Nevin Manimala

Cancer Treat Rev. 2021 Jul 22;99:102261. doi: 10.1016/j.ctrv.2021.102261. Online ahead of print.

ABSTRACT

BACKGROUND: Temozolomide (TEM) is an active treatment in metastatic neuroendocrine tumors (NETs). Patients affected by glioblastoma multiforme or advanced melanoma treated with TEM who have deficiency of O⁶-methylguanine DNA methyltransferase (MGMT) have a better responses and survival. However, the predictive role of MGMT in patients with NETs treated with TEM is still debated.

METHODS: We conducted a systematic review of the literature and meta-analysis, based on PRISMA methodology, searching in the main databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library and clinical trial.gov) and the proceedings of the main international congresses, until April 26, 2021.

RESULTS: Twelve out of 616 articles were selected for our analysis, regarding a total of 858 NET patients treated with TEM-based chemotherapy. The status of MGMT had been tested in 513 (60%) patients, using various methods. The pooled overall response rate (ORR) was higher in MGMT-deficient compared with MGMT-proficient NETs, with a risk difference of 0.31 (95% confidence interval, CI: 0.13-0.50; p < 0.001; I²: 73%) and risk ratio of 2.29 (95% CI: 1.34-3.91; p < 0.001; I²: 55%). The pooled progression free survival (PFS) (hazard ratio, HR = 0.56; 95% CI: 0.43-0.74; p < 0.001) and overall survival (OS) (HR = 0.41; 95% CI: 0.20-0.62; p = 0.011) were longer in MGMT-deficient versus MGMT-proficient NETs.

CONCLUSIONS: Our meta-analysis suggested that MGMT status may be predictive of TEM efficacy. However, due to the high heterogeneity of the evaluated studies the risk of biases should be considered. On this hypothesis future homogeneous prospective studies are warranted.

PMID:34332293 | DOI:10.1016/j.ctrv.2021.102261

J Psychosom Res. 2021 Jul 16;149:110572. doi: 10.1016/j.jpsychores.2021.110572. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine if there is a synergistic effect between clinically relevant depressive symptoms and cardiovascular risk factors that disproportionately increases the risk of cardiovascular disease (CVD) among older adults with depressive symptoms.

METHODS: Data were obtained from the Longitudinal Aging Study Amsterdam, a longitudinal cohort study. N = 3091 respondents with up to seven years of follow-up were included. Incident CVD was based on self-report, medication use, general practitioners’ diagnoses and causes of death. A score of ≥16 points on the Center for Epidemiological Studies Depression Scale indicated clinically relevant depressive symptoms. Risk factors included were sex, education, obesity, smoking, alcohol use, physical inactivity and diabetes mellitus. Data were analysed with Cox regression models. Measures of multiplicative and additive interaction were calculated to determine if the presence of both depressive symptoms and a risk factor amplified the risk of CVD.

RESULTS: Of all participants, 12.6% had clinically relevant depressive symptoms and, after a median follow-up of six years, 15.7% developed CVD. Only the additive interaction between physical inactivity and depressive symptoms was statistically significant and explained 40.6% of the CVD risk among inactive persons with depressive symptoms.

CONCLUSION: In the general population, we did not detect synergistic effects for most risk factors. However, older adults with clinically relevant depressive symptoms and a physically inactive lifestyle appeared to be at a particularly high risk to develop CVD and may represent an important target for cardiovascular prevention.

PMID:34332270 | DOI:10.1016/j.jpsychores.2021.110572

Infant Behav Dev. 2021 Jul 28;64:101612. doi: 10.1016/j.infbeh.2021.101612. Online ahead of print.

ABSTRACT

Social interactions are known to be an essential component of infant development. For this reason, exploring functional neural activity while infants are engaged in social interactions will enable a better understanding of the infant social brain. This in turn, will enable the beginning of disentangling the neural basis of social and non-social interactions as well as the influence that maternal engagement has on infant brain function. Maternal sensitivity serves as a model for socio-emotional development during infancy, which poses the question: do interactions between parents and their offspring present altered electrophysiological responses in comparison to the general population if said parents are at risk of mental health disorders? The current research aimed to observe the oscillatory activity of 6-month-old infants during spontaneous free-play interactions with their mother. A 5-minute unconstrained free-play session was recorded between infant-mother dyads with EEG recordings taken from the 6-month-old infants (n = 64). During the recording, social and non-social behaviours were coded and EEG assessed with these epochs. Results showed an increase in oscillatory activity both when an infant played independently or interacted with their mother and oscillatory power was greatest in the alpha and theta bands. In the present 6-month-old cohort, no hemispheric power differences were observed as oscillatory power in the corresponding neural regions (i.e. left and right temporal regions) appeared to mirror each other. Instead, temporal estimates were larger and different from all other regions, whilst the frontal and parietal regions bihemispherically displayed similar estimates, which were larger than those observed centrally, but smaller than those displayed in the temporal locations. The interactions observed between the behavioural events and frequency bands demonstrated a significant reduction in power comparative to the power observed in the gamma band during the baseline event. The present research sought to explore the obstacle of artificial play paradigms for neuroscience research, whereby researchers question how much these paradigms relate to reality. The present manuscript will discuss the strengths and limitations of taking an unconstrained free-play approach.

