Pathology of breast cancer metastasis and a view of metastasis to the brain.

Despite the advances in diagnosis and management of breast cancer, metastasis has been responsible for the staggering percentage of breast cancer-related death. Mortality threat can be explained mostly by the lack of proper understanding of the diversity of pathological features and underlying mechanism of breast cancer metastasis and effective targeted therapy. Breast cancer stem cells (BCSCs) are the potential source of tumor cells spread to distant organs. BCSCs targeted therapy can suppress the breast cancer progression to metastasis. Spreading of tumor cells to the bone, lung, liver, and brain occurs through a distinct non-random process; called metastasis organotropism. Recently, brain metastasis in breast cancer patients has been detected more frequently, causing a significant clinical burden. BRCA1 and BRCA2 associated breast cancers carry a remarkably higher propensity of CNS metastasis. BRCA1 and BRCA2 associated breast cancers commonly have the propensity to be the triple-negative (TN) and hormone receptors (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative molecular subtypes, respectively. Regardless of molecular subtypes, metastasis is most commonly evident at the bone. Heterogeneity is a critical pathological feature, leads to therapeutic resistance. BCSCs, biomarkers expression patterns, and mutations contribute to heterogeneity. In this paper, we discuss crucial pathological features of breast cancer metastasis, emphasizing metastasis organotropism and heterogeneity; and mechanisms of breast cancer metastasis, highlighting the pathways of metastasis to the brain. We consider that this paper reinforces future research areas and benefits the general readers, physicians, and researchers to identify potential areas to develop targeted therapies.

The impact of MELD exception points for hydrothorax on posttransplant mortality: a propensity score-matched analysis.

BACKGROUND: Hepatic hydrothorax is a challenging complication of end-stage liver disease, and.patients with this complication can receive model for end-stage liver disease (MELD) exception points if they meet specific criteria as defined by United Network for Organ Sharing (UNOS). This research aimed to analyze the effect of receiving MELD exception points for hepatic hydrothorax on posttransplant mortality, using a national transplant database. METHODS: Patients >18 years in the UNOS database awaiting liver transplant between 2012 and 2023 were identified based on their petition for MELD exception points. Using a 1: 1 propensity score-matched analysis, 302 patients who received MELD exception points for hepatic hydrothorax were compared with 302 patients who did not receive MELD exception points.Demographic, clinical and laboratory values were compared. The primary outcome was posttransplant mortality. Multivariate logistic regression controlled for potential confounders. RESULTS: No significant difference was observed in mean age (58.20 vs 57.62 years), mean initial MELD score (16.93 vs 16.54), or mean Child-Pugh score (9.77 vs 9.74) in patients with hepatic hydrothorax receiving MELD exception points versus their matched cohort who did not recieve exception points. The proportion of males was slightly higher among patients who received MELD exception points (57.6% males vs 53.6% males). A majority of patients in both groups had Child-Pugh grade C (>56%). Patients receiving MELD exception points for hepatic hydrothorax had a statistically significant 44% decrease in the odds of posttransplant death compared to those who did not (OR 0.56; 95% CI 0.37-0.88; P  = 0.01). Among the combined cohort, each year increase in age resulted in a 3.9% increase in mortality (OR 1.04; 95% CI 1.01-1.07; P  = 0.005), and every one-unit increase in serum creatinine resulted in a 40% increase in mortality (OR 1.40; 95% CI 1.03-1.92; P  = 0.03). CONCLUSION: Receiving MELD exception points for hepatic hydrothorax is associated with a significant reduction in the odds of posttransplant mortality. These findings underscore the importance of MELD exception points for hepatic hydrothorax among patients with decompensated cirrhosis, potentially improving patient prioritization for liver transplantation and influencing clinical decision-making.

Pharmacologic Management of Obesity after Liver Transplantation: A Critical Review.

