Showing papers by "Saint Francis University published in 2013"

Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches

Abstract: Osteoporosis is a skeletal disorder characterized by bone loss, which results in architectural deterioration of the skeleton, compromised bone strength and an increased risk of fragility fractures. Most current therapies for osteoporosis stabilize the skeleton by inhibiting bone resorption (antiresorptive agents), but the development of anabolic therapies that can increase bone formation and bone mass is of great interest. Wnt signalling induces differentiation of bone-forming cells (osteoblasts) and suppresses the development of bone-resorbing cells (osteoclasts). The Wnt pathway is controlled by antagonists that interact either directly with Wnt proteins or with Wnt co-receptors. The importance of Wnt signalling in bone formation is indicated by skeletal disorders such as sclerosteosis and van Buchem syndrome, which are caused by mutations in the gene encoding the Wnt antagonist sclerostin (SOST). Experiments in mice have shown that downregulation or neutralization of Wnt antagonists enhances bone formation. Phase II clinical trials show that 1-year treatment with antisclerostin antibodies increases bone formation, decreases bone resorption and leads to a substantial increase in BMD. Consequently, Wnt signalling can be targeted by the neutralization of its extracellular antagonists to obtain a skeletal anabolic response.

Disparities in Ovarian Cancer Care Quality and Survival According to Race and Socioeconomic Status

Abstract: cancer diagnosed in the period from 1998 to 2002 was done using data from patients classified as white or black. Adherence to National Comprehensive Cancer Network (NCCN) guideline care was defined by stage-appropriate surgical procedures and recommended chemotherapy. The main outcome measures were differences in adherence to NCCN guidelines and overall survival according to race and SES and were analyzed using binomial logistic regression and multilevel survival analysis. Results A total of 47 160 patients (white = 43 995; black = 3165) were identified. Non-NCCN-guideline-adherent care was an independent predictor of inferior overall survival (hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.38 to 1.47). Demographic characteristics independently associated with a higher likelihood of not receiving NCCN guideline-adherent care were black race (odds ratio [OR] = 1.36, 95% CI = 1.25 to 1.48), Medicare payer status (OR = 1.20, 95% CI = 1.12 to 1.28), and not insured payer status (OR = 1.33, 95% CI = 1.19 to 1.49). After controlling for disease and treatment-related variables, independent racial and SES predictors of survival were black race (HR = 1.29, 95% CI = 1.22 to 1.36), Medicaid payer status (HR = 1.29, 95% CI = 1.20 to 1.38), not insured payer status (HR = 1.32, 95% CI = 1.20 to 1.44), and median household income less than $35 000 (HR = 1.06, 95% CI = 1.02 to 1.11). Conclusions These data highlight statistically and clinically significant disparities in the quality of o varian cancer care and overall survival, independent of NCCN guidelines, along racial and SES parameters. Increased efforts are needed to more precisely define the patient, provider, health-care system, and societal factors leading to these observed disparities and guide targeted interventions.

Osteoblast Lineage-Specific Effects of Notch Activation in the Skeleton

Abstract: Transgenic overexpression of the Notch1 intracellular domain inhibits osteoblast differentiation and causes osteopenia, and inactivation of Notch1 and Notch2 increases bone volume transiently and induces osteoblastic differentiation. However, the biology of Notch is cell-context-dependent, and consequences of Notch activation in cells of the osteoblastic lineage at various stages of differentiation and in osteocytes have not been defined. For this purpose, Rosa(Notch) mice, where a loxP-flanked STOP cassette placed between the Rosa26 promoter and the NICD coding sequence, were crossed with transgenics expressing the Cre recombinase under the control of the Osterix (Osx), Osteocalcin (Oc), Collagen 1a1 (Col2.3), or Dentin matrix protein1 (Dmp1) promoters. At 1 month, Osx-Cre;Rosa(Notch) and Oc-Cre;Rosa(Notch) mice exhibited osteopenia due to impaired bone formation. In contrast, Col2.3-Cre;Rosa(Notch) and Dmp1-Cre;Rosa(Notch) exhibited increased femoral trabecular bone volume due to a decrease in osteoclast number and eroded surface. In the four lines studied, cortical bone was either not present, was porous, or had the appearance of trabecular bone. Oc-Cre;Rosa(Notch) and Col2.3-Cre;Rosa(Notch) mice exhibited early lethality so that their adult phenotype was not established. At 3 months, Osx-Cre;Rosa(Notch) and Dmp1-Cre;Rosa(Notch) mice displayed increased bone volume, and increased osteoblasts although calcein-demeclocycline labels were diffuse and fragmented, indicating abnormal bone formation. In conclusion, Notch effects in the skeleton are cell-context-dependent. When expressed in immature osteoblasts, Notch arrests their differentiation, causing osteopenia, and when expressed in osteocytes, it causes an initial suppression of bone resorption and increased bone volume, a phenotype that evolves as the mice mature.

