Therapeutic Intent Research Articles

"We Copy to Join in, to Not Be Lonely": Adolescents in Special Education Reflect on Using Dramatic Imitation in Group Dramatherapy to Enhance Relational Connection and Belonging.

This paper focuses on doctoral research which explored relationships and interpersonal learning through group dramatherapy and creative interviewing with adolescents in special education. A constructivist grounded theory study, positioning adolescents with intellectual/developmental disabilities as experts of their own relational experiences, revealed a tendency to “copy others.” The final grounded theory presented “copying” as a tool which participants consciously employed “to play with,” “learn from,” and “join in with” others. Commonly experiencing social ostracism, participants reflected awareness of their tendency to “copy others” being underpinned by a need to belong. Belonging was therefore expressed as the ultimate therapeutic experience participants wished to have. Participant responses which link dramatic imitation to a self-identified tendency “to copy,” are discussed with regard to how imitation provides an accessible point of dramatic entry from which adolescents in special education begin to explore new ways of being and inter-relating. Recommendations for how dramatherapists might centralize imitative aspects of the dramatic process to achieve therapeutic intent when working alongside adolescents in special education are discussed with specific focus on creating a space of belonging.Note on type: Participant quotes extracted from the data are included throughout this article. In order to highlight participant’s contributions quotes are italicized and presented within speech marks.

Safety and efficacy of magnetic seed localisation of non-palpable breast lesions: pilot study in a Chinese population

INTRODUCTION A magnetic seed marker system (Magseed, Endomagnetics, Cambridge, United Kingdom) is used as a localisation method for non-palpable breast lesions in the United States, Europe, and Hong Kong. It overcomes many limitations of conventional techniques and allows scheduling flexibility. We sought to evaluate its efficacy and safety in the Chinese population. METHODS We retrospectively reviewed all Chinese women who underwent magnetic seed marker-guided breast lesion excision from June 2019 to February 2020 at a single institution. Placement success (final target-to-seed distance <10 mm) was evaluated by imaging on the day of surgery. Specimen radiographs and pathology reports were reviewed for magnetic seed markers and target removal. Margin clearance and re-excision rates were analysed. RESULTS Twenty two magnetic seed markers were placed in 21 patients under sonographic or stereotactic guidance to localise 21 target lesions. One target lesion required two magnetic seed markers for bracketing. There was no migration of nine markers placed 6 to 56 days before the day of surgery. Placement success was achieved in 20 (90.9%) cases. Mean final target-to-seed distance was 3.1 mm. Two out of 21 (9.5%) lesions required alternative localisation due to marker migration ≥10 mm, while 19 (90.5%) lesions underwent successful magnetic seed marker-guided excision. Three of these 19 lesions (15.8%) were excised with therapeutic intent, one of which (33%) required re-excision due to a close margin. All 22 magnetic seed markers were successfully removed. No complications were reported. CONCLUSION Magnetic seed markers demonstrated safety and efficacy in Chinese women for breast lesion localisation and excision.

Outcome of Endoscopic Retrograde Cholangio-Pancreatography at Nobel Medical College Teaching Hospital: A Single Centre Experience

Background: Endoscopic retrograde cholangiopancreatography is a technically demanding endoscopic procedure for both diagnostic and therapeutic purpose in treating various pancreaticobiliary diseases. This service is very limited in tertiary care center of our country Nepal mostly limited to Kathmandu valley and Dhulikhel hospital.&#x0D; Materials and Methods: This is a descriptive cross-sectional study patients who underwent ERCP with therapeutic intent in Nobel Medical College Teaching Hospital, Biratnagar from April 2019 to April 2020. Total 148 patients were included in this study for analysis.&#x0D; Results: The most common finding was choledocholithiasis in 132(89.2%) patients. Benign biliary stricture was found in 7 (4.7%). Biliary obstruction due to periampullary growth was found in 7 (4.7%) patients. Bile duct injury was found in 1(0.7%) and chronic pancreatitis in 1 (0.7%) patient. The therapeutic success of ERCP was for choledocholithiasis, Stone Clearance in 1st attempt 68.9%, in multiple attempts18.2%, failed stone extraction in 3 cases (2.0%) only biliary stenting was done in 15 (10.3%) patients of various biliary disease for therapeutic and palliative reason. Pancreatic stenting was done in1 (0.7%) patient. The most common complication was Acute Pancreatitis in 6(4.1%), Post-Sphincterotomy bleeding in 1 (0.7%), biliary septic shock in 1 (0.7%) and 1 death (0.7%).&#x0D; Conclusion: ERCP can be continued in Nobel Medical College Teaching Hospital as it has lots of benefits with minimal acceptable complications.

