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Psoriasis is a common chronic inflammatory skin disease, associated with substantial comorbidity. TH17 lymphocytes, differentiating under the influence of dendritic cell-derived IL-23, and mediating their effects via IL-17A, are believed to be central effector cells in psoriasis. This concept is underlined by the unprecedented efficacy of therapeutics targeting this pathogenetic axis. In recent years, numerous observations made it necessary to revisit and refine this simple "linear" pathogenetic model. It became evident that IL-23 independent cells exist that produce IL-17A, that IL-17 homologues may exhibit synergistic biological effects, and that the blockade of IL-17A alone is clinically less effective compared to the inhibition of several IL-17 homologues. In this review, we will summarize the current knowledge around IL-17A and its five currently known homologues, namely IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25) and IL-17F, in relation to skin inflammation in general and psoriasis in particular. We will also re-visit the above-mentioned observations and integrate them into a more comprehensive pathogenetic model. This may help to appreciate current as well as developing anti-psoriatic therapies and to prioritize the selection of future drugs' mode(s) of action., Competing Interests: W-HB has received honoraria as a speaker and/or advisor from Abbvie, Almirall, BMS, Janssen, Leo, Lilly, Novartis, and UCB. The remaining author declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Brembilla and Boehncke.)

Study Design: This was a narrative review., Objective: The objective of this study was to review the standards of care and triage protocol for gunshot wounds to the spine, highlighting innovative future treatment options that may be implemented in patients with spinal cord injury (SCI)., Summary of Background Data: With the increased availability of firearms among the United States population, gunshot wounds to the spine are becoming a clinically relevant and devastating issue. Such injuries result in severe and diverse complications. SCIs due to gunshot wounds are the leading cause of morbidity and mortality, as they often result in complete or incomplete paraplegia. Current standards of care focus on preventing further damage rather than total cure or treatment of SCI., Methods: A literature review was performed on the standards of care, triage protocol, associated conditions, current therapeutic options, and innovative treatment options for patients with gunshot wounds to the spine., Results: The general standards of care for spinal gunshot wounds involve maintaining or renewal of mechanical spinal steadiness and neurological activity while limiting complications of treatment. Current treatment options include management of mean arterial pressure goals, drug therapies consisting of antibiotics, and surgical approaches. With recent innovations in molecular biology and cell transplantation, potentially new and promising treatment options for patients with SCI exist. These options include cell transplantation therapies, platelet-rich plasma administration, exosomal treatments, and mitochondrial-targeted therapeutics. Stem cell transplantation is promising, as several clinical studies have been completed. However, loss-to-follow-up, lack of long-term evaluation, and questionable randomization has limited the use of stem cells in the standard of care practice. Although not studied on human models to a gunshot wound, exosomal and mitochondrial-based treatment options have been studied both in vitro and in animal models with SCI., Conclusion: Newly emerging molecular and cellular therapy modalities for SCI contribute to the recovery process and may be utilized in conjunction with the current modalities for better outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To explore the experiences, approaches, and challenges of physicians consulting patients about experimental stem cell and regenerative medicine interventions (SCRIs)., Participants and Methods: From August 21, 2018, through July 30, 2019, semistructured interviews of 25 specialists in cardiology, ophthalmology, orthopedics, pulmonology, and neurology were conducted and qualitatively analyzed using modified grounded theory., Results: All specialists used informational approaches to counsel patients, especially orthopedists. Informational approaches included explaining stem cell science, sharing risks, and providing principles. Several specialists also used relational counseling approaches including emphasizing that physicians want what is best for patients, acknowledging suffering, reassuring continued care, empathizing with patients and families, and underscoring that patients have the final decision. Many specialists reported being comfortable with the conversation, although some were less comfortable and several noted challenges in the consultation including wanting to support a patient's decision but worrying about harms from unproven SCRIs, navigating family pressure, and addressing stem cell hype and unrealistic expectations. Specialists also desired that additional resources be available for them and patients., Conclusion: Physicians relied more heavily on providing patients with information about SCRIs than using relational counseling approaches. Efforts should be directed at helping physicians address the informational and relational needs of patients, including providing tools and resources that inform physicians about the unproven SCRI industry, building skills in empathic communication, and the creation and dissemination of evidence-based resources to offer patients., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Gastrointestinal side effects are the dose-limiting toxicity of high-dose melphalan (HDM) in autologous hematopoietic stem-cell transplantation, but there are limited contemporary data on the incidence and severity of gastrointestinal toxicity associated with this regimen. We retrospectively studied 100 consecutive patients who received HDM alone or in combination with other conditioning agents. Patients had a median age of 56 (range 20-73); underlying diseases were myeloma (42%), lymphoma (42%), or amyloidosis (16%) and melphalan dosages were 200 (40%), 140 (59%), or 100 mg/m 2 (1%). Ninety-seven percent of patients experienced diarrhea with a range of 1-18 bowel movements per day, 88% developed nausea, and 60% experienced vomiting. Abdominal CT scans rarely altered patient management, but stool studies were useful in identifying a treatable infectious source. Grade ≥ 2 diarrhea was associated with longer duration of diarrhea, longer length of stay, worse hypoalbuminemia, higher use of antibiotics, abdominal imaging, electrolyte repletions, and anti-diarrheal agents. Risk factors for severe diarrhea were female sex, melphalan dose, age > 50, creatinine clearance < 60 ml/min, and having a plasma cell neoplasm as opposed to lymphoma. Female sex was also associated with more severe nausea and vomiting. In summary, diarrhea remains an important toxicity of HDM and novel therapies for chemotherapy-induced diarrhea for patients undergoing stem-cell transplantation are needed. Grade 2 or higher diarrhea is associated with significant clinical consequences and should be used as the primary endpoint in prospective clinical trials.