Notch signaling in skeletal health and disease.

Abstract: Notch receptors are single-pass transmembrane proteins that determine cell fate. Upon Notch ligand interactions, proteolytic cleavages release the Notch intracellular domain, which translocates to the nucleus to regulate the transcription of target genes, including Hairy enhancer of split (Hes) and Hes related to YRPW motif (Hey). Notch is critical for skeletal development and activity of skeletal cells, and dysregulation of Notch signaling is associated with human diseases affecting the skeleton. Inherited or sporadic mutations in components of the Notch signaling pathway are associated with spondylocostal dysostosis, spondylothoracic dysostosis and recessive brachydactyly, diseases characterized by skeletal patterning defects. Inactivating mutations of the Notch ligand JAG1 or of NOTCH2 are associated with Alagille syndrome, and activating mutations in NOTCH2 are associated with Hajdu-Cheney syndrome (HCS). Individuals affected by HCS exhibit osteolysis in distal phalanges and osteoporosis. NOTCH is activated in selected tumors, such as osteosarcoma, and in breast cancer cells that form osteolytic bone metastases. In conclusion, Notch regulates skeletal development and bone remodeling, and gain- or loss-of-function mutations of Notch signaling result in important skeletal diseases.

The Balance Error Scoring System Learned Response Among Young Adults

Abstract: BACKGROUND: Concussion management practices are important for athlete safety. Baseline testing provides a benchmark to which post-injury assessments are compared. Yet few neurophysical concussion assessment studies have examined learned response. The Balance Error Scoring System (BESS) measures postural stability through 6 conditions by counting the errors committed during each condition. In a study examining the performance of high school-aged athletes on the BESS, the learned response extinguished in 3 weeks. However, this phenomenon has not been studied in the college-aged population. HYPOTHESIS: College-aged adults performing the BESS will have a learned response at 1 and 2 weeks but would have no change from baseline at or after 3 weeks, as found previously in high school-aged subjects. STUDY DESIGN: Randomized controlled clinical trial. METHODS: Three groups of college-aged adults ages 18 to 26 years were tested using the BESS at scheduled intervals. Each subject was randomly assigned into 1 of 3 groups to determine learned response at weeks 1, 2, and 4. Changes in pretest and posttest BESS scores were compared using the paired t test for each group at week 4 and other intervals. Differences among groups were compared using analysis of variance for means or the chi-square test for proportions. RESULTS: After 4 weeks, participants exhibited a mean (95% confidence interval) change from pretest baseline of -2.30 (-4.75, 0.16) in the control group (P = 0.065), -3.13 (-4.84, -1.41) in Group 1 (P = 0.001), and -2.57 (-5.28, 0.15) in Group 2 (P = 0.063). There were no statistically significant differences between the 3 groups for week 4 BESS score (P = 0.291) or changes from baseline to week 4 BESS scores (P = 0.868). Overall, participant score changes from baseline to the 4-week follow-up still showed a statistically significant or close to significant reduction across the 3 groups, indicating the learned response did not extinguish after 4 weeks. CONCLUSION: Repeated BESS testing results in a learned effect in college-aged adults did not extinguish after 4 weeks. These results question the ability of the BESS to assess an athlete's balance deficits following a concussion. CLINICAL RELEVANCE: Given learned response did not extinguish in this sample and the BESS has a minimal detectable change/reliable change index of 7 or greater, the effectiveness of the BESS to assess balance may be limited. Language: en

The use of Integra® Dermal Regeneration Template in the reconstruction of traumatic degloving injuries.

