Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma

Purpose: To determine the feasibility of using radiofrequency hyperthermia (RFH) and to enhance the therapeutic effect of herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) for the treatment of hepatocellular carcinoma (HCC).

Materials and methods: Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For both in vitro confirmation and in vivo validation, luciferase-labeled HCC cells and HCC tumour xenografts on mice received different treatments: (i) combination therapy of intratumoral HSV-TK/GCV-mediated gene therapy plus magnetic resonance imaging heating guidewire (MRIHG)-mediated RFH; (ii) gene therapy only; (iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control. Cell proliferation was quantified. Tumour changes were monitored by ultrasound imaging and bioluminescence optical imaging before and at days 7 and 14 after treatments, which were correlated with subsequent histology.

Results: In vitro, the lowest cell proliferation was seen in the combination therapy group compared with control groups (29?±?6% vs. 56?±?9%, 93?±?4%, and 100?±?5%, p?p?p?Conclusion: RFH can enhance HSV-TK/GCV-mediated gene therapy of HepG2 cell line and mice human HCC xenografts, which may open new avenues for effective management of HCC using MR/RFH integrated interventional gene therapy.     

The genetics of platelet count and volume in humans

The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical capacities has enabled the genetic investigation of human traits and disease in thousands to now millions of participants. Investigators have taken advantage of these advancements to gain insight into platelet biology and the platelet’s role in human disease. To do so, large human genetics studies have examined the association of genetic variation with two quantitative traits measured in many population and patient based cohorts: platelet count (PLT) and mean platelet volume (MPV). This article will review the many human genetic strategies—ranging from genome-wide association study (GWAS), Exomechip, whole exome sequencing (WES), to whole genome sequencing (WGS)—employed to identify genes and variants that contribute to platelet traits. Additionally, we will discuss how these investigations have examined and interpreted the functional implications of these newly identified genetic factors and whether they also impart risk to human disease. The depth and size of genetic, phenotypic, and other -omic data are primed to continue their growth in the coming years and provide unprecedented opportunities to gain critical insights into platelet biology and how platelets contribute to disease.     

Re-emergence of Posttraumatic Stress Disorder Nightmares With Nursing Home Admission: Treatment With Prazosin

Seniors with a history of emotional trauma decades earlier can experience a recurrence of posttraumatic stress disorder symptoms when transitioning to a nursing home. We present the case of an 86-year-old male Holocaust survivor admitted to a nursing home for physical therapy and rehabilitation 6 weeks after the death of his wife; the patient was expressing a persistent death wish. Despite the multiple risk factors for depression, his distress was specifically related to the reemergence of nightly posttraumatic nightmares. Over the course of 1 week of treatment with 1 mg prazosin at bedtime, his nightmares and his death wish completely resolved. He achieved his rehabilitation goals and was discharged to a community setting. This report highlights the importance of considering posttraumatic stress disorder in nursing home residents with a history of emotional trauma, and understanding how to address these symptoms pharmacologically and nonpharmacologically.     

Development and standardization of single and double dichotic digit tests in the Malay language

Single and double dichotic digit tests in Malay language were developed and standardized as an initial attempt to incorporate tests of auditory processing within the scope of audiology practice in Malaysia. Normative data under free recall, directed right-ear first, and directed left-ear first listening conditions were determined using 120 Malay children between the ages of 6 and 11 years old with normal hearing and normal academic performance. Test-retest reliability was assessed in 15 of the study subjects. In general, the double dichotic digit test produced greater differences in scores between age groups, and a greater right-ear advantage than the single dichotic digit test. In addition, the double dichotic digit test also had higher test-retest reliability. These findings suggest the double dichotic digit test is more clinically applicable.     