Triheptanoin Mitigates Brain ATP Depletion and Mitochondrial Dysfunction in a Mouse Model of Alzheimer's Disease.

Brain energy failure is an early pathological event associated with synaptic dysfunction in Alzheimer's disease (AD). Thus, mitigation or enhancement of brain energy metabolism may offer a therapeutic avenue. However, there is uncertainty as to what metabolic process(es) may be more appropriate to support or augment since metabolism is a multiform process such that each of the various metabolic precursors available is utilized via a specific metabolic pathway. In the brain, these pathways sustain not only a robust rate of energy production but also of carbon replenishment. Triheptanoin, an edible odd-chain fatty acid triglyceride, is uncommon in that it replenishes metabolites in the tricarboxylic acid cycle (TCA) cycle via anaplerosis in addition to fueling the cycle via oxidation, thus potentially leading to both carbon replenishment and enhanced mitochondrial ATP production. To test the hypothesis that triheptanoin is protective in AD, we supplied mice with severe brain amyloidosis (5×FAD mice) with dietary triheptanoin for four and a half months, followed by biological and biochemical experiments to examine mice metabolic as well as synaptic function. Triheptanoin treatment had minimal impact on systemic metabolism and brain amyloidosis as well as tauopathy while attenuating brain ATP deficiency and mitochondrial dysfunction including respiration and redox balance in 5×FAD mice. Synaptic density, a disease hallmark, was also preserved in hippocampus and neocortex despite profound amyloid deposition. None of these effects took place in treated control mice. These findings support the energy failure hypothesis of AD and justify investigating the mechanisms in greater depth with ultimate therapeutic intent.

Phase I trials and therapeutic intent in the age of precision oncology: What is a patient's chance of response?

The advancement of therapeutic strategies in oncology such as precision oncology has generated significant interest in better estimating the response of modern phase I cancer clinical trials. These estimates have varied widely. In this commentary, we provide an umbrella review of phase I response rates and discuss methodological reasons for variation in prior estimates which include limited use of unpublished data, the inclusion of expansion cohorts that artificially raise response rates of cumulative response rates, varying enrolment of haematologic malignancies, and increased next in class drugs.

Clinical adoption of robotics in endoscopy: Challenges and solutions.

The endoscope was traditionally used as a diagnostic instrument. In past decades, it has increasingly been adapted for therapeutic intents. Subsequently, the master–slave robotic concept was introduced into the field of endoscopy to potentially reduce the difficulty and complication rates of endoscopic therapeutic procedures. As interest in robotic endoscopy intensified, progressively more robotic endoscopic platforms were developed, tested, and introduced. Nevertheless, the future of robotic endoscopy hinges on the ability to meet specific clinical needs of procedurists. Three aspects are vital in ensuring continued success and clinical adoption of the robotic endoscope—demonstration of clinical safety and cost‐efficacy of the device, widespread availability of directed training opportunities to enhance technical skills and clinical decision‐making capabilities of the procedurist, and continued identification of new clinical applications beyond the current uses of the device. This review provides a brief discussion of the historical development of robotic endoscopy, current robotic endoscopic platforms, use of robotic endoscopy in conventional therapeutic endoscopic procedures, and the future of robotic endoscopy.

Semantic Deep Learning: Prior Knowledge and a Type of Four-Term Embedding Analogy to Acquire Treatments for Well-Known Diseases.

