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Nevin Manimala Statistics

Palbociclib and letrozole in hormone-receptor positive advanced breast cancer: Predictive response and prognostic factors

Curr Probl Cancer. 2022 Mar 28;46(3):100859. doi: 10.1016/j.currproblcancer.2022.100859. Online ahead of print.

ABSTRACT

CDK 4/6 inhibitors have been yielding propitious results when with hormone therapy in the management of Her2-negative and hormone-receptor (HR)-positive metastatic breast cancer, palbociclib being one of the first molecules investigated in this setting. However, the response to CDK4/6 inhibitors is variable. To identify predictive and prognostic factors of response to this therapeutic regimen. Eligible patients were females with HR+ and Her2- advanced breast cancer, receiving Palbociclib in combination with Letrozole. PFS was the primary endpoint in the evaluation of response to treatment. This survival was then further segregated according to various characteristics: histological (type, grade, hormone receptors), metastatic site, line of treatment, response type at initial assessment, and best response achieved. The data was then processed by two statistical analysis models: Kaplan-Meier and univariate preceding multivariate Cox proportional risks. Sixty patients were included and followed for a median follow-up duration of 15.98 months. PFS recorded a median of 19.07 months (95% CI=15.43-22.71). PFS had a median of 12.99 months in the absence of progesterone receptors (vs 20.05 months in the case of positive estrogen and progesterone receptors; P = 0.046), a median of 13.02 months in the presence of liver metastases (vs 22.98 months in the absence of liver metastases; P = 0.007), and 15.94 months in the case of second-line and beyond (vs 22.98 months in the case of first-line; P = 0.033). Regarding the Hazard Ratio of progression, we note age (HR 0.941; P = 0.019), liver metastases (HR 2.751; P = 0.051), response at initial evaluation (HR<1; P < 0.001) and best response (HR<1; P = 0.003). PFS reached similar figures to those of international studies. The absence of progesterone receptors, presence of liver metastases, and use as second-line or beyond are associated with a reduced median PFS. One year age increase (protective factor), liver metastases (risk factor), response at initial evaluation, and best response achieved are identified as the most predictive factors of the response to this treatment regimen and of the progression risk.

PMID:35378469 | DOI:10.1016/j.currproblcancer.2022.100859

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Epidemiology of paratuberculosis in sheep and goats in southern Spain

Prev Vet Med. 2022 Apr 1;202:105637. doi: 10.1016/j.prevetmed.2022.105637. Online ahead of print.

ABSTRACT

Paratuberculosis is a worldwide, chronic infectious disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that mainly affects ruminant species. This disease has a significant economic impact on small ruminant production due to the costs of implementing control measures and production losses. A cross-sectional study was carried out to determine the seroprevalence, spatial distribution and risk factors associated with MAP exposure in sheep and goats in Andalusia (southern Spain). Serum samples from 4134 small ruminants (2266 sheep and 1868 goats) in 153 flocks were tested by an in-house ELISA for antibodies against MAP using paratuberculosis protoplasmic antigen 3 (PPA3) as coating antigen. Antibodies against MAP were detected in 8.1% (183/2266; 95% CI: 7.0-9.2%) of sheep and 20.0% (374/1868; 95% CI: 18.2-21.8%) of goats. The true individual seroprevalence was 8.4% (95% CI: 6.9-10.1%) in sheep and 25.2% (95% CI: 22.7-27.8%) in goats. Seropositivity was detected in 66.3% (55/83; 95% CI: 56.1-76.4%) of sheep herds and 90.0% (63/70; 95% CI: 83.0-97.0%) of goat herds. Spatial analysis identified three statistically significant clusters (p < 0.05) associated with areas with higher seroprevalence of MAP. The main risk factors potentially associated with MAP exposure were: species (goat) and absence of perimeter livestock fencing. The results of this study show that MAP is widespread in small ruminant populations in southern Spain and suggest that goats may play a more important role than sheep in the transmission and maintenance of MAP. Because of animal health concerns and the economic consequences of paratuberculosis, appropriate surveillance and control programs are required to reduce the risk of MAP infections in small ruminant flocks in this country.

PMID:35378433 | DOI:10.1016/j.prevetmed.2022.105637

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COVID-19 prognostic modeling using CT radiomic features and machine learning algorithms: Analysis of a multi-institutional dataset of 14,339 patients

Comput Biol Med. 2022 Mar 29;145:105467. doi: 10.1016/j.compbiomed.2022.105467. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients.

METHODS: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported.

RESULTS: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance.

CONCLUSION: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.

