University Medical Center of El Paso

Most methods of defining a statistical relationship between variables require that errors in prediction not be correlated. That is, knowledge of the error in one instance should not give information about the likely error in the next measurement. Real data frequently fail this requirement. If a Durbin-Watson statistic reveals that there is autocorrelation of sequential data points, analysis of variance and regression results will be invalid and possibly misleading. Such data sets may be analyzed by time series methodologies such as autoregressive integrated moving average (ARIMA) modeling. This method is demonstrated by an example from a public policy intervention.

Purpose To compare the ability of margin classification systems to determine local recurrence (LR) risk after soft tissue sarcoma (STS) resection. Methods Two thousand two hundred seventeen patients with nonmetastatic extremity and truncal STS treated with surgical resection and multidisciplinary consideration of perioperative radiotherapy were retrospectively reviewed. Margins were coded by residual tumor (R) classification (in which microscopic tumor at inked margin defines R1), the R+1mm classification (in which microscopic tumor within 1 mm of ink defines R1), and the Toronto Margin Context Classification (TMCC; in which positive margins are separated into planned close but positive at critical structures, positive after whoops re-excision, and inadvertent positive margins). Multivariate competing risk regression models were created. Results By R classification, LR rates at 10-year follow-up were 8%, 21%, and 44% in R0, R1, and R2, respectively. R+1mm classification resulted in increased R1 margins (726 v 278, P < .001), but led to decreased LR for R1 margins without changing R0 LR; for R0, the 10-year LR rate was 8% (range, 7% to 10%); for R1, the 10-year LR rate was 12% (10% to 15%) . The TMCC also showed various LR rates among its tiers ( P < .001). LR rates for positive margins on critical structures were not different from R0 at 10 years (11% v 8%, P = .18), whereas inadvertent positive margins had high LR (5-year, 28% [95% CI, 19% to 37%]; 10-year, 35% [95% CI, 25% to 46%]; P < .001). Conclusion The R classification identified three distinct risk levels for LR in STS. An R+1mm classification reduced LR differences between R1 and R0, suggesting that a negative but < 1-mm margin may be adequate with multidisciplinary treatment. The TMCC provides additional stratification of positive margins that may aid in surgical planning and patient education.

Despite increasing awareness of the clinical incidence of venous air embolism, the pathophysiology of the resultant cardiovascular collapse is still obscure. Since venous air emboli frequently result from gradual aspiration of air into a vein opened surgically, slow infusion (0.01 to 2.00 mg/kg/min)

INTRODUCTION: The extracellular matrix (ECM) plays an integral role in wound healing. It provides both structure and growth factors that allow for the organised cell proliferation. Large or complex tissue defects may compromise host ECM, creating an environment that is unfavourable for the recovery of anatomical function and appearance. Acellular dermal matrices (ADMs) have been developed from a variety of sources, including human (HADM), porcine (PADM) and bovine (BADM), with multiple different processing protocols. The objective of this report is to provide an overview of current literature assessing the clinical utility of ADMs across a broad spectrum of applications. METHODS: PubMed, MEDLINE, EMBASE, Scopus, Cochrane and Web of Science were searched using keywords 'acellular dermal matrix', 'acellular dermal matrices' and brand names for commercially available ADMs. Our search was limited to English language articles published from 1999 to 2020 and focused on clinical data. RESULTS: A total of 2443 records underwent screening. After removing non-clinical studies and correspondence, 222 were assessed for eligibility. Of these, 170 were included in our synthesis of the literature. While the earliest ADMs were used in severe burn injuries, usage has expanded to a number of surgical subspecialties and procedures, including orthopaedic surgery (e.g. tendon and ligament reconstructions), otolaryngology, oral surgery (e.g. treating gingival recession), abdominal wall surgery (e.g. hernia repair), plastic surgery (e.g. breast reconstruction and penile augmentation), and chronic wounds (e.g. diabetic ulcers). CONCLUSION: Our understanding of ADM's clinical utility continues to evolve. More research is needed to determine which ADM has the best outcomes for each clinical scenario. LAY SUMMARY: Large or complex wounds present unique reconstructive and healing challenges. In normal healing, the extracellular matrix (ECM) provides both structural and growth factors that allow tissue to regenerate in an organised fashion to close the wound. In difficult or large soft-tissue defects, however, the ECM is often compromised. Acellular dermal matrix (ADM) products have been developed to mimic the benefits of host ECM, allowing for improved outcomes in a variety of clinical scenarios. This review summarises the current clinical evidence regarding commercially available ADMs in a wide variety of clinical contexts.

