ADAM8 is expressed widely in breast cancer and predicts poor outcome in hormone receptor positive, HER-2 negative patients.

BACKGROUND: Breast malignancies are the predominant cancer-related cause of death in women. New methods of diagnosis, prognosis and treatment are necessary. Previously, we identified the breast cancer cell surface protein ADAM8 as a marker of poor survival, and a driver of Triple-Negative Breast Cancer (TNBC) growth and spread. Immunohistochemistry (IHC) with a research-only anti-ADAM8 antibody revealed 34.0% of TNBCs (17/50) expressed ADAM8. To identify those patients who could benefit from future ADAM8-based interventions, new clinical tests are needed. Here, we report on the preclinical development of a highly specific IHC assay for detection of ADAM8-positive breast tumors. METHODS: Formalin-fixed paraffin-embedded sections of ADAM8-positive breast cell lines and patient-derived xenograft tumors were used in IHC to identify a lead antibody, appropriate staining conditions and controls. Patient breast cancer samples (n = 490) were used to validate the assay. Cox proportional hazards models assessed association between survival and ADAM8 expression. RESULTS: ADAM8 staining conditions were optimized, a lead anti-human ADAM8 monoclonal IHC antibody (ADP2) identified, and a breast staining/scoring control cell line microarray (CCM) generated expressing a range of ADAM8 levels. Assay specificity, reproducibility, and appropriateness of the CCM for scoring tumor samples were demonstrated. Consistent with earlier findings, 36.1% (22/61) of patient TNBCs expressed ADAM8. Overall, 33.9% (166/490) of the breast cancer population was ADAM8-positive, including Hormone Receptor (HR) and Human Epidermal Growth Factor Receptor-2 (HER2) positive cancers, which were tested for the first time. For the most prevalent HR-positive/HER2-negative subtype, high ADAM8 expression identified patients at risk of poor survival. CONCLUSIONS: Our studies show ADAM8 is widely expressed in breast cancer and provide support for both a diagnostic and prognostic value of the ADP2 IHC assay. As ADAM8 has been implicated in multiple solid malignancies, continued development of this assay may have broad impact on cancer management.

No seasonality in the risk of multiple sclerosis in an equatorial country: A case-control ecological study.

BACKGROUND: Multiple sclerosis risk has been shown to have seasonal variations that are more pronounced in higher latitudes. However, this phenomenon has not been adequately studied near the Equator. OBJECTIVE: To explore the risk of multiple sclerosis associated with month, season of birth, and sunlight exposure variables in Colombia. METHODS: In this case-control study, 668 multiple sclerosis cases were matched to 2672 controls by sex and age. Association of multiple sclerosis with each month/season of birth and sunlight exposure variables was estimated with multilevel mixed-effects logistic regression and ecological regression models, respectively. Seasonality in the births of multiple sclerosis was assessed with a non-parametric seasonality test. RESULTS: We found a higher probability of multiple sclerosis in September (0.25; 95% confidence interval (CI) = 0.21-0.31) and lower in March (0.15; 95% CI = 0.10-0.18), which turned non-significant after a multiple comparisons test. Sunlight exposure variables had no significant effect on the risk of MS, and the tests of seasonality in the births of MS did not show significant results. CONCLUSION: Our results show no seasonality in the risk of multiple sclerosis near the Equator, supporting the hypothesis that this phenomenon is latitude dependent.

Case Report: Deficiency of Adenosine Deaminase 2 (DADA2) as a Cause of Brainstem Stroke in a 3-Year-Old Girl and the Importance of Early Fast-Track Genetic Diagnostics to Influence Therapy.

Deficiency of adenosine deaminase 2 (DADA2) is a rare Mendelian, autoinflammatory multiorgan disease. We report the case of a 3.8-year-old female patient who was admitted with an acute brainstem stroke and was diagnosed with DADA2 by early initiation of exome sequencing. We recommend that DADA2 and a genetic workup should be taken into account, when evaluating strokes in children even if no other than neurological symptoms are evident.

Pain and Moderate to Vigorous Physical Activity in Adolescence: An International Population-Based Survey.

OBJECTIVE: To evaluate whether individual types of pain (headache, stomach-ache, and backache) or multiple pains affect the odds of young people achieving the recommended 60 minutes of moderate to vigorous physical activity (MVPA) per day in a large representative sample. DESIGN: Multicenter cross-sectional survey. SETTING: Twenty-eight countries across Europe and North America. SUBJECTS: Adolescents (N = 242,103). METHODS: An analysis of data collected in two waves (2001/02 and 2005/06) of the health behavior in school-aged children (HBSC) study was performed. Survey questions included the HBSC symptoms checklist and the amount of regular physical activity. Multilevel logistic regression was used to account for clustering effect of MVPA within countries. Models investigated the relationship between pain and physical activity, adjusted for the HBSC study year. Six models were conducted separately for gender and age-group (11, 13, and 15 years) strata. RESULTS: In general, the presence of pain was associated with reduced physical activity. Headache alone was associated with reduced physical activity in all six strata (odd ratios 0.77-0.84), stomach-ache alone in five strata (0.77-0.92), and backache alone in four strata (0.86-0.96). In 11- and 13-year-old girls, headache, stomach-ache, and backache, individually and in combination, were associated with decreased odds of being physically active (odds ratios ranging from 0.73 to 0.91). Within the other four age and gender strata, the relationship was less consistent. CONCLUSION: Pain is associated with reduced physical activity in adolescents but this association varies according to gender, age, and the type of pain experienced.

An international survey of pain in adolescents.

BACKGROUND: A common belief is that pain is uncommon and short lived in adolescents. However, the burden of pain in adolescents is unclear because of limitations in previous research. The aim of this study is to estimate the prevalence of headache, stomach-ache and backache in adolescents and to explore the extent to which these three forms of pain coexist based upon a representative sample of adolescents from 28 countries. METHODS: Data were analysed from three consecutive waves (1997/98, 2001/02 and 2005/06) of the Health Behavior in School-aged Children: WHO Collaborative Cross-National survey (HBSC). Prevalence estimates are based upon adolescents who reported experiencing headache, stomach-ache or backache at least monthly for the last 6 months. RESULTS: There were a total of 404,206 participants with a mean (±SD) age of 13.6 (±1.7) years (range 9.8 to 17.3 years). The prevalence of headache was 54.1%, stomach-ache 49.8%, backache 37%, and at least one of the three pains 74.4%. Girls had a higher prevalence of the three pains than boys and the prevalence of pain increased with age. Headache, stomach-ache and backache frequently coexist, for example, of those with headache: 21.2% had headache alone, 31% suffered from both headache and stomach-ache, 12.1% suffered from backache and headache, and 35.7% had all three pains. CONCLUSIONS: Somatic pain is very common in adolescents, more often coexisting than occurring in isolation. Our data supports the need for further research to improve the understanding of these pains in adolescents.

Seasonality and clinical characteristics of MS in an equatorial country.

BACKGROUND: Month and season of birth have been associated with risk of multiple sclerosis (MS), but there is relatively little evidence regarding their influence on the timing and severity of disease at onset. OBJECTIVE: To assess whether month and season of birth influence the age and phenotype at onset of MS as well as its severity in a cohort of Colombian patients. METHODS: This study is an analysis on MS cases only, drawn from a previously published case-control study. MS cases confirmed with current diagnostic criteria cared for at least once in our center were included. We assessed the influence of the month and season of birth in the age at MS onset, MS severity score, and age-related MS severity score using multiple and pairwise comparisons. Age at onset was also studied using Kaplan-Meier survival estimates compared with the log-rank test. The likelihood of progressive MS onset was evaluated with OR estimated from logistic regression models adjusted for age at onset and sex. RESULTS: 668 MS cases were included. No significant differences were found in the age at MS onset according to month of birth or season of birth. Neither month of birth nor season of birth conferred significant differences in MS severity score or age-related MS severity score. No significant association was found between month (ORs ranging from 0.62 to 3.11, none significant) or season of birth (OR 0.91; 95 %CI: 0.46-1.84) with primary progressive MS. CONCLUSION: The month or season of birth do not appear to influence the age onset and phenotype of MS in our country.

