ResearchPad - 3 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Vitamin D Supplementation Rescues Aberrant NF-κB Pathway Activation and Partially Ameliorates Rett Syndrome Phenotypes in <i>Mecp2</i> Mutant Mice]]> https://www.researchpad.co/article/elastic_article_13342 Rett syndrome (RTT) is a severe, progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MECP2. We previously identified aberrant NF-κB pathway upregulation in brains of Mecp2-null mice and demonstrated that genetically attenuating NF-κB rescues some characteristic neuronal RTT phenotypes. These results raised the intriguing question of whether NF-κB pathway inhibitors might provide a therapeutic avenue in RTT. Here, we investigate whether the known NF-κB pathway inhibitor vitamin D ameliorates neuronal phenotypes in Mecp2-mutant mice. Vitamin D deficiency is prevalent among RTT patients, and we find that Mecp2-null mice similarly have significantly reduced 25(OH)D serum levels compared with wild-type littermates. We identify that vitamin D rescues aberrant NF-κB pathway activation and reduced neurite outgrowth of Mecp2 knock-down cortical neurons in vitro. Further, dietary supplementation with vitamin D in early symptomatic male Mecp2 hemizygous null and female Mecp2 heterozygous mice ameliorates reduced neocortical dendritic morphology and soma size phenotypes and modestly improves reduced lifespan of Mecp2-nulls. These results elucidate fundamental neurobiology of RTT and provide foundation that NF-κB pathway inhibition might be a therapeutic target for RTT.

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<![CDATA[Agrariër Vraagt Niet Snel Om Hulp]]> https://www.researchpad.co/article/elastic_article_12817 <![CDATA[Reduced TUBA1A Tubulin Causes Defects in Trafficking and Impaired Adult Motor Behavior]]> https://www.researchpad.co/article/elastic_article_8074 Newly born neurons express high levels of TUBA1A α-tubulin to assemble microtubules for neurite extension and to provide tracks for intracellular transport. In the adult brain, Tuba1a expression decreases dramatically. A mouse that harbors a loss-of-function mutation in the gene encoding TUBA1A (Tuba1aND/+) allows us to ask whether TUBA1A is important for the function of mature neurons. α-Tubulin levels are about half of wild type in juvenile Tuba1aND/+ brains, but are close to normal in older animals. In postnatal day (P)0 cultured neurons, reduced TUBA1A allows for assembly of less microtubules in axons resulting in more pausing during organelle trafficking. While Tuba1aND/+ mouse behavior is indistinguishable from wild-type siblings at weaning, Tuba1aND/+ mice develop adult-onset ataxia. Neurons important for motor function in Tuba1aND/+ remain indistinguishable from wild-type with respect to morphology and number and display no evidence of axon degeneration. Tuba1aND/+ neuromuscular junction (NMJ) synapses are the same size as wild-type before the onset of ataxia, but are reduced in size in older animals. Together, these data indicate that the TUBA1A-rich microtubule tracks that are assembled during development are essential for mature neuron function and maintenance of synapses over time.

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<![CDATA[EGFR Signaling Causes Morphine Tolerance and Mechanical Sensitization in Rats]]> https://www.researchpad.co/article/elastic_article_8067 The safety and efficacy of opioids are compromised as analgesic tolerance develops. Opioids are also ineffective against neuropathic pain. Recent reports have suggested that inhibitors of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK), may have analgesic effects in cancer patients suffering from neuropathic pain. It has been shown that the platelet-derived growth factor receptor-β (PDGFR-β), an RTK that has been shown to interact with the EGFR, mediates opioid tolerance but does not induce analgesia. Therefore, we sought to determine whether EGFR signaling was involved in opioid tolerance and whether EGFR and PDGFR signaling could induce pain in rats. We found that gefitinib, an EGFR antagonist, eliminated morphine tolerance. In addition, repeated EGF administration rendered animals unresponsive to subsequent analgesic doses of morphine, a phenomenon we call “pre-tolerance.” Using a nerve injury model, we found that gefitinib alone was not analgesic. Rather, it reversed insensitivity to morphine analgesia (pre-tolerance) caused by the release of EGF by injured nerves. We also showed that repeated, but not acute EGF or PDGF-BB administration induced mechanical hypersensitivity in rats. EGFR and PDGFR-β signaling interacted to produce this sensitization. EGFR was widely expressed in primary sensory afferent cell bodies, demonstrating a neuroanatomical substrate for our findings. Taken together, our results suggest a direct mechanistic link between opioid tolerance and mechanical sensitization. EGFR antagonism could eventually play an important clinical role in the treatment of opioid tolerance and neuropathic pain that is refractory to opioid treatment.