BackgroundHow to treat a disease remains to be the most common type of clinical question. Obtaining evidence-based answers from biomedical literature is difficult. Analogical reasoning with embeddings from deep learning (embedding analogies) may extract such biomedical facts, although the state-of-the-art focuses on pair-based proportional (pairwise) analogies such as man:woman::king:queen (“queen = −man +king +woman”).ObjectiveThis study aimed to systematically extract disease treatment statements with a Semantic Deep Learning (SemDeep) approach underpinned by prior knowledge and another type of 4-term analogy (other than pairwise).MethodsAs preliminaries, we investigated Continuous Bag-of-Words (CBOW) embedding analogies in a common-English corpus with five lines of text and observed a type of 4-term analogy (not pairwise) applying the 3CosAdd formula and relating the semantic fields person and death: “dagger = −Romeo +die +died” (search query: −Romeo +die +died). Our SemDeep approach worked with pre-existing items of knowledge (what is known) to make inferences sanctioned by a 4-term analogy (search query −x +z1 +z2) from CBOW and Skip-gram embeddings created with a PubMed systematic reviews subset (PMSB dataset). Stage1: Knowledge acquisition. Obtaining a set of terms, candidate y, from embeddings using vector arithmetic. Some n-gram pairs from the cosine and validated with evidence (prior knowledge) are the input for the 3cosAdd, seeking a type of 4-term analogy relating the semantic fields disease and treatment. Stage 2: Knowledge organization. Identification of candidates sanctioned by the analogy belonging to the semantic field treatment and mapping these candidates to unified medical language system Metathesaurus concepts with MetaMap. A concept pair is a brief disease treatment statement (biomedical fact). Stage 3: Knowledge validation. An evidence-based evaluation followed by human validation of biomedical facts potentially useful for clinicians.ResultsWe obtained 5352 n-gram pairs from 446 search queries by applying the 3CosAdd. The microaveraging performance of MetaMap for candidate y belonging to the semantic field treatment was F-measure=80.00% (precision=77.00%, recall=83.25%). We developed an empirical heuristic with some predictive power for clinical winners, that is, search queries bringing candidate y with evidence of a therapeutic intent for target disease x. The search queries -asthma +inhaled_corticosteroids +inhaled_corticosteroid and -epilepsy +valproate +antiepileptic_drug were clinical winners, finding eight evidence-based beneficial treatments.ConclusionsExtracting treatments with therapeutic intent by analogical reasoning from embeddings (423K n-grams from the PMSB dataset) is an ambitious goal. Our SemDeep approach is knowledge-based, underpinned by embedding analogies that exploit prior knowledge. Biomedical facts from embedding analogies (4-term type, not pairwise) are potentially useful for clinicians. The heuristic offers a practical way to discover beneficial treatments for well-known diseases. Learning from deep learning models does not require a massive amount of data. Embedding analogies are not limited to pairwise analogies; hence, analogical reasoning with embeddings is underexploited.

Barriers and facilitators towards colonoscopy: a qualitative systematic review.

Colonoscopy is integral in the early detection of colorectal cancer (CRC), be it for screening, diagnostic or therapeutic intentions. Despite the presence of multiple screening modalities, colonoscopy remains integral in providing a definitive CRC diagnosis. However, uptake rates remain low worldwide with minimal understanding towards stakeholders' perspectives. This systematic review is the first to outline the barriers and facilitators faced by providers and patients in receiving colonoscopy specifically. Using PRISMA guidelines, our systematic review consolidates findings from Medline, Embase, CINAHL, PsycINFO and Web of Science Core collection. All perceptions of healthcare providers and screening participants aged 45 and above towards colonoscopy were included. Forty-five articles were included in our review. Five major analytical themes were identified - procedural perceptions, personal experiences, thoughts and concerns, societal influences, doctor-patient relationship and healthcare system. The discrepancies in knowledge between patients and providers have evidently reduced in the present decade, potentially attributable to the rising influence of social media. The sharing of providers' personal experiences, involvement of patients' family in colonoscopy recommendations and propagation of patients' positive recounts were also more apparent in the past compared to the present decade, highlighting the need to reevaluate the balance between medical confidentiality and personal touch. Additionally, Asian patients were reportedly more apathetic towards CRC diagnosis due to their strong belief in destiny, a crucial association consistent with present studies. This study highlights pertinent gaps in our healthcare system, providing crucial groundwork for interventions to be enacted in engendering higher colonoscopy uptake rates.

