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Partial-breast irradiation (PBI) has been performed as alternative to whole-breast irradiation (WBI) in breast-conserving therapy (BCT). Recently, the 21-gene recurrence score (RS) was introduced to determine the adjuvant therapy for estrogen receptor (ER)-positive, and human epidermal growth factor receptor 2 (HER2)-negative diseases. However, the impact of RS-based systemic therapy on locoregional recurrence (LRR) following BCT with PBI remains uninvestigated. Patients with ER-positive, HER2-negative, and node-negative breast cancer who underwent BCT with PBI were examined during May 2012–March 2022. In addition to immunohistochemistry (IHC), RS was available to decide on adjuvant therapy. In total, 431 patients were evaluated with a median followup of 48.6 months. The 4-year LRR-free survival rates were 97.3% and 96.4% in the IHC and RS cohorts, respectively (p = 0.50). Ki67 of >20% was significantly associated with LRR in the multivariate analysis (HR 4.39, p < 0.05). For patients with Ki67 > 20%, 29 of 71 (40.8%) and 46 of 59 (78.0%) patients received only endocrine therapy in the IHC and RS cohorts, respectively (p < 0.0001). For patients with Ki67 >20% who received only endocrine therapy, the 4-year LRR-free survival rates were 91.8% in the IHC cohort and 94.6% in the RS cohort (p = 0.29) Although the introduction of RS increased the number of patients receiving endocrine therapy alone for Ki67 >20% of disease by two times, the LRR-free survival after BCT with PBI could be maintained. However, further studies from multiple institutions with longer followup data are required. [ABSTRACT FROM AUTHOR]

Purpose of Review : Breast cancer is the most commonly diagnosed cancer and is the second leading cause of cancer death in women. Breast cancer screening has significantly improved detection of cancer and reduced mortality however, mortality has plateaued in recent years. As such, identifying ways to improve management decisions to further reduce mortality remains a high priority. Herein, we review the current evidence for locoregional management recommendations in patients with hereditary breast cancer mutations. Additionally, we discuss the potential utility of gene assays in locoregional management decision-making. Recent Findings: Gene assays are currently used to identify patients who would benefit from systemic adjuvant therapy, and their uptake has improved clinical outcomes. There is growing evidence supporting their utility in determining patients at a higher risk for locoregional recurrence. As such, gene assays may have a role in decision-making regarding the locoregional management of breast cancer, and specifically the use of adjuvant RT. Summary: Risk reduction is central to the management of patients with hereditary breast cancer mutations. In patients with BRCA1/2 mutations, risk-reducing mastectomy (RRM) ± adjuvant radiotherapy (RT) or breast conserving therapy (BCS) with adjuvant RT is often an appropriate treatment regimen. A similar treatment approach is likely appropriate in other high-penetrance mutations, although RT should be used cautiously in patients with TP53 mutations. In patients with low-moderate penetrance mutations, BCS with adjuvant RT or RRM in conjunction with patient preference is likely appropriate, although RT should be avoided in patients with ATM mutations. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate factors associated with successful comprehensive genomic sequencing of image-guided percutaneous needle biopsies in patients with lung cancer using a broad hybrid capture-based next-generation sequencing assay (CHCA). Methods: We conducted a single-institution retrospective review of image-guided percutaneous transthoracic needle biopsies from January 2018 to December 2019. Samples with confirmed diagnosis of primary lung cancer and for which CHCA had been attempted were identified. Pathologic, clinical data and results of the CHCA were reviewed. Covariates associated with CHCA success were tested for using Fisher’s exact test or Wilcoxon ranked sum test. Logistic regression was used to identify factors independently associated with likelihood of CHCA success. Results: CHCA was requested for 479 samples and was successful for 433 (91%), with a median coverage depth of 659X. Factors independently associated with lower likelihood of CHCA success included small tumor size (OR = 0.26 [95% confidence interval (CI): 0.11–0.62, p = 0.002]), intraoperative inadequacy on cytologic assessment (OR = 0.18 [95% CI: 0.06–0.63, p = 0.005]), small caliber needles (≥20-gauge) (OR = 0.22 [95% CI: 0.10–0.45, p < 0.001]), and presence of lung parenchymal abnormalities (OR = 0.12 [95% CI: 0.05–0.25, p < 0.001]). Pneumothorax requiring chest tube insertion occurred in 6% of the procedures. No grade IV complications or procedure-related deaths were reported. Conclusions: Percutaneous image-guided transthoracic needle biopsy is safe and has 91% success rate for CHCA in primary lung cancer. Intraoperative inadequacy, small caliber needle, presence of parenchymal abnormalities, and small tumor size (≤1 cm) are independently associated with likelihood of failure.