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<![CDATA[Impaired Motor Recycling during Action Selection in Parkinson’s Disease]]> https://www.researchpad.co/article/elastic_article_8059 Behavioral studies have shown that the human motor system recycles motor parameters of previous actions, such as movement amplitude, when programming new actions. Shifting motor plans toward a new action forms a particularly severe problem for patients with Parkinson’s disease (PD), a disorder that, in its early stage, is dominated by basal ganglia dysfunction. Here, we test whether this action selection deficit in Parkinson’s patients arises from an impaired ability to recycle motor parameters shared across subsequent actions. Parkinson’s patients off dopaminergic medication (n = 16) and matched healthy controls (n = 16) performed a task that involved moving a handheld dowel over an obstacle in the context of a sequence of aiming movements. Consistent with previous research, healthy participants continued making unnecessarily large hand movements after clearing the obstacle (defined as “hand path priming effect”), even after switching movements between hands. In contrast, Parkinson’s patients showed a reduced hand path priming effect, i.e., they performed biomechanically more efficient movements than controls, but only when switching movements between hands. This effect correlated with disease severity, such that patients with more severe motor symptoms had a smaller hand path priming effect. We propose that the basal ganglia mediate recycling of movement parameters across subsequent actions.

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<![CDATA[Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes]]> https://www.researchpad.co/article/N6964f0da-e6b4-4f5b-86a0-5e5ef8e23ad0 The major function of B lymphocytes is to sense antigens and to produce protective antibodies after activation. This function requires the expression of a B-cell antigen receptor (BCR), and evolutionary conserved mechanisms seem to exist that ensure that B cells without a BCR do not develop nor survive in the periphery. Here, we show that the loss of BCR expression on Burkitt lymphoma cells leads to decreased mitochondrial function and impaired metabolic flexibility. Strikingly, this phenotype does not result from the absence of a classical Syk-dependent BCR signal but rather from compromised ER expansion. We show that the reexpression of immunoglobulins (Ig) in the absence of the BCR signaling subunits Igα and Igβ rescues the observed metabolic defects. We demonstrate that immunoglobulin expression is needed to maintain ER homeostasis not only in lymphoma cells but also in resting B cells. Our study provides evidence that the expression of BCR components, which is sensed in the ER and shapes mitochondrial function, represents a novel mechanism of metabolic control in B cells.

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<![CDATA[Case Report of a SARS-CoV-2 Infection in a Patient With Ulcerative Colitis on Tofacitinib]]> https://www.researchpad.co/article/Na052592a-75a2-48c3-921a-e472dfbbcf33 <![CDATA[The Epileptor Model: A Systematic Mathematical Analysis Linked to the Dynamics of Seizures, Refractory Status Epilepticus, and Depolarization Block]]> https://www.researchpad.co/article/N538242ca-4a1f-4816-abe7-9afbd7e687e4

Abstract

One characteristic of epilepsy is the variety of mechanisms leading to the epileptic state, which are still largely unknown. Refractory status epilepticus (RSE) and depolarization block (DB) are other pathological brain activities linked to epilepsy, whose patterns are different and whose mechanisms remain poorly understood. In epileptogenic network modeling, the Epileptor is a generic phenomenological model that has been recently developed to describe the dynamics of seizures. Here, we performed a detailed qualitative analysis of the Epileptor model based on dynamical systems theory and bifurcation analysis, and investigate the dynamic evolution of “normal” activity toward seizures and to the pathological RSE and DB states. The mechanisms of the transition between states are called bifurcations. Our detailed analysis demonstrates that the generic model undergoes different bifurcation types at seizure offset, when varying some selected parameters. We show that the pathological and normal activities can coexist within the same model under some conditions, and demonstrate that there are many pathways leading to and away from these activities. We here archive systematically all behaviors and dynamic regimes of the Epileptor model to serve as a resource in the development of patient-specific brain network models, and more generally in epilepsy research.

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<![CDATA[Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer]]> https://www.researchpad.co/article/N711332f9-c9cf-4b1c-add5-d871710ae8b7

The molecular phenotype of circulating tumor cells is associated with clinical outcome of patients with breast cancer. The aim of this study was to enhance the prognostic accuracy of the circulating tumor cell phenotype in metastatic breast cancer by incorporating miRNA into a combined prediction model.