Self-Medication Practices among a Sample of University Students Attending College of Science in Diyala Province

Background: Self-medication is the use of drugs and painkillers by manypeople with therapeutic or preventive intent without prior professionaladvice or prescribed by a physician, including adults to treat their selfrecognizeddiseases and symptoms. Objectives: Determine the rate of self-medication practice amonguniversity students and determine the most common area to be selfmedicatedand the most common drug group for self-medication. Subjects and Methods: An analytical cross-sectional study of a randomsample of students attending two branches of college of science (biologyand chemistry) from the period of 10th December 2018 to 15th April2019 through purposive sampling technique to collect responses fromstudents using structured questionnaire which was divided into manysections including demographic details of research participants, historyof taking medication to treat a health problem without a prescriptionat the last month, the reasons of self-medication practice. Sample sizewas 220 university students. All data were entered on Microsoft Excel2010, and managed and analyzed on SPSS version 19. The means andstandard deviations were calculated and both t-test and chi-squaretests were used to identify the associations between variables. Theconfidence level was set at 95%, and the p value of less than 0.05 wasthe limit value of significance. Result: The rate of practicing self-medication was significantly higheramong studied university students and it accounted for (64.1%). Andit was significantly higher in females (62.4%) than males (37.6%). Mostof the self-medications (59.6%) were practiced for the pains originatingfrom head and neck. The vast majority of students (80.9%) significantlywere using analgesics and antipyretic, and most of them (71.6%) werepracticing it at any time during the year. Conclusion: The study concluded that the rate of self-medicationamong university students was at the high level, the self-medicationwas practiced anytime during the year and the use of analgesics wassignificantly dominant among other drug groups. How to cite this article:Noaman AA, Hussein MA, Mohammed SQ.Self-Medication Practices among a Sample ofUniversity Students Attending College of Sciencein Diyala Province. J Adv Res Med Sci Tech 2019;6(3&amp;4): 13-18. DOI: https://doi.org/10.24321/2394.6539.201907

SPARC: A Road Map for Vagus Nerve Stimulation: Evidence of Vagotopy in a Swine Model

Cervical vagal nerve stimulation (VNS) is an FDA approved treatment for epilepsy and depression and is currently being evaluated for treatment of numerous other disorders including pain, anxiety, and inflammation. VNS also received European market approval for heart failure, bronchoconstriction, and diabetes; however, approval for these indications was based on studies in animals, such as dogs and rats, whose vagal nerve size may not have been representative of humans. When subjected to double‐blinded, randomized, sham controlled studies for subsequent U.S. approval, many of these CE‐marked VNS indications failed to meet their primary efficacy endpoints. More than 100,000 patients have undergone VNS, but despite the efficacy of vagal nerve stimulation in a subset of patients, many fail to reach stimulation levels that result in alleviation of symptoms without triggering unwanted side effects. Post hoc studies of the patient population suggested that VNS may not engage the intended fiber pathways in humans, despite engagement in preclinical studies in mouse, rat, or dog. Stimulation parameters were limited in these studies as higher parameters caused side effects such as cough, voice alteration, and dyspnea. Discrepancies between stimulation amplitude needed for intended effect versus unwanted side effect could be directly related to the relative size of the vagus nerve across animal models, variations in fascicle organization, or variations in branching patterns.To address translating improvements in VNS from the lab to the clinic, we evaluated the swine as a potential model for approximating the clinical environment. The size and fascicular organization of the swine vagus nerve is more representative of the human nerve than previously used models. We used a combination of histology, microdissection, and ultrasound to establish a distinct bimodal organization of groups of fascicles stemming from one large fascicle at the inferior (nodose) ganglion, an organization we have termed ‘vagotopy’. We demonstrated that with the use of ultrasound we can visualize the fascicular organization in vivo, an approach that could be used clinically to target stimulation of either sensory fibers or parasympathetic efferents, depending on therapeutic intent. These advances in a clinically relevant model not only inform electrode placement for target engagement, but provide an approach for reduction of side effects.Support or Funding InformationAcknowledgementsFunded by TL1TR002380 andThe Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO) Targeted Neuroplasticity Training Program under the auspices of Doug Weber and Tristan McClure‐Begley through the Space and Naval Warfare Systems Command (SPAWAR) Systems Center with (SSC) Pacific grants no. N66001‐17‐2‐4010, and the NIH SPARC Program Award OT2 OD025340.