Insulin resistance or its sequelae may be the common etiology of maladies associated with metabolic syndrome (eg, hypertension, type 2 diabetes, atherosclerosis, heart attack, stroke, and kidney failure). It is thus important to understand those factors that affect insulin sensitivity. This review stems from the surprising discovery that interference with angiotensin signaling improves insulin sensitivity, and it provides a general overview of insulin action and factors that control insulin sensitivity.

Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. Although the great majority of pregnant women have no pre-existing endocrine abnormalities, a small number of women can have certain endocrine alterations that could potentially lead to recurrent pregnancy losses. It is estimated that approximately 8 to 12% of all pregnancy losses are the result of endocrine factors. During the preimplantation period, the uterus undergoes important developmental changes stimulated by estrogen, and more importantly, progesterone. Progesterone is essential for the successful implantation and maintenance of pregnancy. Therefore, disorders related to inadequate progesterone secretion by the corpus luteum are likely to affect the outcome of the pregnancy. Luteal phase deficiency, hyperprolactinemia, and polycystic ovarian syndrome are some examples. Several other endocrinological abnormalities such as thyroid disease, hypoparathyroidism, uncontrolled diabetes, and decreased ovarian reserve have been implicated as etiologic factors for recurrent pregnancy loss.

BACKGROUND: The 'Golden Hour' emphasizes the importance of rapidly providing definitive care to trauma patients. Dispatch time, defined as the time it takes the Helicopter Emergency Medical Service (HEMS) to dispatch from their base and reach the patient, and on-scene time, defined as the time spent with the patient prior to departure to a trauma center, can impact how quickly the patient will reach definitive care. We evaluated HEMS dispatch and on-scene times by investigating the survival rates among patients transported by air to a level 1 trauma center. We hypothesize that longer HEMS dispatch and on-scene times are associated with worse patient outcomes. METHODS: A retrospective, single institution analysis was performed on patients transported by HEMS. Inclusion criteria were air transported patients aged 18 years and above admitted to a level 1 trauma center from January 1, 2005 to January 1, 2015. Total dispatch time and on-scene times were divided into five incremental groups and mortality data were analyzed. Mortality was defined as death during initial hospital admission. A Pearson's correlation was used to analyze relationship between dispatch times, on-scene times, and mortality. Simple binary logistic regression was used to run a multivariate analysis on confounding variables of Injury Severity Score (ISS), gender, age, and Glasgow Coma Scale. RESULTS: There was a strong positive linear correlation between HEMS on-scene time and mortality, R=0.962, p=0.038. Additionally, there was a positive trend between HEMS dispatch time and mortality. ISS was found to be a significant confounder of mortality in our cohort with on-scene times >20 min, with mortality increasing by 7.5% for every 0.1 increase in ISS score (p=0.01). CONCLUSION: Longer HEMS on-scene and dispatch times appeared to be associated with increased mortality in trauma patients. However, those with higher ISS require longer on-scene times, increasing mortality. Regardless, efforts should focus on reducing on-scene and dispatch times. LEVEL OF EVIDENCE AND STUDY TYPE: Level III; Therapeutic/Care Management.

Abstract Esophageal squamous carcinoma (ESCC) may be developed through a progressive sequence from mild to severe dysplasia, carcinoma in situ, and finally, invasive carcinoma. Chemoprevention can block or weaken the influence of development. Recent study has shown luteolin, a bioflavonoid, possesses anti-inflammatory, antioxidant, and anti-proliferative effects, and it might have a preventive effect in this progress. In this study, we focused on the effect of luteolin on cell cycle regulation in human Esophageal Squamous Carcinoma Cell Line EC1 and KYSE450 Cells in vitro and its potential mechanisms. Observations by flow cytometer showed that luteolin inhibited cell cycle progression at G2/M phase in a dose- and time-dependent manner. We also found that luteolin could induce cell apoptosis via decreasing activation of caspase-3 and down-regulation of mitochondrial membrane potential. Western blot results showed the protein expression of cycle related protein CyclinD1 and apoptosis related proteins caspase-3, caspase-9, and Bak were also significantly decreased in luteolin treated cells compared with the non-luteolin treated cells. Our results suggest that the proper use of luteolin might be a practical approach to the prevention of esophageal carcinoma via the inhibition of cell proliferation and other potential high risk regions for this disease. Citation Format: Ping Chen, Tao Hu, Yane Ma, Xiaoyu Chen, Liping Dai, Ningjing Lei, Ziming Dong, Pei Li. Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2808. doi:10.1158/1538-7445.AM2015-2808

