Therapeutic Intent Research Articles

Extracorporeal Life Support in Organ Transplant Donors.

BackgroundExtracorporeal life support (ECLS) can be applied in brain-dead donors for organ perfusion before donation, thereby expanding the donor pool. The aim of this study was to examine the benefits and early clinical outcomes of ECLS for organ preservation.MethodsBetween June 2012 and April 2017, 9 patients received ECLS with therapeutic intent or for organ preservation. The following data were collected: demographics, purpose and duration of ECLS, cause of death, dose of vasoactive drugs, and need for temporary dialysis before organ retrieval. The early clinical outcomes of recipients were studied, as well as survival and graft function at 1 month.ResultsECLS was initiated for extracorporeal cardiopulmonary resuscitation in 5 patients. The other patients needed ECLS due to hemodynamic deterioration during the assessment of brain death. We successfully retrieved 18 kidneys, 7 livers, and 1 heart from 9 donors. All organs were transplanted and none were discarded. Only 1 case of delayed kidney graft function was noted, and all 26 recipients were discharged without any significant complications.ConclusionThe benefits of protecting the vital organs of donors is significant, and ECLS for organ preservation can be widely used in the transplantation field.

A Coil Calamity

Management of acute upper gastrointestinal bleeding (GIB) is standardized with initial approach focusing on resuscitation and endoscopic evaluation with therapeutic intent. In the event that a lesion is not amenable to endoscopic therapy, endovascular treatments have been successfully utilized, ranging from foam gel to selective vascular coil embolization. Endovascular therapy has been shown to be successful with several peri-procedural and long term adverse events. Here we describe a case of a 66-year-old female with past medical history of acute myeloid leukemia (AML) and recent allogenic stem cell transplant who presented with melena for one month and labs demonstrating profound anemia without evidence of hemorrhagic shock. She had a history of GIB previously treated with transcatheter arterial embolization (TAE) of the gastroduodenal artery (GDA) five years prior to this presentation. On current hospitalization, an EGD demonstrated several duodenal ulcers and three micro coils extruding from the base of the ulcer. No endoscopic interventions were attempted. Her melena persisted with ongoing anemia. An angiography failed to identify source of bleeding, but due to high surgical risk from comorbid conditions, a conservative approach was undertaken with acid suppression therapy and as needed blood transfusions. Her hemoglobin stabilized and the patient was successfully discharged. She has not experienced recurrence of bleeding at three months follow-up appointment. Coil migrations through the gastric and duodenal wall is a rare but possible complication of TAE that has previously been reported in the literature in up to 3% cases. More typical complications of TAE include occlusion of a nontarget vessel, vessel injury, local abscess, and allergic reaction to coils. Bleeding after coil migration may occur from weeks to several years after TAE as in our patient. Unlike the high risk stigmata of rebleeding that has been well described, the prognostic value of finding migrated coils on endoscopy has not been assessed in the literature for predicting likelihood of rebleeding. Due to the paucity of data, the approach to patient management should remain individualized, utilizing a multidisciplinary approach, including surgery, interventional radiology and gastroenterology.1951_A Figure 1. Duodenal Bulb/ sweep: Large ulcer1951_B Figure 2. Duodenal sweep: Coils protruding from ulcer base

Gender differences in doxorubicin pharmacology for subjects with chemosensitive cancers of young adulthood.

For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap. A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics. The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1-3.9L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI - 0.005 to - 0.0002h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09-1.4). Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups.

Interface Problems Between Inpatient, GP and Outpatient Specialist Care: Viewpoint of General Practitioners in Dresden