ACR-ASTRO Practice Parameter for the Performance of Proton Beam Radiation Therapy.

The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for proton beam radiation therapy. Proton radiotherapy is the application of a high-energy proton beam to a patient in a clinical setting with therapeutic intent. Proton radiotherapy may permit improved therapeutic ratios with lower doses to sensitive normal structures and greater dose to target tumor tissues. A literature search was performed to identify published articles regarding clinical outcomes, reviews, quality assurance methodologies, and guidelines and standards for proton radiation therapy. Selected articles are referenced in the text. The following recommendations are based on firsthand experiences of multiple clinical authorities who employ proton therapy and have been peer reviewed by experts at different practicing institutions. This practice parameter is developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance standards, indications, and suggested documentation. This practice parameter is a tool to guide technical use of proton therapy and does not assess the relative clinical indication of proton radiotherapy when compared with other forms of radiotherapy, but to focus on the best practices required to deliver proton therapy safely and effectively, when clinically indicated. Costs of proton treatments are high, and the economic costs of proton radiotherapy may also need to be considered.

Adventure Therapy Treatment for Young Adult Males Struggling with Addictions

Adventure therapy is the prescriptive use of adventure experiences conducted in natural settings by mental health professionals that kinesthetically engage clients on cognitive, affective, and behavioral levels. Meta-analyses, specific research on skills developed through the experience, and theoretically reasoned factors inherent in the adventure therapy experience suggest that adventure therapy is a promising treatment option for adolescents and young adults. AT treatment programs are slowly gaining traction, and more families are receiving insurance reimbursement support. The American Hospital Association recognizes adventure therapy as a viable form of treatment, and the National Uniform Billing Committee established an insurance billing code for it in July 2016. Tips for practice include allowing clients to co-construct their treatment experience, matching therapeutic intentions with adventure activities rather than prescribing uniform experiences, and having clients share their therapeutic intentions to receive feedback from their cohort group before and after the experience.

Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care. To assess the effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources. Randomised clinical trials (RCTs) comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen. Two review authors independently assessed the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity. In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I2 = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I2 = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m2) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/m2) (HR 0.93, 95% CI 0.83 to 1.04; I2 = 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I2 = 68%; 10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I2 = 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; I2 = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I2 = 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% CI 0.79 to 2.38; I2 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I2 = 94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales. In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured. Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.

Evaluation of Stem Cell-Derived Cellular Therapy Products.

Although there is an increase in the development of new cellular therapies, few guidelines have been published to assist in the design of preclinical studies. As no product and therapeutic intention is entirely alike regulators and Contract Research Organizations need to treat each project on a case-by-case basis. One of the most important considerations in study design is to retain all tissues from the study, thereby allowing for further analysis of tissues should unexpected effects be seen in clinical studies. Input from the pathologist at the earliest stages of study design regarding animal selection, cell markers, and phased tissue examination improves the scientific integrity of the study.

The Fas/FasL Signaling Pathway: Its Role in the Metastatic Process and as a Target for Treating Osteosarcoma Lung Metastases.