AIM: To evaluate glycemic control among women with gestational diabetes mellitus (GDM) under insulin versus metformin (with or without insulin supplementation), and to identify metformin poor responders requiring supplemental insulin. METHODS: In Ain Shams University Hospital, mothers with 26-32-week GDM pregnancies, failing diet control, were randomized to receive metformin (n = 47) or insulin (n = 48). The primary outcome was glycemic control. Secondary outcomes included maternal weight, parameters predicting successful metformin monotherapy, neonatal hypoglycemia, and birthweight. RESULTS: Women using metformin (23.4% needing supplemental insulin) gained less weight (P < 0.001), and had lower fasting glucose during the first and last 2 weeks of treatment (P = 0.014 and 0.008, respectively) when compared with insulin monotherapy. Insulin supplementation in the metformin group was related to initial body mass index, HbA1c, oral glucose tolerance test (GTT), and first week mean glucose level. The 1-h glucose level during initial GTT (Hr1-GTT) and the mean fasting glucose level during the first week of therapy (Wk1-mFG) were the two independent parameters associated with requiring supplemental insulin. Women with Hr1-GTT >212 mg/dL and Wk1-mFG >95 mg/dL had a risk ratio of 58.6 (95%CI: 3.68-933.35, P = 0.004) and 11.5 (95%CI: 2.77-47.34,= 0.0008), respectively for needing supplemental insulin during the course of the study compared with women without. CONCLUSION: Metformin is an effective and safe alternative to insulin in GDM. Women using metformin (± supplemental insulin) had similar glycemic control, less weight gain, and similar rates of side-effects as those on insulin monotherapy. Insulin supplementation to metformin therapy was more likely with elevated Hr1-GTT and Wk1-mFG.

In this review article, the authors offer their perspective on nerve surgery for nerve injury, with a focus on recent evolution of management and the current surgical management. The authors provide a brief historical perspective to lay the foundations of the modern understanding of clinical nerve injury and its evolving management, especially over the last century. The shift from evaluation of the nerve injury using macroscopic techniques of exploration and external neurolysis to microscopic interrogation, interfascicular dissection, and internal neurolysis along with the use of intraoperative electrophysiology were important advances of the past 50 years. By the late 20th century, the advent and popularization of interfascicular nerve grafting techniques heralded a major advance in nerve reconstruction and allowed good outcomes to be achieved in a large percentage of nerve injury repair cases. In the past 2 decades, there has been a paradigm shift in surgical nerve repair, wherein surgeons are not only directing the repair at the injury zone, but also are deliberately performing distal-targeted nerve transfers as a preferred alternative in an attempt to restore function. The peripheral rewiring approach allows the surgeon to convert a very proximal injury with long regeneration distances and (often) uncertain outcomes to a distal injury and repair with a greater potential of regenerative success and functional recovery. Nerve transfers, originally performed as a salvage procedure for severe brachial plexus avulsion injuries, are now routinely done for various less severe brachial plexus injuries and many other proximal nerve injuries, with reliably good to even excellent results. The outcomes from nerve transfers for select clinical nerve injury are emphasized in this review. Extension of the rewiring paradigm with nerve transfers for CNS lesions such as spinal cord injury and stroke are showing great potential and promise. Cortical reeducation is required for success, and an emerging field of rehabilitation and restorative neurosciences is evident, which couples a nerve transfer procedure to robotically controlled limbs and mind-machine interfacing. The future for peripheral nerve repair has never been more exciting.

