Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors

Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW) with breast cancer, third-generation aromatase inhibitors (AIs) as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence

A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever - single centre experience.

Objective: To compare the original (1997) and revised (2009) versions of World Health Organization guidelines for dengue patientsMethods: Adult patients with a positive dengue Immunoglobulin M serology, and a diagnosis of dengue were included in the study at Aga Khan University Hospital during a three-year period from January 2005 to December 2007. Data related to these dengue patients was collected from their medical records. Guidelines were then applied by the research assistant and correlation among these guidelines was computed. SPSS 19 was used for statistical analysis.Results: A total of 612 patients were found with a diagnosis of dengue, but only 439 (71.73%) had a positive IgM. The median age of these 439 patients was 28 (interquartile range: 18) years and majority of them were males, 295 (67%). According to the 1997 guidelines, 383 (87%) patients were classified as having dengue, while according to the 2009 guidelines, all the 439 (100%) patients were classified with a dengue infection. Under WHO 1997, 21 (5.5%) cases were classified as dengue shock syndrome, while 2009 guidelines labelled 88 (20%) cases as severe dengue. There was a consensus on only 11 severe cases by both the guidelines, showing different results between the two.Conclusion: By using 2009 guidelines, a physician would classify more dengue patients as having severe disease

Minimization of total harmonic distortions of cascaded H-bridge multilevel inverter by utilizing bio inspired AI algorithm

Minimizing total harmonic distortion (THD) with less system complexity and computation time is a stringent constraint for many power systems. The multilevel inverter can have low THD when switching angles are selected at the fundamental frequency. For low-order harmonic minimization, selective harmonic elimination (SHE) is the most adopted and proficient technique but it involves the non-linear transcendental equations which are very difficult to solve analytically and numerically. This paper proposes a genetic algorithm (GA)-based optimization technique to minimize the THD of cascaded H-bridge multilevel inverter. The GA is the finest approach for solving such complex equations by obtaining optimized switching angles. The switching angles are calculated by the genetic algorithm by solving the nonlinear transcendental equations. This paper has modeled and simulated a five-level inverter in MATLAB Simulink. The THD comparison is carried out between step modulation method and optimization method. The results reveal that THD has been reduced from 17.88 to 16.74% while third and fifth harmonics have been reduced from 3.24%, 3.7% to 0.84% and 3.3%, respectively. The optimization method along with LC filter significantly improves the power quality providing a complete sinusoidal signal for varying load

Theoretical and experimental analysis of multifunctional high performance cement mortar matrices reinforced with varying lengths of carbon fibers

An effective scheme to formulate high performance and multifunctional cement based mortar composites reinforced with varying lengths of carbon fibers has been devised. The detailed investigations pertaining to the fracture response of composites in cracks initiation and progression phases, their conducting mechanism and volumetric stability were performed with varying loads of 6mm and 12mm long carbon fibers at two different w/c ratios i.e. 0.45 and 0.50. The experiments concluded that an optimum addition of carbon fibers results in substantial improvement of fracture properties alongside significant reduction in electrical resistivity and total plastic shrinkage. The field emission scanning electron microscopy of the cryofractured specimen revealed crack arresting actions of uniformly distributed carbon fibers through successful crack bridging and branching phenomenon

Mammographic density does not correlate with Ki-67 expression or cytomorphology in benign breast cells obtained by random periareolar fine needle aspiration from women at high risk for breast cancer

BACKGROUND:Ki-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. Mammographic breast density is a risk biomarker and is also being used as a response biomarker. We previously showed that Ki-67 expression is higher in specimens of benign breast cells exhibiting cytologic atypia that are obtained by random periareolar fine needle aspiration (RPFNA). It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA.METHODS:Included in the study were 344 women at high risk for developing breast cancer (based on personal or family history), seen at The University of Kansas Medical Center high-risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment plus a mammogram. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by ?2 test, and continuous variables were analyzed by nonparametric test and linear regression.RESULTS:Forty-seven per cent of women were premenopausal and 53% were postmenopausal. The median age was 48 years, median 5-year Gail Risk was 2.2%, and median Ki-67 was 1.9%. The median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality (atypia versus no atypia; P = 0.001) and younger age (=50 years versus >50 years; P = 0.001). Mammographic density was higher in premenopausal women (P = 0.001), those with lower body mass index (P < 0.001), and those with lower 5-year Gail risk (P = 0.001). Mammographic density exhibited no correlation with Ki-67 expression or cytomorphology.CONCLUSION:Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers in breast cancer chemoprevention trials

Enhanced serum concentrations of transforming growth factor-beta1 in simple fatty liver: is it really benign?