PMID:34332261 | DOI:10.1016/j.infbeh.2021.101612

Leg Med (Tokyo). 2021 Jul 25;53:101948. doi: 10.1016/j.legalmed.2021.101948. Online ahead of print.

ABSTRACT

The presented study evaluated the expression of dystrophin and MMP-9 in cases of sudden cardiac death (SCD) due to coronary atherosclerotic disease (CAD) in order to analyze the characteristics and the chronology of their expression, providing evidence on the possible role in post-mortem diagnosis of myocardial ischemia. The expression of these proteins was also compared to C5b-9 complex and fibronectin expression to evaluate any differences. Two groups of CAD-related SCD, respectively group 1 with gross and/or histological evidence and group 2 with no specific histological signs of myocardial ischemia, were used. A third group formed by cases of acute mechanical asphyxiation was used as a control. The immunohistochemical staining by dystrophin, MMP-9, C5b-9, and fibronectin antibodies was performed. The study revealed that dystrophin and MMP-9 showed different expression in group 1 and group 2 as, respectively, different degree of sarcolemmal staining depletion and increasing of interstitial and granulocytes immunopositivity. Moreover, loss of dystrophin staining and C5b-9 immunopositivity were more significant when compared to MMP-9 increasing. Dystrophin and MMP-9 seemed to be useful immunohistochemical markers for the detection of myocardial ischemic damage. However, the comparison of the four markers suggested that loss of dystrophin could be considered as an earlier marker.

PMID:34332258 | DOI:10.1016/j.legalmed.2021.101948

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Jul 22;263:120190. doi: 10.1016/j.saa.2021.120190. Online ahead of print.

ABSTRACT

This study proposed simple and reliable spectrophotometry method for simultaneous analysis of hepatitis C antiviral binary mixture containing sofosbuvir (SOF) and daclatasvir (DAC). This technique is based on the use of feed-forward artificial neural network (FF-ANN) and least square support vector machine (LS-SVM). FF-NN with Levenberg-Marquardt (LM) and Cartesian genetic programming (CGP) algorithms was trained to determine the best number of hidden layers and the number of neurons. This comparison demonstrated that the LM algorithm had the minimum mean square error (MSE) for SOF (1.59 × 10^-28) and DAC (4.71 × 10^-28). In LS-SVM model, the optimum regularization parameter (γ) and width of the function (σ) were achieved with root mean square error (RMSE) of 0.9355 and 0.2641 for SOF and DAC, respectively. The coefficient of determination (R²) value of mixtures containing SOF and DAC was 0.996 and 0.997, respectively. The percentage recovery values were in the range of 94.03-104.58 and 94.04-106.41 for SOF and DAC, respectively. Statistical test (ANOVA) was implemented to compare high-performance liquid chromatography (HPLC) and spectrophotometry, which showed no significant difference. These results indicate that the proposed method possesses great potential ability for prediction of concentration of components in pharmaceutical formulations.

PMID:34332240 | DOI:10.1016/j.saa.2021.120190

J Stroke Cerebrovasc Dis. 2021 Jul 28;30(10):106003. doi: 10.1016/j.jstrokecerebrovasdis.2021.106003. Online ahead of print.

ABSTRACT

BACKGROUND: Stroke risk can be quantified using risk factors whose effect sizes vary by geography and race. No stroke risk assessment tool exists to estimate aggregate stroke risk for indigenous African.

OBJECTIVES: To develop Afrocentric risk-scoring models for stroke occurrence.