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<![CDATA[Talazoparib in Patients with a Germline BRCA‐Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial]]> https://www.researchpad.co/article/N6ecc4bdf-e429-404f-8dcc-def44777f426

Abstract

Background

In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression‐free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2‐mutated HER2‐negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail.

Materials and Methods

Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time‐varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient‐reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms.

Results

The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3–4 months of receiving talazoparib. Grade 3‐4 anemia lasted approximately 7 days for both arms. Overlapping grade 3‐4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low (<2%). A total of 150 (52.4%) patients receiving talazoparib had AEs associated with dose reduction. Hematologic toxicities were managed by supportive care medication (including transfusion) and dose modifications. Among patients with anemia or nausea and/or vomiting AEs, PROs favored talazoparib. After accounting for the treatment‐emergent period, talazoparib was generally associated with a lower rate of hospitalization and supportive care medication use compared with chemotherapy.

Conclusion

Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA‐mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care.

Implications for Practice

Talazoparib was generally well tolerated in patients with germline BRCA‐mutated HER2‐negative advanced breast cancer in the EMBRACA trial. Common toxicities with talazoparib were primarily hematologic and infrequently resulted in permanent drug discontinuation (<2% of patients discontinued talazoparib due to hematologic toxicity). Hematologic toxicities typically occurred during the first 3–4 months of treatment and were managed by dose modifications and supportive care measures. A significant efficacy benefit, improved patient‐reported outcomes, lower rate of health resource utilization and a tolerable safety profile support incorporating talazoparib into routine management of germline BRCA‐mutated locally advanced/metastatic breast cancer.

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<![CDATA[Association of collective attitudes and contraceptive practice in nine sub-Saharan African countries]]> https://www.researchpad.co/article/Nfbc5f123-66e7-4f47-9ba5-5c5797b3512b

Background

There is ample evidence that gender norms affect contraceptive practice; however, data are mostly qualitative with limited geographical scope. We investigated that association quantitatively using collective community-level attitudes towards premarital sex and wife-beating as proxies for gender norms.

Methods

Data came from nationally representative Demographic and Health Surveys (2005-2009) for women of reproductive age (15-49 years) in nine sub-Saharan African countries. Using multilevel logistic models, controlling for individual covariates and community-level indicators of women’s empowerment, we assessed the community-level association of gender norms regarding premarital sex and wife-beating with individual contraception uptake and demand satisfied among fecund sexually active women. Norms were approximated as ‘collective attitudinal norms’ from female/male residents (aged 15-49 years) from the same community. We assessed the magnitude and significance of the community-level effects and attributed variance across communities. The same analysis was replicated for each country.

Results

In a fully-adjusted model with a pooled sample of 24 404 adolescent women, the odds of contraception use increased with a 1 standard deviation (SD) increase in the variation of collective permissive attitudes towards premarital sex of female (odds ratio (OR) = 1.08, 95% confidence interval (CI) = 1.02-1.15) and male (OR = 1.11, 95% CI = 1.05-1.17) peers (15-24 years), while odds of contraceptive use declined by 10% (OR = 0.90, 95% CI = 0.85-0.96) with collective accepting attitudes towards wife-beating of women aged 15-49 years. Similar results were found in separate models that controlled for adults’ permissive attitudes towards premarital sex. The community-level attributed variance (V2 = 1.62, 95% CI = 1.45-1.80) represented 33% (intra-class correlation (ICC) = 33.0, 95% CI = 30.0-35.4) of the total variation of contraception use, and attitudes towards premarital sex and violence jointly explained nearly 26% of that V2 variance. The community-level shared of attributed variation of contraceptive use varied significantly across countries, from 3.5% in Swaziland (ICC = 3.5, 95% CI = 0.8-13.7) to 60.2% in Nigeria (OR = 60.2, 95% CI = 56.0-64.2).

Conclusions

Overall, significant positive associations of collective permissive attitudes of both adolescent and adult women towards premarital sex were found for use of, and demand for, contraception, whereas collective accepting attitudes towards wife-beating were negatively associated with the use and demand for contraception. Ours is the first study to define quantitatively the influence of proxies for gender norms at the community level on women’s family planning decisions. These findings offer new insights for understanding the role of sex-related attitudes and norms as important factors in shaping contraceptive practices and improving the effectiveness of family planning policies by targeting individuals as well as their groups of influence.