Innate and acquired resistance towards the conventional therapeutic regimen imposes a significant challenge for the successful management of cancer for decades. In patients with advanced carcinomas, acquisition of drug resistance often leads to tumor recurrence and poor prognosis after the first therapeutic cycle. In this context, cancer stem cells (CSCs) are considered as the prime drivers of therapy resistance in cancer due to their 'non-targetable' nature. Drug resistance in cancer is immensely influenced by different properties of CSCs such as epithelial-to-mesenchymal transition (EMT), a profound expression of drug efflux pump genes, detoxification genes, quiescence, and evasion of apoptosis, has been highlighted in this review article. The crucial epigenetic alterations that are intricately associated with regulating different mechanisms of drug resistance, have been discussed thoroughly. Additionally, special attention is drawn towards the epigenetic mechanisms behind the interaction between the cancer cells and their microenvironment which assists in tumor progression and therapy resistance. Finally, we have provided a cumulative overview of the alternative treatment strategies and epigenome-modifying therapies that show the potential of sensitizing the resistant cells towards the conventional treatment strategies. Thus, this review summarizes the epigenetic and molecular background behind therapy resistance, the prime hindrance of present day anti-cancer therapies, and provides an account of the novel complementary epi-drug-based therapeutic strategies to combat drug resistance.

STUDY OBJECTIVE: We evaluated thromboembolic events after vitamin K antagonist reversal in post hoc analyses of pooled data from 2 randomized trials comparing 4-factor prothrombin complex concentrate (4F-PCC) (Beriplex/Kcentra) with plasma. METHODS: Unblinded investigators identified thromboembolic events, using standardized terms (such as "myocardial infarction," "deep vein thrombosis," "pulmonary embolism," and "ischemic stroke"). A blinded safety adjudication board reviewed serious thromboembolic events, as well as those referred by an independent unblinded data and safety monitoring board. We descriptively compared thromboembolic event and patient characteristics between treatment groups and included detailed patient-level outcome descriptions. We did not power the trials to assess safety. RESULTS: We enrolled 388 patients (4F-PCC: n=191; plasma: n=197) in the trials. Thromboembolic events occurred in 14 of 191 patients (7.3%) in the 4F-PCC group and 14 of 197 (7.1%) in the plasma group (risk difference 0.2%; 95% confidence interval -5.5% to 6.0%). Investigators reported serious thromboembolic events in 16 patients (4F-PCC: n=8; plasma: n=8); the data and safety monitoring board referred 2 additional myocardial ischemia events (plasma group) to the safety adjudication board for review. The safety adjudication board judged serious thromboembolic events in 10 patients (4F-PCC: n=4; plasma: n=6) as possibly treatment related. There were 8 vascular thromboembolic events in the 4F-PCC group versus 4 in the plasma group, and 1 versus 6 cardiac events, respectively. Among patients with thromboembolic events, 3 deaths occurred in each treatment group. All-cause mortality for the pooled population was 13 per group. We observed no relationship between thromboembolic event occurrence and factor levels transiently above the upper limit of normal; there were no notable differences in median factor or proteins C and S levels up to 24 hours postinfusion start in patients with and without thromboembolic events. CONCLUSION: The incidence of thromboembolic events after vitamin K antagonist reversal with 4F-PCC or plasma was similar and independent of coagulation factor levels; small differences in the number of thromboembolic event subtypes were observed between treatment groups.

Healthcare delivery in the Unites States stimulates policy change at a rapid pace. The Patient Protection and Affordable Care Act of 2010 (ACA) is intended to expand access to care and ultimately improve the health of Americans. The Triple Aim, created by The Institute for Healthcare Improvement, delineates policy implications for improving population health, the healthcare experience, and per capita cost. The Quadruple Aim adds a fourth policy implication, for example, addressing the needs of the healthcare provider. Advanced practice registered nurses are key in carrying out the goals of the ACA and achieving the Triple and Quadruple Aims, via the formation of interprofessional teams. This article offers insight into these policy implications and identifies filters through which related nursing policy will be developed.

