium effect sizes, the group differences were statistically non-significant (all P>0.05, unpaired t-tests). Improvement in SIS physical problems was significantly higher in IHMs than placebos (mean difference 2.0, 95% confidence interval 0.3 to 3.8, P = 0.025, unpaired t-test). Causticum, Lachesis mutus, and Nux vomica were the most frequently prescribed medicines. No harms, unintended effects, homeopathic aggravations or any serious adverse events were reported from either group.

CONCLUSION: There was a small, but non-significant direction of effect favoring homeopathy against placebos in treatment of post-stroke hemiparesis.

TRIAL REGISTRATION: CTRI/2018/10/016196; UTN: U1111-1221-7664.

PMID:36115790 | DOI:10.1016/j.explore.2022.08.017

Explore (NY). 2022 Sep 8:S1550-8307(22)00162-8. doi: 10.1016/j.explore.2022.09.001. Online ahead of print.

ABSTRACT

CONTEXT: The aim of neonatal pain management is to reduce pain and help the baby cope with pain.

OBJECTIVE: This study aimed to determine the effect of Helfer skin tap technique (HSTT) on hepatitis B vaccine intramuscular (IM) injection pain in neonetes.

DESIGN: Randomized controlled study SETTING: This study was conducted with neonatal infants born vaginally in the delivery room of a state hospital in Turkey.

PARTICIPANTS: This study was conducted total 60 neonates including 30 in the HSTT group and 30 in the Routine Technique (RT) group.

INTERVENTIONS: Participants were randomized into the HSTT group and the Routine Technique (RT) group.

MAIN OUTCOME MEASURES: Data were collected using a questionnaire form and the Neonatal Infant Pain Scale (NIPS).

RESULTS: While the means of the total pain scores in the HSTT group were found to be 1.73 ± 2.04 during injection and 1.73 ± 0.98 after injection, in the RT group, the mean scores were 5.56 ± 0.92 during injection and 4.90 ± 1.25 after injection. The difference between the groups arising in the comparison of means of the total pain scores obtained during and after injection in HSTT and RT groups was determined to be statistically significant (p <0.05).

CONCLUSION: In conclusion, HSTT was proven to be effective in reducing hepatitis B vaccine intramuscular (IM) injection pain in neonates. This study demonstrates that HSTT is associated with reduced pain in newborns during hepatitis B vaccine IM injections.

PMID:36115789 | DOI:10.1016/j.explore.2022.09.001

Eur Urol Focus. 2022 Sep 14:S2405-4569(22)00204-8. doi: 10.1016/j.euf.2022.08.015. Online ahead of print.

ABSTRACT

BACKGROUND: Bladder cancer (BC) treatment algorithms depend on accurate tumor staging. To date, computed tomography (CT) is recommended for assessment of lymph node (LN) metastatic spread in muscle-invasive and high-risk BC. However, the diagnostic efficacy of radiologist-evaluated CT imaging studies is limited.

OBJECTIVE: To evaluate the performance of quantitative radiomics signatures for detection of LN metastases in BC.

DESIGN, SETTING, AND PARTICIPANTS: Of 1354 patients with BC who underwent radical cystectomy (RC) with lymphadenectomy who were screened, 391 with pathological nodal staging (pN0: n = 297; pN+: n = 94) were included and randomized into training (n = 274) and test (n = 117) cohorts. Pelvic LNs were segmented manually and automatically. A total of 1004 radiomics features were extracted from each LN and a machine learning model was trained to assess pN status using histopathology labels as the ground truth.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Radiologist assessment was compared to radiomics-based analysis using manual and automated LN segmentations for detection of LN metastases in BC. Statistical analysis was performed using the receiver operating characteristics curve method and evaluated in terms of sensitivity, specificity, and area under the curve (AUC).

RESULTS AND LIMITATIONS: In total, 1845 LNs were manually segmented. Automated segmentation correctly located 361/557 LNs in the test cohort. Manual and automatic masks achieved an AUC of 0.80 (95% confidence interval [CI] 0.69-0.91; p = 0.64) and 0.70 (95% CI: 0.58-0.82; p = 0.17), respectively, in the test cohort compared to radiologist assessment, with an AUC of 0.78 (95% CI 0.67-0.89). A combined model of a manually segmented radiomics signature and radiologist assessment reached an AUC of 0.81 (95% CI 0.71-0.92; p = 0.63).

