Use of magnetic resonance imaging for evaluation of therapeutic response in breast cancer-related lymphedema: A systematic review.

Breast cancer treatment-related lymphedema (BCRL) is a common comorbidity in breast cancer survivors. Although magnetic resonance imaging (MRI) is widely used to evaluate therapeutic response of patients with various medical conditions, it is not routinely used to evaluate lymphedema patients. We conducted a systematic review of the literature to identify studies on the use of MRI to evaluate therapy for BCRL. We hypothesized that MRI could provide information otherwise not possible through other examinations. On October 21, 2019, we conducted a systematic review on the PubMed/MEDLINE and Scopus databases, without time frame or language limitations, to identify studies on the use of MRI to evaluate therapy for BCRL. We excluded studies that investigated other applications of MRI, such as lymphedema diagnosis and surgical planning. Of 63 potential articles identified with the search, three case series fulfilled the eligibility criteria. In total, 53 patients with BCRL were included and quantitatively evaluated with MRI before and after manual lymphatic drainage. Authors used MRI or MR lymphagiography to investigate factors such as lymphatic vessel cross-sectional area, tissue water relaxation time (T2), and chemical exchange saturation transfer. The only study that compared MRI measurement with standard examinations reported that MRI added information to the therapy evaluation. MRI seems to be a promising tool for quantitative measurement of therapeutic response in patients with BCRL. However, the identified studies focused on only manual lymphatic drainage and were limited by the small numbers of patients. More studies are necessary to shed light on the topic.

Antibiotic Susceptibility and Therapy in Central Line Infections in Pediatric Home Parenteral Nutrition Patients.

BACKGROUND: Patients receiving home parenteral nutrition (HPN) are at high-risk for central line-associated bloodstream infections (CLABSI). There are no published management guidelines, however, for the antibiotic treatment of suspected CLABSI in this population. Historical microbiology data may help inform empiric antimicrobial regimens in this population. OBJECTIVE: The aim of the study was to describe antimicrobial resistance patterns and determine the most appropriate empiric antibiotic therapy in HPN-dependent children experiencing a community-acquired CLABSI. METHODS: Single-center retrospective cohort study evaluating potential coverage of empiric antibiotic regimens in children on HPN who developed a community-acquired CLABSI. RESULTS: From October 1, 2011 to September 30, 2017, there were 309 CLABSI episodes among 90 HPN-dependent children with median age 3.8 years old.Fifty-nine percent of patients carried the diagnosis of surgical short bowel syndrome. Organisms isolated during these infections included 60% Gram-positive bacteria, 34% Gram-negative bacteria, and 6% fungi. Among all staphylococcal isolates, 51% were methicillin sensitive. Among enteric Gram-negative organisms, sensitivities were piperacillin-tazobactam 71%, cefepime 97%, and meropenem 99%. Organisms were sensitive to current institutional standard therapy with vancomycin and piperacillin-tazobactam in 69% of cases compared with vancomycin and cefepime or vancomycin an meropenem in 85% and 96% of cases (both P < 0.01). CONCLUSIONS: Empiric antimicrobial therapy for suspected CLABSI in HPN-dependent children should include therapy for methicillin-resistant staphylococci as well as enteric Gram-negative organisms. Future studies are needed to evaluate clinical outcomes based upon evidence-based antimicrobial regimens.

Comparison of 99mTc-Sestamibi Molecular Breast Imaging and Breast MRI in Patients With Invasive Breast Cancer Receiving Neoadjuvant Chemotherapy.

OBJECTIVE. The purpose of this study is to prospectively compare the size of invasive breast cancer before and after neoadjuvant chemotherapy (NAC) at breast MRI and molecular breast imaging (MBI) and to assess the accuracy of post-NAC MBI and MRI relative to pathologic analysis. SUBJECTS AND METHODS. Women with invasive breast cancer greater than or equal to 1.5 cm were enrolled to compare the longest dimension before and after NAC at MRI and MBI. MBI was performed on a dual-detector cadmium zinc telluride system after administration of 6.5 mCi (240 MBq) 99mTc-sestamibi. The accuracy of MRI and MBI in assessing residual disease (invasive disease or ductal carcinoma in situ) was determined relative to pathologic examination. RESULTS. The longest dimension at MRI was within 1.0 cm of that at MBI in 72.3% of cases before NAC and 70.1% of cases after NAC. The difference between the longest dimension at imaging after NAC and pathologic tumor size was within 1 cm for 58.7% of breast MRI cases and 59.6% of MBI cases. Ninety patients underwent both MRI and MBI after NAC. In the 56 patients with invasive residual disease, 10 (17.9%) cases were negative at MRI and 23 (41.1%) cases were negative at MBI. In the 34 patients with breast pathologic complete response, there was enhancement in 10 cases (29.4%) at MRI and uptake in six cases (17.6%) at MBI. Sensitivity, specificity, positive predictive value, and negative predictive value after NAC were 82.8%, 69.4%, 81.4%, and 71.4%, respectively, for MRI and 58.9%, 82.4%, 84.6%, and 54.9%, respectively, for MBI. CONCLUSION. Breast MRI and MBI showed similar disease extent before NAC. MBI may be an alternative to breast MRI in patients with a contraindication to breast MRI. Neither modality showed sufficient accuracy after NAC in predicting breast pathologic complete response to obviate tissue diagnosis to assess for residual invasive disease. Defining the extent of residual disease compared with pathologic evaluation was also limited after NAC for both breast MRI and MBI.