Abstract: Traumatic soft tissue, or "degloving" injuries from trauma are common. These injuries are a result of shearing and disrupt tissue planes, such as the junction between muscle and bone. Traditional repair involves debridement followed by skin grafting or flap reconstruction. Many degloving injuries, however, extend to bone or tendon and the decreased vascularity of the wound bed can compromise the success of traditional repairs. Additionally, medical comorbidities make some patients poor candidates for flap reconstruction. The purpose of this study was to evaluate the success of a dermal regeneration template in the treatment of complex traumatic degloving injuries at an American College of Surgeons verified Level 1 Trauma Center. A retrospective review was conducted on all patients sustaining traumatic degloving injuries from January 2009 to July 2010, who were treated with Integra Dermal Regeneration Template followed by split-thickness autografting. Medical records were reviewed and patient demographics, injury characteristics, comorbidities, hospital course, and outcomes were summarized. Ten patients were studied. All had traumatic degloving injuries of an extremity ranging from 50 to 1000 cm. Nine had injuries extending to bone and/or tendon. After debridement, patients underwent placement of Integra followed by a split-thickness skin graft. Of the 10 patients nine had complete take of their grafts with excellent cosmetic and functional results. Degloving injuries are common in trauma. These injuries often extend to tendon and bone, which poses challenges to repair because of decreased vascularity. Placement of a dermal regeneration template followed by a split-thickness autograft is a viable alternative to traditional methods of repair.

Immune alterations and immunotherapy prospects in head and neck cancer.

Abstract: Introduction: Several literature sources have suggested that subjects with head and neck squamous cell carcinoma (HNSCC) display significant abnormalities of immunocompetent cells and cytokine secretion. Serious side effects and only a limited success with traditional therapies in HNSCC dictate the need for newer therapies. Areas covered: This article comprehensively reviews the immune system alterations in HNSCC and the rationale behind various experimental immunotherapies, aiming at keeping this disease under control. Relevant publications were identified through the PubMed database search. The ongoing clinical trials regarding experimental immunotherapy agents in HNSCC were accessed at www.clinicaltrials.gov. The obtained information was thoroughly analyzed and systematized. Expert opinion: Important and severe immune defects including T-cell dysfunction, cytokine alterations and antigen presentation defects are present in patients with HNSCC. In addition, tumor microenvironment was shown to play a cri...

Comparison of manual, digital and lateral CBCT cephalometric analyses

Abstract: Objective: The aim of this study was to compare the reliability of three different methods of cephalometric analysis. Material and Methods: Conventional pretreatment lateral cephalograms and cone beam computed tomography (CBCT) scans from 50 subjects from a radiological clinic were selected in order to test the three methods: manual tracings (MT), digitized lateral cephalograms (DLC), and lateral cephalograms from CBCT (LC-CBCT). The lateral cephalograms were manually analyzed through the Dolphin Imaging 11.0™ software. Twenty measurements were performed under the same conditions, and retraced after a 30-day period. Paired t tests and the Dahlberg formula were used to evaluate the intra-examiner errors. The Pearson's correlation coefficient and one-way analysis of variance (ANOVA) tests were used to compare the differences between the methods. Results: Intra-examiner reliability occurred for all methods for most of the measurements. Only six measurements were different between the methods and an agreement was observed in the analyses among the 3 methods. Conclusions: The results demonstrated that all evaluated methodologies are reliable and valid for scientific research, however, the method used in the lateral cephalograms from the CBCT proved the most reliable.

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania

Abstract: Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naive patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6%) and specificity at 100% (95% CI, 98.9-100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0-6.4%) of patients. This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.

The effect of squat depth on multiarticular muscle activation in collegiate cross-country runners.

Abstract: The squat is a closed-chain lower body exercise commonly performed by many athletes. Muscle activity has been examined during partial and parallel squats in male weightlifters, but not in male and female runners. Therefore, this study measured muscle activity with surface electromyography (EMG) during partial and parallel squats in 20 Division I collegiate cross-country runners (10 males and 10 females) in a randomized crossover design. We hypothesized the parallel squat would increase extensor muscle activitation (i.e. hamstrings and erector spinae). Furthermore, we sought to determine if changes in muscle activity were different between males and females. Participants performed 6 repetitions using their 10 repetition maximum loads for each condition during EMG testing. EMG was performed on the right rectus femoris, biceps femoris, lumbar erector spinae, and lateral head of the gastrocnemius. Rectus femoris activity (0.18 ± 0.01 vs. 0.14 ± 0.01 mV) and erector spinae activity (0.16 ± 0.01 vs. 0.13 ± 0.01 mV) were significantly higher (p 0.05). During preliminary isokinetic testing, both male and female runners demonstrated deficient hamstrings-to-quadriceps ratios, which would not likely improve by performing parallel squats based on our EMG findings. Despite the reduced load of the parallel squat, rectus femoris and erector spinae activity were elevated. Thus, parallel squats may help runners to train muscles vital for uphill running and correct posture, while preventing injury by using lighter weights through a larger range of motion.

