Differential Gene Expression of fresh tissue and patient-derived explants' matricellular proteins augment inflammatory breast cancer metastasis: the possible role of IL-6 and MCP-1.

BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome. METHODS: Fifty patients (31 non-IBC and 19 IBC) were enrolled in the present study. To test their validation in clinical studies, PDEs were cultured as an ex vivo model. Gene expression and cytokine array were used to identify candidate genes and cytokines contributing to metastasis in the examined fresh tissues and PDEs. Bioinformatics analysis was applied on identified differentially expressed genes using GeneMANIA and Metascape gene annotation and analysis resource to identify pathways involved in IBC metastasis. RESULTS: Normal and cancer fresh tissues and PDEs of IBC were characterized by overexpression of CDH1 and MMP14 and downregulation of CTNNA1 and TIMP1 compared with non-IBC. The secretome of IBC cancer PDEs is characterized by significantly high expression of interleukin 6 and monocyte chemoattractant protein-1 (CCL2) compared with non-IBC. CONCLUSION: Genes expressed by adhisome and matrisome play a significant role in IBC metastasis and should be considered novel target therapy.

Detecting Cognitive Impairment and Dementia in the Emergency Department: A Scoping Review.

OBJECTIVES: To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED). DESIGN: Literature review and consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners. SETTING AND PARTICIPANTS: Scoping reviews focused on adult ED patients. METHODS: Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and abstracted for relevant information and presented at the stakeholder consensus conference for discussion and ranked prioritization. RESULTS: We identified a total of 1464 publications and included 45 to review for accurate tools and approaches for detecting cognitive impairment and dementia. Twenty-seven different assessments and instruments have been studied in the ED setting to evaluate cognitive impairment and dementia, with many focusing on sensitivity and specificity of instruments to screen for cognitive impairment. For pragmatic tools, we identified a total of 2166 publications and included 66 in the review. Most extensively studied tools included the Ottawa 3DY and Six-Item Screener (SIS). The SIS was the shortest to administer (1 minute). Instruments with the highest negative predictive value were the SIS (vs MMSE) and the 4 A's Test (vs expert diagnosis). The GEAR 2.0 Advancing Dementia Care Consensus conference ranked research priorities that included the need for more approaches to recognize more effectively and efficiently persons who may be at risk for cognitive impairment and dementia, while balancing the importance of equitable screening, purpose, and consequences of differentiating various forms of cognitive impairment. CONCLUSIONS AND IMPLICATIONS: The scoping review and consensus process identified gaps in clinical care that should be prioritized for research efforts to detect cognitive impairment and dementia in the ED setting. These gaps will be addressed as future GEAR 2.0 research funding priorities.

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers.

Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.

Patient Satisfaction with a Tertiary Hospital in Egypt using a HCAHPS-Derived Survey.

STUDY DESIGN: Retrograde cross-sectional study. OBJECTIVE: To assess patient satisfaction and outcomes in polytraumatized patients in EL-Demerdash hospital. BACKGROUND: This is the first study that assessed patient satisfaction with a tertiary hospital in Egypt. Ain Shams University Surgery Hospital, which is one of the largest hospitals in Egypt and serves millions of patients each year, was the site of the study. METHODS: A version of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey was used to query 361 patients from November 2015 until July 2018 Survey questions were divided into the following categories: communication with doctors, responsiveness of hospital staff, cleanliness of the hospital environment, quietness of the hospital environment, pain management, communication about medicines, discharge information, overall rating of the hospital, and willingness to recommend the hospital. RESULTS: A total of 361 patients were interviewed. The results showed both positive and negative levels of satisfaction. The positive results included no delay in admission, friendly staff including nurses and doctors, better patient outcomes regarding pain management and adverse side effects, and the overall rating of the hospital was good, which reflected patient satisfaction. The negative findings were lack of proper communication between the medical staff and patients. Patients indicated they did not get a satisfactory explanation of their prescribed drug doses and drug adverse effects. In addition, they did not get enough instruction on what to do after being released from the hospital. CONCLUSION: The medical staff at Ain Shams University Surgery Hospital should focus more on the patient's own preferences and communicate better with patients. We recommended that the hospital organize regular communication skills courses for medical students, physicians, and nurses. Patients should understand the discharge report and indications and side effects of the medications before leaving the hospital.