Osteoarticular tuberculosis (TB), a form of extrapulmonary tuberculosis, refers to the involvement of Mycobacterium tuberculosis (M.tb) in the bones and joints. While pulmonary tuberculosis is the most common form, osteoarticular TB represents a relatively rare but significant manifestation, accounting for approximately 1–3% of all TB cases. Accurate and timely diagnosis plays a pivotal role in the management of osteoarticular TB. Conventional diagnostic methods for osteoarticular TB, such as acid-fast bacilli smear microscopy and culture, have limitations in terms of sensitivity, specificity, and turnaround time. The purpose of this review is to comprehensively evaluate and synthesize the existing literature on molecular pioneering in osteoarticular TB diagnosis. Molecular techniques, such as nucleic acid amplification tests and gene-based assays, have emerged as promising tools for diagnosing TB. These techniques target specific genetic sequences of M.tb , enabling rapid and sensitive detection of the pathogen. However, the diagnostic accuracy, advantages, and limitations of these molecular techniques in the context of osteoarticular TB diagnosis require further investigation and consolidation of evidence. Furthermore, this review aims to identify areas for future research and development in the field of molecular diagnostics for osteoarticular TB. [ABSTRACT FROM AUTHOR]

Purpose of Review: Active surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes. Recent Findings: Patient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30-50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer. Summary: The optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial. [ABSTRACT FROM AUTHOR]

The authors describe a fluorescence polarization (FP) based strategy for HIV detection. The assay is based on T7 exonuclease assisted quadratic recycling amplification using graphene oxide (GO) as an amplifier of FP. The effect is caused by the finding that the binding forces between GO and ssDNA are much stronger than those between GO and dsDNA. The two probes, P1 and dye labeled P2, resist digestion by T7 exonuclease (T7exo) due to the 5′-termini protrusion. The hairpin probes are absorbed on the surface of GO without the target DNA. While the presence of the target DNA leads to two independent and simultaneous recycling processes with the assistance of T7exo. Due to this quadratic amplification, a large quantity of ssDNA will be absorbed onto the surface of GO, and this will cause a strong enhancement of FP. This polarization assay was applied to design a method for the determination of HIV DNA which displays a detection limit of 9.12 pmol·L. It is highly selective and can be performed in homogeneous solutions. The cascade amplification strategy is not limited to this particular DNA but is perceived to provide a universal platform for sensitive determination of a wide spectrum of DNA target analytes. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We describe a sensitive enzyme-free bioassay for the determination of microRNA-21. It is based on a combination of target-triggered hybridization chain reaction, tagging with CdTe quantum dots (QDs), and anodic stripping voltammetry. Firstly, a thiolated capture hairpin probe SH-HP1 was immobilized on the surface of a gold electrode. HP1 unfolds in the presence of microRNA-21. If hairpin probe 2 (HP2) is present, a HP1-HP2 complex will be formed which possesses an exposed stem of HP2, and microRNA is released in parallel. The released microRNA-21 triggers a hybridization chain reaction and this leads to form an exposed DNA segment of HP2 and cycle use microRNA-21. With the aid of assistant DNA A1 and A2, the exposed DNA segment of HP2 progressed to a long double strand. The strand is rich in CdTe QDs with the help of QDs-A1. Then, the attached QDs were dissolved with HNO to give dissolved Cd(II) ions. Finally, the corresponding electrochemical current response of Cd(II) is monitored by anodic stripping voltammetry and used to quantify the concentration of microRNA-21. More microRNA-21 participated in this reaction increases the number of CdTe QDs, which results in increased electrochemical current. Thus, an ultrasensitive detection of microRNA-21 is accomplished by anodic stripping voltammetry. This gene assay displays a detection limit as low as 33 aM. It can discriminate between complementary DNA sequence and single-base mismatched DNA, indicating its high specificity. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common female cancer and is associated with a significant clinical and economic burden. Multigene assays and molecular markers represent an opportunity to direct chemotherapy only to patients likely to have significant benefit. This systematic review examines published health economic analyses to assess the support for adjuvant therapy decision making. Literature searches of PubMed, the Cochrane Library, and congress databases were carried out to identify economic evaluations of multigene assays and molecular markers published between 2002 and 2012. After screening and data extraction, study quality was assessed using the Quality of Health Economic Studies instrument. The review identified 29 publications that reported evaluations of two assays: Onco type DX and MammaPrint. Studies of both tests provided evidence that their routine use was cost saving or cost-effective versus conventional approaches. Benefits were driven by optimal allocation of adjuvant chemotherapy and reduction in chemotherapy utilization. Findings were sensitive to variation in the frequency of chemotherapy prescription, chemotherapy costs, and patients' risk profiles. Evidence suggests that multigene assays are likely cost saving or cost-effective relative to current approaches to adjuvant therapy. They should benefit decision making in early-stage breast cancer in a variety of settings worldwide. [ABSTRACT FROM AUTHOR]