Integrated Rehabilitation for Breast Cancer Survivors.

The physical and psychological side effects of breast cancer therapies can have substantial impact on survivors' physical and social functioning. Roughly half of the more than 3 million Americans alive with a history of breast cancer report adverse, function-degrading sequelae related to their oncologic treatments. Care delivery models for the timely delivery of rehabilitation services have been proposed yet limitedly vetted or implemented. These include the prospective surveillance model, procedure-linked referrals, survivorship care plans, and risk stratification. Patients' capacity to engage in the rehabilitative process varies during cancer therapy and into survivorship. Perioperative attention generally focuses on managing premorbid impairments and normalizing shoulder function. In contrast, during chemotherapy and radiation therapy, symptom control, constructive coping, and role preservation may become more salient. Risk-stratified, individualized screening and prevention activities for specific impairments have become increasingly feasible through predictive models and analytics. Impairments' severity deleterious impact can be mitigated, as has been established for lymphedema, shoulder dysfunction, chemotherapy-induced peripheral neuropathy, cognitive dysfunction, fatigue, and sexual side effects. Integrated rehabilitative programs, often initiated after the completion of cancer treatment, are available in some countries outside of the United States and may offer survivors vital vocation- and avocation-directed services.

Altering calcium influx for selective destruction of breast tumor.

BACKGROUND: Human triple-negative breast cancer has limited therapeutic choices. Breast tumor cells have depolarized plasma membrane potential. Using this unique electrical property, we aim to develop an effective selective killing of triple-negative breast cancer. METHODS: We used an engineered L-type voltage-gated calcium channel (Cec), activated by membrane depolarization without inactivation, to induce excessive calcium influx in breast tumor cells. Patch clamp and flow cytometry were used in testing the killing selectivity and efficiency of human breast tumor cells in vitro. Bioluminescence and ultrasound imaging were used in studies of human triple-negative breast cancer cell MDA-MB-231 xenograft in mice. Histological staining, immunoblotting and immunohistochemistry were used to investigate mechanism that mediates Cec-induced cell death. RESULTS: Activating Cec channels expressed in human breast cancer MCF7 cells produced enormous calcium influx at depolarized membrane. Activating the wild-type Cav1.2 channels expressed in MCF7 cells also produced a large calcium influx at depolarized membrane, but this calcium influx was diminished at the sustained membrane depolarization due to channel inactivation. MCF7 cells expressing Cec died when the membrane potential was held at -10 mV for 1 hr, while non-Cec-expressing MCF7 cells were alive. MCF7 cell death was 8-fold higher in Cec-expressing cells than in non-Cec-expressing cells. Direct injection of lentivirus containing Cec into MDA-MB-231 xenograft in mice inhibited tumor growth. Activated caspase-3 protein was detected only in MDA-MB-231 cells expressing Cec, along with a significantly increased expression of activated caspase-3 in xenograft tumor treated with Cec. CONCLUSIONS: We demonstrated a novel strategy to induce constant calcium influx that selectively kills human triple-negative breast tumor cells.

Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics.

Nanomaterial production is expanding as new industrial and consumer applications are introduced. Nevertheless, the impacts of exposure to these compounds are not fully realized. The present study was designed to determine whether gestational nano-sized titanium dioxide exposure impacts cardiac and metabolic function of developing progeny. Pregnant Sprague-Dawley rats were exposed to nano-aerosols (~10 mg/m3, 130- to 150-nm count median aerodynamic diameter) for 7-8 nonconsecutive days, beginning at gestational day 5-6 Physiological and bioenergetic effects on heart function and cardiomyocytes across three time points, fetal (gestational day 20), neonatal (4-10 days), and young adult (6-12 wk), were evaluated. Functional analysis utilizing echocardiography, speckle-tracking based strain, and cardiomyocyte contractility, coupled with mitochondrial energetics, revealed effects of nano-exposure. Maternal exposed progeny demonstrated a decrease in E- and A-wave velocities, with a 15% higher E-to-A ratio than controls. Myocytes isolated from exposed animals exhibited ~30% decrease in total contractility, departure velocity, and area of contraction. Bioenergetic analysis revealed a significant increase in proton leak across all ages, accompanied by decreases in metabolic function, including basal respiration, maximal respiration, and spare capacity. Finally, electron transport chain complex I and IV activities were negatively impacted in the exposed group, which may be linked to a metabolic shift. Molecular data suggest that an increase in fatty acid metabolism, uncoupling, and cellular stress proteins may be associated with functional deficits of the heart. In conclusion, gestational nano-exposure significantly impairs the functional capabilities of the heart through cardiomyocyte impairment, which is associated with mitochondrial dysfunction.NEW & NOTEWORTHY Cardiac function is evaluated, for the first time, in progeny following maternal nanomaterial inhalation. The findings indicate that exposure to nano-sized titanium dioxide (nano-TiO2) during gestation negatively impacts cardiac function and mitochondrial respiration and bioenergetics. We conclude that maternal nano-TiO2 inhalation contributes to adverse cardiovascular health effects, lasting into adulthood.