MATERIALS AND METHODS: We evaluated 3533 radiologically confirmed West African stroke cases paired 1:1 with age-, and sex-matched stroke-free controls in the SIREN study. The 7,066 subjects were randomly split into a training and testing set at the ratio of 85:15. Conditional logistic regression models were constructed by including 17 putative factors linked to stroke occurrence using the training set. Significant risk factors were assigned constant and standardized statistical weights based on regression coefficients (β) to develop an additive risk scoring system on a scale of 0-100%. Using the testing set, Receiver Operating Characteristics (ROC) curves were constructed to obtain a total score to serve as cut-off to discriminate between cases and controls. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at this cut-off.

RESULTS: For stroke occurrence, we identified 15 traditional vascular factors. Cohen’s kappa for validity was maximal at a total risk score of 56% using both statistical weighting approaches to risk quantification and in both datasets. The risk score had a predictive accuracy of 76% (95%CI: 74-79%), sensitivity of 80.3%, specificity of 63.0%, PPV of 68.5% and NPV of 76.2% in the test dataset. For ischemic strokes, 12 risk factors had predictive accuracy of 78% (95%CI: 74-81%). For hemorrhagic strokes, 7 factors had a predictive accuracy of 79% (95%CI: 73-84%).

CONCLUSIONS: The SIREN models quantify aggregate stroke risk in indigenous West Africans with good accuracy. Prospective studies are needed to validate this instrument for stroke prevention.

PMID:34332227 | DOI:10.1016/j.jstrokecerebrovasdis.2021.106003

Pathol Res Pract. 2021 Jul 9;224:153546. doi: 10.1016/j.prp.2021.153546. Online ahead of print.

ABSTRACT

BACKGROUND: Long non-coding RNAs (lncRNAs) are often aberrantly expressed in hepatocellular carcinoma (HCC). The role of lncRNAs in the diagnosis of HCC has attracted increasing attention. Hence, we performed a meta-analysis based on current studies to assess the diagnostic value of lncRNAs for HCC.

METHODS: A systematic search was performed using PubMed, Web of Science, and Embase databases for relevant studies. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). A fixed-effect model was used if the value of I² statistics < 50%; otherwise, a bivariate random effects model was applied (I² ≥ 50%). In addition, subgroup analysis and meta-regression analysis were conducted to explore the sources of heterogeneity. Statistical analyses were based on Meta-Disc statistical software (Version 1.4) and STATA software (Version 15.1).

RESULTS: A total of 52 studies in 20 related articles were selected for this meta-analysis, including 4930 patients and 4614 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.85 [95% confidence interval (CI) 0.82-0.88], 0.76 (95% CI 0.73-0.80), 3.6 (95% CI 3.1-4.2), 0.19 (95% CI 0.16-0.24), 19 (95% CI 14-26), and 0.88 (95% CI 0.85-0.91), respectively. The publication bias was evaluated by the Deek’s funnel plot in our meta-analysis.

CONCLUSIONS: LncRNAs can serve as feasible HCC diagnostic biomarkers. However, further studies are necessary to confirm its diagnostic and clinical value.

PMID:34332221 | DOI:10.1016/j.prp.2021.153546

Eur J Obstet Gynecol Reprod Biol. 2021 Jul 22;264:224-231. doi: 10.1016/j.ejogrb.2021.07.030. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the association between demographic and ultrasound variables and major intra-operative blood loss during surgical transcervical evacuation of live caesarean scar pregnancies.

STUDY DESIGN: This was a retrospective cohort study conducted in a tertiary referral center between 2008 and 2019. We included all women diagnosed with a live caesarean scar ectopic pregnancy who chose to have surgical management in the study center. A preoperative ultrasound was performed in each patient. All women underwent transcervical suction curettage under ultrasound guidance. Our primary outcome was the rate of postoperative blood transfusion. The secondary outcomes were estimated intra-operative blood loss (ml), rate of retained products of conception, need for repeat surgery, need for uterine artery embolization and hysterectomy rate. Descriptive statistics were used to describe the variables. Univariate and multivariable logistic regression models were constructed using the relevant covariates to identify the significant predictors for severe blood loss.

RESULTS: During the study period, 80 women were diagnosed with a live caesarean scar pregnancy, of whom 62 (78%) opted for surgical management at our center. The median crown-rump length was 9.3 mm (range 1.4-85.7). Median blood loss at the time of surgery was 100 ml (range, 10-2300), and six women (10%; 95%CI 3.6-20) required blood transfusion. Crown-rump length and presence of placental lacunae were significant predictive factors for the need for blood transfusion and blood loss > 500 ml at univariate analysis (p < .01); on multivariate analysis, only crown-rump length was a significant predictor for need for blood transfusion (OR = 1.072; 95% CI 1.02-1.11). Blood transfusion was required in 6/18 (33%) cases with the crown-rump length ≥ 23 mm (≥9⁺⁰ weeks of gestation), but in none of 44 women presenting with a crown-rump length < 23 mm (p < .01).