As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug-drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for 'COVID-19', '2019-nCoV', '2019 novel coronavirus' and 'SARS-CoV-2'. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms 'COVID-19', 'Comorbidity' and 'Epidemiological Factors'. Potential drug-drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug-drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug-drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug-drug interaction resource to facilitate medication review for the critically ill patient., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The objective of this study was to report the 5-year outcomes of the Food and Drug Administration investigational device exemption clinical trial of endovascular aneurysm repair (EVAR) with the Ovation stent graft (Endologix, Irvine, Calif) for elective treatment of abdominal aortic aneurysm (AAA)., Methods: The study comprised 161 patients who underwent EVAR as part of the prospective, international, multicenter pivotal Ovation stent graft trial. The main inclusion criteria were AAA diameter ≥5 cm, proximal neck length ≥7 mm, neck angulation ≤60 degrees, and bilateral iliac fixation length ≥10 mm. The primary end point was a composite outcome of primary clinical success at 5 years. Primary clinical success was defined in accordance with the Society for Vascular Surgery guidelines as successful aneurysm exclusion without aneurysm-related death, type I or type III endoleak, graft infection or thrombosis, aneurysm expansion, aneurysm rupture, graft migration, or conversion to open repair. Secondary end points included freedom from reintervention, all-cause mortality, and aneurysm-related mortality., Results: Patients were predominantly male (87.6%) and elderly with a mean age of 73 ± 7.7 years; 66 patients (41%) had challenging anatomy and would be considered outside the instructions for use with other stent grafts, 26 (16.2%) had a proximal neck length <10 mm, and 53 (33%) had a minimum access vessel diameter <6 mm. Technical success was 100%. Of 126 surviving patients, 84 (66.7%) completed 5-year follow-up. The 5-year primary clinical success rate was 78%, aneurysm-related mortality was 1% (one patient), and all-cause mortality was 25%. The AAA-related death resulted from AAA post-EVAR rupture at 49 months in a patient who refused treatment for a type IB endoleak. Freedom from type I or type III endoleak was 95.1%. Freedom from secondary interventions was 80.2%. Most of the reinterventions were performed for type II endoleak (24 [63.1%]) or for limb thrombosis or stenosis (7 [18.4%]). There was no graft migration. None of the patients required open conversion., Conclusions: Five-year results from the Ovation pivotal and continued access investigational device exemption trials demonstrate excellent long-term durability of this endograft despite that 41% of patients had anatomy unfit for other stent grafts. There were no migrations or conversions to open repair and 99% freedom from aneurysm-related mortality. These results suggest a less invasive on-label endovascular option for patients with challenging anatomy who may otherwise require hybrid or open repair., (Published by Elsevier Inc.)