Surgical and procedural antibiotic prophylaxis in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document.

The use of prophylactic measures, including perioperative antibiotics, for the prevention of surgical site infections is a standard of care across surgical specialties. Unfortunately, the routine guidelines used for routine procedures do not always account for many of the factors encountered with urgent/emergent operations and critically ill or high-risk patients. This clinical consensus document created by the American Association for the Surgery of Trauma Critical Care Committee is one of a three-part series and reviews surgical and procedural antibiotic prophylaxis in the surgical intensive care unit. The purpose of this clinical consensus document is to provide practical recommendations, based on expert opinion, to assist intensive care providers with decision-making for surgical prophylaxis. We specifically evaluate the current state of periprocedural antibiotic management of external ventricular drains, orthopedic operations (closed and open fractures, silver dressings, local, antimicrobial adjuncts, spine surgery, subfascial drains), abdominal operations (bowel injury and open abdomen), and bedside procedures (thoracostomy tube, gastrostomy tube, tracheostomy).

Fever and infections in surgical intensive care: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document.

The evaluation and workup of fever and the use of antibiotics to treat infections is part of daily practice in the surgical intensive care unit (ICU). Fever can be infectious or non-infectious; it is important to distinguish between the two entities wherever possible. The evidence is growing for shortening the duration of antibiotic treatment of common infections. The purpose of this clinical consensus document, created by the American Association for the Surgery of Trauma Critical Care Committee, is to synthesize the available evidence, and to provide practical recommendations. We discuss the evaluation of fever, the indications to obtain cultures including urine, blood, and respiratory specimens for diagnosis of infections, the use of procalcitonin, and the decision to initiate empiric antibiotics. We then describe the treatment of common infections, specifically ventilator-associated pneumonia, catheter-associated urinary infection, catheter-related bloodstream infection, bacteremia, surgical site infection, intra-abdominal infection, ventriculitis, and necrotizing soft tissue infection.

Video media-induced aggressiveness in children.

Transmission of aggressive behaviors to children through modeling by adults has long been a commonly held psychological concept; however, with the advent of technological innovations during the last 30 years, video media-television, movies, video games, and the Internet-has become the primary model for transmitting aggressiveness to children. This review explores the acquisition of aggressive behaviors by children through modeling behaviors in violent video media. The impact of aggressive behaviors on the child, the family, and society is addressed. Suggestive action plans to curb this societal ill are presented.

Long-term complications of the transmeatal approach (Open Transcanal) in cochlear implants: A follow-up study.

Objective: Multiple alternative approaches of cochlear implant surgery have been described, such as the suprameatal approach, transcanal approach, transmeatal approach and middle cranial fossa approach. Transmeatal (open trnascanal) approach has not been adapted since first described in the clinical field. we aimed to assess the long-term complications of the transmeatal approach in a series of 131 patients at our center between 2004 and 2008. Methods: This study was a retrospective case series of all patients who underwent cochlear implants with the transmeatal (open transcanal) approach from May 2004 to December 2008 at King Faisal Specialist and Research Hospital (Riyadh, Saudi Arabia), which were conducted by the same surgeon. Results: Complications were observed often with various combinations-recurrent otitis externa, posterior tympanic membrane perforation, electrode extrusion, cholesteatoma, and chronic mastoiditis. The overall long-term complication rate was 16% (21/131). The gap between the implantation and the diagnosis of a complication ranged from <1 year to 11 years. Major complications were as follows: cholesteatoma in 5 (3.8%) patients, extrusion of the electrode in 5 (3.8%) patients, and tympanic membrane perforation or deep retractions in 5 (3.8%) patients. Minor complications were as follows: recurrent mastoiditis with/without concomitant temporary facial nerve palsy in 4 (3%) patients, recurrent otitis externa infections in 7 (5%) patients, and weakness of the posterior canal wall in 1 patient. Conclusion: The transmeatal approach posed an high rate of complications on long-term follow-up such as cholestetoma formation, extrusion of electrode or perielectrode reaction formation to tympanic membrane and external auditory canal.