Objective: Onco type DX, a 21-gene assay, was clinically validated as a predictor of 10-year recurrence-free survival and treatment response in patients with early-stage estrogen-receptor-positive, lymph-node negative breast cancer (ER+ LN- ESBC). This study determined “real-life” alteration in treatment decision and economic implications of Onco type DX use in women with ER+ LN- ESBC. Methods: Clalit Health Services (CHS, Tel Aviv, Israel), determined the proportion of women in low, intermediate and high-risk groups in the first 368 Onco type DX assays performed, the change of adjuvant therapy recommendation following the recurrence (RS) results from Onco type DX use, and associated chemotherapy costs. The risk of recurrence-free survival was derived from prespecified statistical protocols of NCI-sponsored trials conducted by NSABP (B-14 and B-20). Utilities were literature based. A 3% discount rate was employed. Results: Onco type DX altered recommendations of 40% of patients, 84% of whom were changed from hormone + chemotherapy to hormonal therapy alone. Among high-risk women, 8% switched actual treatment from hormonal therapy to hormone + chemotherapy. By reducing the chemotherapy disutility, quality-adjusted life-years (QALY) increased 0.170 years. Use of Onco type DX costs $10,770 per QALY gained. Sensitivity analyses revealed that risk reduction in the low-risk population, the cost of adverse events, and the relative risk reduction of recurrence were the most influential variables. Conclusion: Onco type DX resulted in net QALY gain and increased overall costs, with an incremental cost-effectiveness ratio of $10,770. For CHS, Onco type DX represents an effective and affordable approach to favorably affect the lives of women with ESBC. [ABSTRACT FROM AUTHOR]

Global gene expression profiling is used to generate novel insight into a variety of disease states. Such studies yield a bewildering number of data points, making it a challenge to validate which genes specifically contribute to a disease phenotype. Aerobic exercise training represents a plausible model for identification of molecular mechanisms that cause metabolic-related changes in human skeletal muscle. We carried out the first transcriptome-wide characterization of human skeletal muscle responses to 6 wk of supervised aerobic exercise training in 8 sedentary volunteers. Biopsy samples before and after training allowed us to identify ∼470 differentially regulated genes using the Affymetrix U95 platform (80 individual hybridization steps). Gene ontology analysis indicated that extracellular matrix and calcium binding gene families were most up-regulated after training. An electronic reanalysis of a Duchenne muscular dystrophy (DMD) transcript expression dataset allowed us to identify ∼90 genes modulated in a nearly identical fashion to that observed in the endurance exercise dataset. Trophoblast noncoding RNA, an interfering RNA species, was the singular exception--being up-regulated by exercise and down-regulated in DMD. The common overlap between gene expression datasets may be explained by enhanced α7β1 integrin signaling, and specific genes in this signaling pathway were up-regulated in both datasets. In contrast to these common features, OXPHOS gene expression is subdued in DMD yet elevated by exercise, indicating that more than one major mechanism must exist in human skeletal muscle to sense activity and therefore regulate gene expression. Exercise training modulated diabetes-related genes, suggesting our dataset may contain additional and novel gene expression changes relevant for the anti-diabetic properties of exercise. In conclusion, gene expression profiling after endurance exercise training identified a... [ABSTRACT FROM AUTHOR]

