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Murray S.,GeneKOR | Briasoulis E.,University of Ioannina | Linardou H.,Metropolitan Hospital | Bafaloukos D.,University of Ioannina | Papadimitriou C.,National and Kapodistrian University of Athens
Cancer Treatment Reviews | Year: 2012

Background: Taxanes are established in the treatment of metastatic breast cancer (MBC) and early breast cancer (EBC) as potent chemotherapy agents. However, their therapeutic usefulness is limited by de-novo refractoriness or acquired resistance, which are common drawbacks to most anti-cancer cytotoxics. Considering that the taxanes will remain principle chemotherapeutic agents for the treatment of breast cancer, we reviewed known mechanisms of resistance in with an outlook of optimizing their clinical use. Methods: We searched the PubMed and MEDLINE databases for articles (from inception through to 9th January 2012; last search 10/01/2012) and journals known to publish information relevant to taxane chemotherapy. We imposed no language restrictions. Search terms included: cancer, breast cancer, response, resistance, taxane, paclitaxel, docetaxel, taxol. Due to the possibility of alternative mechanisms of resistance all combination chemotherapy treated data sets were removed from our overview. Results: Over-expression of the MDR-1 gene product Pgp was extensively studied in vitro in association with taxane resistance, but data are conflicting. Similarly, the target components microtubules, which are thought to mediate refractoriness through alterations of the expression pattern of tubulins or microtubule associated proteins and the expression of alternative tubulin isoforms, failed to confirm such associations. Little consensus has been generated for reported associations between taxane-sensitivity and mutated p53, or taxane-resistance and overexpression of Bcl-2, Bcl-xL or NFkB. In contrary sufficient in vitro data support an association of spindle assembly checkpoint (SAC) defects with resistance. Clinical data have been limited and inconsistent, which relate to the variety of methods used, lack of standardization of cut-offs for quantitation, differences in clinical endpoints measured and in methods of tissue collection preparation and storage, and study/patient heterogeneity. The most prominent finding is that pharmaceutical down-regulation of HER-2 appears to reverse the taxane resistance. Conclusions: Currently no valid practical biomarkers exist that can predict resistance to the taxanes in breast cancer supporting the principle of individualized cancer therapy. The incorporation of several biomarker analyses into prospectively designed studies in this setting are needed. © 2012 Elsevier Ltd.


Dahabreh I.J.,Tufts University | Linardou H.,Metropolitan Hospital | Kosmidis P.,Hygeia Hospital | Bafaloukos D.,Metropolitan Hospital | Murray S.,BioMarker Solutions
Annals of Oncology | Year: 2011

Introduction: We conducted a systematic review and meta-analysis to assess epidermal growth factor receptor (EGFR) gene copy number as a potential biomarker of survival for patients with advanced non-small-cell lung cancer (NSCLC) receiving single-agent treatment with EGFR tyrosine kinase inhibitors (TKIs). Methods: We systematically identified articles investigating EGFR gene copy number by fluorescent or chromogenic in situ hybridization in patients with advanced or recurrent NSCLC treated with the TKIs erlotinib or gefitinib, (last search: 31 June 2009). Eligible studies had to report on overall survival (OS), progression-free survival (PFS) or time-toprogression (TTP), stratified by EGFR gene copy number. Summary hazard ratios (HRs) were calculated using random-effects models. Results: Among 255 identified studies, 20 (1689 patients, 594 with increased gene copy number), 10 (822 patients, 290 with increased gene copy number) and 5 (294 patients, 129 with increased gene copy number) were eligible for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR gene copy number was associated with increased OS (HR = 0.77; 95% CI 0.66-0.89; P = 0.001), PFS (HR = 0.60; 95% CI 0.46-0.79; P<0.001) and TTP (HR = 0.50; 95% CI 0.28-0.91; P = 0.02). Among predominantly white populations, increased EGFR gene copy number was strongly associated with improved survival (HR = 0.70; 95% CI 0.59-0.82; P<0.001), whereas it did not influence survival in East Asians (HR = 1.11; 95% CI 0.82-1.50; P=0.50). This difference was statistically significant (P=0.02). Conclusion: Among TKI-treated patients, increased EGFR gene copy number appears to be associated with improved survival outcomes. The effect on OS appears to be limited to patients of non-Asian descent. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Panagopoulos A.,University of Patras | Van Niekerk L.,Friarage and Duchess of Kent Military Hospitals | Triantafillopoulos I.,Metropolitan Hospital
Orthopedics | Year: 2012