Repercussions of occult malignancy – An etiologic basis for rheumatic disease

Paraneoplastic syndromes and infection are known causes of autoimmunity, but the etiology of most autoimmune syndromes remains unknown. If the immune system can effectively fight malignant cell lines, it is likely that many potential tumors are controlled before becoming clinically apparent. This phenomenon is a potential explanation for all non-infectious auto-immunity including many rheumatic diseases. The presented discussion argues that all auto-immune disease is secondary to infection or neoplasia, and occult neoplasia is responsible for rheumatic diseases. Detecting occult neoplasia is inherently not possible, but if this theory bears truth, induced autoimmune disease could become a powerful treatment of malignancy.     

Applications of the transfibular approach to the hindfoot: A systematic review and description of a preferred technique

BackgroundThe indications and technique for the transfibular approach to the tibiotalar joint have evolved since its initial popularization in 1942. The purpose of this systematic review is to assess the indications, techniques, and postoperative outcomes among procedures performed with the transfibular approach.MethodsA comprehensive search of PubMed, Medline, and Embase databases from 1942 to 2018 was performed in accordance with PRISMA guidelines. After an initial broad search of transfibular approach indications, articles were stratified into 4 major surgical categories for assessment: (1) tibiotalar arthrodesis (2) tibiotalocalcaneal arthrodesis (3) total ankle replacement and (4) distal tibial tumor excision. Data was analyzed according to these 4 categories.ResultsA total of 32 studies (874 ankles) were included. Fibular non-union rates were 0.7 % (5 of 672) across all studies, 0.6% (2 of 329) for tibiotalar arthrodesis, 0.0% (0 of 12) for tibiotalocalcaneal arthrodesis, 1.0 % (3 of 296) for total ankle arthroplasty and 0.0% (0 of 15) for other procedures. Rates of deep infection were 2.5% (23 of 903) across all studies, 3.2% (15 of 466) for tibiotalar arthrodesis, 3.7% (4 of 106) for tibiotalocalcaneal arthrodesis, 1.3% (4 of 296) for total ankle arthroplasty, and 0.0% (0 of 15) for other procedures.ConclusionsThe transfibular approach is useful for cases requiring extensile exposure of the tibiotalar joint. This study provides evidence that the transfibular approach yields satisfactory results, with low complication and infection rates.Level of evidenceIV     

Abnormal Agitated Saline Study Results after Tetralogy of Fallot Repair

Residual intracardiac or extracardiac shunting is frequently seen in patients with repaired congenital heart disease and can cause systemic hypoxemia. We present the case of an adult with tetralogy of Fallot who underwent two corrective surgical procedures as a child with subsequent pulmonary valve replacement due to residual pulmonary insufficiency. Further details of her operative history were otherwise unknown. After being lost to follow‐up for many years, she presented with unexplained cyanosis and a markedly abnormal agitated saline study on transthoracic echocardiography in which only the left heart filled after contrast administration. We review the differential diagnosis for such a presentation and discuss the utility of cardiac magnetic resonance imaging (MRI) to define the etiology. Cardiac MRI, a frequently used imaging modality to longitudinally assess adult patients with congenital heart disease, provides excellent image quality of cardiac structures and the ability to perform angiography in a variety of imaging planes. These advantages render cardiac MRI, a useful modality to determine the etiology of unexplained cyanosis in these patients as both intracardiac and extracardiac shunts can be detected.     

Personality disorders at the interface of psychiatry and the law: legal use and clinical classification

Personality disorders have a complex relationship with the law that in many ways reflects their complexity within the clinical and research communities. This paper addresses expert testimony about personality disorders, outlines how personality disorders are assessed in forensic cases, and describes how personality disorders are viewed in different legal contexts. Reasons are identified why personality disorders are not generally accepted as significant mental illness within the legal system, including high incidence of personality dysfunction in criminal populations, frequent comorbidity of personality disorders making it difficult to determine direct causation, and difficulty determining where on a continuum personality traits should be defined as illness (or not). In summary, the legal system, to a significant degree, mirrors the clinical conception of personality disorders as not severe mental diseases or defects, not likely to change, and most often, under volitional control.