The aim of the study was to identify interface problems between inpatient, GP and outpatient specialist care from the perspective of general practitioners in Dresden, especially in older multimorbid patients. The data were collected in the context of the pilot study "Multimedication and its Consequences for the Primary Care of Patients in Saxony" and included guided interviews with 7 general practitioners. The interviews were transcribed and analyzed according to the inductive content analysis of Mayring. At the interface of inpatient to outpatient care, several problems regarding discharge management, intersectoral communication and cooperation as well as in the management of medication were found. Concerning the interface between general practitioners and outpatient specialist care, problems were particularly marked with regard to free choice of doctors, appointment management, medical decision-making process, medication management as well as the use of the electronic health card. Regardless of the interfaces, the lack of communication could be worked out as a central challenge. There are several problems with all adjacent interfaces. What is striking here is the lack of communication and cooperation between all parties involved. Possible causes were the often very different working methods and framework conditions, human and material resources and therapeutic intentions and approaches between the different interfaces. One possible approach to improve the situation may be the law regarding secure digital communications and healthcare applications, which exists since 2016. Among other things, it promises a secure and rapid inter- and intrasectoral exchange of patient data. The overall goal of healthcare in Germany should be an optimized and process-oriented interface management in order to ensure a secure and seamless sectoral transition to patients.

TREATMENT OF PATIENTS WITH ADVANCED CANCER FOLLOWING CHEMOTHERAPY AND TRADITIONAL MEDICINE - LONG TERM FOLLOW UP OF 75 CASES

Objective: Traditional systems of medicine all over the world even traditional medicine and cancer have been using plants and plants products for therapeutic intention. The purpose of these retrospective trials is to assess the clinical efficacy of chemotherapy in conjunction with TCM for a broad variety of cancers. Methods: 75 patients with available cancers were concluded in the study during September1993 – May 2018.The sex ratio of male: female was 50:25 respectively. The mean age at onset was 46.9 years（range 10-79 years. All patients were treated with different dosage of various chemotherapy in combination with TCM or traditional medicine alone. The basic chemotherapeutic regimen consisted of vincristine（VCR, 1-2 mg/week)、cyclophosphamide（CTX, 200-1, 000mg/ week), mitomycin C(MMC, 2-4mg/week) and 5-fluorouracil（5-Fu,250-500mg/ day). The detail prescription of TCM varied among a broad variety of carcinomas. The criteria of complete remission（CR）and/or partial remission（PR）is according to the rules where physicians have in common with in clinics. In 75 cases, the CR was obtained in 33(44%) advanced cancers, a short CR in 11(14.7%) cases, PR in 25 (33.3%) cancers, stable disease in 6 cases.. The crude herbs consisted of sargassum, tangle, Oyster（mussels), Poria cocos, Ophiopogon japonicus, Prunella vulgaris, Taraxacum, Scrophularia ningpoensis, Cremastra appendiculata, Trichosanthes Kirilowii, Sophora subprostrata, Houttuynia cordata, Scutellaria barbata d. don and Oldenlandia diffusa roxb. Results: Among those long-term survivors, 31 carcinomas obtained in disease-free survival over 5 years, 20 cancers were survival over 10 years, the longest four patients over 25 years. Conclusion: In this study, it was experienced that a CR was a pivotal influencing factor in those longest survival patients, and traditional medicine was also recommended. Down regulating oncogenic receptors may be useful paradigm and perspective in currently the third line setting of clinical target therapy and in rendering our better understanding of cancer biology. Peer Review History: Received 5 June 2018; Revised 4 July; Accepted 8 July, Available online 15 July 2018 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5/10 Average Peer review marks at publication stage: 8.5/10 Reviewer(s) detail: Dr. Nuray Ari, Ankara University, Turkiye, ari@ankara.edu.tr Dr. Mohamed Salama, Modern University for Technology & Information, Egypt, salama47@yahoo.com Similar Articles: ESTIMATION OF ANTI-INFLAMMATORY ACTIVITY AS WELL AS APOPTOTIC ACTIVITY OF ETHANOLIC EXTRACTS OF CROCUS SATIVUS

Traction Force Screening Enabled by Compliant PDMS Elastomers

Actomyosin contractility is an essential element of many aspects of cellular biology and manifests as traction forces that cells exert on their surroundings. The central role of these forces makes them a novel principal therapeutic target in diverse diseases. This requires accurate and higher-capacity measurements of traction forces; however, existing methods are largely low throughput, limiting their utility in broader applications. To address this need, we employ Fourier-transform traction force microscopy in a parallelized 96-well format, which we refer to as contractile force screening. Critically, rather than the frequently employed hydrogel polyacrylamide, we fabricate these plates using polydimethylsiloxane rubber. Key to this approach is that the polydimethylsiloxane used is very compliant, with a lower-bound Young’s modulus of ∼0.4 kPa. We subdivide these monolithic substrates spatially into biochemically independent wells, creating a uniform multiwell platform for traction force screening. We demonstrate the utility and versatility of this platform by quantifying the compound and dose-dependent contractility responses of human airway smooth muscle cells and retinal pigment epithelial cells. By directly quantifying the endpoint of therapeutic intent, airway-smooth-muscle contractile force, this approach fills an important methodological void in current screening approaches for bronchodilator drug discovery, and, more generally, in measuring contractile response for a broad range of cell types and pathologies.

Safety and Feasibility of Lung Resection After Immunotherapy for Metastatic or Unresectable Tumors

Surgeons are increasingly asked to operate on patients with residual disease after immunotherapy. The safety and utility of lung resection in this setting are unknown. We retrospectively reviewed patients who underwent lung resection within 6 months of treatment with checkpoint blockade agents for metastatic or unresectable cancer. Survival was estimated from the first resection using the Kaplan-Meier approach. Database query identified 19 patients who underwent 22 resections for suspected residual disease with therapeutic intent after immunotherapy between 2012 and 2016. Lung cancer was the most common diagnosis (47%), followed by metastatic melanoma (37%). The most frequently used agents were nivolumab (32%), pembrolizumab (32%), and ipilimumab (16%). Patients received a mean of 21 doses (range, 1 to 70 doses). The final dose was administered at an average of 75 days (range, 7 to 183 days) before the operation. Anatomic resection (lobectomy or greater) was performed in 11 patients (50%). Four lobectomies were attempted minimally invasively, and one required conversion to thoracotomy. Of the resected patients, 68% had viable tumor remaining. R0 resection was achieved in 95%. Mean operative time for lobectomy was 227 minutes (range, 150 to 394 minutes). Complications occurred in 32% of patients; all but 1 were minor (grade 1/2). The 2-year overall and disease-free survival were 77% and 42%, respectively. In patients with previously metastatic or unresectable cancer, lung resection for suspected residual disease after immunotherapy is feasible, with high rates of R0 resection. Operations can be technically challenging, but significant morbidity appears to be rare. Outcomes are encouraging, with reasonable survivals during short-interval follow-up.

J. Marion Sims and the Vesicovaginal Fistula: Historical Understanding, Medical Ethics, and Modern Political Sensibilities.

To review the historical background surrounding the early work of Dr. J. Marion Sims, who developed the first consistently successful surgical technique for the repair of obstetric vesicovaginal fistulas by operating on a group of young, enslaved, African American women who had this condition between 1846 and 1849. Review of primary source documents on Sims and his operations, early 19th century clinical literature on the treatment of vesicovaginal fistula, the introduction of ether and chloroform anesthesia into surgical practice, and the literature on the early 19th century medical ethics pertaining to surgical innovation. The goals are to understand Sims's operations within the clinical context of the 1840s and to avoid the problems of "presentism," in which beliefs, attitudes, and practices of the 21st century are anachronistically projected backward into the early 19th century. The object is to judge Sims within the context of his time, not to hold him accountable to standards of practice which were not developed until a century after his death. A narrative of what Sims did is presented within the context of the therapeutic options available to those with fistula in the early 19th century. Review of the available material demonstrates that Sims' first fistula operations were legal, that they were carried out with express therapeutic intent for the purpose of repairing these women's injuries, that they conformed to the ethical requirements of his time, and that they were performed with the patients' knowledge, cooperation, assent, and assistance.

Human salivary microRNAs in Cancer.

Circulating microRNAs (miRNAs) have emerged as excellent candidates for cancer biomarkers. Several recent studies have highlighted the potential use of saliva for the identification of miRNAs as novel biomarkers, which represents a great opportunity to improve diagnosis and monitor general health and disease. This review summarises the mechanisms of miRNAs deregulation in cancer, the value of targeting them with a therapeutic intention and the evidence of the potential clinical use of miRNAs expressed in saliva for the detection of different cancer types. We also provide a comprehensive review of the different methods for normalising the levels of specific miRNAs present in saliva, as this is a critical step in their analysis, and the challenge to validate salivary miRNAs as a reality to manage cancer patients.

Bile Duct Injuries with Loss of Confluence

Introduction: Iatrogenic bile duct injuries (IBDI) with loss of confluence are understood as those where right and left hepatic ducts lose continuity with the common biliary tree. These represent 4% of all IBDI and are considered a very demanding surgical challenge. Study design: This is a series of case in a reference center during an eight-year period (2008 – 2016), where all patients with IBDI and loss of confluence submitted to any bilioenteric derivation procedure were included. Results: From a total of 11 cases, 10 of them (90.1%) were treated with double bilioenteric derivation and 1 (9%) with a neo-confluence. In 90.9% (n=10) of the patients a percutaneous catheter of biliary drainage was placed before the surgical procedure. Within a 34.5 months follow-up, the initial approach was successful in 54.5% (n=6), meanwhile accumulated achievement was 81.8% (n=9) considering dilatation and remodeling procedures. From this, 18.2% (n=2) are still with stenosis of derivation in a dilatation protocol with percutaneous catheter. Conclusions: Double hepatojejunostomy with transanastomotic stents and management of eventual stenosis with percutaneous dilatation as a first therapeutic intention results in a standardized practice that leads to reasonable results compared with other high volume centers.

Delphi consensus of an expert committee in oncogeriatrics regarding comprehensive geriatric assessment in seniors with cancer in Spain.

The aim of this work was to reach a national consensus in Spain regarding the Comprehensive Geriatric Assessment (CGA) domains in older oncological patients and the CGA scales to be used as a foundation for widespread use. The Delphi method was implemented to attain consensus. Representatives of the panel were chosen from among the members of the Oncogeriatric Working Group of the Spanish Society of Medical Oncology (SEOM). Consensus was defined as ≥66.7% coincidence in responses and by the stability of said coincidence (changes ≤15% between rounds). The study was conducted between July and December 2016. Of the 17 people invited to participate, 16 agreed. The panel concluded by consensus that the following domains should be included in the CGA:(and the scales to evaluate them): functional (Barthel Index, Lawton-Brody scale, gait speed), cognitive (Pfeiffer questionnaire), nutritional (Mini Nutritional Assessment - MNA), psychological/mood (Yesavage scale), social-familial (Gijon scale), comorbidity (Charlson index), medications, and geriatric syndromes (urinary and/or fecal incontinence, low auditory and/or visual acuity, presence of falls, pressure sores, insomnia, and abuse). Also by consensus, the CGA should be administered to older patients with cancer for whom there is a subsequent therapeutic intent and who scored positive on a previous frailty-screening questionnaire. After 3 rounds, consensus was reached regarding CGA domains to be used in older patients with cancer, the scales to be administered for each of these domains, as well as the timeline to be followed during consultation.

Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells “immune checkpoint” has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc). Current data suggest that PD-1 and CTLA-4 receptors can inhibit T-cell receptors and T-cell proliferation. Blockade of PD-1/PD-L1 and/or CTLA-4/CD28 pathways has shown promising tumor outcomes in clinical trials for advanced solid tumors like melanoma, renal cell cancer, and non-small cell lung cancer. The present review attempts to explore what is known about PD-1/PD-L1 and CTLA-4/CD28 pathways with a focus on HNSCC. We further discuss how these pathways can be manipulated with therapeutic intent.

Impact of age, sex, therapeutic intent, race and severity of advanced heart failure on short-term principal outcomes in the MOMENTUM 3 trial

Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. Cox proportional hazard models were used to analyze patients enrolled in the "as-treated cohort" (n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. Baseline characteristics were well balanced among HM3 (n = 151) and HMII (n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned.

Continuous lateral rotational therapy in trauma-A systematic review and meta-analysis.

The purpose of this study was to evaluate the impact of continuous lateral rotational therapy (CLRT) on respiratory complications and mortality in patients suffering from trauma. The literature databases PubMed®/Medline® and the Cochrane Library® were systematically searched for prospective controlled trials comparing continuous lateral rotational therapy to conventional manual positioning in trauma patients. A total of 8 publications (n= 422 patients) with comparable age and injury severity were included in the meta-analysis. A significant reduction in the incidence of nosocomial pneumonia (OR: 0.33, [95%CI: 0.17, 0.65], p=0.001) was observed in patients treated prophylactically with continuous lateral rotational therapy. When used with therapeutic intention, CLRT had no impact on the incidence of pneumonia. There were no significant differences in mortality, duration of mechanical ventilation, or ICU length of stay. Analogous to studies evaluating CLRT in medical or mixed patient collectives, CLRT reduced the rates of nosocomial pneumonia in trauma patients. This, however, had no impact on overall mortality. The level of evidence of the studies included was limited by several factors. An adequately powered, well-designed multi-centre randomised controlled trial is required, to validly assess the utility of CLRT for the prevention and treatment of pulmonary complications in patients suffering from trauma. Systematic review and meta-analysis, level III.

Immune recognition of irradiated cancer cells.

Ionizing irradiation has been extensively employed for the clinical management of solid tumors, with therapeutic or palliative intents, for decades. Until recently, radiation therapy (RT) was believed to mediate antineoplastic activity mostly (if not only) as a consequence of cancer cell-intrinsic effects. Indeed, the macromolecular damage imposed to malignant cells by RT initiates one or multiple signal transduction cascades that drive a permanent proliferative arrest (cellular senescence) or regulated cell death. Both these phenomena show a rather linear dose-response correlation. However, RT also mediates consistent immunological activity, not only as an "on-target effect" originating within irradiated cancer cells, but also as an "off-target effect" depending on the interaction between RT and stromal, endothelial, and immune components of the tumor microenvironment. Interestingly, the immunological activity of RT does not exhibit linear dose-response correlation. Here, we discuss the mechanisms whereby RT alters the capacity of the immune system to recognize and eliminate irradiated cancer cells, either as an "on-target" or as on "off-target" effect. In particular, we discuss the antagonism between the immunostimulatory and immunosuppressive effects of RT as we delineate combinatorial strategies to boost the former at the expenses of the latter.

Isolated sphenoid sinus opacifications: a systematic review and meta-analysis.

Isolated sphenoid sinus opacifications (ISSOs) represent a relatively uncommon disease with the potential for serious complications. To better understand this disease, we performed a systematic review to further characterize the underlying pathologies, associated symptoms, and treatment outcomes of patients with ISSOs. A systematic review of ISSO case series was performed utilizing the Medline, Embase, Web of Science, and Cochrane databases in accordance with guidelines established by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Data of interest included disease pathology, associated symptoms, and treatment outcomes. Of the initial 1051 hits from the 4 databases, 17 articles, with a combined 1133 ISSO patients, were ultimately included in the review. On a weighted analysis, the underlying pathologies were classified as chronic rhinosinusitis without nasal polyps (CRSsNP) (28.3%), mucoceles (20.3%), fungal sinusitis (12.5%), malignant neoplasms (7.7%), intracranial lesions (7.0%), benign neoplasms (5.7%), chronic rhinosinusitis with nasal polyps (CRSwNP) (3.4%), and other lesions (4.7%). Cranial neuropathies were present in 16.3% (95% confidence interval [CI], 10.1-22.5%) of ISSO patients. A favorable surgical complication rate of 1.5% (95% CI, -0.1% to 3.2%) was found in patients undergoing surgery for an ISSO. ISSOs are caused by diverse pathologies. Given the considerable rates of neoplastic disease and cranial neuropathies, patients affected by an ISSO should be monitored closely and treated aggressively. Prompt surgical intervention, with either diagnostic or therapeutic intent, is often indicated.

Beliefs, endorsement and application of homeopathy disclosed: a survey among ambulatory care physicians.

Explanation models for the effectiveness of homeopathy are not supported by natural sciences and the aggregated evidence from clinical trials is unconvincing. From this standpoint, placebo effects seem the most obvious explanation for the therapeutic effects experienced in homeopathy. Still, many physicians continue to prescribe homeopathic treatments. Whether physicians who prescribe homeopathic treatments aim to achieve placebo effects or actually believe in specific effects is poorly understood. However, this distinction has important educational and ethical implications. Therefore, we aimed to describe the use of homeopathy among physicians working in outpatient care, factors associated with prescribing homeopathy, and the therapeutic intentions and attitudes involved. All physicians working in outpatient care in the Swiss Canton of Zurich in the year 2015 (n = 4072) were approached. Outcomes of the study were: association of prescribing homeopathy with medical specialties (odds ratios [OR] and 95% confidence intervals [95% CI] from multivariable logistic regression); intentions behind prescriptions (to induce specific or nonspecific/placebo effects); level of agreement with specific attitudes; and views towards homeopathy including explanatory models, rating of homeopathy's evidence base, the endorsement of indications, and reimbursement of homeopathic treatment by statutory health insurance providers. The participation rate was 38%, mean age 54 years, 61% male, and 40% specialised in general internal medicine. Homeopathy was prescribed at least once a year by 23% of the respondents. Medical specialisations associated with prescribing homeopathy were: no medical specialisation (OR 3.9; 95% CI 1.7-9.0), specialisation in paediatrics (OR 3.8 95% CI 1.8-8.0) and gynaecology/obstetrics (OR 3.1 95% CI 1.5-6.7). Among prescribers, only 50% clearly intended to induce specific homeopathic effects, only 27% strongly adhered to homeopathic prescription doctrines, and only 23% thought there was scientific evidence to prove homeopathy's effectiveness. Seeing homeopathy as a way to induce placebo effects had the strongest endorsement among prescribers and non-prescribers of homeopathy (63% and 74% endorsement respectively). Reimbursement of homeopathic remedies by statutory health insurance was rejected by 61% of all respondents. Medical specialties use homeopathy with significantly varying frequency and only half of the prescribers clearly intend to achieve specific effects. Moreover, the majority of prescribers acknowledge that effectiveness is unproven and give little importance to traditional principles behind homeopathy. Medical specialties and associated patient demands but also physicians' openness towards placebo interventions may play a role in homeopathy prescriptions. Education should therefore address not only the evidence base of homeopathy, but also ethical dilemmas with placebo interventions.

Morbidity of central neck dissection for papillary thyroid cancer.

Thyroid cancer has a very well-known propensity for nodal involvement, either in the central and lateral neck compartments. Neck dissection addressing the central compartment may be performed with an elective or therapeutic intent, the former concomitantly to a thyroidectomy whereas the latter may be accomplished also as a revision procedure for recurrent disease. In this paper complications of central compartment neck dissection will be described, analyzing separately primary and revision procedures.

Cardiac fibrosis in the ageing heart: Contributors and mechanisms.

Cardiac fibrosis refers to an excessive deposition of extracellular matrix (ECM) in cardiac tissue. Fibrotic tissue is stiffer and less compliant, resulting in subsequent cardiac dysfunction and heart failure. Cardiac fibrosis in the ageing heart may involve activation of fibrogenic signalling and inhibition of anti-fibrotic signalling, leading to an imbalance of ECM turnover. Excessive accumulation of ECM such as collagen in older patients contributes to progressive ventricular dysfunction. Overexpression of collagen is derived from various sources, including higher levels of fibrogenic growth factors, proliferation of fibroblasts and cellular transdifferentiation. These may be triggered by factors, such as oxidative stress, inflammation, hypertension, cellular senescence and cell death, contributing to age-related fibrotic cardiac remodelling. In this review, we will discuss the fibrogenic contributors in age-related cardiac fibrosis, and the potential mechanisms by which fibrogenic processes can be interrupted for therapeutic intent.

Quality matters: immunotherapy and the evolving landscape of advanced cancer care

ABSTRACTIntroduction: Immunotherapy has been FDA approved in several first line and many more second line settings in patients with advanced cancer. While only a subset of patients derive benefit from checkpoint blockade, the potential for durable responses and tolerable adverse effects make it an appealing option. Patient quality of life on the therapy is a particularly important consideration given its therapeutic intent is non-curative.Areas covered: The primary focus of this review is exploring studies which led to the approval of checkpoint inhibitors in a variety of tumor types, with a specific emphasis on studies looking at patient related outcomes (PRO). The latter part of the review focuses on identification and management of unique immune related toxicities.Expert commentary: PROs are improved with immunotherapy compared to chemotherapy largely by reducing functional decline and impacting global health less negatively in patients. There remain numerous questions about checkpoint inhibitors inclu...