Few studies have assessed the results of autologous chondrocyte implantation in patients with high-impact activities. The purpose of this study was to evaluate the early functional outcome and activity level after 2-stage autologous chondrocyte implantation in professional soldiers and athletes. Nineteen patients with an average age of 32.2 years were treated with autologous chondrocyte implantation and followed up for a minimum of 2 years. All patients except 2 had received previous arthroscopic treatment with debridement and/or microfracture. The mean size of the postdebridement defect was 6.54 cm 2. Using Novocart technology (B. Braun-Tetec, Reutlingen, Germany), periosteal patch and matrix-assisted autologous chondrocyte implantation was sequentially performed with no randomization. The average subjective knee evaluation score and Lysholm score improved from 39.16 and 42.42, respectively, preoperatively to 62.4 and 69.4, respectively, at latest follow-up. Median Tegner activity score was 8.8 before injury, 3.8 preoperatively, and 6.15 at latest follow-up. Second-look arthroscopy was performed in 11 patients due to persistent pain, decreased range of movement, and mechanical symptoms. Six of 19 (31.5%) patients with professional or recreational athletic activities returned to preinjury levels of athletic performance. This study shows that mid-term results with autologous chondrocyte implantation in high-performance patients are not as good as have been reported with other similar technologies. Motivational issues during prolonged rehabilitation, multiple surgical interventions before autologous chondrocyte implantation, patient age, and large defects can potentially influence the outcome and overall performance in this selected group of patients.


The International Association of HealthCare Professionals is pleased to welcome Santha Mohan, MD, Pediatrician, to their prestigious organization with her upcoming publication in The Leading Physicians of the World. Dr. Mohan is a highly trained and qualified pediatrician with an extensive expertise in all facets of her work. Dr. Mohan has been in practice for over three decades and is currently serving patients at the Randall Medical Offices in the Bronx, New York and the Medical Office in New York, New York. Additionally, Dr. Mohan is affiliated with Mount Sinai Health System, Bronx-Lebanon Hospital Center, St. Luke’s Hospital, and St. Barnabas Hospital, and Metropolitan Hospital in Manhattan. Dr. Mohan’s career in medicine began in 1976 when she graduated with her Medical Degree from Nagpur Medical College in India. Dr. Mohan is certified by the American Board of Pediatrics, has earned the coveted title of Fellow of the American Academy of Pediatrics, and for her excellence, was honored with a Congressional Award by Congressman Charles B. Rangel for her leadership and contribution to the field of pediatrics in New York City. Dr. Mohan spends a lot of time with children with asthma and obesity, and works closely with her patients in the prevention and treatment of these conditions. Dr. Mohan keeps up to date with the latest advances and developments in her field through her professional membership with the American Medical Association and the American Academy of Pediatrics. She attributes her great success to her keen interest in the well being of her patients. When she is not assisting her patients, Dr. Mohan enjoys cooking, reading, and traveling. Learn more about Dr. Mohan by reading her upcoming publication in The Leading Physicians of the World. FindaTopDoc.com is a hub for all things medicine, featuring detailed descriptions of medical professionals across all areas of expertise, and information on thousands of healthcare topics.  Each month, millions of patients use FindaTopDoc to find a doctor nearby and instantly book an appointment online or create a review.  FindaTopDoc.com features each doctor’s full professional biography highlighting their achievements, experience, patient reviews, and areas of expertise.  A leading provider of valuable health information that helps empower patient and doctor alike, FindaTopDoc enables readers to live a happier and healthier life.  For more information about FindaTopDoc, visit:http://www.findatopdoc.com