Improving specialty care follow-up after an ED visit using a unique referral system.

Abstract: Objective Many patients discharged from the emergency department (ED) require urgent follow-up with specialty providers. We hypothesized that a unique specialty referral mechanism that minimized barriers would increase follow-up compliance over reported and historical benchmarks. Methods Retrospective review of all patients requiring urgent (within 1 month) specialty referrals in 2010 from a safety net hospital ED to dermatology, otolaryngology, neurology, neurosurgery, ophthalmology, urology, plastic surgery, general surgery, or vascular surgery clinics. After specialist input, all patients received a specific follow-up appointment before ED discharge via a specific scheduling service. Necessity for payment at the follow-up visit was waived. Results Of the 1174 receiving referrals, 85.6% of patients scheduled an appointment and 80.1% kept that appointment. After logistic regression analysis, the factors that remained significantly associated ( P 64 years, 93.9%), and mean length of time between ED visit and clinic appointment (kept, 10.5 days; not kept, 14.3 days). The specialty clinic (neurology, 72.8%, to vascular surgery, 100%; P Conclusion A referral process that minimizes barriers can achieve an 80% follow-up compliance rate. Age, insurance, specialty type, and time to appointment are associated with noncompliance.

Notch suppresses nuclear factor of activated T cells (NFAT) transactivation and Nfatc1 expression in chondrocytes.

Abstract: Notch1 to Notch4 transmembrane receptors determine cell fate, and release of the Notch intracellular domain (NICD) in the cytoplasm induces gene expression. Notch regulates endochondral ossification, but it is not clear whether Notch interacts with signals controlling chondrocyte differentiation. Nuclear factor of activated T cells (Nfatc) transcription factors regulate chondrogenesis, and we asked whether Notch modifies Nfat signaling in chondrocytes. Notch was induced in teratocarcinoma ATDC5 chondrogenic cells infected with a retroviral vector, where the cytomegalovirus (CMV) promoter directs NICD expression. NICD suppressed chondrocyte differentiation and inhibited Nfat transactivation and Nfatc1 expression. Notch was activated in chondrocytes from Rosa(Notch) mice, where the Rosa26 promoter is upstream of a loxP-flanked STOP cassette and NICD. To excise the STOP cassette and express NICD, Rosa(Notch) chondrocytes were infected with an adenoviral vector where the CMV promoter directs Cre expression (Ad-CMV-Cre). Notch1 and Notch2 mediate the effects of Notch in skeletal cells, and to inhibit Notch signaling, chondrocytes from mice homozygous for Notch1 and Notch2 alleles targeted with loxP sites were infected with Ad-CMV-Cre. NICD suppressed chondrogenic nodules formation and expression of selected chondrocyte gene markers, induced Col10a1 and Mmp13, and suppressed Nfat transactivation and Nfatc1 expression, whereas inactivation of Notch1 and Notch2 did not affect chondrocyte differentiation. To investigate Nfatc1 function in chondrocytes, Nfatc1 was induced in Rosa(Notch) chondrocytes overexpressing NICD or controls. Nfatc1 suppressed chondrocyte differentiation and opposed Col10a1 induction by Notch. In conclusion, Notch suppresses Nfat transactivation in chondrocytes and Notch and Nfatc1 regulate chondrocyte differentiation.

Implementation of Geriatric Acute Care Best Practices:Initial Results of The NICHE SITE Self -Evaluation

Abstract: Nurses Improving Care of Healthsystem Elders (NICHE) provides hospitals with tools and resources to implement an initiative to improve health outcomes in older adults and their families. Beginning in 2011, members have engaged in a process of program self-evaluation, designed to evaluate internal progress toward developing, sustaining, and disseminating NICHE. This manuscript describes the NICHE Site Self-evaluation and reports the inaugural self-evaluation data in 180 North American hospitals. NICHE members evaluate their program utilizing the following dimensions of a geriatric acute care program: guiding principles, organizational structures, leadership, geriatric staff competence, interdisciplinary resources and processes, patient- and family-centered approaches, environment of care, and quality metrics. The majority of NICHE sites were at the progressive implementation level (n = 100, 55.6%), having implemented interdisciplinary geriatric education and the geriatric resource nurse (GRN) model on at least one unit; 29% have implemented the GRN model on multiple units, including specialty areas. Bed size, teaching status, and Magnet status were not associated with level of implementation, suggesting that NICHE implementation can be successful in a variety of settings and communities.