Background: Anthracyclines are associated with significant toxicities whereas nonanthracyclines have proven to be better tolerated. A 21-gene assay allows clinicians to predict who will not benefit from adjuvant chemotherapy and avoid systemic toxicities. Physicians are using the recurrence score to guide chemotherapy selection, despite the lack of evidence. In this study we examined factors associated with prescribing patterns for an anthracycline-based chemotherapy in hormone receptor-positive stage I to III breast cancer., Materials and Methods: This was a retrospective study using the Michigan Breast Oncology Quality Initiative data set (February 1, 2006 to December 31, 2015). Women with histologically confirmed stage I to III invasive breast cancer with estrogen receptor and/or progesterone receptor-positive, HER2/neu-negative receptor status were included. We used χ 2 analysis to determine associations of these characteristics with the 21-gene assay score and anthracycline use., Results: A total of 17,788 patients were evaluated. Most tumors were stage I (60%). Most procedures were lumpectomy with radiation (66%). Anthracyclines were used more often in stage III patients (69%), younger patients (40% for patients younger than 65 years), and those with higher 21-gene recurrence scores. Patients with low recurrence scores were more likely to receive anthracyclines if lymph node-positive (10%) than if lymph node-negative (1%; P < .001). Patients with high recurrence scores and lymph node-positive status were just as likely to receive an anthracycline-based as a nonanthracycline-based regimen (47.5% vs. 49.2%; P = .89)., Conclusion: These data indicate that medical oncologists might be anticipating the results of Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer study (TAILORx) and the Clinical Outcomes in ER+HER2-node-positive Breast Cancer Patients Who Were Treated According to the Recurrence Score Results: Evidence From a Large Prospectively Designed Registry (RxPonder) trials and are avoiding the potential serious complications associated with anthracycline treatment in patients least likely to receive benefit., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Bacterial L-forms have always been considered as osmotic-pressure-sensitive cell-wall-deficient bacteria and isolation culture of L-forms must use media with high osmotic pressure. However, isolation culture of stable L-forms formed in humans and animals is very difficult because they have adapted to the physiological osmotic pressure condition of the host. We use a non-high osmotic isolation technique to isolate stable L-forms of Salmonella Typhi and Salmonella Paratyphi A from bile-inducer cultures in vitro and from patients' gallbladder specimens. Multiplex PCR assay for Salmonella-specific genes and nucleotide sequencing are used to identify the Salmonella L-forms in stable L-form isolates. Using this method, we confirmed that Salmonella Paratyphi A and Salmonella Typhi cannot be isolated from bile-inducer cultures cultured for 6 h or 48 h, but the L-forms can be isolated from 1 h to 45 days. In the 524 gallbladder samples, the positive rate for bacterial forms was 19.7% and the positive rate for Salmonella spp. was 0.6% by routine bacteriological methods. The positive rate for bacterial L-forms was 75.4% using non-high osmotic isolation culture. In the L-form isolates, the positive rate of Salmonella invA gene was 3.1%. In these invA-positive L-form isolates, four were positive for the invA and flic-d genes of Salmonella Typhi, and ten were positive for the invA and flic-a genes of Salmonella Paratyphi A., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Estrogen Receptor-positive/HER-2 negative breast cancers represent a heterogeneous group of tumors. Luminal A and B tumor subtypes can be identified through immunohistochemical assessment of estrogen and progesterone receptor, Ki-67 and HER-2 status. Patients with high levels of expression of steroid hormone receptors and low proliferation (Luminal A) are commonly cured with endocrine therapy alone. Patients with doubtful endocrine responsiveness or with high proliferation index (Luminal B/Her-negative) require the addition of chemotherapy to the best endocrine therapy. Controversies still exist on the identification of those patients who do not benefit from chemotherapy. Tailored adjuvant treatments should be considered in the therapeutic algorithm of patients with luminal tumors., (Copyright © 2013 Elsevier Inc. All rights reserved.)