Impact of comorbidities by ACE‐27 in the revised‐IPSS for patients with myelodysplastic syndromes

Comorbidities significantly affect the prognosis and outcomes of patients with hematological malignancies. We have previously reported the impact of comorbidities on the International Prognostic Scoring System (IPSS) score. The aim of this study was to determine whether comorbidities continued to have a significant impact when patients were reclassified according to the Revised‐IPSS (IPSS‐R). The medical records of 600 consecutive myelodysplastic syndrome patients who presented to MD Anderson Cancer Center between January 2002 and June 2004 were reviewed. The Adult Comorbidity Evaluation‐27 (ACE‐27) was used to assess the severity of comorbid conditions. Four hundred and two (67%) patients were male. Median age at presentation was 66.6 years (17–94). Mean duration of follow‐up was 54 months (1–100). Five hundred and two (84%) patients died, and 54 (9%) patients underwent stem cell transplantation. Overall median survival was 16.8 months (1–100). Median survival by IPSS‐R was 47, 34, 21, 16, and 6 months for patients in very low, low, intermediate, high, and very high‐risk groups, respectively (P < 0.001). The ACE‐27 comorbidity score significantly impacted the median survival of patients in the intermediate (P < 0.001), high (P = 0.045), and very high (P = 0.004) IPSS‐R groups; but did not significantly impact the median survival in the low (P = 0.11) and very low (P = 0.49) IPSS‐R groups. The ACE‐27 comorbidity score significantly impacted the median survival of patients ≤65 years (P < 0.001) but did not significantly impact those >65 years (P = 0.18). Assessment of comorbidity may enhance the prognostic ability of the IPSS‐R. Am. J. Hematol. 89:509–516, 2014. © 2014 Wiley Periodicals, Inc.     

The clinical impact of time to response in de novo accelerated-phase chronic myeloid leukemia

We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated-phase chronic myeloid leukemia (CML-AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 10⁹/L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty-three patients received imatinib; 42 received a second-generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib). We used chi-square and Kaplan-Meier analyses to determine the impact of various degrees of molecular and cytogenetic response at early time points (3 and 6 months) on rates of overall cytogenetic and molecular response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS). After a median follow-up of 96 months (range: 18-224 months), the overall rate of complete cytogenetic response was 79%, of major molecular response, 71%, and of molecular reponse (MR)4.5, 59%. Patients who achieved a major cytogenetic response (MCyR) (n = 49) at 3 months had significantly better 3-year OS (94% vs 75%; P = .002), TFS (98% vs 73%; P < .001), EFS (93% vs 42%; P < .001), and FFS (83% vs 25%; P < .001) rates than patients who did not have MCyR at 3 months. Most (67%) who eventually achieved sustained MR4.5 had achieved MCyR at 3 months. In de novo CML-AP, early response at 3 and 6 months is a strong determinant of long-term outcome.     

Mental stress experienced by first-year residents and expert surgeons with robotic and laparoscopic surgery interfaces

Prior research has indicated that novices experienced a beneficial stress profile in the robotic surgery (da Vinci) training environment when compared to the laparoscopic surgery training environment. The objective of this study was to assess whether this finding generalizes to expert surgeons. Towards that end, first-year residents’ and attending surgeons’ performances and subjective stress experiences were assessed in a surgical training task that was performed with the da Vinci and laparoscopic surgery interfaces. This study indicated that both groups exhibited superior performance and lower stress with the da Vinci surgical system than the laparoscopic system. The results provide further support for the sensitivity of the Dundee Stress State Questionnaire in identifying different stress responses experienced by trainees and experts in the minimally invasive surgery environment.     