CONCLUSION: The risk of severe intraoperative bleeding and need for blood transfusion during or after surgical evacuation of live caesarean scar pregnancies increases with gestational age and is higher in the presence of placental lacunae. One third of women presenting at ≥ 9 weeks of gestation required blood transfusion and their treatment should be ideally arranged in specialized tertiary centers.

PMID:34332219 | DOI:10.1016/j.ejogrb.2021.07.030

Catheter Cardiovasc Interv. 2021 Jul 31. doi: 10.1002/ccd.29889. Online ahead of print.

ABSTRACT

OBJECTIVES: The Evolut R FORWARD study confirmed safety and effectivenesss of the Evolut R THV in routine clinical practice out to 1 year. Herein, we report the final 3-year clinical follow up of the FORWARD study.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a proven alternative to surgery in elderly patients with symptomatic severe aortic stenosis. Long-term clinical outcome data with the Evolut R platform are scarce.

METHODS: FORWARD is a prospective multicenter observational study that evaluated the Evolut R system in routine clinical practice at 53 centres. Eligible patients had symptomatic native aortic valve stenosis or failed surgical aortic bioprosthesis and elevated operative risk per Heart-Team assessment. TAVR was attempted in 1039 patients.

RESULTS: Mean age was 81.8 ± 6.2 years, 64.9% were women, STS score was 5.5 ± 4.5% and 34.2% were frail. Rates of all-cause mortality and disabling stroke were 24.8% and 4.8% at 3 years. Early need for a new pacemaker implantation after TAVR (all-cause mortality: with new PPI; 21.0% vs. without; 22.8%, p = 0.55) and the presence of > trace paravalvular regurgitation (all-cause mortality: no or trace; 22.0% vs. ≥ mild; 25.5%, p = 0.29) did not affect survival. Between 1 and 3 years incidence rates of valve related intervention, endocarditis and clinically relevant valve thrombosis were low.

CONCLUSIONS: The Evolut R valve maintained a favorable safety profile through 3 years in routine clinical practice. Rates of transcatheter heart valve-related adverse events were low.

PMID:34331844 | DOI:10.1002/ccd.29889

Int J Clin Pract. 2021 Jul 31:e14682. doi: 10.1111/ijcp.14682. Online ahead of print.

ABSTRACT

BACKGROUND: Biochemical recurrence (BCR) can be seen in the early or late period after radical prostatectomy (RP). Various models have been developed to predict BCR.

OBJECTIVE: In our study we evaluated accuracy of four pre-operative models (GP score, PRIX, D’Amico risk classification, CAPRA) in predicting BCR after RP in Turkish patients.

METHODS: Age, preoperative total prostate specific antigen (PSA) values, clinical stages, total number of cores taken in biopsy, number of positive cores, preoperative biopsy Gleason score (GS), follow-up time and presence of BCR after RP were recorded. BCR was defined as a total PSA value > 0.2 ng / dl twice consecutively after RP. Classifications or scoring was performed according to pre-operative models. The 1, 3 and 5 year (yr) BCR-free rates of the patients were determined for each model. Also the accuracy of four predictive models for predicting 1, 3 and 5-yr BCR was evaluated.

RESULTS: For all pre-operative models there was statistically significant difference between risk groups in BCR free rates at 1, 3 and 5-yr after RP (p<0.001). The Harrell’s concordance index for 1-yr BCR predictions was 0,802, 0,831, 0,773 and 0,745 for the GP score, PRIX, CAPRA and D’Amico and respectively. For 3-yr BCR predictions it was 0,798, 0,791, 0,723 and 0,714 for the GP score, PRIX, CAPRA and D’Amico and respectively. Finally, The Harrell’s concordance index for 5-yr BCR predictions was 0,778, 0,771, 0,702 and 0,693 for the GP score, PRIX, CAPRA and D’Amico and respectively.

CONCLUSION: In prediction of BCR, accuracy of GP scoring and PRIX seems slightly higher than CAPRA and D’Amico risk classification. Surely our results should be supported by head to head comparisons with in other larger cohorts.

PMID:34331823 | DOI:10.1111/ijcp.14682