Health Effects Reported by Adolescent Water Pipe and/or Cigarette Smokers Compared to Nonsmokers

Purpose

The purpose of this study was to determine the prevalence of respiratory and/or physical fitness health problems in adolescent (ages 18–21) water pipe (WP) smokers (with or without cigarette smoking), cigarette-only smokers, and nonsmokers.

Precision Surgical Therapy for Adenocarcinoma of the Esophagus and Esophagogastric Junction

IntroductionTo facilitate the initial clinical decision regarding whether to use esophagectomy alone or neoadjuvant therapy in surgical care for individual patients with adenocarcinoma of the esophagus and esophagogastric junction—information not available from randomized trials—a machine-learning analysis was performed using worldwide real-world data on patients undergoing different therapies for this rare adenocarcinoma.MethodsUsing random forest technology in a sequential analysis, we (1) identified eligibility for each of four therapies among 13,365 patients: esophagectomy alone (n = 6649), neoadjuvant therapy (n = 4706), esophagectomy and adjuvant therapy (n = 998), and neoadjuvant and adjuvant therapy (n = 1022); (2) performed survival analyses incorporating interactions of patient and cancer characteristics with therapy; (3) determined optimal therapy as that predicted to maximize lifetime within 10 years (restricted mean survival time; RMST) for each patient; and (4) compared lifetime gained from optimal versus actual therapies.ResultsActual therapy was optimal in 61% of those receiving esophagectomy alone; neoadjuvant therapy was optimal for 36% receiving neoadjuvant therapy. Many patients were predicted to benefit from postoperative adjuvant therapy. Total RMST for actual therapy received was 58,825 years. Had patients received optimal therapy, total RMST was predicted to be 62,982 years, a 7% gain.ConclusionsAverage treatment effect for adenocarcinoma of the esophagus yields only crude evidence-based therapy guidelines. However, patient response to therapy is widely variable, and survival after data-driven predicted optimal therapy often differs from actual therapy received. Therapy must address an individual patient’s cancer and clinical characteristics to provide precision surgical therapy for adenocarcinoma of the esophagus and esophagogastric junction.     

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4⁺ and CD8⁺ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.     

Nerve dysfunction leads to muscle morphological abnormalities in chronic inflammatory demyelinating polyneuropathy assessed by MRI

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age-matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413–420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77–84, 2019. © 2019 Wiley Periodicals, Inc.     

A brief fall prevention intervention for manual wheelchair users with spinal cord injuries: A pilot study

Objective: To conduct a pilot study of an intervention to decrease fall incidence and concerns about falling among individuals living with Spinal Cord Injury who use manual wheelchairs full-time.

Design: Pre/post. After a baseline assessment, a structured intervention was implemented. The assessment protocol was repeated 12 weeks after the baseline assessment.

Setting: Research laboratory and community.

Participants: 18 individuals living with SCI who use a manual wheelchair full-time with an average age of 35.78?±?13.89 years, lived with SCI for 17.06?±?14.6 years; 61.1% were female.

Intervention: A 1:1, 45 minute, in-person intervention focused on factors associated with falls and concerns about falling: transfers skills and seated postural control.

Outcome measures: Participants reported fall incidence and completed the Spinal Cord Injury Fall Concerns Scale, Community Participation Indicators and the World Health Organization Quality of Life – short version (WHOQOL-BREF). Transfer quality was assessed with the Transfer Assessment Instrument (TAI) and seated postural control with the Function In Seating Test (FIST).

Results: Recruitment, assessment and delivery of the intervention were successfully completed. After exposure to the intervention, fall incidence significantly decreased, (P?=?0.047, d_{z ?}=?0.507) and FIST scores improved (P?=?0.035, d_z? =?0.54). Significant improvements were also found in the WHOQOL-BREF Physical (P?=?0.05, d_{z ?}=?1.566) and Psychological (P?=?0.040, d_{z ?}=?0.760) domains.

Conclusion: The feasibility of the structured intervention was established and the intervention has the potential to reduce fall incidence and improve quality of life among individuals living with SCI who use a wheelchair. Appropriately powered randomized controlled trials of the program are warranted.