<p>Abstract</p> <p>Background</p> <p>Inside the spectrum of non-alcoholic fatty liver disease, simple fatty liver is generally thought of as being "non progressive", differently from non-alcoholic steatohepatitis, which increases in severity due to the presence of apoptosis/inflammation and fibrosis. The "benignity" of fatty liver is widely accepted but conceptually difficult to maintain because the mechanisms underlying this entity are the same ones that determine the more severe form.</p> <p>Findings provide evidence that iron overload is associated with increased liver damage and collagen deposition. Transforming growth factor-beta1 released by hepatic stellate cells during chronic liver injury plays a critical role in liver apoptosis and fibrogenesis.</p> <p>Objective</p> <p>To verify whether both the forms of non-alcoholic fatty liver disease were really dissimilar, evaluating the serum profile of two key parameters, indexes of severity.</p> <p>Methods</p> <p>A total of 123 patients (57 females) participated, forming three groups: forty five patients with fatty liver, 42 patients with non-alcoholic steatohepatitis and 36 with chronic hepatitis C. All had a biopsy-proven diagnosis.</p> <p>Measurements</p> <p>Serum concentrations of transforming growth factor-beta1 and ferritin.</p> <p>Results</p> <p>High concentrations of transforming growth factor-beta1 were noticed in patients suffering from both fatty liver and non-alcoholic steatohepatitis, 129.1 (45.4) versus 116.8 (42.2) ng/mL, P = 0.2; they were significantly superior to those of chronic hepatitis C patients 87.5 (39.5) ng/mL, P < 0.001. Ferritin levels were on average above normal values and similar in the three groups (P = 0.9), also when adjusted for gender (P = 0.5) and age (P = 0.3).</p> <p>Conclusion</p> <p>No difference between serum concentrations of transforming growth factor-beta1 and ferritin in fatty liver and non-alcoholic steatohepatitis suggests that these forms share more common aspects, regarding their progression, than previously thought.</p

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

Purpose: People living with cancer and haematological malignancies are at increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. Methods: This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. Results: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction (PCR) coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5% respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Lymphoma patients had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01 respectively. p<0.001 for both). Conclusions: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous, and lower than the general population. Many patients with cancer will remain at increased risk of coronavirus infections, even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic

Strategic crossing of biomass and harvest index—source and sink—achieves genetic gains in wheat

To accelerate genetic gains in breeding, physiological trait (PT) characterization of candidate parents can help make more strategic crosses, increasing the probability of accumulating favorable alleles compared to crossing relatively uncharacterized lines. In this study, crosses were designed to complement “source” with “sink” traits, where at least one parent was selected for favorable expression of biomass and/or radiation use efficiency—source—and the other for sink-related traits like harvest-index, kernel weight and grains per spike. Female parents were selected from among genetic resources—including landraces and products of wide-crossing (i.e. synthetic wheat)—that had been evaluated in Mexico at high yield potential or under heat stress, while elite lines were used as males. Progeny of crosses were advanced to the F4 generation within Mexico, and F4-derived F5 and F6 generations were yield tested to populate four international nurseries, targeted to high yield environments (2nd and 3rd WYCYT) for yield potential, and heat stressed environments (2nd and 4th SATYN) for climate resilience, respectively. Each nursery was grown as multi-location yield trials. Genetic gains were achieved in both temperate and hot environments, with most new PT-derived lines expressing superior yield and biomass compared to local checks at almost all international sites. Furthermore, the tendency across all four nurseries indicated either the superiority of the best new PT lines compared with the CIMMYT elite checks, or the superiority of all new PT lines as a group compared with all checks, and in some cases, both. Results support—in a realistic breeding context—the hypothesis that yield and radiation use efficiency can be increased by improving source:sink balance, and validate the feasibility of incorporating exotic germplasm into mainstream breeding efforts to accelerate genetic gains for yield potential and climate resilience