CONCLUSIONS: A radiomics signature allowed discrimination of nodal status with high diagnostic accuracy. The model based on manual LN segmentation outperformed the fully automated approach.

PATIENT SUMMARY: For patients with bladder cancer, evaluation of computed tomography (CT) scans before surgery using a computer-based method for image analysis, called radiomics, may help in standardizing and improving the accuracy of assessment of lymph nodes. This could be a valuable tool for optimizing treatment options.

PMID:36115774 | DOI:10.1016/j.euf.2022.08.015

Br J Clin Pharmacol. 2022 Sep 17. doi: 10.1111/bcp.15538. Online ahead of print.

ABSTRACT

BACKGROUND: Antiretroviral (ARV) therapy reduces inflammation and immune activation in people with HIV, but not down to the levels observed in negative people. Limited drug penetration within tissues has been argued as potential mechanism of persistent inflammation. Data on the inflammation role on ARV plasma/intracellular (IC) pharmacokinetics (PK) through to expression of cytochrome P450 3A/membrane transporters are limited. Aim of this study was to investigate the correlation between inflammation markers (IM) and plasma/IC PK of ARVs regimen in HIV-positive patients.

METHODS: We included ART-experienced patients switching to 3 different ARV regimens. Plasma and IC ARV drugs concentration means at the end of dosing interval (T0), IM on samples concomitantly with ARV PK determination: sCD14, CRP, IL-6 and LPS were analysed.

RESULTS: Plasma and IC drug concentrations were measured in 60 samples. No significative differences between CRP, sCD14, IL-6 and LPS values in the 3 arms were observed. A significant inverse correlation between tenofovir plasma concentration and sCD14 (rho=-0.79, p<0.001), and between DRV IC/plasma ratio and Log10 IL-6 concentrations (rho= -0.36, p=0.040), and a borderline statistical significant positive trend between DRV plasma concentration and sCD14 (rho=0.31, p=0.070) were suggested. Furthermore, a borderline statistical significant inverse trend between DTG IC concentrations and sCD14 (rho=-0.34, p=0.090) was observed in 24 patients on DTG-based-triple therapy.

CONCLUSIONS: Our preliminary data support the hypothesis of lower DRV and DTG IC concentrations and lower TFV plasma exposure in patients with higher plasma IM suggesting an interplay between HIV drug penetration and persistent inflammation in cART-treated HIV-positive patients.

PMID:36115063 | DOI:10.1111/bcp.15538

J Neurosurg Pediatr. 2022 Sep 16:1-9. doi: 10.3171/2022.8.PEDS22144. Online ahead of print.

ABSTRACT

OBJECTIVE: Intraventricular hemorrhage (IVH) is a neurovascular complication due to premature birth that results in blood clots forming within the ventricles. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) has been investigated as a noninvasive treatment to lyse clots. The authors designed and constructed a robotic MRgHIFU platform to treat the neonatal brain that facilitates ergonomic patient positioning. The clot lysis efficacy of the platform is quantified using a brain phantom and clinical MRI system.

METHODS: A thermosensitive brain-mimicking phantom with ventricular cavities was developed to test the clot lysis efficacy of the robotic MRgHIFU platform. Whole porcine blood was clotted within the phantom’s cavities. Using the MRgHIFU platform and a boiling histotripsy treatment procedure (500 W, 10-msec pulse duration, 1.0% duty cycle, and 40-second duration), the clots were lysed inside the phantom. The contents of the cavities were vacuum filtered, and the remaining mass of the solid clot particles was used to quantify the percentage of clot lysis. The interior of the phantom’s cavities was inspected for any collateral damage during treatment.

RESULTS: A total of 9 phantoms were sonicated, yielding an average (± SD) clot lysis of 97.0% ± 2.57%. Treatment resulted in substantial clot lysis within the brain-mimicking phantoms that were apparent on postsonication T2-weighted MR images. No apparent collateral damage was observed within the phantom after treatment. The results from the study showed the MRgHIFU platform was successful at lysing more than 90% of a blood clot at a statistically significant level.

CONCLUSIONS: The robotic MRgHIFU platform was shown to lyse a large percentage of a blood clot with no observable collateral damage. These results demonstrate the platform’s ability to induce clot lysis when targeting through simulated brain matter and show promise toward the final application in neonatal patients.

PMID:36115058 | DOI:10.3171/2022.8.PEDS22144