Understanding how the tumor microenvironment participates in inhibiting or supporting tumor growth is critical for the development of novel therapies. Osteosarcoma (OS) metastasizes almost exclusively to the lung, an organ where Fas ligand (FasL) is constitutively expressed. This chapter focuses on our studies dedicated to the interaction of OS cells with the lung microenvironment. We will summarize our studies conducted over the past 20years showing the importance of the Fas/FasL signaling pathway to the establishment and progression of OS metastases in the lung. We demonstrated that the FasL+ lung microenvironment eliminates Fas-positive (Fas+)OS cells that metastasize to the lungs, through apoptosis induced by Fas signaling following interaction of Fas on the tumor cell surface with FasL on the lung epithelial cells. Expression of the Fas receptor on OS cells inversely correlated with the ability of OS cells to form lung metastases. Blocking this pathway interferes with this process, allowing Fas+ cells to grow in the lung. By contrast, upregulation of Fas on Fas- OS cells inhibited their ability to metastasize to the lung. We demonstrated how the FasL+ lung microenvironment can be leveraged for therapeutic intent through the upregulation of Fas expression. To this end, we demonstrated that the histone deacetylase inhibitor entinostat upregulated Fas expression on OS cells, reduced their ability to form lung metastases, and induced regression of established micrometastases. Fas expression in OS cells is regulated epigenetically by the microRNA miR-20a. We showed that expressions of Fas and miR-20a are inversely correlated, and that delivery of anti-miR-20a in vivo to mice with established osteosarcoma lung metastases resulted in upregulation of Fas and tumor regression. Therefore, targeting the Fas signaling pathway may present therapeutic opportunities, which target the lung microenvironment for elimination of OS lung metastases. We have also shown that in addition to being critically involved in the metastatic potential, the Fas signaling pathway may also contribute to the efficacy of chemotherapy. We demonstrated that the chemotherapeutic agent gemcitabine (GCB) increased Fas expression in both human and mouse OS cells in vitro. In vivo, aerosol GCB therapy induced upregulation of Fas expression and the regression of established osteosarcoma lung metastases. The therapeutic efficacy of GCB was contingent upon a FasL+ lung microenvironment as aerosol GCB had no effect in FasL-deficient mice. Manipulation of Fas expression and the Fas pathway should be considered, as this concept may provide additional novel therapeutic approaches for treating patients with OS lung metastases.

3D laparoscopic common bile duct exploration is safe and feasible

Introduction: 10-15% of patients with gallstones have common bile duct stones. Pre-operative endoscopic retrograde cholangiopancreaticography (ERCP), followed by laparoscopic cholecystectomy (LC) is the common treatment approach. However, recent studies showed that one stage laparoscopic common bile duct exploration (LCBDE) is also feasible though more technically demanding. Three-dimensional (3D) laparoscopy enhances depth perception, facilitates intra-corporeal suturing and is reported to reduce learning curve in laparoscopic surgery. There is no report of application of 3D technology to LCBDE. We report first case series of 3D LCBDE. Materials and Methods: We describe a case series of first 13 consecutive 3D LCBDE. Magnetic resonance cholangiopancreatography (MRCP) is liberally done for patients with deranged liver function test (LFT) and ERCP is reserved only for therapeutic intentions. CBD explorations are done through choledochotomy with 5mm choledochoscope and primarily repaired with absorbable suture without a stent. Clinical profile of patients, intraoperative details and outcomes were reported. Results: Mean age of patients was 70.6 (range 44 – 91) years. 7 patients (53.8%) were male. The indications for surgery were choledocholithasis 69.2% (n=9), cholangitis 15.4% (n=2) and gallstone pancreatitis 15.4% (n=2). More than half of the patients (53.1%, n=7) had pre-operative ERCP. 23% (n=3) had pre-operative biliary stent. The median American Society of Anaesthesiology (ASA) score was 2 (range 2-3) and the commonest comorbidity was hypertension (n=9, 69%). Pre-operative MRCP was done in majority of patients. (n=9,69%) and mean diameter of CBD was 14.6 mm (range 7-30). Median operative time was 125 (range 80 -265) minutes. 69% (n=9) had intra-operative drain inserted and this was removed at a median of 3 (range 3-4) days. There was no open conversion, bile leak and post-operative LFT were normal at one month. There was no mortality. Conclusion: 3D surgery provides binocular vision with depth perception which facilitates intra-corporeal suturing. 3D LCBDE is safe and feasible.