PMID:35378436 | DOI:10.1016/j.compbiomed.2022.105467

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Seasonal changes of heavy metals and health risk assessment based on Monte Carlo simulation in alternate water sources of the Xinbian River in Suzhou City, Huaibei Plain, China

Ecotoxicol Environ Saf. 2022 Apr 1;236:113445. doi: 10.1016/j.ecoenv.2022.113445. Online ahead of print.

ABSTRACT

The urban alternate water source (AWS) is of great significance to the sustainable development of the city, the pollution degree, and source of heavy metals (HMs) in AWS, and whether it will adversely affect human health has received widespread attention. In this study, the urban AWS of Xinbian River in Suzhou City, Huaibei Plain, China, was used as the research object to study the seasonal changes of HMs (As, Cr, Cu, Cd, Pb, and Zn), quantitative identification of pollution sources, and human health risks (HHR). Research results show that the contents of those HMs, except As, are less than the drinking standards limit set by the World Health Organization (WHO), and the contents of As, Cr, and Zn are the largest in summer. The multivariate statistical analysis combined with positive matrix factorization (PMF) model analysis revealed that industrial sources accounted for 44.83%, and agricultural sources accounted for 55.17%. HHR assessment based on Monte Carlo simulation shows that the noncarcinogenic risks of adults and children are in the acceptable range (hazardous ingestion (HI) < 1), and the probability of carcinogenic risk values of children and adults are 95.03% and 38.96%, respectively, which are exceed the acceptable range (1 × 10-4) recommended by the United States Environment Protection Agency (USEPA). Approximately 30.75% of the carcinogenic risk value of agricultural source HMs to children exceeds the acceptable range (1 × 10-4). The above research results indicate that the effect of agricultural non-point source pollution on AWS should be prevented.

PMID:35378402 | DOI:10.1016/j.ecoenv.2022.113445

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Positive psychology mediates the relationship between symptom frequency and quality of life among colorectal cancer survivors during acute cancer survivorship

Eur J Oncol Nurs. 2022 Mar 28;58:102136. doi: 10.1016/j.ejon.2022.102136. Online ahead of print.

ABSTRACT

PURPOSE: Colorectal cancer (CRC) survivors are living longer; therefore, factors that improve outcomes, like symptom management and quality of life (QoL), have increasingly become important. This study examined CRC survivors’ symptom(s) characteristics, positive psychology (benefit finding and post-traumatic growth), and QoL, and determined whether positive psychology mediates symptom(s) and QoL relationship during acute cancer survivorship.

METHODS: A cross-sectional study of 117 CRC survivors was conducted at a National Cancer Institute-Designated Cancer Center. Data were collected by demographic questionnaire, Therapy-Related Symptom Checklist, QoL Inventory, and positive psychology assessed by Carver Benefit-Finding Scale and Post-Traumatic Growth Inventory. Descriptive statistics, between-group differences, multiple linear regression, and mediation analyses were performed.

RESULTS: Top common symptoms were peripheral neuropathy, fatigue/feeling sluggish, skin changes, sleep disturbances, and weakness. Psychological distress symptoms were reported in 38.46% of CRC survivors, and moderate-to-high positive psychology (3.21 ± 1.09) and QoL (5.15 ±0 .52) levels were reported during acute cancer survivorship. Significant (p < 0.05) relationships were observed between QoL and (a) number of symptoms, (b) psychological distress symptoms, (c) benefit finding, (d) post-traumatic growth, and (e) positive psychology. Positive psychology partially mediated the relationship between symptom frequency and QoL (p < 0.05).

CONCLUSION: Our study’s findings suggest that CRC survivors positively cope with their cancer and treatment, and positive psychology partially mediates the relationship between symptoms frequency (almost daily and daily vs. random) and QoL across acute cancer survivorship. Identifying how CRC survivors adjust to their cancer may help healthcare teams provide tailored self-management skills to promote QoL and reduce symptom burden throughout cancer survivorship.

PMID:35378393 | DOI:10.1016/j.ejon.2022.102136

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The value of placental vascularization indices for predicting preeclampsia and fetal growth restriction in different stages of gestation: A prospective and longitudinal study

Placenta. 2022 Mar 26;122:1-8. doi: 10.1016/j.placenta.2022.03.124. Online ahead of print.

ABSTRACT

INTRODUCTION: To assess value of placental vascularization indices (PVIs) for predicting preeclampsia (PE) and fetal growth restriction (FGR) in different stages of pregnancy in high-risk women.