Context: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied., Objective: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly., Design and Setting: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center., Patients: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment., Intervention: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day)., Main Outcome Measure: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy., Results: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ± 1375 per month), arm C was most expensive (mean, $22543 ± 11158 per month), and arm A had an intermediate cost (mean, $14261 ± 1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%., Conclusions: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Many people with schizophrenia do not achieve satisfactory improvements in their mental state, particularly the symptom of hearing voices (hallucinations), with medical treatment., Objectives: To examine the effects of Avatar Therapy for people with schizophrenia or related disorders., Search Methods: In December 2016, November 2018 and April 2019, the Cochrane Schizophrenia Group's Study-Based Register of Trials (including registries of clinical trials) was searched, review authors checked references of all identified relevant reports to identify more studies and contacted authors of trials for additional information., Selection Criteria: All randomised clinical trials focusing on Avatar Therapy for people with schizophrenia or related disorders., Data Collection and Analysis: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and 95% confidence intervals (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and 95% CIs. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. Our main outcomes of interest were clinically important change in; mental state, insight, global state, quality of life and functioning as well as adverse effects and leaving the study early., Main Results: We found 14 potentially relevant references for three studies (participants = 195) comparing Avatar Therapy with two other interventions; treatment as usual or supportive counselling. Both Avatar Therapy and supportive counselling were given in addition (add-on) to the participants' normal care. All of the studies had high risk of bias across one or more domains for methodology and, for other risks of bias, authors from one of the studies were involved in the development of the avatar systems on trial and in another trial, authors had patents on the avatar system pending. 1. Avatar Therapy compared with treatment as usual When Avatar Therapy was compared with treatment as usual average endpoint Positive and Negative Syndrome Scale - Positive (PANSS-P) scores were not different between treatment groups (MD -1.93, 95% CI -5.10 to 1.24; studies = 1, participants = 19; very low-certainty evidence). A measure of insight (Revised Beliefs about Voices Questionnaire; BAVQ-R) showed an effect in favour of Avatar Therapy (MD -5.97, 95% CI -10.98 to -0.96; studies = 1, participants = 19; very low-certainty evidence). No one was rehospitalised in either group in the short term (risk difference (RD) 0.00, 95% CI -0.20 to 0.20; studies = 1, participants = 19; low-certainty evidence). Numbers leaving the study early from each group were not clearly different - although more did leave from the Avatar Therapy group (6/14 versus 0/12; RR 11.27, 95% CI 0.70 to 181.41; studies = 1, participants = 26; low-certainty evidence). There was no clear difference in anxiety between treatment groups (RR 5.54, 95% CI 0.34 to 89.80; studies = 1, participants = 19; low-certainty evidence). For quality of life, average Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (QLESQ-SF) scores favoured Avatar Therapy (MD 9.99, 95% CI 3.89 to 16.09; studies = 1, participants = 19; very low-certainty evidence). No study reported data for functioning. 2. Avatar Therapy compared with supportive counselling When Avatar Therapy was compared with supportive counselling (all short-term), general mental state (Psychotic Symptom Rating Scale (PSYRATS)) scores favoured the Avatar Therapy group (MD -4.74, 95% CI -8.01 to -1.47; studies = 1, participants = 124; low-certainty evidence). For insight (BAVQ-R), there was a small effect in favour of Avatar Therapy (MD -8.39, 95% CI -14.31 to -2.47; studies = 1, participants = 124; low-certainty evidence). Around 20% of each group left the study early (risk ratio (RR) 1.06, 95% CI 0.59 to 1.89; studies = 1, participants = 150; moderate-certainty evidence). Analysis of quality of life scores (Manchester Short Assessment of Quality of Life (MANSA)) showed no clear difference between groups (MD 2.69, 95% CI -1.48 to 6.86; studies = 1, participants = 120; low-certainty evidence). No data were available for rehospitalisation rates, adverse events or functioning., Authors' Conclusions: Our analyses of available data shows few, if any, consistent effects of Avatar Therapy for people living with schizophrenia who experience auditory hallucinations. Where there are effects, or suggestions of effects, we are uncertain because of their risk of bias and their unclear clinical meaning. The theory behind Avatar Therapy is compelling but the practice needs testing in large, long, well-designed, well-reported randomised trials undertaken with help from - but not under the direction of - Avatar Therapy pioneers., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Phase II trials are designed to assess the efficacy/toxicity ratio of experimental treatments and select those worth being tested in phase III trials. Although crucial limitations were identified when concurrent chemoradiation (cCRT) phase III trials characteristics were assessed, features of cCRT phase II trials have never been reported. The objective was to describe features of all cCRT phase II trials. Methods and material: Requests were performed in the Medline database (via PubMed). The latest update was performed in April 2016, using the following MESH terms: 'clinical trials: phase II as topic', 'chemoradiotherapy'. Results: Four hundred and fifty-eight cCRT phase II trials were identified. They were mainly multicenter (51.5%), single arm studies (77.7%) published after 2011 (55.0%). The median number of included patients was 52. Primary endpoints were mainly response rate (20.5%), pathological complete response (14.4%) and overall survival (12.6%). The primary endpoint was not defined in 22% of studies. Tumors were mostly lung (23.1%), head and neck (20.3%), colorectal (16.6%) and esophagogastric cancer (14.6%) treated at a locally advanced setting (81.7%). 55.2% of trials used 3D-conformal radiotherapy and 9.1% intensity-modulated radiotherapy, mainly with normo-fractionation (82.0% of the 573 arms with radiotherapy). Radiation technique was not reported in 19.9% of studies. Associated anticancer drugs (563 arms) were mainly conventional chemotherapies (559 arms): cisplatin (46.2%) and 5-fluorouracil (28.3%). Non cytotoxic agents (targeted therapies, immunotherapies) were tested in 97 arms (17%). With a median follow-up of 31 months, acute grades 3-5 were reported in 98.5% of studies and late toxicities in 44.5%. Follow-up was not reported in 17% of studies. Conclusions: cCRT phase II trials featured severe limitations, with outdated radiation techniques, insufficient reporting of crucial data and a small number of included patients. This certainly limited the impact of conclusions and hindered the development of successful phase III trials.

New drugs against advanced melanoma have emerged during last decade. Target therapy and immunotherapy have changed the management of patients with metastatic disease. Along with its generalized use, drug toxicities have appeared and the skin is the target organ of a significant part of them. This revision summarizes the most common side effects and consensus management to improve the compliance of therapies and patients' quality of life. Among the BRAF inhibitors, main cutaneous side effects are photosensitivity, plantar hyperkeratosis, and the appearance of verrucal keratosis or squamous cell carcinoma. Special attention must be paid to the development of new primary melanomas or changes on nevi during BRAF inhibitor therapy. The most common cutaneous side effects of immunotherapy are rash, pruritus, and vitiligo. It remains controversial the possible role of these toxicities as markers of response to therapy.

Background and Objective: Immuno-oncology therapies represent a new treatment opportunity for patients affected by metastatic melanoma. The purpose of this study was to estimate the costs of immune-related adverse events (irAEs) associated with the new anti-PD1 immuno-oncology therapies, with the anti-CTLA-4 immuno-oncology therapy and with the combined therapy (CTLA4 + anti-PD1) in patients affected by metastatic melanoma., Materials and Methods: A probabilistic cost-of-illness (COI) model was developed to estimate the management costs of grade ≥ 3 adverse events associated with the new anti-PD1 therapies (pembrolizumab and nivolumab), the anti-CTLA-4 therapy (ipilimumab) and the combined therapy CTLA4 + anti-PD1 (nivolumab + ipilimumab) for the treatment of patients with metastatic melanoma from the National Health Service (NHS) perspective in Italy. Identification of the epidemiological and cost parameters was carried out through a systematic literature review (SLR). Univariate and probabilistic sensitivity analyses were performed to account for uncertainty and variation in the model results., Results: The model estimated a cost associated with the management of grade ≥ 3 immune-related adverse events in patients with metastatic melanoma equal to €176.2 (95% CI 63.5-335.0) for anti-CTLA-4 therapy, €48.6 (95% CI 40.1-58.5) for the new anti-PDI therapies and €276.8 (95% CI 240.4-316.2) for the combined therapy. Among the innovative therapies for the considered metastatic melanoma, the combined therapy was the most expensive innovative treatment in terms of event management of immune-related grade ≥ 3 adverse events., Conclusion: This study may represent a useful tool to understand the economic burden associated with the management of irAEs associated with patients affected by metastatic melanoma.