OBJECT: The prognosis for intraventricular neurocysticercosis (IVNCC) is poorer than that for parenchymal NCC, making prompt diagnosis and treatment especially important. Although active, viable intraventricular cysts produce no reaction in the host; they can cause noncommunicating hydrocephalus, the onset of which is frequently abrupt. With the death of the larva comes a local granulomatous ependymitis, generalized ventriculitis, and meningoencephalitis. The authors report on 18 patients with IVNCC (accrued from a larger case series of 62 patients with NCC treated over an 11-year period), detailing clinical presentation, neuroimaging findings, treatment, and outcome. METHODS: All patients presented with hydrocephalus and/or meningitis. The most valuable diagnostic tests were magnetic resonance imaging of the brain and EITB of serum and/or cerebrospinal fluid. Treatment included albendazole and steroid therapy in all cases, and when necessary in cases requiring urgent or emergency ventriculostomy and/or surgical removal of the obstructing cyst (followed by shunt placement if indicated). CONCLUSIONS: An extensive review of the literature on IVNCC has been prepared, with the goal of providing the reader with the information necessary to diagnose and treat this complex and potentially fatal disease in a timely and effective manner.

Abstract The change in properties of several anionic polyacrylamides that were used in various EOR projects around the world is discussed. Due to mechanical, radical and/or thermal degradations reported, the molecular weight, anionicity and viscosity of polymer change from the time it is injected until breakthrough when it is produced. Strategies for optimizing the long term stability of EOR polymers have been developed for various polymer types combined with protective additives. Polymers investigated are acrylamide (AMD) based co- and ter-polymers functionalized with monomers such as sodium acrylate (AA), sodium acrylamido-tertiary-butyl sulfonate (ATBS) or N-vinyl pyrrolidone (NVP). The additives belong to five families: free radical absorber, oxygen scavenger, metal precipitant, chelating chemicals, and sacrificial agent. The additives have been selected in addition to their chemical properties for their physical and toxicological characteristics to allow to be formulated as one single formulation under the ready-to-use powder or inverse emulsion form. Chemical and thermal stability for polymer solutions containing 50 to 500 ppb of oxygen have been evaluated using a new test apparatus that allows precise control of the oxygen level. The "as is" stabilized polymer compositions can be used for polymer, surfactant polymer and alkaline surfactant polymer floods. With this technology, polymer viscosity is stable while it propagates through the reservoir and a favorable mobility ratio is maintained from injectors to producers. This enables better sweep efficiency and more efficient oil recovery. Laboratory data shows that new acrylamide based polymer compositions maintain viscosity in the presence of oxygen and iron at high temperature and salinity. ATBS, NVP containing polyacrylamides with protective additives are shown to have the best resistance to radical and thermal degradation. The viscosity of polymer solutions aged up to 120°C can typically reach 60 - 110 % of initial viscosity after a few months compared to 10-40% of previous systems. The polymer and additive combination must be optimized in order to achieve long term thermal and chemical stability at specific reservoir conditions. Results show that polymer flooding can be successful in reservoirs with relatively high temperature and poor water quality. Improved polymer compositions stability leads to increased oil recovery from chemical floods used in EOR.

STUDY OBJECTIVE: To evaluate the use of complementary and alternative medicine (CAM) in the El Paso, Texas, region. DESIGN: Prospective observational study conducted from April-October 2000. SETTING: Several hospitals and clinics. SUBJECTS: Five hundred forty-seven participants. INTERVENTION: Semi-structured interview with a bilingual questionnaire. MEASUREMENTS AND MAIN RESULTS: Complementary and alternative medicine was used in 77% of our population. The most common CAM providers were massage therapists (19.4%) and herbalists (12.4%). The most common herbal or home remedies were chamomile (13.1%) and aloe vera (8.5%). The most common nutritional or commercial products were multivitamins (16%), ginseng (3.6%), and ginkgo biloba (2.8%). We identified 599 CAM usages that could result in drug interactions, disease interactions, or adverse reactions. CONCLUSIONS: A wide range of CAM use was documented in this study. Our results indicate that Hispanics in this area use CAM at a higher rate than national trends. Many of these therapies can adversely affect a variety of disease states and drug therapies.

Embryology is integrated into the Clinically Oriented Anatomy course at the Texas Tech University Health Sciences Center School of Medicine. Before 2008, the same instructor presented embryology in 13 face-to-face lectures distributed by organ systems throughout the course. For the 2008 and 2009 offerings of the course, a hybrid embryology instruction model with four face-to-face classes that supplemented online recorded lectures was used. One instructor delivered the lectures face-to-face in 2007 and by online videos in 2008-2009, while a second instructor provided the supplemental face-to-face classes in 2008-2009. The same embryology learning objectives and selected examination questions were used for each of the three years. This allowed direct comparison of learning outcomes, as measured by examination performance, for students receiving only face-to-face embryology instruction versus the hybrid approach. Comparison of the face-to-face lectures to the hybrid approach showed no difference in overall class performance on embryology questions that were used all three years. Moreover, there was no differential effect of the delivery method on the examination scores for bottom quartile students. Students completed an end-of-course survey to assess their opinions. They rated the two forms of delivery similarly on a six-point Likert scale and reported that face-to-face lectures have the advantage of allowing them to interact with the instructor, whereas online lectures could be paused, replayed, and viewed at any time. These experiences suggest the need for well-designed prospective studies to determine whether online lectures can be used to enhance the efficacy of embryology instruction.