Post liver transplant obesity is associated with the development of metabolic disorders such as diabetes mellitus and nonalcoholic fatty liver disease and is a strong predictor of post-transplant mortality. Anti-obesity pharmacotherapy could serve as an effective adjunct to lifestyle modification in the post-transplant setting. Currently, utilization of anti-obesity medication in post liver transplant patients is limited by scarce data on their efficacy and safety in the post-transplant setting. Newer classes of anti-obesity medications, including the glucagon-like peptide 1 agonists (GLP-1) do not only help with weight loss but are effective anti-diabetic agents and are in further development for their potential hepatoprotective and renoprotective effects and reduction in cardiovascular risk. The objective of this manuscript was to critically review the efficacy and safety of anti-obesity pharmacotherapy in post-liver transplant patients.

Detecting professional interpreter use among patients with limited English proficiency: Derivation and validation study.

Objectives: The objective of this derivation and validation study was to develop and validate a search strategy algorithm to detect patients who used professional interpreter services. Methods: We identified all adults who had at least one intensive care unit admission during their hospital stay across the Mayo Clinic Enterprise between 1 January 2015 and 30 June 2020. Three random subsets of 100 patients were extracted from 60,268 patients to develop the search strategy algorithm. Two physician reviewers conducted gold standard manual chart review and any discrepancies were resolved by a third reviewer. These results were compared with the search strategy algorithm each time it was refined. Sensitivity and specificity were calculated during each phase by comparing the search strategy results to the reference gold standard for both derivation cohorts and the final validation cohort. Results: The first search strategy resulted in a sensitivity of 100% and a specificity of 89%. The second revised search strategy achieved a sensitivity of 100% and a specificity of 87%. The final version of the search strategy was applied to the validation subset and sensitivity and specificity were 100% and 89%, respectively. Conclusion: We derived and validated a search strategy algorithm to assess interpreter use among hospitalized patients. Using a search strategy algorithm with high sensitivity and specificity can reduce the time required to abstract data from the electronic medical records compared with manual data abstraction.

Information and Data Visualization Needs among Direct Care Nurses in the Intensive Care Unit.

OBJECTIVES: Intensive care unit (ICU) direct care nurses spend 22% of their shift completing tasks within the electronic health record (EHR). Miscommunications and inefficiencies occur, particularly during patient hand-off, placing patient safety at risk. Redesigning how direct care nurses visualize and interact with patient information during hand-off is one opportunity to improve EHR use. A web-based survey was deployed to better understand the information and visualization needs at patient hand-off to inform redesign. METHODS: A multicenter anonymous web-based survey of direct care ICU nurses was conducted (9-12/2021). Semi-structured interviews with stakeholders informed survey development. The primary outcome was identifying primary EHR data needs at patient hand-off for inclusion in future EHR visualization and interface development. Secondary outcomes included current use of the EHR at patient hand-off, EHR satisfaction, and visualization preferences. Frequencies, means, and medians were calculated for each data item then ranked in descending order to generate proportional quarters using SAS v9.4. RESULTS: In total, 107 direct care ICU nurses completed the survey. The majority (46%, n = 49/107) use the EHR at patient hand-off to verify exchanged verbal information. Sixty-four percent (n = 68/107) indicated that current EHR visualization was insufficient. At the start of an ICU shift, primary EHR data needs included hemodynamics (mean 4.89 ± 0.37, 98%, n = 105), continuous IV medications (4.55 ± 0.73, 93%, n = 99), laboratory results (4.60 ± 0.56, 96%, n = 103), mechanical circulatory support devices (4.62 ± 0.72, 90%, n = 97), code status (4.40 ± 0.85, 59%, n = 108), and ventilation status (4.35 + 0.79, 51%, n = 108). Secondary outcomes included mean EHR satisfaction of 65 (0-100 scale, standard deviation = ± 21) and preferred future EHR user-interfaces to be organized by organ system (53%, n = 57/107) and visualized by tasks/schedule (61%, n = 65/107). CONCLUSION: We identified information and visualization needs of direct care ICU nurses. The study findings could serve as a baseline toward redesigning an EHR interface.