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<![CDATA[Perpetration of intimate partner violence and mental health outcomes: sex- and gender-disaggregated associations among adolescents and young adults in Nigeria]]> https://www.researchpad.co/article/N6d73e0ea-c03b-42cf-b2cf-841adf657822

Background

The association between intimate partner violence (IPV) victimisation and poor mental health outcomes is well established. Less is known about the correlation between IPV perpetration and mental health, particularly among adolescents and young adults. Using data from the nationally representative Violence Against Children Survey, this analysis examines the association between IPV perpetration and mental health for male and female adolescents and young adults in Nigeria.

Methods

Multivariate logistic regression models were used to examine associations between ever-perpetration of IPV and four self-reported mental health variables: severe sadness, feelings of worthlessness, suicide ideation, and alcohol use. Models were sex-disaggregated, controlled for age, marital status, and schooling, and tested with and without past exposure to violence. Standard errors were adjusted for sampling stratification and clustering. Observations were weighted to be representative of 13-24 year-olds in Nigeria.

Results

Males were nearly twice as likely as females to perpetrate IPV (9% v. 5%, respectively; P < 0.001), while odds of perpetration for both sexes were higher for those ever experiencing IPV (adjusted odds ratio (aOR) = 4.60 for males; aOR = 2.71 for females). Female perpetrators had 2.73 higher odds of reporting severe sadness (95% confidence interval CI = 1.44, 5.17; P = 0.002) and 2.72 times greater odds of reporting suicide ideation (1.28, 5.79; P = 0.010) than non-perpetrating females, even when controlling for past-year violence victimisation. In contrast, male perpetrators had 2.65 times greater odds of feeling worthless (1.09, 6.43; P = 0.031), and 2.36 times greater odds of reporting alcohol use in the last 30 days (1.50, 3.73; P < 0.001), as compared to non-perpetrating males.

Conclusions

Among adolescents and young adults in Nigeria, IPV perpetration and negative mental health outcomes are associated but differ for males and females. Mindful of the cross-sectional nature of the data, it is possible that socially determined gender norms may shape the ways in which distress from IPV perpetration is understood and expressed. Additional research is needed to clarify these associations and inform violence prevention efforts.

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<![CDATA[Improved child marriage laws and its association with changing attitudes and experiences of intimate partner violence: a comparative multi-national study]]> https://www.researchpad.co/article/Nbdaffe2f-0f2c-48e1-b5be-d2d9fb478e79

Background

Intimate partner violence (IPV) is a multi-national problem with many health consequences. Some research suggests that reducing rates of child marriage can improve gender norms and health outcomes related to IPV. Here, we examine whether changes in national child marriage laws can improve attitudes about domestic violence and reduce intimate partner violence at scale.

Methods

Data on attitudes towards violence and violence experienced were obtained from the Demographic and Health Surveys (DHS) and longitudinal data on child marriage policy from WORLD and MACHEquity databases (1995-2012). Treatment countries were included if they improved their national child marriage policies from harmful (under 18) to more protective and control countries were included if they had a constant child-marriage policy that allowed girls to marry under the age of 18. Our final data set included 5 treatment and 14 control countries for women’s outcomes, 2 treatment and 9 control countries for men’s outcomes and 2 treatment and 7 control countries for IPV outcomes (for which fewer countries collect data). We combined individual level responses to five questions on attitudes about domestic violence to create a scale from 0 (always unacceptable) to 5 (always acceptable). All analyses employed a difference-in-differences approach adjusting for individual and country level predictors.

Results

Data were available for 532 255 women, of which 96 414 also completed the domestic violence modules, and 104 704 men. National changes to a protective child marriage policy were associated with improved attitudes towards violence among women (-0.21 points, 95% confidence interval (CI) = -0.28, -0.14) and men (-0.98 points, 95% CI = -1.13, -0.83). Additionally, the risk of women experiencing physical and sexual abuse reduced by a greater proportion in treatment compared to control countries (odds ratio OR = 0.65, 95% CI = 0.50, 0.84; OR = 0.63, 95% CI = 0.45, 0.88, respectively).

Conclusions

Our large multi-national study is the first of its kind to critically evaluate the role of national policy on attitudes towards and experiences of IPV among both men and women, and finds that these laws have protective outcomes. Our results are consistent with the hypothesis that gender egalitarian laws positively influence norms and health at the national level.

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<![CDATA[Gender equality and global health: intersecting political challenges]]> https://www.researchpad.co/article/Nccb8a02c-44a1-4ea9-aac6-dbc058f8e6ab

Background

Women’s and men’s health outcomes are different. Some differences are biological, related to male and female sex, while others are related to their gender. Sex- and gender-related issues require different solutions, but policy makers lack straightforward heuristic strategies to identify gender-related health inequities.