Hair repigmentation associated with the use of lenalidomide: Graying may not be an irreversible process!

Abstract: We report the first case of progressive hair repigmentation associated with the use of lenalidomide in an elderly patient with multiple myeloma. The influence of lenalidomide on follicular melanogenesis may involve removing the inhibitory influences of some cytokines such as IL-1, IL-6 and TNF-α. In addition, certain endocrine effects of lenalidomide on the hypophyseal-adrenal axis could explain its action on hair pigmentation. We further hypothesize that lenalidomide may be capable of stimulating migration and/or differentiation of melanocytes to promote repigmentation of gray hair follicles. Pending the clarification of how hair repigmentation occurs with lenalidomide, our observation materializes the concept that hair graying may not be an irreversible process, which opens avenues for targeted therapeutics in the fields of cosmetics and anti-aging medicine.

Retrospective review of the use and costs of routine chest x rays in a trauma setting

Abstract: Introduction: Chest x-rays (CXR) are routinely obtained on blunt trauma patients. Many patients also receive additional imaging with thoracic computed tomography scans for other indications. We hypothesized that in hemodynamically normal, awake and alert blunt trauma patients, CXR can be deferred in those who will also receive a TCT with significant cost savings. Methods: We retrospectively reviewed the charts of trauma patients from 1/1/2010 to 12/31/2010 who received both a CXR and TCT in the trauma room. Billing and cost data were collected from various hospital sources. Results: 239 patients who met inclusion and exclusion criteria and received CXR and TCT between 1/1/2010 and 12/31/2010. The sensitivity of CXR was 19% (95% CI: 10.8% to 31%) and the specificity was 91.7% (95% CI: 86.7% to 95%). The false positive rate for CXR was 35.8% (95% CI: 21.7% to 52.8%) and the false negative rate was 24.5% (95% CI: 18.8% to 31.2%). The precision of CXR was 42.3% (95% CI: 25.5% to 61.1%) and the overall accuracy was 74.1% (95% CI: 68.1% to 79.2%). If routine chest xray were eliminated in these patients, the estimated cost savings ranged from $14,641 to $142,185, using three different methods of cost analysis. Conclusions: In patients who are hemodynamically normal and who will be receiving a TCT, deferring a CXR would result in an estimated cost savings up to $142,185. Additionally, TCT is more sensitive and specific than CXR in identifying injuries in patients who have sustained blunt trauma to the thorax.

Optimism, Coping, and Posttraumatic Stress Severity in Women in the Childbearing Year.

Abstract: PTSD symptoms in pregnancy may cause adverse effects on both mother and infant child. Identifying and addressing PTSD in pregnancy may help to alleviate the impact of PTSD on pregnancy. Optimism has been examined as a protective factor in the development of PTSD; however no study to date has looked at the relationship between optimism and PTSD in pregnant women. The current study examined the role of optimism on PTSD symptom severity, coping and somatization among women in the childbearing year. We examined data from 1581 completed interviews with nulliparous, pregnant women from the first wave telephone interview conducted as part of a longitudinal outcomes study, “Psychobiology of PTSD & Adverse Outcomes of Childbearing” (NIH NR008767; common name “the STACY project”). Four trauma exposure group cohorts (PTSD-positive, trauma-positive, non-exposed, and partial PTSD) were differentiated and two coping variables (active and avoidant) were examined. The relationships between demographics, trauma exposure groups, optimism and PTSD were examined. In addition, we examined the impact of these factors on coping and somatization. In general, the PTSD-positive group reported significantly less optimism than the trauma-positive and non-exposed groups. SES and number of reported traumas contributed to PTSD severity, as well as optimism. For those women reporting more optimism, they reported more use of active coping, less engagement in avoidant coping, and less somatization.