News Article | December 23, 2016
Site: www.prweb.com

The Texas Cord Blood Bank, a program of nonprofit biomedical organization GenCure and the designated public cord blood bank for the state of Texas, has received a grant to help minimize time between collection of donated umbilical cord blood and preserving those donations so they’re available for patients in need of a transplant. The grant is from the National Marrow Donor Program/Be The Match®. The Texas Cord Blood Bank (TCBB) and GenCure partner with Be The Match to add donors to a national registry for bone marrow, peripheral blood stem cells (PBSCs) and umbilical cord blood for patients who need transplants to help cure blood cancers and other diseases. Umbilical cord blood is rich in blood-forming stem cells, and though it’s normally discarded, moms can choose to donate their newborns’ umbilical cord blood after healthy births through TCBB. Cord blood stem cell transplantation can be an alternative treatment for patients when a bone marrow or PBSC match cannot be found. The $67,000 grant will help TCBB add an extra courier pickup of cord blood donations from Methodist Metropolitan Hospital in San Antonio as well as an extra laboratory shift to process the donations and get them into storage and onto the registry, ready for patients who are searching for them. “Reducing the time between collection and processing of generously donated umbilical cord blood may serve two purposes,” said Rogelio Zamilpa, director of the GenCure cord blood center. “It will help improve the quality of the donations, making them more effective for patients, and it will help us add more donations from minorities to the registry, which are desperately needed.” Because the biological markers used in matching are inherited, patients are more likely to match someone from their own race or ethnicity. Adding more donors from diverse racial and ethnic backgrounds to the registry increases the likelihood all patients will find the match they need. TCBB piloted a similar program at an Edinburg, Texas, hospital. In that pilot, donated cord blood units TCBB was able to collect for the registry increased by 58 percent; the majority were from minority donors. “The NMDP grant will allow us to improve our processes to ultimately serve patients better. Increasing donated cord blood collections, the quality of those collections and the number of minority collections will help ensure the availability of transplants for patients who are counting on them,” Zamilpa said. The Texas Cord Blood Bank has provided about 400 transplant matches around the world and currently banks 1,200 units that are available to patients. About GenCure: GenCure, a Texas nonprofit, focuses on regenerative medicine and uses the power of human cells and tissues to inspire hope, enhance lives and enable clinical advancements. Using processed tissue and cell-based therapies, GenCure works to connect health care requirements with innovative solutions that best serve the needs of the global patient community. The Texas Cord Blood Bank, established by the state legislature in 2003, is a program of GenCure. Visit us at http://www.gencure.org.


Dumitru S.V.,Metropolitan Hospital | Kosmas E.N.,Metropolitan Hospital
Current Respiratory Medicine Reviews | Year: 2015

Obstructive sleep apnea syndrome (OSAS) is a common sleep-related breathing disorder that affects up to 7-10% of men and 4-5% of women. It is characterized by repeated events of complete or partial upper airway occlusion occurring during sleep, accompanied by a gradually increasing effort to breathe and terminated by an arousal when the upper airway patency is restored. The most effective treatment option for OSAS is continuous positive airway pressure (CPAP) therapy. There are numerous studies that had linked, without any scientific doubt, OSAS with cardiovascular diseases, morbidity and mortality. In the recent years it became evident as well that acute cerebrovascular events, such as stroke, are also a consequence of obstructive sleep apnea, although the pathophysiology and the mechanisms are not clear as of yet. This mini-review attempts to clarify and to highlight clinically important issues concerning sleep apnea and stroke patients with the aim of their optimal, effective and safe management. © 2015 Bentham Science Publishers.


Gonzalez-Andrade F.,Metropolitan Hospital | Lopez-Pulles R.,Central University of Ecuador
Public Health Genomics | Year: 2010

Ecuador has a heterogeneous population of almost 14 million people and a complex health care system provided through provincial and national health programs by government and private hospitals. There are public health facilities at regional and territorial level. Ecuador has a small cadre of genetic professionals that provide clinical genetic services in a few private medical centers in the main cities. Prenatal screening is offered exclusively in a few individual hospitals, with variable uptake as part of prenatal care. Surveillance of the effect of prenatal screening and diagnosis on the birth prevalence of congenital anomalies is limited by gaps and variations in surveillance systems. Newborn screening programs are almost inexistent. There is broad variation in optional participation in laboratory quality assurance schemes, and there are no regulatory frameworks that are directly pertinent to genetic testing services or population genetics. Health technology assessment in Ecuador is conducted by a diverse collection of organizations, several of which have produced reports related to genetics. Copyright © 2009 S. Karger AG.