Methods

Using 169 causes of disability-adjusted life years (DALYs) from the 2017 Global Burden of Disease, we calculated the female-to-male (f:m) and male-to-female (m:f) ratios of global DALYs, rank-ordered the ratios by size and calculated the proportion of all-cause DALYs that each cause explained, separately for males and females 15-49 years old. Gender-related vs sex-related causes were categorised using literature on the drivers for the 15 causes with highest f:m and m:f ratios.

Results

Causes of DALYs with high m:f ratios appear to be gendered and include: road injuries, interpersonal violence, and drowning – totaling 12.4% of men’s (15-49 years) all-cause DALYs. However, causes of DALYs with high f:m ratios are more likely a mix of sex-related and gender-related factors – including headache disorders, depressive disorders, and dietary iron deficiency – totaling 13.4% of women’s (15-49 years) all-cause DALYs. Ratios vary by age, geography and Socio-demographic Index.

Conclusions

Gender-related vs sex-related causes were categorised using available literature on the drivers for selected causes, illustrating that sex-disaggregated data represents a mix of social and biological influences. This analysis offers a model that policy makers can use to uncover potential gender inequalities in health, including intersections with other social factors. From it, new challenges emerge for global health policy makers and practitioners willing to address them. Global health actors will need to achieve a balance between the two agendas of global health and gender equality.

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<![CDATA[The efficacy and tolerance of intranasal interferons: studies at the Common Cold Unit]]> https://www.researchpad.co/article/Nf4272498-fb1d-4c01-af26-16e3c6875c61

Abstract

Intranasal sprays of interferons (IFNs) given one day before and for three days after virus challenge can protect human volunteers from infection with rhinoviruses, corona virus, and influenza. Longer dosage of IFN gives rise to nasal symptoms and signs such as bloodstained nasal discharge. More effective IFNs and regimes are therefore needed. IFNβ is active but the degree to which it will irritate the nose is unknown. Combining IFNs with synthetic antiviral drugs can produce synergistic increases in antiviral activity. It is suggested that these increases may be exploited in future experiments.

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<![CDATA[IDR2D identifies reproducible genomic interactions]]> https://www.researchpad.co/article/Nef0ffebe-61d3-4baf-b291-7020b4b04c56

Abstract

Chromatin interaction data from protocols such as ChIA-PET, HiChIP and Hi-C provide valuable insights into genome organization and gene regulation, but can include spurious interactions that do not reflect underlying genome biology. We introduce an extension of the Irreproducible Discovery Rate (IDR) method called IDR2D that identifies replicable interactions shared by chromatin interaction experiments. IDR2D provides a principled set of interactions and eliminates artifacts from single experiments. The method is available as a Bioconductor package for the R community, as well as an online service at https://idr2d.mit.edu.

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<![CDATA[Übersicht Über neue ernährungswissenschaftliche Publikationen]]> https://www.researchpad.co/article/Nb841871e-edea-40e9-b9de-d0c2cb16d027 ]]> <![CDATA[Oral Care Evaluation to Prevent Oral Mucositis in Estrogen Receptor‐Positive Metastatic Breast Cancer Patients Treated with Everolimus (Oral Care‐BC): A Randomized Controlled Phase III Trial]]> https://www.researchpad.co/article/N55d95938-a9e1-4de7-b0f8-3e004139eb3c

Abstract

Background

The incidence of oral mucositis (any grade) after everolimus treatment is 58% in the general population and 81% in Asian patients. This study hypothesized that professional oral care (POC) before everolimus treatment could reduce the incidence of everolimus‐induced oral mucositis.

Materials and Methods

This randomized, multicenter, open‐label, phase III study evaluated the efficacy of POC in preventing everolimus‐induced mucositis. Patients were randomized into POC and control groups (1:1 ratio) and received everolimus with exemestane. Patients in the POC group underwent teeth surface cleaning, scaling, and tongue cleaning before everolimus initiation and continued to receive weekly POC throughout the 8‐week treatment period. Patients in the control group brushed their own teeth and gargled with 0.9% sodium chloride solution or water. The primary endpoint was the incidence of all grades of oral mucositis. We targeted acquisition of 200 patients with a 2‐sided type I error rate of 5% and 80% power to detect 25% risk reduction.