Non-operative management of blunt abdominal solid organ trauma in adult patients.

INTRODUCTION: Despite agreement in the literature that "stable" blunt trauma patients may be managed conservatively, in Egypt many such patients receive operative management. This paper presents the results of a pragmatic, prospective, observational study to evaluate outcomes of non-operative (NOP) versus operative (OP) management of blunt abdominal solid organ trauma in hemodynamically stable adults admitted to Tanta University Emergency Hospital (TUH) in Egypt. METHODS: A prospective observational study enrolled adult blunt abdominal trauma patients with solid organ injury at TUH over a 3-year period (June 2014-June 2017). Inclusion criteria were age ≥18 yr, mean arterial pressure >65 mm Hg, heart rate <110 bpm, hematocrit ≥7 mg/dl, and abdominal organ injury diagnosed by ultrasound or computed tomography (CT). Excluded patients were those with pelvis and femur fractures; patients with penetrating abdominal trauma; predominate burn injuries, children and pregnant women. All patients were assigned to non-operative or operative management based on clinician preference. Outcomes of interest were 30-day mortality, blood transfusion volume, and length of stay. Descriptive statistics and χ2 were used to compare outcomes. RESULTS: During the study period, 4254 trauma patients presented to TUH. Of these, 790 had blunt abdominal trauma and 111 (14.1%) met inclusion criteria. Injury severity scores for each group were comparable (24 ± 10 - NOP vs. 28 ± 11 - OP, p = 0.126). NOP received less transfused blood (213.41 ± 360.3 ml [NOP] vs.1155.17 ± 380.4 ml [OP] (p < 0.0001)) but had a longer length of stay (8.29 ± 2.8 [NOP] vs. 6.45 ± 1.97 days [OP] (p = 0.012)). There was no difference in mortality between groups (p = 0.091). CONCLUSION: Our study demonstrated that non-operative management in Egypt of blunt abdominal trauma was safe and resulted in fewer procedures, fewer units of blood transfused, and no increase in mortality. Longer length of stay for non-operative patients might reflect treating physician caution in their management.

Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant.

Importance: Median survival after lung transplant is less than 6 years. Standard maintenance therapy typically includes tacrolimus and an antimetabolite (mycophenolate mofetil or azathioprine). Replacing the antimetabolite with sirolimus after postoperative wound healing may improve long-term survival due to antifibrotic, antiproliferative, and antiaging effects of sirolimus. Objectives: To compare survival between patients receiving sirolimus plus tacrolimus vs mycophenolate mofetil plus tacrolimus (the most common maintenance therapy) and to identify the combination of induction and maintenance therapy associated with the highest survival. Design, Setting, and Participants: This cohort study of US recipients of lung transplants from January 1, 2003, through August 31, 2016, analyzed United Network for Organ Sharing (UNOS) data from January 1 through September 13, 2018. Because initiation of sirolimus therapy is usually delayed 3 to 12 months after lung transplant, primary analyses were based on patients alive and free of chronic rejection and malignant disease at 1 year in all groups, whereas sensitivity analyses used appropriate methods to include all patients from transplant time. Regression models adjusted for available potential confounders, including transplant center performance. Exposures: Cell cycle inhibitor maintenance therapies, including sirolimus (n = 219), mycophenolate mofetil (n = 5782), mycophenolate sodium (n = 408), azathioprine (n = 2556), and concurrent sirolimus plus mycophenolate mofetil (n = 54), were compared within a tacrolimus-based regimen. Combinations of each induction (basiliximab, daclizumab, antithymocyte globulin, alemtuzumab, or none) and maintenance (tacrolimus plus sirolimus, mycophenolate mofetil, or azathioprine) therapy were also compared. Main Outcomes and Measures: Survival was the primary outcome; chronic rejection incidence and subsequent mortality were secondary outcomes. Results: Among this population of 9019 patients (median age, 57 years [interquartile range {IQR}, 46-63 years]; 5194 men [57.6%]), sirolimus plus tacrolimus was associated with better survival than mycophenolate mofetil plus tacrolimus (median, 8.9 years [IQR, 4.4-12.7 years] vs 7.1 years [IQR, 3.6-12.1 years]; adjusted hazard ratio [aHR], 0.71; 95% CI, 0.56-0.89; P = .003). Chronic rejection incidence (aHR, 0.75; 95% CI, 0.61-0.92) and mortality after chronic rejection (aHR, 0.52; 95% CI, 0.31-0.81) were lower with sirolimus plus tacrolimus. Compared with mycophenolate mofetil plus tacrolimus, survival differences for sirolimus plus mycophenolate mofetil plus tacrolimus (aHR, 1.14; 95% CI, 0.79-1.65), mycophenolate sodium plus tacrolimus (aHR, 0.95; 95% CI, 0.77-1.17), and azathioprine plus tacrolimus (aHR, 0.93; 95% CI, 0.84-1.02) were not significant. The induction-maintenance combination with the highest survival was sirolimus plus tacrolimus without induction therapy (median survival, 10.7 years [IQR, 7.3-12.7 years]; aHR, 0.48; 95% CI, 0.31-0.76; P = .002) compared with mycophenolate mofetil plus tacrolimus with induction therapy (median survival, 7.4 years [IQR, 3.9-12.6 years]). Conclusions and Relevance: Sirolimus plus tacrolimus was associated with improved patient survival after lung transplant compared with mycophenolate mofetil plus tacrolimus; no antibody induction therapy with sirolimus plus tacrolimus was associated with maximal survival.

Perceived barriers by health care providers for screening and management of excessive alcohol use in an emergency department of a low-income country.

Annually, alcohol causes 3.3 million deaths; countless more alcohol-related injury patients are treated in emergency departments (EDs) worldwide. Studies show that alcohol-related injury patients reduce their at-risk alcohol-use behavior with a brief negotiational interview (BNI) in the ED. This project aims to identify potential perceived barriers to implementing a BNI in Tanzania. A knowledge, attitude, and practice questionnaire was piloted and administered to all emergency department health care practitioners, including physicians, advanced medical officers, and nurses. The questionnaire included the Perceived Alcohol Stigma (PAS) Scale. The survey was self-administered in English, the language of health care instruction, with a Swahili translation available if preferred. Data were analyzed with relative and absolute frequencies and Spearman's correlation. Thirty-four (100%) health care practitioners completed the survey. Our results found positive attitudes toward addressing alcohol misuse (88%), but very poor knowledge of recommended alcohol-use limits (24%). Participants were willing to discuss alcohol use (88%) and to screen (71%) for alcohol-use disorders. Most health care practitioners report significant stigma against those with alcohol-use disorders (39% discrimination, 53% devaluation, 71% either). Counseling patients about high-risk alcohol use was directly and positively associated with at-risk alcohol and counseling education and believing it was common to ask patients about tobacco and alcohol use; it was negatively associated with believing it was 'not my role' or that knowing about alcohol use 'won't make a difference'. Stigma was negatively and indirectly associated with counseling patients. In conclusion, in an ED in Tanzania, health care practitioners have positive attitudes toward addressing at-risk alcohol use, and endorsed having training in alcohol misuse in school. Unfortunately, participants did not demonstrate knowledge of recommended alcohol limit guidelines. Similarly, among practitioners, there is a significant discrimination and devaluation stigma against those who misuse alcohol. These factors must be addressed prior to a successful implementation of an alcohol harm reduction intervention.

Failure to clear elevated lactate predicts 24-hour mortality in trauma patients.

BACKGROUND: Lactate clearance is a standard resuscitation goal in patients in nontraumatic shock but has not been investigated adequately as a tool to identify trauma patients at risk of dying. Our objective was to determine if trauma patients with impaired lactate clearance have a higher 24-hour mortality rate than patients whose lactate concentration normalizes. METHODS: A retrospective chart review identified patients who were admitted directly from the scene of injury to an urban trauma center between 2010 and 2013 and who had at least one lactate concentration measurement within 24 hours. Transfers, patients without lactate measurement, and those who were dead on arrival were excluded. Of the 26,545 screened patients, 18,304 constituted the initial lactate measurement population, and 3,887 were the lactate clearance cohorts. RESULTS: Initial lactate had an area under the receiver operating characteristic curve of 0.86 and 0.73 for mortality at 24 hours and in the hospital, respectively. An initial concentration of 3 mmol/L or greater had a sensitivity of 0.86 and a specificity of 0.73 for mortality at 24 hours. The mortality rate among patients with elevated lactate concentrations (n = 2,381; 5.6 [2.8] mmol/L) that did not decline to less than 2.0 mmol/L in response to resuscitative efforts (mean [SD] second measurement, 3.7 [1.9] mmol/L) was nearly seven times higher (4.1% vs. 0.6%, p < 0.001) than among those with an elevated concentration (n = 1,506, 5.3 [2.7] mmol/L) that normalized (1.4 [0.4] mmol/L). Logistic regression analysis showed that failure to clear lactate was associated with death more than any other feature (odds ratio, 7.4; 95% confidence interval, 1.5-35.5), except having an Injury Severity Score (ISS) greater than 25 (odds ratio, 8.2; 95% confidence interval, 2.7-25.2). CONCLUSION: Failure to clear lactate is a strong negative prognostic marker after injury. An initial lactate measurement combined with a second measurement for high-risk individuals might constitute a useful method of risk stratifying injured patients. LEVEL OF EVIDENCE: Prognostic study, level III.

Marked elevation of cerebrospinal fluid white blood cell count: an unusual case of Streptococcus pneumoniae meningitis, differential diagnosis, and a brief review of current epidemiology and treatment recommendations.

The diagnosis of bacterial meningitis is rarely a difficult diagnostic dilemma when a patient presents with fever, headache, neck stiffness, and altered mental status. Unfortunately for the practicing clinician, patients are rarely that straightforward. Patients who are elderly, very young, or immuno-compromised often present with subtle findings, making the correct diagnosis a challenge. In addition, patients being treated with antibiotics may be misleading in their clinical presentation, leading to a missed diagnosis of meningitis. Only when one considers the diagnosis or obtains a sample of cerebrospinal fluid is the correct diagnosis made. Although the clinical scenario may suggest meningitis, it is the cerebrospinal fluid white blood cell count that establishes the definitive diagnosis. Despite the advent of systemic antibiotics over 50 years ago, bacterial meningitis continues to cause considerable morbidity and mortality worldwide. The following case report details a woman diagnosed with Streptococcus pneumoniae meningitis with an extremely high cerebrospinal white blood cell count. Although this is typically thought to be caused by abscesses or malignancy, meningitis alone may cause such an elevation. In addition, a brief review of the current epidemiology and treatment regimens for meningitis is discussed.

Use of epidemiology in clinical medical publications, 1983-1999: a citation analysis.

Epidemiologists respond to the information needs of health professionals. Although medical professionals are routine users of epidemiologic information, use within medical specialties varies remarkably. To explore the variation in use of epidemiologic information across clinical medical specialties, the authors examined the scientific literature by analyzing patterns of citation of specific journal articles to and by the American Journal of Epidemiology (AJE). A total of 178,396 journal citations to and 126,478 citations by AJE were made from 1983 through 1999; citations were classified according to the subject category of the referencing or referenced journal. Clinical medical journals accounted for 50.6% of all citations combined (both referenced to and referenced by AJE); general/internal medicine (17.9%), cancer (10.4%), and cardiovascular (4.9%) journals had the highest number of citations. Few citations to and by AJE were found in publications specializing in dermatology, gastroenterology, orthopedics, allergy, anesthesiology, surgery, rheumatology, and other areas. Trend patterns of citations between clinical and epidemiologic literature indicated that citations to the fields of cardiovascular disease and cancer are increasing, whereas citations regarding pediatrics have remained stable. This analysis suggests an increasing interchange of information between epidemiologists and clinicians specializing in certain fields, uncovering potential research opportunities for epidemiologists.