An Overview of Performance Enhancing Drugs (PED’s) in Sports and WADA

<p style="text-align: justify;">The use of certain banned and illegal substances either to improve one&rsquo;s cognitive skills or to enhance their performance by athletes has become widely prevalent. These substances are commonly referred as performance enhancing drugs or PED&rsquo;s and are used without any therapeutic intent. They belong to a wide variety of classes, some of which include the anabolic steroids, hormonal agents, diuretics and the CNS stimulants. The WADA (World Anti-Doping Agency), a collaborated network between the sports authorities and the global governments was established to fight against doping so as to have a fair competition among the athletes. Although, the regulatory bodies have put forth stringent legislations that can prevent their misuse and safeguards the athletes against the adverse effects of such drugs, it has become rather difficult to keep doping under check as the recent developments have resulted in the emergence of so called designer drugs that are difficult to detect with the available analytical techniques. Subsequently, WADA came up with the concept of ABP (Athlete Biological Passport) which helped resolve some of these issues. This review tries to look into PED&rsquo;s, the way they act, their ill-effects and also in brief about the designer drugs. It also highlights the role of WADA, ABP and the prohibited list of substances and methods for the year 2019. <p style="text-align: justify;"><strong>Key words:</strong> Anabolic steroids, Erythropoietin, World Anti-Doping Agency, Athlete Biological Passport, CNS stimulants.

The Co-Active Therapeutic theatre model: A manualized approach to creating therapeutic theatre with persons in recovery

Therapeutic theatre is the intentional use of the process and performance of a theatrical piece with specific therapeutic goals and intentions for an identified population. Study and replication of this modality may benefit from manualization. This article presents an outline of a manualized approach called The Co-Active Therapeutic theatre (CoATT) model, which has been used as a successful intervention for individuals post-intensive treatment who are working towards independent recovery from eating disorders, aphasia and substance use disorders. This preliminary instruction of CoATT emphasizes a solution-focused, manualized process to support recovery and operationalize therapeutic theatre in the service of empirical research.

PhaseI trials as valid therapeutic options for patients with cancer.

For many years, oncology phaseI trials have been referred to as 'toxicity trials' and have been believed to have low clinical utility other than that of establishing the adverse event profile of novel therapeutic agents. The traditional distinction of clinical trials into three phases has been challenged in the past few years by the introduction of targeted therapies and immunotherapies into the routine management of patients with cancer. This transformation has especially affected early phasetrials, leading to the current situation in which response rates are increasingly reported from phaseI trials. In this Perspectives, we highlight key elements of phaseI trials and discuss how each one of them contributes to a new paradigm whereby preliminary measurements of the clinical benefit from a novel treatment can be obtained in current phaseI trials, which can therefore be considered to have a therapeutic intent.

Evaluation of Traditional Chinese Medicine Herbs in Oncology Clinical Trials.

Despite wide empirical use and demand for traditional Chinese medicine (TCM) herbs worldwide, high-quality clinical trials of TCM herbs in oncology are limited. We developed recommendations for rigorous clinical trials to evaluate their safety and efficacy for oncology patients. To accomplish this goal, the TCM & Cancer Research Committee of the Chinese Pharmaceutical Association convened a working group of oncologists, TCM experts, clinical researchers, biostatisticians, and industry/government representatives to develop principles and approaches for TCM cancer drug clinical trials. They identified 2 categories of herbal drugs based on therapeutic intent: survival improvement and symptom management. The working group also emphasized the need to adopt international standards when appropriate for TCM herbal drug approval and to develop methodology to standardize diagnostic criteria, treatment approaches, and outcome measures according to defining TCM characteristics. These recommendations aim to improve study design and methods to inform rigorous investigation of TCM herbs in patients with cancer.