An Update on Treatment Options for Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: A Systematic Review.

Since the last century, methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has become a major global and public health concern not only in terms of morbidity and mortality but also the duration of hospital stay, healthcare cost, and antimicrobial choices. Especially alarming is the growing antimicrobial resistance due to their misuse and overuse, which has led the world to be exhausted of its effective antibiotic resources. In this review article, we sought to figure out the most efficacious antimicrobial agents to treat MRSA-related bloodstream infections. We compared the data from reviewing reports from 2017 to 2022 and summarized their comparative efficacy and cost-effectiveness. Although we focused on vancomycin and daptomycin, which are the current Infectious Disease Society Of America (IDSA)-recommended antibiotics for MRSA bacteremia treatment, a deep dive into the newer agents revealed better efficacy and treatment outcome in the combination of ceftaroline (ß-lactam) with daptomycin compared to traditional standard monotherapy (vancomycin/daptomycin monotherapy). Also, the IDSA recommended high-dose daptomycin (8-10 mg/kg) therapy for MRSA bacteremia treatment to be more effective in cases with vancomycin-reduced susceptibility. Moreover, we did not find any trial or study describing the use of ceftaroline as a monotherapy to compare its efficacy in MRSA bacteremia with the current standard therapy. The upshot is that we need more large-scale clinical trials exploring in-depth effectiveness and adverse effects to decide on newer agents like ß-lactams to use as routine therapy for MRSA bacteremia.

Lumbar radiculopathy associated radicular schwannoma: A case report and literature review.

Lumbar radiculopathy is a clinical condition defined by symptoms of pain, weakness, numbness, or tingling due to lumbar nerve root compression in levels L1-L4. Typically, it is characterized by a narrowing near the nerve root possibly caused by stenosis, bone osteophytes, disc herniation, and similar conditions. Reports of lumbar radiculopathy brought about by the presence of a radicular schwannoma are exceedingly rare. In this paper, we discuss the case of a 67-year-old female patient, presenting with complaints of low back pain, numbness, and antalgic gait for the past eight months. Her physical examination revealed motor and sensor neurological deficits affecting the left lower limb. The electromyoneurography evaluation showed neurogenic atrophy of the left radicular area, while the MRI revealed the presence of a giant, radicular schwannoma at L4-L5 level. This case report aims to underscore the clinical course and management of lumbar radiculopathy caused by a rare L4-L5 radicular schwannoma. Our patient had no significant risk factors or previous spinal pathology.

The importance of computed tomography (CT) scans in the early diagnosis of Gorham-Stout Disease - A case report.

Gorham Stout disease (GSD) or vanishing bone disease is an infrequent entity in clinical practice characterized by gross and progressive bone loss along with excessive growth of vascular and lymphatic tissue. Very little is known about the pathogenesis of GSD, which makes the diagnosis challenging. Due to the rarity of the disease, no treatment guidelines have been created yet. We report a case of GSD in a 53-year-old male patient. He presented with bone pain and initial imaging showed widespread osteolytic lesions in the cervical and mid thoracic spine, ribs, sternum, clavicles, scapula and humerus. Two percutaneous bone biopsies were performed, followed by an open spine biopsy of the L2 spinous processes for histological examination. Unfortunately, no diagnosis was established. Although, he was treated symptomatically, he kept enduring pain and presented again after seven months. His laboratory values were out of the normal range which prompted thorough investigations. New imaging and bone biopsy revealed multiple osteolytic lesions and vascular lesions with cavernous morphology. GSD was diagnosed after ruling out a neoplastic process and confirming the cavernous morphology with immunohistochemical stain. He was treated symptomatically with immunomodulators, bisphosphonates and supplements. Regular follow-up with a specialist was recommended. We hope this case will raise awareness of GSD in common clinical practice and shed some insight on its clinical presentation and the role CT and other imaging modalities play in the diagnosis of GSD.