Glycemic Variability in Hospitalized Patients: Choosing Metrics While Awaiting the Evidence

Abstract: Hyperglycemia, hypoglycemia, preexisting diabetes, and glycemic variability each may affect hospital outcomes. Observational findings derived from randomized trials or retrospective studies suggest that independent of hypoglycemia and hyperglycemia, a relationship exists between variability and hospital outcomes. A review of studies conducted in diverse hospital populations is reported here, showing a relationship between measures of variability and nonglycemic outcomes, including ICU and hospital mortality and length of stay. “Glycemic variability” has an intuitive meaning, understood as a propensity of a single patient to develop repeated episodes of excursions of BG over a relatively short period of time that exceed the amplitude expected in normal physiology. It is proposed that each of 3 dimensions of variability should be separately studied: (1) magnitude of glycemic excursions during intervals of relative stability of the moving average of BG, (2) frequency with which a critical magnitude of excursion is exceeded, and (3) presence or absence of fine tuning. Multiple hospital studies have found that the standard deviation (SD) of the data set of blood glucose values (BG) of individual patients predicts outcomes. An appropriate refinement would be to report the “Reverse-transformed group mean of the SD of the logarithmically transformed BG data set of each patient,” with confidence intervals. In logarithmic space, group means of the SD of BGs of each patient may be compared, using an appropriate parametric test. Upon reverse transformation, the upper and lower bounds of the confidence intervals become asymmetric about the reverse-transformed group mean of the SD. There is a need to understand what patterns of dispersion of BG over time are captured by SD as a predictor of outcomes. Among the causes of high SD, a subgroup may consist of patients having frequent oscillations of BG. Another subgroup may consist of patients experiencing a major change of overall glycemia during the timeframe of data collection. Appropriate metrics should be developed to recognize both variability in the sense of recurrent large oscillations of BG, and separately to recognize any time-dependent change of overall glycemia during hospitalization. Especially in relation to uncontrolled diabetes, there is a need to know whether rapid correction of chronic hyperglycemia adversely affects hospital outcomes. We have some understanding of how to control or prevent change of overall glycemia, and less understanding of how to control variability. Each may be associated with outcomes, and each may be detected by a high SD, but it remains uncertain whether intervention to prevent either pattern of changing glycemia would affect outcomes.

Immune alterations in malignant melanoma and current immunotherapy concepts

Abstract: Introduction: Malignant melanoma is a highly aggressive, immunogenic tumor that has the ability to modulate the immune system to its own advantage. Patients with melanoma present numerous cellular immune defects and cytokine abnormalities, all leading to suppression of the host anti-tumor immune response. Innovative treatment strategies can be achieved through employing our knowledge of the melanoma-induced immune alterations. Areas covered: The authors review comprehensively the immune abnormalities in individuals with melanoma, and provide a summary of currently available melanoma immunotherapy agents that are currently on the market or undergoing clinical trials. Expert opinion: Ipilimumab, a monoclonal antibody directed against the CTLA-4, is one of the current forefront treatment strategies in malignant melanoma. Novel immunomodulating agents have shown clear activity in patients with malignant melanoma. These include anti-PD-1 and anti-PD-1 ligand antibodies that may soon become important items in t...

Plasmablastic haemato-lymphoid neoplasm with a complex genetic signature of Burkitt lymphoma responding to bortezomib.

Abstract: Plasmablastic lymphoma shares many morphologic features with plasmablastic plasma cell myeloma. The activation of MYC oncogene in these lymphomas may be an important pathogenetic element associated with Epstein-Barr virus infection. We describe herein an elderly man with a plasmablastic lymphoid neoplasm displaying unique morphologic, cytogenetic and clinical features. This case might offer additional insights to the complex but fascinating topic of hybrid haemato-lymphoid neoplasms such as plasmablastic lymphoma-myeloma. In addition, the patient responded to the treatment with bortezomib. Newer antimyeloma agents such as bortezomib have shown promise in the treatment of these neoplasms and should further be explored for their therapy.

Intrinsic immune alterations in renal cell carcinoma and emerging immunotherapeutic approaches.

Abstract: Introduction: Individuals affected by kidney cancer present a variety of immune abnormalities including cellular immune dysfunction, cytokine alterations and antigen presentation defects On the other hand, spontaneous remissions are seen in up to 4% of renal cell carcinoma (RCC) patients and they are thought to occur via immune mechanisms Areas covered: The authors comprehensively review the immune abnormalities in RCC patient and describe the kidney cancer immunotherapy candidates that are most advanced in their clinical development Most relevant publications were identified through searching the PubMed database; the obtained information was thoroughly analyzed and synthesized Expert opinion: As cure in advanced RCC cannot be accomplished with the current therapy standards such as tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, new treatment strategies are being sought Enhancing the immune system represents an appealing avenue for kidney cancer therapy Disappointingly, high