Purpose of Review: As benign prostatic hypertrophy (BPH) becomes a more common disease, there has been a dramatic rise in the number of investigational procedures being developed to manage it. We seek to present an overview of the most recently developed treatments and present clinical data related to application wherever available., Recent Findings: As a greater number of treatments become available for BPH, improved diagnostic testing could prove beneficial in helping guide patient selection. Efforts are underway to identify serum biomarkers associated with BPH as well as new classifications strategies, specifically with MRI, to determine both the anatomy of BPH as well as its histologic distribution. Outpatient-based procedures for BPH currently being developed include the temporary implantable nitinol device as well as intraprostatic injections such as Botox and PRX302. Aquablation is a novel technique that uses robotically guided high-pressured saline to ablate prostate tissue. Early data suggests noninferiority compared with TURP. Finally, efforts are underway to apply robotics to BPH with the advent of a robotic transurethral platform being designed for prostate enucleation., Summary: Many new techniques are poised to be introduced to the BPH market over the coming years. The unique risk/benefit profiles as well as associated clinical outcomes of each will need to be studied in detail in order to help identify proper roles in the management of patients with symptomatic disease.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Important advances are afoot in the field of neurosurgery-particularly in the realms of deep brain stimulation (DBS), deep brain manipulation (DBM), and the newly introduced refinement "closed-loop" deep brain stimulation (CLDBS). Use of closed-loop technology will make both DBS and DBM more precise as procedures and will broaden their indications. CLDBS utilizes as feedback a variety of sources of electrophysiological and neurochemical afferent information about the function of the brain structures to be treated or studied. The efferent actions will be either electric, i.e. the classic excitatory or inhibitory ones, or micro-injection of such things as neural proteins and transmitters, neural grafts, implants of pluripotent stem cells or mesenchymal stem cells, and some variants of gene therapy. The pathologies to be treated, beside Parkinson's disease and movement disorders, include repair of neural tissues, neurodegenerative pathologies, psychiatric and behavioral dysfunctions, i.e. schizophrenia in its various guises, bipolar disorders, obesity, anorexia, drug addiction, and alcoholism. The possibility of using these new modalities to treat a number of cognitive dysfunctions is also under consideration. Because the DBS-CLDBS technology brings about a cross-fertilization between scientific investigation and surgical practice, it will also contribute to an enhanced understanding of brain function., (Copyright © 2017. Published by Elsevier Inc.)

Access to the CNS and delivery of therapeutics across the blood-brain barrier remains a challenge for most treatments of major neurological diseases such as AD or PD. Focused ultrasound represents a potential approach for overcoming these barriers to treating AD and PD and perhaps other neurological diseases. Ultrasound (US) is best known for its imaging capabilities of organs in the periphery, but various arrangements of the transducers producing the acoustic signal allow the energy to be precisely focused (F) within the skull. Using FUS in combination with MRI and contrast agents further enhances accuracy by providing clear information on location. Varying the acoustic power allows FUS to be used in applications ranging from imaging, stimulation of brain circuits, to ablation of tissue. In several transgenic mouse models of AD, the use of FUS with microbubbles reduces plaque load and improves cognition and suggests the need to investigate this technology for plaque removal in AD. In PD, FUS is being explored as a way to non-invasively ablate the brain areas responsible for the tremor and dyskinesia associated with the disease, but has yet to be utilized for non-invasive delivery of putative therapeutics. The FUS approach also greatly increases the range of possible CNS therapeutics as it overcomes the issues of BBB penetration. In this review we discuss how the characteristics and various applications of FUS may advance the therapeutics available for treating or preventing neurodegenerative disorders with an emphasis on treating AD and PD., (Copyright © 2017. Published by Elsevier Inc.)

Recent advances in deep brain stimulators and brain-machine interfaces have greatly expanded the possibilities of neuroprosthetics and neuromodulation. Together with advances in neuroengineering, nanotechnology, molecular biology and material sciences, it is now possible to address fundamental questions in neuroscience in new, more powerful ways. It is now possible to apply these new technologies in ways that range from augmenting and restoring function to neuromodulation modalities that treat neuropsychiatric disorders. Recent developments in neuromodulation methods offer significant advantages and potential clinical benefits for a variety of disorders. Here we describe the current state of the art in neuromodulation methods, and some advances in brain-machine interfaces, describing the advantages and limitations of the clinical applications of each method. The future applications of these new methods and how they will shape the future of psychiatry and medicine, along with safety and ethical implications, are also discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: During early clinical testing of a new medication, it is critical to understand and characterise patient tolerability. However, in early clinical studies, it is difficult for patients to contribute directly to the sponsors' understanding of a new compound. Patient reported opinions about clinical tolerability (PROACT) provides a new, simple and innovative way in which patients can collaborate using an application downloaded to a mobile computer or smartphone., Methods: PROACT was designed with special consideration given to patient confidentiality, patient engagement and data security. A pilot study was conducted to investigate patient uptake of PROACT and to characterize clinical trial information it captured. Patients recruited to Phase I oncology trials at a UK center were eligible to participate but were required to have a tablet computer or smartphone. Patients used PROACT to upload audio/video messages that became available instantly to their clinical team, who were able to reply to the patient within PROACT. The patient's message was also analyzed, personally-identifiable information removed and anonymized information then made available to the sponsor in an analytics module for decision-making. In parallel, a patient focus group was engaged to provide feedback on communication needs during early clinical trials and the PROACT concept., Results: Of the 16 patients informed of PROACT, 8 had a smart device and consented to take part. Use of PROACT varied and all messages volunteered were relevant and informative for drug development. Topics disclosed included tolerability impacts, study design, and drug formulation. Alignment with the clinical study data provided a richer understanding of tolerability and treatment consequences. This information was available to be shared among the clinical team and the sponsor, to improve patient support and experience. Patient forum feedback endorsed the concept and provided further information to enhance the application., Conclusion: Overall, PROACT achieved proof of concept in this small pilot study and delivered a secure end-to-end system that protected patient privacy and provided preliminary insight into patient experiences beyond the usual clinical trial data set. The use of mobile devices to interact actively with participants in clinical trials may be a new way of engaging and empowering patients. Further validation of this technology in larger patient cohorts is ongoing., Funding: AstraZeneca.

Competing Interests: M.J.C. has received research funding from CSL, Kowa, MSD, Pfizer and Randox Laboratories, and honoraria for participation in Speakers Bureaux and Advisory Boards of Amgen, AstraZeneca, Kowa, Merck, Pfizer, Sanofi-Regeneron, and Unilever. U.L. has received lecture/advisory board honoraria or research funding from Roche, Sanofi, Amgen, MSD, Pfizer, Servier, Menarini, Astra, St Jude, Orbus&Neich, and Terumo. S.B. reports no disclosures. S.B. has received research funding from Abbott, Abbott Diagnostics, Bayer, Boehringer Ingelheim, SIEMENS and Thermo Fisher. He received honoraria for lectures from Abbott, Abbott Diagnostics, Astra Zeneca, Bayer, Boehringer Ingelheim, Medtronic, Pfizer, Roche, SIEMENS Diagnostics, SIEMENS, Thermo Fisher and as member of Advisory Boards and for consulting for Boehringer Ingelheim, Bayer, Novartis, Roche and Thermo Fisher.

Background: Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment., Methods: We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006., Results: We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches., Conclusions: Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Charcot neuroarthropathy (CN) of the ankle and hindfoot (Sanders/Frykberg Type IV) is challenging to treat surgically or nonsurgically. The deformities associated with ankle/hindfoot CN are often multiplanar, resulting in sagittal, frontal and rotational malalignment. In addition, shortening of the limb often occurs from collapse of the distal tibia, talus and calcaneus. These deformities also result in significant alterations in the biomechanics of the foot. For example, a varus ankle/hindfoot results in increased lateral column plantar pressure of the foot, predisposing the patient to lateral foot ulceration. Collapse of the talus, secondary to avascular necrosis or neuropathic fracture, further accentuates these deformities and contributes to a limb-length inequality., Surgical Management: The primary indication for surgical reconstruction is a nonbraceable deformity associated with instability. Other indications include impending ulceration, inability to heal an ulcer, recurrent ulcers, presence of osteomyelitis and/or significant pain. Arthrodesis of the ankle and/or hindfoot is the method of choice when surgically correcting CN deformities in this region. The choice of fixation (i.e. internal or external fixation) depends on largely on the presence or absence of active infection and bone quality., Conclusion: Surgical reconstruction of ankle and hindfoot CN is associated with a high rate of infectious and noninfectious complications. Despite this high complication rate, surgeons embarking on surgical reconstruction of ankle and hindfoot CN should strive for limb salvage rates approximating 90%. Preoperative measures that can improve outcomes include assessment of vascular status, optimization of glycemic control, correction of vitamin D deficiency and cessation of tobacco use., (Copyright © 2016 John Wiley & Sons, Ltd.)

The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality., (Copyright © 2015 John Wiley & Sons, Ltd.)

With the increased number of diabetics worldwide and the increased incidence of morbid obesity in more prosperous cultures, there has become an increased awareness of Charcot arthropathy of the foot and ankle. Outcome studies would suggest that patients with deformity associated with Charcot Foot arthropathy have impaired health related quality of life. This awareness has led reconstructive-minded foot and ankle surgeons to develop surgical strategies to treat these acquired deformities. This article outlines the current clinical approach to this disabling medical condition., (Copyright © 2016 John Wiley & Sons, Ltd.)

The treatment of diabetic foot ulceration is complex with multiple factors involved, and it may often lead to limb amputation. Hence, a multidisciplinary approach is warranted to cover the spectrum of treatment for diabetic foot, but in complex wounds, surgical treatment is inevitable. Surgery may involve the decision to preserve the limb by reconstruction or to amputate it. Reconstruction involves preserving the limb with secure coverage. Local flaps usually are able to provide sufficient coverage for small or moderate sized wound, but for larger wounds, soft tissue coverage involves flaps that are distantly located from the wound. Reconstruction of distant flap usually involves microsurgery, and now, further innovative methods such as supermicrosurgery have further given complex wounds a better chance to be reconstructed and limbs salvaged. This article reviews the microsurgery involved in reconstruction and introduces the new method of supermicrosurgery., (Copyright © 2016 John Wiley & Sons, Ltd.)

Charcot neuro-osteoarthropathy (CN) is one of the most challenging foot complications in diabetes. Common predisposing and precipitating factors include neuropathy and increased mechanical forces, fracture and bone resorption, trauma and inflammation. In the last 15 years, considerable progress has been made in the early recognition of the acute Charcot foot when the X ray is still negative (stage 0 or incipient Charcot foot). Recent advances in imaging modalities have enabled the detection of initial signs of inflammation and underlying bone damage before overt bone and joint destruction has occurred. Casting therapy remains the mainstay of medical therapy of acute CN. If timely instituted, offloading can arrest disease activity and prevent foot deformity. In cases with severe deformity, modern surgical techniques can correct the unstable deformity for improved functional outcome and limb survival. Emerging new studies into the cellular mechanisms of severe bone destruction have furthered our understanding of the mechanisms of pathological bone and joint destruction in CN. It is hoped that these studies may provide a scientific basis for new interventions with biological agents., (Copyright © 2016 John Wiley & Sons, Ltd.)

With the growing demand for the specialized care of wounds, there is an ever expanding abundance of wound care modalities available. It is difficult to identify which products or devices enhance wound healing, and thus, a critical and continual look at new advances is necessary. The goal of any wound regimen should be to optimize wound healing by combining basic wound care modalities including debridement, off-loading, and infection control with the addition of advanced therapies when necessary. This review takes a closer look at current uses of negative pressure wound therapy, bioengineered alternative tissues, and amniotic membrane products. While robust literature may be lacking, current wound care advances are showing great promise in wound healing., (Copyright © 2016 John Wiley & Sons, Ltd.)

Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012, a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 to June 2014. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 56 articles were eligible for full-text review. There were no randomized controlled trials, but there were four nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70-89%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular techniques. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of conservatively treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients., (Copyright © 2015 John Wiley & Sons, Ltd.)

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation., (Copyright © 2015 John Wiley & Sons, Ltd.)

Aim: To assess effects of umbilical cord milking (UCM) on early blood pressure stabilization, hemoglobin (Hb), as well as incidence of transfusion and complications in preterm infants., Methods: This meta-analysis was conducted by searching the Pubmed, EMBASE and Cochrane Library (until July 2014) databases. Any clinical trials, including randomized control trials, comparing UCM to immediate cord clamping (ICC) were analyzed., Results: Six studies were included in this meta-analysis. In total, 292 preterm infants were treated with UCM, while 295 received ICC. Compared to ICC, UCM increased initial Hb significantly by 1.84 g/dL (weighted mean difference; 95%CI: 0.91-2.76; P < 0.0001) and decreased the incidence of transfusion with a pooled risk ratio of 0.74 (95%CI: 0.61-0.90; P = 0.002). Incidence of necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH) and mortality were significantly lower with UCM compared with ICC. Apgar score and temperature were not significantly different between the two groups., Conclusions: By facilitating the early stabilization of blood pressure, UCM at preterm birth was found to be comparatively safe and associated with lower blood transfusion exposure and lower incidence of IVH, NEC and death., (© 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.)

The management of asthma treatment is likely to change in coming years, with the development of a more personalized approach. Biological therapies targeting Th2 cytokines (IL-4, IL-5 and IL-13) offer new treatment pathways for patients with severe asthma and high Th2 activity. Bronchial thermoplasty is the only treatment for severe asthma that could provide a long standing effect, but many questions still remain and its use is restricted to clinical research. Weight loss should be a goal during long-term management of obese asthmatics. Involvement of a new inflammatory pathway including IL-1 and IL-17 in a murine model of obesity and asthma may lead to new therapies in this subgroup of asthmatics., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

In recent years the therapy of metastatic melanoma has been revolutionized from a disease with very few efficient treatment options to one with access to multiple therapies which can impact on patient survival. Two main classes of therapies have been developed: 1. Immunotherapy by immune checkpoint inhibitors and 2. Small molecule inhibitors of the MAPK pathway. Immunotherapies achieved by either inhibition of CTLA-4 or the PD1/PD-Ll axes are impacting the overall survival in an important fraction of patients. In addition, the side effects of these immune therapy approaches require early detection by all the specialists involved as well as early management according to precise guidelines for optimal outcome.

Despite the application of deep brain stimulation (DBS) as an efficient treatment modality for psychiatric disorders, such as obsessive-compulsive disorder (OCD), Gilles de la Tourette Syndrome (GTS), and treatment refractory major depression (TRD), few patients are operated or included in clinical trials, often for fear of the potential risks of an approach deemed too dangerous. To assess the surgical risks, we conducted an analysis of publications on DBS for psychiatric disorders. A PubMed search was conducted on reports on DBS for OCD, GTS, and TRD. Forty-nine articles were included. Only reports on complications related to DBS were selected and analyzed. Two hundred seventy-two patients with a mean follow-up of 22 months were included in our analysis. Surgical mortality was nil. The overall mortality was 1.1 %: two suicides were unrelated to DBS and one death was reported to be unlikely due to DBS. The majority of complications were transient and related to stimulation. Long-term morbidity occurred in 16.5 % of cases. Three patients had permanent neurological complications due to intracerebral hemorrhage (2.2 %). Complications reported in DBS for psychiatric diseases appear to be similar to those reported for DBS in movement disorders. But class I evidence is lacking. Our analysis was based mainly on small non-randomized studies. A significant number of patients (approximately 150 patients) who were treated with DBS for psychiatric diseases had to be excluded from our analysis as no data on complications was available. The exact prevalence of complications of DBS in psychiatric diseases could not be established. DBS for psychiatric diseases is promising, but remains an experimental technique in need of further evaluation. A close surveillance of patients undergoing DBS for psychiatric diseases is mandatory.

Background: Ulcerative colitis (UC), a chronic inflammatory disease of the large intestine, is characterized by a dysregulated immune reaction. UC is associated with fecal dysbiosis. Human and animal studies support the fact that the gastrointestinal microbiome may trigger the intestinal immune response, resulting in UC. Fecal microbial transplantation (FMT), by changing the gastrointestinal microbiome of patients with UC, may be a therapeutic option., Methods: Four patients with moderate symptoms defined by the Pediatric Ulcerative Colitis Activity Index were enrolled in a prospective, open-label study of FMT via nasogastric tube in pediatric UC (US Food and Drug Administration IND 14942). After the donor and patient evaluation, patients received FMT with follow-up evaluations at 2, 6, and 12 weeks after transplantation. Study subjects were maintained on their pretransplant medications. The Pediatric Ulcerative Colitis Activity Index score, C-reactive protein, and stool calprotectin were completed during each study visit., Results: Four patients with UC were enrolled (all boys). Ages ranged from 13 to 16 years. Patients tolerated FMT without adverse effects. None of the patients clinically improved with FMT, nor were there any significant changes in stool calprotectin or laboratory values, including C-reactive protein, albumin, and hematocrit. Three individuals received additional standard medical therapies before the end of the study., Conclusions: This study, although showing that single-dose FMT via nasogastric tube is well tolerated in active pediatric UC, did not show any clinical or laboratory benefit.

Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.

Radiotherapy is used for inoperable lung cancers, sometimes in association with chemotherapy. Outcomes of conventional radiotherapy are disappointing. New techniques improve adaptation to tumour volume, decrease normal tissue irradiation and lead to increasing tumour dose with the opportunity for improved survival. With intensity-modulated radiation therapy, isodoses can conform to complex volumes. It is widely used and seems to be indicated in locally advanced stages. Its dosimetric improvements have been demonstrated but outcomes are still heterogeneous. Stereotactic radiotherapy allows treatment of small volumes with many narrow beams. Dedicated devices or appropriate equipment on classical devices are needed. In early stages, its efficacy is comparable to surgery with an acceptable toxicity. Endobronchial brachytherapy could be used for early stages with specific criteria. Hadrontherapy is still experimental regarding lung cancer. Hadrons have physical properties leading to very accurate dose distribution. In the rare published studies, toxicities are roughly lower than others techniques but for early stages its effectiveness is not better than stereotactic radiotherapy. These techniques are optimized by metabolic imaging which precisely defines the target volume and assesses the therapeutic response; image-guided radiation therapy which allows a more accurate patient set up and by respiratory tracking or gating which takes account of tumour respiratory motions., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Chronic abruption-oligohydramnios sequence (CAOS), characterized by chronic vaginal bleeding and oligohydramnios, is associated with adverse pregnancy outcomes, including preterm delivery and lung problems in the infant. Fetal lung damage may be induced by not only oligohydramnios but also iron-induced oxidative stress through chronic aspiration of bloody substances in amniotic fluid. We describe a pregnancy complicated with CAOS that was managed with repeated amnioinfusions. This is the first report showing that amnioinfusions succeeded in a significant reduction in high concentrations of iron, lactose dehydrogenase, and 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage, in the amniotic fluid complicated by CAOS. The baby, born at 26 weeks' gestation via cesarean, was discharged home without supplemental oxygen 116 days after birth., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Aim: The prognosis for severe fetal growth restriction (FGR) with severe oligohydramnios before 26 weeks' gestation (WG) is currently poor; furthermore, its management is controversial. We report the innovative new management of FGR, such as therapeutic amnioinfusion and tocolysis., Material and Methods: For FGR and severe oligohydramnios before 26 WG complicated with absent or reversed umbilical artery end-diastolic flow velocity and/or deceleration by ultrasonography, we performed transabdominal amnioinfusion with tocolysis. Cases with multiple anomalies were excluded. Survival rate and long-term prognosis were analyzed., Results: Among 570 FGR cases, 18 were included in the study. Mean diagnosis and delivery were at 22.6 ± 2.0 and 28.7 ± 3.3 WG. Median birthweight was 625 g (-4.2 standard deviation). Final survival rate was 11/13 (85%). There were five fetal deaths. In seven cases, oligohydramnios improved. Growth was detected in 10/18 fetuses. Furthermore, 8/8 decelerations, 4/12 cases of reversed umbilical artery end-diastolic flow velocity, 7/14 cases of brain-sparing effect, and 6/13 venous Doppler abnormalities were improved. When we detected umbilical cord compression, 8/10 cases were rescued. Eleven infants were followed up for an average of 5 years; one case of cerebral palsy with normal development and 10 cases with intact motor functions without major neurological handicap were confirmed., Conclusions: In cases of extremely severe FGR before 26 WG with oligohydramnios and circulatory failure, amnioinfusion might be a promising, innovative tool., (© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.)

It is now appreciated that over 90% of the human genome is comprised of noncoding RNAs that have the ability to affect other components of the genome and regulate gene expression. This has galvanized the development of RNA-based therapeutics for a myriad of diseases, including cancer, inflammatory conditions, and cardiovascular disease. Several classes of RNA therapeutics are currently under clinical development, including antisense oligonucleotides, small interfering RNA, and microRNA mimetics and inhibitors. The field of antisense technology saw a huge leap forward with the recent Food and Drug Administration approval of the first antisense therapy, directed against apolipoprotein B, for the treatment of familial hypercholesterolemia. In addition, recent progress in the development of approaches to inhibit microRNAs has helped to illuminate their roles in repressing gene networks and also revealed their potential as therapeutic targets. In this review, these exciting opportunities in the field of drug discovery, with a focus on emerging therapeutics in the field of cardiovascular disease, are summarized.

Background and Objective: Colonic dysbiosis contributes to the development of colonic inflammation in ulcerative colitis (UC). Fecal microbial transplantation (FMT) is being proposed as a novel treatment for UC because it can eliminate dysbiosis; however, no prospective data exist. We initiated a pilot study to evaluate feasibility and safety of FMT in children with UC., Methods: Ten children, 7 to 21 years of age, with mild-to-moderate UC (pediatric UC activity index [PUCAI] between 15 and 65) received freshly prepared fecal enemas daily for 5 days. Data on tolerability, adverse events, and disease activity were collected during FMT and weekly for 4 weeks after FMT. Clinical response was defined as decrease in PUCAI by >15, and decrease in PUCAI to <10 was considered clinical remission., Results: No serious adverse events were noted. Mild (cramping, fullness, flatulence, bloating, diarrhea, and blood in stool) to moderate (fever) adverse events were self-limiting. One subject could not retain fecal enemas. Average tolerated enema volume by remaining 9 subjects was 165 mL/day. After FMT, 7 of the 9 (78%) subjects showed clinical response within 1 week, 6 of the 9 (67%) subjects maintained clinical response at 1 month, and 3 of the 9 (33%) subjects achieved clinical remission at 1 week after FMT. Median PUCAI significantly improved after FMT (P = 0.03) compared with the baseline., Conclusions: Fecal enemas were feasible and tolerated by children with UC. Adverse events were acceptable, self-limiting, and manageable by subjects. FMT indicated efficacy in the treatment of UC.

To compare the incidence and degree of hematological toxicity between innovator and generic cisplatin formulations, decreases in white blood cell (WBC) count (leukopenia) and platelet counts (thrombocytopenia) were retrospectively examined, using the Common Toxicity Criteria for Adverse Events ver. 4.0, in patients with uterine cervical cancer treated with concurrent chemoradiotherapy using innovator (innovator group, n = 22) or generic (generic group, n = 22) cisplatin formulations. There were no significant differences in patient characteristics except in the technique of external irradiation; larger numbers of patients in the innovator and generic groups were irradiated using the parallel-opposed two-field technique and the four-field box technique, respectively (P = 0.00012), which is in line with the historical progress of external beam radiation therapy. The numbers of patients showing Grade 1, 2, 3 and 4 leukopenia were 1 (4.5%), 14 (64%), 7 (32%) and 0 (0.0%) in the innovator group, and 1 (4.5%), 6 (27%), 13 (59%) and 2 (9.0%) in the generic group, respectively. The number of patients showing Grade 3-4 leukopenia was significantly greater in the generic group than in the innovator group (P = 0.034). There was no significant relationship between the incidence of Grade 3-4 leukopenia and the technique of external irradiation. There were no significant differences in the incidence and degree of thrombocytopenia between the two groups. These results indicate the possibility that the generic cisplatin formulation may have a different toxicity profile compared to the innovator formulation in terms of the incidence of leukopenia.

Background: Electrocautery has been proven to be associated with prolonged serous drainage that might result in several complications in patients requiring axillary lymph node dissection for breast cancer. We proposed that the Harmonic Focus might outperform electrocautery in axillary lymph node dissection, resulting in shorter operative times and reduced postoperative complications., Patients and Methods: One hundred twenty-eight women with confirmed T1-3 N1-2 breast cancer were randomly assigned to undergo mastectomy or breast-conserving surgery with axillary dissection by using Harmonic Focus or electrocautery. Sixty-four has surgery with Harmonic Focus (group A) and 64 with electrocautery (group B) by the same surgical team. Operative time, blood loss, total drainage volume and days, incidence of seroma, hematoma, pain score, and flap necrosis were recorded., Results: Using Harmonic Focus significantly diminished operative time, blood loss, total drainage volume, days of stay, and visual analogue scale as compared with traditional electrocautery. There was no statistical difference between the 2 groups regarding seroma, hematoma, and flap necrosis., Conclusion: Axillary lymph node dissection using Harmonic Focus is feasible, safe, and a more comfortable design for the surgeon., (Copyright © 2012 Elsevier Inc. All rights reserved.)

As cancer treatment becomes more and more effective, there is greater life expectancy for cancer patients. Because of this, depending upon the modality used in the treatment of cancer, the matter of infertility emerges before us as an issue of increasing significance. Sperm cryopreservation and embryo cryopreservation are well-established methods of fertility preservation (FP). Besides these validated FP options, some FP techniques such as oocyte cryopreservation and ovarian tissue cryopreservation are as yet in the experimental stage. FP medicine has experienced some rapid developments in recent years. The advances in this branch of medicine, however, have also brought about new ethical, medical and legal issues. Some of these include problems with obtaining the informed consent of minors, issues that arise because of the experimental nature of some methods, financial problems and the accessibility of FP methods, and the question of what happens to gametes when a patient dies. This review seeks to discuss, in the light of current literature, some ethical and technical issues and risks related to the implementation of FP methods in women with cancer.