Clinical Impact of the Early Use of Monoclonal Antibody LY-CoV555 (Bamlanivimab) on Mortality and Hospitalization Among Elderly Nursing Home Patients: A Multicenter Retrospective Study.

Importance Coronavirus disease 2019 (COVID-19) outbreaks are frequent occurrences in nursing homes and long-term care facilities (LTCFs), resulting in subsequent hospitalization and death. Rationale Virus-neutralizing monoclonal antibodies demonstrate a significant decrease in both viral load and hospital transfer rate among patients with mild-to-moderate COVID-19 infection. Objective To assess the clinical outcomes of COVID-19 patients with mild-to-moderate symptoms in LTCFs who received LY-CoV555 as compared to those who did not receive this treatment. Design Retrospective case-control study and logistic regression analysis. Setting LTCFs in New York. Participants Two-hundred forty-six (246) LTCF patients diagnosed with mild-to-moderate COVID-19 infection with positive COVID-19 polymerase chain reaction (PCR) from November 15, 2020, to January 31, 2021. Methods Two-hundred forty-six (246) COVID-19 patients were identified from electronic medical records, out of which 160 cases were exposed to LY-CoV555 treatment (700 mg single dose, intravenous infusion). Eighty-six (86) patients were unexposed controls who did not receive monoclonal antibodies, LY-CoV555. Outcome We assessed the odds of death and hospitalization of exposed cases as compared to unexposed controls. Using logistic regression analysis, we also assessed the risk factors associated with these outcomes in the entire sample population. Results The mean age of the entire sample was 82.4 years. Fifty-two percent (52%) of patients (n = 129) were female and 48% (n = 117) were male. The mean ages of the exposed group and the unexposed group were 81 years and 84 years, respectively. At the end of the study, 92% (148/160) of the exposed group were alive or not transferred to the hospital as compared to 79% (68/86) patients of the unexposed group (OR 3.23, 95% CI: (1.48, 7.31), p-value = 0.0032). Three percent (3%; 5/160) of patients died in the exposed group compared to 10% (9/86) of patients who died in the unexposed group (OR = 0.25, 95% CI: (0.1, 0.85), p-value = 0.0257). Four point thirty-seven percent (4.37%; 7/160) of patients in the exposed group and 10.46% (9/86) of patients in the unexposed group were transferred to the hospital (OR = 0.35, 95% CI: (0.15, 1.08), p-value = 0.0793). Conclusion Early treatment with monoclonal antibody LY-CoV555 is associated with decreased mortality among high-risk patients with mild-to-moderate COVID-19 infection in LTCFs. Although not statistically significant, there was a trend towards a lower risk of hospitalization in patients treated with LY-CoV555.

Mediterranean Diet and Physical Activity: Two Imperative Components in Breast Cancer Prevention.

Despite tremendous advances in medicine over the past few decades and significantly improved understanding of the symptomology and contributors to breast cancer (BC) incidence, BC rates continue to rise worldwide, with BC being a leading cause of cancer-related death among women. To reduce BC incidence, it is necessary to focus on promoting prevention strategies through a population-based approach of lowering exposure to modifiable risk factors in addition to the application of newer drug interventions (chemoprevention) for prevention in high-risk populations. Currently, available data suggest that lifestyle modifications through a healthy diet and increased physical activity (PA) play a crucial role in BC prevention; specifically, there is growing evidence to indicate that the Mediterranean diet (MeD) lowers cancer risk. This review summarizes the potential role of the MeD and PA in reducing BC risk, with an additional focus on microbial modulation in BC prevention, based on the current evidence obtained from PubMed. After reviewing the immunomodulatory and anticarcinogenic effects of both the MeD and PA, we conclude that further evaluation and proper implementation of both interventions can significantly reduce the risk of BC and associated mortality in the general population.