METHOD: PVIs derived from 3-dimensional power doppler(3DPD) imaging were measured at seven stages of pregnancy: 11-13+6w, 15-19+6w, 20-23+6w, 24-27+6w, 28-31+6w, 32-36+6w, and ≥37w. PE and FGR were used as outcomes in logistic regression models. Area under the receiver operating characteristic (ROC) curve (AUC) of each PVI was calculated, cut-off points were determined to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Finally, AUCs combined with baseline characteristics, uterine artery pulsatility index (UTPI) and PVIs were used to determine whether PVIs could increase the predictive value.

RESULTS: Adverse outcomes occurred in 10.9% of pregnancies. Statistical differences appeared in 32-36+6w only. AUCs of vascularization index (VI) and vascularization flow index (VFI) for 32-36+6w were 0.79 (0.70-0.87, p: 0.000), and 0.78 (0.69-0.88, p: 0.000). Sensitivity, specificity, PPV, NPV, PLR, and NLR for VI were 0.91, 0.63, 20%, 98%, 2.39, and 0.15, and those for VFI were 0.62, 0.84, 29%, 95%, 3.75, and 0.45. AUC increased from 0.79 to 0.85 by adding PVIs to baseline characteristics and UTPI model. No statistical significance was found before 32w.

DISCUSSION: VI and VFI were valuable for predicting PE and FGR at the 32-36+6w stage, while their values before 32w were poor.

PMID:35378370 | DOI:10.1016/j.placenta.2022.03.124

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Geographic distribution of malignant mesothelioma incidence and survival in Australia

Lung Cancer. 2022 Mar 24;167:17-24. doi: 10.1016/j.lungcan.2022.03.017. Online ahead of print.

ABSTRACT

OBJECTIVES: To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia.

MATERIALS AND METHODS: Generalised linear models and Bayesian spatial models were fitted using population registry data. Area-level covariates were socioeconomic quintile, remoteness category and state or territory. The maximised excess events test was used to test for spatial heterogeneity.

RESULTS: There was strong evidence of spatial differences in standardised incidence rates for malignant mesothelioma but survival was uniformly poor. Incidence rates varied by state or territory and were lower in remote areas. Patterns in the geographic distribution of modelled incidence counts for malignant mesothelioma differed substantially from patterns of standardised incidence rates.

CONCLUSIONS: Geographic variation in the modelled incidence counts of malignant mesothelioma demonstrates varying demand for diagnostic and management services. The long latency period for this cancer coupled with migration complicates any associations with patterns of exposure, however some of the geographic distribution of diagnoses can be explained by the location of historical mines and asbestos-related industries.

PMID:35378379 | DOI:10.1016/j.lungcan.2022.03.017

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The effects of feed restriction, time of day, and time since feeding on behavioral and physiological indicators of hunger in broiler breeder hens

Poult Sci. 2022 Mar 10;101(5):101838. doi: 10.1016/j.psj.2022.101838. Online ahead of print.

ABSTRACT

Broiler breeder chickens are commercially feed restricted to slow their growth and improve their health and production, however, there is research demonstrating that this leads to chronic hunger resulting in poor welfare. A challenge in these studies is to account for possible daily rhythms or the effects of time since last meal on measures relating hunger. To address this, we used 3 feed treatments: AL (ad libitum fed), Ram (restricted, fed in the morning), and Rpm (restricted, fed in the afternoon) to control for diurnal effects. We then conducted foraging motivation tests and collected home pen behavior and physiological samples at 4 times relative to feeding throughout a 24-h period. The feed treatment had the largest influence on the data, with AL birds weighing more, having lower concentrations of plasma NEFA, and mRNA expression of AGRP and NPY alongside higher expression of POMC in the basal hypothalamus than Ram or Rpm birds (P < 0.001). R birds were more successful at and had a shorter latency to complete the motivation test, and did more walking and less feeding than AL birds in the home pen (P < 0.01). There was little effect of time since last meal on many measures (P > 0.05) but AGRP expression was highest in the basal hypothalamus shortly after a meal (P < 0.05), blood plasma NEFA was higher in R birds just before feeding (P < 0.001) and glucose was higher in Ram birds just after feeding (P < 0.001), and the latency to complete the motivation test was shortest before the next meal (P < 0.05). Time of day effects were mainly found in the difference in activity levels in the home pen when during lights on and lights off periods. In conclusion, many behavioral and physiological hunger measures were not significantly influenced by time of day or time since the last meal. For the measures that do change, future studies should be designed so that sampling is balanced in such a way as to minimize bias due to these effects.

PMID:35378348 | DOI:10.1016/j.psj.2022.101838

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Dietary administration of silk microparticles improves the epidermal and dermal regeneration after a skin wounding in gilthead seabream (Sparus aurata L.)

Fish Shellfish Immunol. 2022 Apr 1:S1050-4648(22)00175-9. doi: 10.1016/j.fsi.2022.03.049. Online ahead of print.