State Indoor Tanning Laws and Adolescent Indoor Tanning

Objectives. Recently, several state indoor tanning laws, including age restrictions, were promulgated to reduce indoor tanning among minors. We examined the effects of these laws on adolescent indoor tanning.Methods. We used nationally representative data from the 2009 and 2011 national Youth Risk Behavior Surveys (n = 31 835). Using multivariable logistic regression, we examined the association between state indoor tanning laws and indoor tanning among US high school students.Results. Female students in states with indoor tanning laws were less likely to engage in indoor tanning than those in states without any laws. We observed a stronger association among female students in states with systems access, parental permission, and age restriction laws than among those in states without any laws. We found no significant association among female students in states with only systems access and parental permission laws or among male students.Conclusions. Indoor tanning laws, particularly those including age restrictions, may be effective in reducing indoor tanning among female high school students, for whom rates are the highest. Such reductions have the potential to reduce the health and economic burden of skin cancer.Skin cancer is the most common cancer in the United States. Approximately 3.5 million cases of nonmelanoma skin cancers are treated annually, while more than 60 000 melanomas are diagnosed annually.1,2 In addition, skin cancer poses a substantial economic burden, with annual direct medical costs of treatment estimated at $1.7 billion in 2004.3 During the past decade, while most cancers decreased, melanoma increased, especially among young adult women.4 Indoor tanning is thought to be partially responsible for this increase.4–6 Indoor tanning before age 35 years increases the risk of melanoma by 59%,5,7 and indoor tanning before age 25 years increases the risk of basal cell carcinoma by 40% and squamous cell carcinoma by 102%.8 Despite these known health risks, indoor tanning is common among adolescents—6.2% of male high school students and 20.9% of female high school students engaged in indoor tanning in 2011.9In recent years, several states have enacted laws restricting youth access to indoor tanning and laws aimed at reducing consumers’ risk, including facility and operator responsibilities, safety and equipment standards, enforcement authority, and penalties.10 Previous studies that were primarily focused on youth access laws found poor compliance rates among tanning facilities for parental permission laws.11–13 In addition, such laws were ineffective in reducing indoor tanning among adolescents.14,15 Since these earlier studies were conducted, the number of states implementing youth access laws, particularly age restrictions, has increased substantially.16 Although some evidence has suggested that age restrictions may reduce access to indoor tanning among minors,17 no national or international studies have examined the effects these laws have on adolescent indoor tanning behavior. We examined the association between state indoor tanning laws, including age restrictions, and indoor tanning among high school students.     

Profile patterns,consistency, and change in the millon clinical multiaxial inventory-II in cocaine abusers

This study examined the MCMI-II in samples of cocaine-dependent subjects who were receiving treatment in three separate residential facilities. Profile characteristics, patterns of scale stability, and change are reported. MCMI-II elevations are found in all three samples on the Antisocial, Aggressive/Sadistic, Narcissistic, Passive-Aggressive, Borderline, Drug Dependence, and Alcohol Dependence scales at both intake into treatment and discharge. Moderate stability coefficients are found on Basic Personality, Pathological Personality, and Symptom scales. Although some statistically significant mean scale changes between intake and discharge are noted in each sample, few involve change from clinically elevated to below clinical levels. © 1996 John Wiley & Sons, Inc.     

Stimulation of ras GTPase activity by an anti-ras monoclonal antibody

Wild-type ras has GTPase activity, and this activity is accelerated substantially by GTPase-activating proteins (GAPs). Oncogenic ras species have an abnormally low intrinsic GTPase activity, and this activity is insensitive to GAPs. We confirmed that the anti-ras monoclonal antibody Y13-238 inhibited GAP activity in vitro, but we also noted that this antibody had GAP activity of its own. We studied the GAP activity of Y13-238 in circumstances in which ras GTPase activity was influenced by the GTPase-inhibitory antibody Y13-259 or by substitutions in ras. The GTPase-inhibitory antibody Y13-259 blocked the GAP associated with Y13-238. A ras species with a substitution in the effector loop that blocked conventional GAP activity was sensitive to stimulation by Y13-238. Both Y13-238 and Y13-259 stimulated the autophosphorylation of Ala59Thr ras. We interpreted these data in terms of a model in which the extrinsic factors influence the ras GTPase reaction by affecting the balance between “committed” and “uncommitted” states. We suggest that there is a mechanism distinct from that exploited by conventional GAPs for stimulating ras GTPase activity. © 1996 Wiley-Liss, Inc.     

Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Study Design and Rationale

Neurocritical Care - As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological...