Long-term outcome and complications of children born with meningomyelocele

The long-term functional outcome of 101 children born with meningomyelocele between 1971 and 1981 was assessed, by a combination of retrospective chart review and follow-up assessments. The children had been managed at birth using a process ofnonstandardized selection. Eighty-three of the 101 patients survived after a minimum follow-up of 8.6 years, for a mortality rate of 18%. Forty-four of 83 children (53%) were community ambulators, and this correlated well with the presence of intact quadriceps function. Forty-eight children (58%) attended normal school and were grade-appropriate. Sixty-two of 83 patients (75%) were socially continent of urine, and 71/83 (86%) were socially continent of stool. Hydrocephalus was present in 93 of the 101 children in the study, and 85 children were shunted. Half of the shunted children required a shunt revision in the first year of life, and thereafter the rate of revision decreased, so that after 2 years the risk of revision was approximately 10% per year.     

Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.

PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application.     

Pain after pacemaker/ICD implants

A retrospective study of 322 patient experiences of post-operative pain, short term and long term, following a cardiac implantable electronic device (CIED) procedure. Pain from pacemaker and ICD (implantable cardioverter-defibrillator) implant surgery remains a problem both in terms of severity and longevity. There is a subset of patients receiving implants that have severe pain that may be of a long duration. Patient advice needs to be appropriate to these findings.This study illustrates a need for better pain management by physicians, support, and realistic communication with their patients.Key words: cardiac implantable electronic device (CIED), communication, implantable cardioverter-defibrillator (ICD), pacemaker, pain measurement     

Hypoxia drives transient site-specific copy gain and drug-resistant gene expression

Copy number heterogeneity is a prominent feature within tumors. The molecular basis for this heterogeneity remains poorly characterized. Here, we demonstrate that hypoxia induces transient site-specific copy gains (TSSGs) in primary, nontransformed, and transformed human cells. Hypoxia-driven copy gains are not dependent on HIF1α or HIF2α; however, they are dependent on the KDM4A histone demethylase and are blocked by inhibition of KDM4A with a small molecule or the natural metabolite succinate. Furthermore, this response is conserved at a syntenic region in zebrafish cells. Regions with site-specific copy gain are also enriched for amplifications in hypoxic primary tumors. These tumors exhibited amplification and overexpression of the drug resistance gene CKS1B, which we recapitulated in hypoxic breast cancer cells. Our results demonstrate that hypoxia provides a biological stimulus to create transient site-specific copy alterations that could result in heterogeneity within tumors and cell populations. These findings have major implications in our understanding of copy number heterogeneity and the emergence of drug resistance genes in cancer.     

Physical activity correlates in people living with HIV/AIDS: a systematic review of 45 studies

Purpose: Understanding barriers and facilitators of physical activity participation in persons living with HIV/AIDS is an essential first step in order to devise effective interventions. The present review provides a systematic quantitative review of the physical activity correlates in people with HIV/AIDS.

Methods: Major electronic databases were searched till August 2016. Keywords included “physical activity” or “exercise” or “sports” and “AIDS” or “HIV”.

Results: Out of 55 correlates from 45 studies (N?=?13,167; mean age range?=?30.5–58.3?years; 63.2% male) five consistent (i.e., reported in four or more studies) correlates were identified. Lower levels of physical activity were consistently associated with older age (6/10 studies), a lower educational level (6/7), a lower number of CD4 cells/μl (7/11), exposure to antiviral therapy (4/6), and the presence of lipodystrophy (4/4). Other important barriers were the presence of bodily pain (2/2), depression (3/3), and opportunistic infections (3/4). Facilitators were a higher cardiorespiratory fitness level (3/3), a higher self-efficacy (2/2), more perceived benefits (2/2), and a better health motivation (3/3).

Conclusions: The current review has elucidated that participation in physical activity by people with HIV/AIDS is associated with a range of complex factors which should be considered in rehabilitation programs.

• Implications for Rehabilitation

• Health care professionals should consider HIV-related bodily pain and feelings of depression when assisting people living with HIV in inititiating and maintaining an active lifestyle.

• Interventions to improve self-efficacy and motivation, and to help people living with HIV in understanding the benefits of exercise, may encourage greater participation.

     

The short-term effects of high-dose testosterone on sleep,breathing, and function in older men

Androgen therapy may precipitate obstructive sleep apnea in men. Despite increasing androgen use in older men, few studies have examined sleep and breathing. Randomized, double-blind, placebo-controlled studies examining effects of testosterone simultaneously on sleep, breathing, and function in older men are not available. Seventeen community-dwelling healthy men over the age of 60 yr were randomized to receive three injections of im testosterone esters at weekly intervals (500 mg, 250 mg, and 250 mg) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout. Polysomnography, anthropometry, and physical, mental, and metabolic function were assessed at baseline and after each treatment period. Testosterone treatment reduced total time slept ( approximately 1 h), increased the duration of hypoxemia ( approximately 5 min/night), and disrupted breathing during sleep (total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour) (all P < 0.05). Despite expected effects on body composition (increase in total and lean mass, reduction in fat mass, P < 0.05, bioimpedance method), upper airway dimensions did not change (acoustic reflectometry). Driving ability (computer simulation), physical activity (accelerometry, Physical Activity Scale in the Elderly), quality of life (SF36, Functional Outcomes of Sleep Questionnaire), mood (Profile of Mood States Questionnaire), sleepiness (Epworth, Stanford scales), and insulin resistance (homeostasis model) also were not changed by treatment. Short-term administration of high-dose testosterone shortens sleep and worsens sleep apnea in older men but did not alter physical, mental, or metabolic function. These changes did not appear to be due to upper airway narrowing. Further study of longer-term lower-dose androgen therapy on sleep and breathing is needed to evaluate its safety in older men.     

Joint Trauma System,Defense Committee on Trauma,and Armed Services Blood Program consensus statement on whole blood

Hemorrhage is the most common mechanism of death in battlefield casualties with potentially survivable injuries. There is evidence that early blood product transfusion saves lives among combat casualties. When compared to component therapy, fresh whole blood transfusion improves outcomes in military settings. Cold-stored whole blood also improves outcomes in trauma patients. Whole blood has the advantage of providing red cells, plasma, and platelets together in a single unit, which simplifies and speeds the process of resuscitation, particularly in austere environments. The Joint Trauma System, the Defense Committee on Trauma, and the Armed Services Blood Program endorse the following: (1) whole blood should be used to treat hemorrhagic shock; (2) low-titer group O whole blood is the resuscitation product of choice for the treatment of hemorrhagic shock for all casualties at all roles of care; (3) whole blood should be available within 30 min of casualty wounding, on all medical evacuation platforms, and at all resuscitation and surgical team locations; (4) when whole blood is not available, component therapy should be available within 30 min of casualty wounding; (5) all prehospital medical providers should be trained and logistically supported to screen donors, collect fresh whole blood from designated donors, transfuse blood products, recognize and treat transfusion reactions, and complete the minimum documentation requirements; (6) all deploying military personnel should undergo walking blood bank prescreen laboratory testing for transfusion transmitted disease immediately prior to deployment. Those who are blood group O should undergo anti-A/anti-B antibody titer testing.