Future Perspective and Technological Innovation in Cheese Making Using Artichoke (Cynara scolymus) as Vegetable Rennet: A Review.

Milk coagulation is a process used for the formulation of different dairy products such as cheese. In this process, milk undergoes changes in its chemical stability thanks to acidification or enzymatic reactions. Traditionally, milk coagulation has been carried out with rennet of animal origin, but recently, the research of new types of rennet such as microbial rennet and vegetable rennet has increased. This study aims to present an organized review of the most relevant information on lactic coagulation, its relationship with vegetable rennets, and the importance of the botanical genus Cynara in the extraction of vegetable rennets, focusing on the coagulant potential of artichoke (Cynara scolymus). We conducted this literature review and found that lactic coagulation and vegetable rennets are linked through the enzymatic activity of the latter. The results of the main studies demonstrated a strong relationship between vegetable rennets and protease enzymes as well as the presence of these enzymes in extracts of cardoon (Cynara scolymus) and artichoke (Cynara scolymus). In addition, studies highlight the presence of thistle extracts in artisanal cheese preparations in the Iberian Peninsula. Based on the results of the studies, a comparison between cheeses made with vegetable rennet and those made with traditional rennet was also carried out. Although the results show that the use of vegetable rennet in the manufacture of cheese can confer undesirable characteristics, the use of extracts from Cynara plants demonstrates that vegetable rennets have an industrial potential, especially the one obtained from artichoke (Cynara scolymus) due to its high availability. Nevertheless, specific studies are required for a better understanding and application of this rennet.

Operative rates in acute diverticulitis with concurrent small bowel obstruction.

Background: The prevalence of diverticulitis has steadily increased during the past century. One possible complication of large bowel diverticulitis (LBD) is the concurrent development of a small bowel obstruction (SBO). The literature regarding these joint diagnoses is primarily limited to small case series from the 1950s. Consequently, no official recommendations or recent literature exists to guide decision making. Methods: This is a retrospective case-control study with 5:1 matching by demographics, comorbidities, and Hinchey classification of patients presenting with concomitant LBD and SBO and patients with LBD alone. The primary outcome assessed was the need for same admission surgical intervention. Results: Patients with concurrent LBD and SBO were more likely to require surgical intervention (OR 4.2, p<0.001) and more likely to receive an open operation than patients with only LBD (p<0.001). The length of stay (LOS) was longer for LBD with SBO (mean LOS +3.2 days, p=0.003). Discussion: Patients with concurrent LBD and SBO are more likely to fail non-operative management. Given this, along with their longer LOS and higher rate of open surgery, earlier surgical intervention may improve outcomes and reduce hospital LOS. Level of evidence: 4.

Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis.

The bioinformatic pipeline previously developed in our research laboratory is used to identify potential general and specific deregulated tumor genes and transcription factors related to the establishment and progression of tumoral diseases, now comparing lung cancer with other two types of cancer. Twenty microarray datasets were selected and analyzed separately to identify hub differentiated expressed genes and compared to identify all the deregulated genes and transcription factors in common between the three types of cancer and those unique to lung cancer. The winning DEGs analysis allowed to identify an important number of TFs deregulated in the majority of microarray datasets, which can become key biomarkers of general tumors and specific to lung cancer. A coexpression network was constructed for every dataset with all deregulated genes associated with lung cancer, according to DAVID's tool enrichment analysis, and transcription factors capable of regulating them, according to oPOSSUM´s tool. Several genes and transcription factors are coexpressed in the networks, suggesting that they could be related to the establishment or progression of the tumoral pathology in any tissue and specifically in the lung. The comparison of the coexpression networks of lung cancer and other types of cancer allowed the identification of common connectivity patterns with deregulated genes and transcription factors correlated to important tumoral processes and signaling pathways that have not been studied yet to experimentally validate their role in lung cancer. The Kaplan-Meier estimator determined the association of thirteen deregulated top winning transcription factors with the survival of lung cancer patients. The coregulatory analysis identified two top winning transcription factors networks related to the regulatory control of gene expression in lung and breast cancer. Our transcriptomic analysis suggests that cancer has an important coregulatory network of transcription factors related to the acquisition of the hallmarks of cancer. Moreover, lung cancer has a group of genes and transcription factors unique to pulmonary tissue that are coexpressed during tumorigenesis and must be studied experimentally to fully understand their role in the pathogenesis within its very complex transcriptomic scenario. Therefore, the downstream bioinformatic analysis developed was able to identify a coregulatory metafirm of cancer in general and specific to lung cancer taking into account the great heterogeneity of the tumoral process at cellular and population levels.

Prevention of alcohol withdrawal syndrome in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Alcohol withdrawal syndrome is a common and challenging clinical entity present in trauma and surgical intensive care unit (ICU) patients. The screening tools, assessment strategies, and pharmacological methods for preventing alcohol withdrawal have significantly changed during the past 20 years. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews the best practices for screening, monitoring, and prophylactic treatment of alcohol withdrawal in the surgical ICU.

A Rare Case of Solid Pseudopapillary Neoplasm of the Pancreas.

Solid pseudopapillary neoplasm of pancreas (SPN) is a rare entity. It is almost exclusively seen in females within the second and third decades of life with only small minority affecting children. Due to the paucity of the number of cases seen, the natural history of the disease is not fully understood. SPN tumors of the pancreas are usually found incidentally and usually have an excellent prognosis. We herein present a case of a 33-year-old lady diagnosed with SPN, who presented with abdominal fullness, two weeks post cesarean section.

Venous ligation versus venous repair: does the procedure impact venous thromboembolism risk?

BACKGROUND: Traumatic lower extremity venous injuries are most commonly managed with either a vein ligation or repair procedure. Venous injuries are associated with an increased risk of developing venous thromboembolisms (VTE), but little is understood with regard to how specific surgical treatments may impact the risk of developing either a deep vein thrombosis (DVT) or a pulmonary embolism (PE). In this study of lower extremity venous injuries, we hypothesized that venous ligation would be associated with an increased risk of DVT but a lower risk of PE when compared with venous repair. METHODS: Patients were identified from the National Trauma Data Bank (2008 to 2014) with at least one iliac, femoral, popliteal, or tibial venous injury and who received either a vein ligation or repair. The patients were then compared based on the type of procedure and the location of the injury to assess the risk of DVT and PE between the groups. RESULTS: A total of 1214 patients were identified. There was no difference between patients who received a vein ligation versus a repair with respect to age, injury severity score, or initial systolic blood pressure. There was no difference in the odds of developing either a DVT or PE between patients who were treated with vein ligation versus repair. There was also no difference in VTE rates when stratified by the location of the injury. CONCLUSIONS: In individuals with lower extremity venous injuries, there is no difference in the rate of DVT or PE complications when comparing venous repair and ligation procedures. The role of anticoagulation remains to be elucidated following operative treatment. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level IV.

Delayed diagnosis of multiple sclerosis in a low prevalence country.

Background: Early diagnosis and treatment of multiple sclerosis (MS) is crucial to avoid future disability. The factors that influence diagnostic delay in low prevalence settings have been poorly studied.Objectives: To evaluate the factors associated with a delayed diagnosis of MS after the symptomatic onset.Methods: Clinical records of confirmed MS patients were reviewed. Diagnostic delay was calculated by subtracting the date of onset from the date of diagnosis and categorized as early and delayed, when below and above than 1 year. Logistic regression was performed to evaluate the likelihood of a delayed diagnosis according to age at first symptom, gender, type of the first symptom, progressive vs relapsing onset, diagnostic criteria prevailing at the time of symptom onset, comorbidities, and family history of MS.Results: Data of 525 (95.6%) from a cohort of 549 patients were analyzed. About 69.1% were women. The mean age was 43.2 years. About 86.3% had relapsing-remitting MS. The mean overall diagnostic delay was 3.07 years. About 45.7% of the patients had a delayed diagnosis, and it was dependent on the symptom and the diagnostic criteria prevailing at the onset. Multivariate logistic regression showed onset during the Schumacher (OR = 10.03 [95%CI 1.30-77.1], p = 0.027) and Poser (OR = 4.26 [95%CI 1.25-15.15], p = 0.021) years were associated with delayed MS diagnosis.Conclusions: MS onset before the McDonald diagnostic criteria era is associated with delayed diagnosis.

Case Report: Sudden Splenic Rupture in a Plasmodium falciparum-Infected Patient.

Spontaneous splenic rupture is a rare and life-threatening complication of severe malaria. It demands particular attention since delayed or missed diagnosis can be potentially fatal. The exact incidence is unknown largely due to underreporting. Acute malarial infection accounts for most of the spontaneous splenic rupture. Plasmodium vivax has been associated with the majority of them; however, on rare occasion, other Plasmodium infections have also resulted in splenic rupture. We report the case of a 74-year-old male who was diagnosed with severe malaria caused by Plasmodium falciparum (P. falciparum) infection and developed an acute abdomen while on treatment due to spontaneous splenic rupture which necessitated emergency splenectomy.

Congenital presentation of synchronous Atypical Teratoid Rhabdoid Tumor and Malignant Rhabdoid Tumor of the urinary bladder in a term infant.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare central nervous system (CNS) tumor diagnosed primarily in infants and usually portends a poor prognosis. Despite being the most common embryonal tumor in children less than 1 year old, diagnosis is difficult to make based on clinical findings or imaging alone. A complete diagnosis of AT/RT requires identification of loss of integrase interactor 1 (INI1) protein or the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) gene, in its most common presentation. Moreover, their presentation with other primary rhabdoid tumors in the body raises significant suspicion for rhabdoid tumor predisposition syndrome (RTPS). We report a case of a one-month-old infant admitted for worsening emesis and failure to thrive, who was later found to have brain and bladder masses on radiologic imaging. Autopsy with subsequent immunoprofile and molecular testing were crucial in establishing the absence of INI1 nuclear expression and possible homozygous deletion of SMARCB1 in the urinary bladder tumor tissue. Sequencing of the peripheral blood demonstrated probable single copy loss at the SMARCB1 locus. The constellation of findings in tumor and peripheral blood sequencing suggested the possibility of germline single copy SMARCB1 loss, followed by somatic loss of the remaining SMARCB1 allele due to copy neutral loss-of-heterozygosity. Such a sequence of genetic events has been described in malignant rhabdoid tumors (MRT). Dedicated germline testing of this patient's family members could yield answers as to whether rhabdoid tumor predisposition syndrome will continue to have implications for the patient's family.

Emulation of dynamic wavefront disturbances using a deformable mirror.

Boundary-layer turbulence resulting from uneven airflow around window interfaces can impact airborne laser communications (lasercom). In the focal plane, these distortions can produce fast jitter and beam break-up, posing challenges for tracking and communications. We demonstrate an experimental emulator that reproduces aircraft aero-optical distortions using a deformable mirror. This boundary-layer emulator resides in a hardware testbed that experimentally mimics air-to-space lasercom links in a controlled, laboratory environment. The boundary-layer emulator operates in the 1.55-mum band and accurately recreates aero-optical distortions at a rate of 2 kilo-frames per second.