ABSTRACT

The impact of dietary supplementation with silk fibroin (SF) microparticles on the wound healing process in gilthead seabream (Sparus aurata) skin was studied. A control diet was enriched with different SF levels: 0 (control), 50 (SF50 diet), and 100 (SF100 diet) mg Kg-1 to form three experimental diets and was fed to seabream for 30 days. Experimental wounds were performed and after 7 days post-wounding (dpw) skin mucus immunity, macroscopic wound closure, and skin regeneration were studied at a microscopic and genetic level. Results indicated that fish fed SF100 did not suffer the decreases in protease and IgM levels observed in the skin mucus of wounded fish fed with the control diet. Macroscopic findings illustrated that dietary SF100 significantly improved the wound closure ratio compared to those reared in the control group. At a microscopic level, changes in the shape of keratocyte cells were evident in the wounded fish. In addition, the intercellular spaces present between epidermal cells and their proliferation in the epidermis, as well as the presence of blood vessels in the dermis were significantly statistically higher in the skin of fish fed the SF100 diet and sampled at 7 dpw compared to those observed in the skin of fish fed the control or SF50 diets. Moreover, regarding the RNA: DNA ratio, statistically significant increases and decreases were observed in fish fed the control and SF100 diet, respectively, in non-wounded and wounded fish. Interestingly, dietary SF100 supplementation improved skin cell proliferation, enhanced the inflammatory phase, and increased the expression of important genes involved in tissue repair and extracellular matrix formation. In conclusion, the SF100 diet can be considered as an appropriate feed additive to improve wound healing in gilthead seabream.

PMID:35378308 | DOI:10.1016/j.fsi.2022.03.049

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Humeral Offset as a Predictor of Outcomes After Reverse Shoulder Arthroplasty

J Shoulder Elbow Surg. 2022 Apr 1:S1058-2746(22)00335-4. doi: 10.1016/j.jse.2022.02.029. Online ahead of print.

ABSTRACT

INTRODUCTION: The Grammont-style reverse shoulder arthroplasty (RSA) relies on medialization and distalization of the shoulder center of rotation. Lateralized designs have recently gained popularity. The amount of lateralization, however, remains a controversial topic. The purpose of this study was to correlate the change in humeral offset (HO) with outcomes and complications following RSA. We hypothesized that a lateralized HO following RSA would be associated with improved range of motion (ROM), better patient reported outcomes (PROs), and less complications.

MATERIALS AND METHODS: A consecutive series of 104 patients (109 shoulders) was retrospectively evaluated. All patients underwent primary RSA by two Shoulder and Elbow fellowship-trained orthopedic surgeons at two different centers. Inclusion criteria was a primary RSA with at least 1-year follow-up. All patients had the HO measured on a preoperative and a postoperative Grashey radiograph and the change in HO was calculated (ΔHO = PostHO – PreHO). A negative value was defined as a medialized HO and a positive value as a lateralized HO. ROM and primary outcomes, including forward elevation (FE), external rotation (ER), Internal Rotation (IR), Subjective Shoulder Value (SSV), and American Shoulder and Elbow Surgeons (ASES) score were collected. Complications and revisions were also reported.

RESULTS: The mean age was 72 years with a mean follow-up of 22.3 months. The average FE (92° vs 148°), ER (34° vs 44°), SSV (35% vs 87%), and ASES score (37.2 vs 81.2) increased significantly (all, P < .01) compared to preoperative values. The HO was medialized postoperatively in 63 shoulders and lateralized in 46 shoulders. No statistically significant differences in the mean values for postoperative FE (147° vs 146°, P=0.892), ER (43° vs 45°, P=0.582), IR (L3 vs L3, P=0.852), SSV (88% vs 85%, P=0.476) and ASES score (81.3 vs 81.1, P=0.961) were found between the groups. However, there was significantly more improvement in ER in the lateralized HO cohort than the medialized cohort (16º vs 7º, P = 0.033). Six shoulders, 5 medialized and 1 lateralized HO, demonstrated scapular notching and remained asymptomatic. Five shoulders, 4 medialized and 1 lateralized HO, experienced at least one instability incident, and 2 shoulders with medialized HO had an acromion/scapular spine fracture. Overall, 2 shoulders with medialized HO underwent revision surgery due to instability.

CONCLUSIONS: While RSA provides significant improvement in ROM and PROs regardless of postoperative HO, restoring baseline HO or lateralization beyond baseline may be favorable for improving ER and decreasing complications following RSA.

PMID:35378314 | DOI:10.1016/j.jse.2022.02.029