Abstract Question: What was the role of fire in montane pine‐oak ( Pinus‐Quercus ) stands under changing human land uses on a temperate forest landscape in eastern North America? Location: Mill Mountain in the central Appalachian Mountains, Virginia, US. Methods: A dendroecological reconstruction of fire history was generated for four stands dominated by xerophytic pine and oak species. The fire chronology began under presettlement conditions following aboriginal depopulation. Subsequent land uses included European settlement, iron mining, logging, and US Forest Service acquisition and fire protection. Results: Fires occurred approximately every 5 years until 1930 without any evidence of a temporal trend in fire frequency. Burning ceased after 1930. Area‐wide fires affecting multiple pine stands were common, occurring at intervals of approximately 16 years. Most living pines became established during the late 1800s and early 1900s. Dead pines indicated that an older cohort established ca. 1730. Most hardwoods were established between the 1920s and 1940s. Conclusions: Except for fire protection, changes in land use had no discernible influence on fire frequency. Lightning ignitions and/or large fire extent may have been important for maintaining frequent burning in the 1700s, while fuel recovery may have constrained fire frequency during later periods. The disturbance regime appears to be characterized by frequent surface fires and occasional severe fires, insect outbreaks or other disturbances followed by pine recruitment episodes. Industrial disturbances appear to have had little influence on the pine stands. The greatest impact of industrial society is fire exclusion, which permitted hardwood establishment.

BACKGROUND: The remarkable ability of the body to adapt to long-term starvation has been critical for survival of primitive man. An appreciation of these processes can provide the clinician better insight into many clinical conditions characterized by ketoacidosis. SUMMARY: The body adapts to long-term fasting by conserving nitrogen, as the brain increasingly utilizes keto acids, sparing the need for glucose. This shift in fuel utilization decreases the need for mobilization of amino acids from the muscle for purposes of gluconeogenesis. Loss of urinary nitrogen is initially in the form of urea when hepatic gluconeogenesis is dominant and later as ammonia reflecting increased glutamine uptake by the kidney. The carbon skeleton of glutamine is utilized for glucose production and regeneration of consumed HCO3-. The replacement of urea with NH4+ provides the osmoles needed for urine flow and waste product excretion. Over time, the urinary loss of nitrogen is minimized as kidney uptake of filtered ketone bodies becomes more complete. Adjustments in urine Na+ serve to minimize kidney K+ wasting and, along with changes in urine pH, minimize the likelihood of uric acid precipitation. There is a sexual dimorphism in response to starvation. Key Message: Ketoacidosis is a major feature of common clinical conditions to include diabetic ketoacidosis, alcoholic ketoacidosis, salicylate intoxication, SGLT2 inhibitor therapy, and calorie sufficient but carbohydrate-restricted diets. Familiarity with the pathophysiology and metabolic consequences of ketogenesis is critical, given the potential for the clinician to encounter one of these conditions.

Cerebral cavernous malformations (CCM) are manifested by microvascular lesions characterized by leaky endothelial cells with minimal intervening parenchyma predominantly in the central nervous system predisposed to hemorrhagic stroke, resulting in focal neurological defects. Till date, three proteins are implicated in this condition: CCM1 (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10). These multi-domain proteins form a protein complex via CCM2 that function as a docking site for the CCM signaling complex, which modulates many signaling pathways. Defects in the formation of this signaling complex have been shown to affect a wide range of cellular processes including cell-cell contact stability, vascular angiogenesis, oxidative damage protection and multiple biogenic events. In this review we provide an update on recent advances in structure and function of these CCM proteins, especially focusing on the signaling cascades involved in CCM pathogenesis and the resultant CCM cellular phenotypes in the past decade.