Singh J.P.,Metropolitan Hospital | Mariadason J.G.,Metropolitan Hospital
Annals of the Royal College of Surgeons of England | Year: 2013

INTRODUCTION: The prevailing view on appendicitis is that the main aetiology is obstruction owing to faecoliths in adults and lymphoid hyperplasia in children. Faecoliths on imaging studies are believed to correlate well with appendicitis. METHODS: A retrospective chart review was conducted of 1,014 emergency appendicectomy patients between 2001 and 2011. Faecolith prevalence in adult and paediatric appendicectomy specimens with and without perforation was studied. The sensitivity and positive predictive value (PPV) of computed tomography (CT) for identifying faecoliths in the pathology specimen were examined. RESULTS: Overall, faecoliths were found in 18.1% (178/986) of appendicitis specimens and 28.6% (8/28) of negative appendicectomies. Faecolith prevalence for positive cases was 29.9% (79/264) in paediatric patients and 13.7% (99/722) in adults (p<0.05). Faecolith prevalence was 39.4% in perforated appendicitis but only 14.6% in non-perforated appendicitis (p<0.05). In adults, faecolith prevalence was 27.5% in perforated appendicitis and 12.0% in non-perforated appendicitis (p<0.05) while in paediatric patients, it was 56.1% in perforated appendicitis and 22.7% in non-perforated appendicitis (p=0.00). Sensitivity and PPV of preoperative CT in identifying faecoliths on pathology were 53.1% (86/162) and 44.8% (86/192) respectively. CONCLUSIONS: Faecolith prevalence is too low to consider the faecolith the most common cause of non-perforated appendicitis. Faecoliths are more prevalent in paediatric appendicitis than in adult appendicitis. Preoperative CT is an unreliable predictor of faecoliths in pathology specimens.


Dimopoulos J.C.A.,Metropolitan Hospital | Schmid M.P.,Medical University of Vienna | Fidarova E.,Medical University of Vienna | Berger D.,Medical University of Vienna | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To investigate the clinical feasibility of magnetic resonance image-guided adaptive brachytherapy (IGABT) for patients with locally advanced vaginal cancer and to report treatment outcomes. Methods and Materials: Thirteen patients with vaginal cancer were treated with external beam radiotherapy (45-50.4 Gy) plus IGABT with or without chemotherapy. Distribution of International Federation of Gynecology and Obstetrics stages among patients were as follows: 4 patients had Stage II cancer, 5 patients had Stage III cancer, and 4 patients had Stage IV cancer. The concept of IGABT as developed for cervix cancer was transferred and adapted for vaginal cancer, with corresponding treatment planning and reporting. Doses were converted to the equivalent dose in 2 Gy, applying the linear quadratic model (α/β = 10 Gy for tumor; α/β = 3 for organs at risk). Endpoints studied were gross tumor volume (GTV), dose-volume parameters for high-risk clinical target volume (HRCTV), and organs at risk, local control (LC), adverse side effects, and survival. Results: The mean GTV (± 1 standard deviation) at diagnosis was 45.3 (±30) cm 3, and the mean GTV at brachytherapy was 10 (±14) cm 3. The mean D90 for the HRCTV was 86 (±13) Gy. The mean D2cc for bladder, urethra, rectum, and sigmoid colon were 80 (±20) Gy, 76 (±16) Gy, 70 (±9) Gy, and 60 (±9) Gy, respectively. After a median follow-up of 43 months (range, 19-87 months), one local recurrence and two distant metastases cases were observed. Actuarial LC and overall survival rates at 3 years were 92% and 85%. One patient with Stage IVA and 1 patient with Stage III disease experienced fistulas (one vesicovaginal, one rectovaginal), and 1 patient developed periurethral necrosis. Conclusions: The concept of IGABT, originally developed for treating cervix cancer, appears to be applicable to vaginal cancer treatment with only minor adaptations. Dose-volume parameters for HRCTV and organs at risk are in a comparable range. First clinical results indicate excellent LC. Further prospective multicenter studies are needed to establish this method and to confirm these results. © 2012 Elsevier Inc.


Banks P.A.,Harvard University | Bollen T.L.,St Antonius Hospital | Dervenis C.,Agia Olga Hospital | Gooszen H.G.,Radboud University Nijmegen | And 4 more authors.
Gut | Year: 2013

Background and objective: The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the disease make a revision necessary. Methods: A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained. Results: The revised classi fication of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images. Conclusions: This international, web-based consensus provides clear de finitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.

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