Results

Between March 2015 and December 2017, we enrolled 175 women from 31 institutions, of which five did not receive the protocol treatment and were excluded. Over the 8 weeks, the incidence of grade 1 oral mucositis was significantly different between the POC group (76.5%, 62 of 82 patients) and control group (89.7%, 78 of 87 patients; p = .034). The incidence of grade 2 (severe) oral mucositis was also significantly different between the POC group (34.6%, 28 of 82 patients) and control group (54%, 47 of 87 patients; p = .015). As a result of oral mucositis, 18 (22.0%) patients in the POC group and 28 (32.2%) in the control group had to undergo everolimus dose reduction.

Conclusion

POC reduced the incidence and severity of oral mucositis in patients receiving everolimus and exemestane. This might be considered as a treatment option of oral care for patients undergoing this treatment. Clinical trial identification number: NCT 02069093.

Implications for Practice

The Oral Care‐BC trial that prophylactically used professional oral care (POC), available worldwide, did not show a greater than 25% difference in mucositis. The 12% difference in grade 1 or higher mucositis and especially the ∼20% difference in grade 2 mucositis are likely clinically meaningful to patients. POC before treatment should be considered as a treatment option of oral care for postmenopausal patients who are receiving everolimus and exemestane for treatment of hormone receptor‐positive, HER2‐negative advanced breast cancer and metastatic breast cancer. However, POC was not adequate for prophylactic oral mucositis in these patients, and dexamethasone mouthwash prophylaxis is standard treatment before everolimus.

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<![CDATA[Mortality of Pregnancy Following Breast Cancer Diagnoses in Taiwanese Women]]> https://www.researchpad.co/article/N097b1eff-3ab4-4755-820a-ce9eb14cfbd2

Abstract

Background

This work examined the association between pregnancy after breast cancer (BC) diagnosis and total mortality in Taiwanese patients with BC.

Materials and Methods

The Taiwan Cancer Registry, National Health Insurance database, and Taiwan National Death Certificate database were reviewed. Patients who became pregnant after being diagnosed with BC were selected (n = 249). Four nonpregnant patients with BC were selected and matched to every pregnant patient with BC by age at diagnosis, year at diagnosis, and propensity score based on disease stage, tumor size, node involvement, and histological grade. The disease‐free time interval for the selected control needed to have been longer than the time interval between the cancer diagnosis and pregnancy for the index case. Follow‐up was calculated from the pregnancy date of the index case to the date of death or December 31, 2014, whichever came first. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

After adjusting for age, year at BC diagnosis, stage, positive nodes, and hormone therapy, patients with BC who became pregnant after their cancer diagnosis had lower total mortality than did the comparison group (HR = 0.44, 95% CI = 0.23–0.84), including that of estrogen receptor‐positive patients (HR = 0.23, 95% CI = 0.07–0.77). The inverse association was more pronounced for those who became pregnant more than 3 years after diagnosis (HR = 0.19, 95% CI = 0.05–0.78).

Conclusion

Our nationwide retrospective analysis revealed that pregnancy after BC diagnosis was associated with lower mortality than that of nonpregnant patients with BC at a similar age, year at diagnosis, and clinical characteristics.

Implications for Practice

This article provides high‐level evidence based on an Asian population for pregnancy counseling after a breast cancer diagnosis, including for patients with estrogen receptor‐positive cancers. The study also revealed the optimal time for patients who would like to become pregnant after breast cancer.

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<![CDATA[Lymph Node Imaging in Patients with Primary Breast Cancer: Concurrent Diagnostic Tools]]> https://www.researchpad.co/article/Nb602c4c4-063d-42c6-a392-9bd95fb8407e

Abstract

The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis. The main goal for the radiologist is to determine and detect the presence of metastatic disease in nonpalpable axillary lymph nodes with a positive predictive value that is high enough to initially select patients for upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with different imaging modalities, but ultrasound is the method of choice for evaluating axillary lymph nodes and for performing image‐guided lymph node interventions. This review aims to provide a comprehensive overview of the available imaging modalities for lymph node assessment in patients diagnosed with primary breast cancer.

Implications for Practice

The detection of lymph node metastasis affects the management of patients with primary breast cancer. The main goal for the radiologist is to detect lymph node metastasis in patients to allow for the selection of patients who should undergo upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with mammography, computed tomography, and magnetic resonance imaging, but ultrasonography is the imaging modality of choice for evaluating axillary lymph nodes. A normal axillary lymph node is characterized by a reniform shape, a maximal cortical thickness of 3 mm without focal bulging, smooth margins, and, depending on size, a discernable central fatty hilum.

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