Search

Vitiligo is an autoimmune skin disease mediated by autoreactive CD8+ T cells that destroy the pigmentproducing cells of the epidermis, melanocytes, leading to areas of depigmentation. Patients with vitiligo require lifelong treatment to regain and maintain their pigment. Clinical observations uncovered the importance of autoimmune memory in vitiligo because cessation of treatment frequently led to relapse of disease at the site of previous lesions. A subset of memory T cells known as CD8+ resident memory T cells (TRM) are long-lived, nonmigratory memory cells that persist in most nonlymphoid tissues, including the skin. Recent reports describe the presence of CD8+ TRM in lesional vitiligo patient skin and suggest their role as active players in disease maintenance. In this review, we will discuss the role of skin CD8+ TRM in maintaining disease in vitiligo and the opportunity to target this population to induce a long-lasting reversal of disease. [ABSTRACT FROM AUTHOR]

Objective: To determine if the use of intraoperative hemostatic agents was a risk factor for post-operative adverse events within 30 days of patients undergoing hysterectomy.Method: A population-based retrospective cohort study included data from patients undergoing hysterectomy for any indication between January 1, 2013, and December 31, 2014, at 52 hospitals in Michigan, USA. Any individuals with missing covariate data were excluded, and multivariable logistic regression and propensity score-matching were used to estimate the rate of post-operative adverse events associated with intra-operative hemostatic agents independent of demographic and surgical factors.Results: There were 17 960 surgical procedures included in the analysis, with 4659 (25.9%) that included the use of hemostatic agents. Hemostatic agent use was associated with an increase in predicted hospital re-admissions (P=0.007). Among all hysterectomy approaches, and after adjusting for demographic and surgical factors, hemostatic agent use during robotic-assisted laparoscopic hysterectomy was associated with an increased predicted rate of blood transfusions (P=0.019), an increased predicted rate of pelvic abscess diagnoses (P=0.001), an increased predicted rate of hospital re-admission (P=0.001), and an increased predicted rate of re-operation (P=0.021).Conclusion: Hemostatic agents should be used carefully owing to associations with increased post-operative re-admissions and re-operations when used during hysterectomy. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30–40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. [ABSTRACT FROM AUTHOR]

The author discusses various articles 25, 50 and 75 years ago. They include "Achalasia of the esophagus: Results of treatment," by C. O. H. Russell and colleagues, "Circulatory refilling after surgery: I-Effects of replacement with whole blood, electrolyte or protein solution," by V. Marshall, and "Pulp traction: The stilette method" by B. T. Keon-Cohen.

This section recalls articles published in 1993, 1968, and 1943 issues of "ANZ Journal of Surgery." Topics of the articles include the case against open neck biopsy, the use of reno-portal anastomosis in the treatment of portal hypertension, and filtration efficiency of surgical masks as a method of evaluation.

The article presents abstracts on surgical topics which include abdominal incisional hernia, pharyngeal pouch treatment, and neck fracture of the femur.

The article presents several papers published in the journal in 1940, 1965 and 1990. The topics of the papers include the decrease in the incidence of stomach carcinoma, considered as one of the most common causes of cancer-related death in the U.S. and Australia, the advances in the treatment of deformities of the spine and lower limbs in spina bifida and the use of thoracoplasty for the treatment of pulmonary tuberculosis.

The article discusses the moderate improvement in survival of breast cancer patients which is attributed to an increased detection of early stage breast cancer. The little improvement of changes in therapy with regards to survival rates is mentioned. The contribution of wider community awareness and education about breast cancer that helped the improvement is also cited.

Background: Norovirus is the leading cause of community-acquired and nosocomial acute gastroenteritis. Routine testing for norovirus is seldom undertaken, and diagnosis is mainly based on presenting symptoms. This makes understanding the burden of medically attended norovirus-attributable gastroenteritis (MA-NGE) and targeting care and prevention strategies challenging.Methods: We used linked population-based healthcare datasets (Clinical Practice Research Datalink General Practice OnLine Database linked with Hospital Episode Statistics Admitted Patient Care) to model the incidence of MA-NGE associated with primary care consultations or hospitalizations according to age groups in England in the period July 2007-June 2013.Results: Mean annual incidence rates of MA-NGE were 4.9/1000 person-years and 0.7/1000 person-years for episodes involving primary care or hospitalizations, respectively. Incidence rates were highest in children aged <5 years: 34.0 consultations/1000 person-years and 3.3 hospitalizations/1000 person-years. Medically attended norovirus-attributable gastroenteritis hospitalization rates were second highest in adults aged >65 years (1.7/1000 person-years).Conclusions: In this particular study, the burden of MA-NGE estimated from healthcare datasets was higher than previously estimated in small cohort studies in England. Routinely collected primary care and hospitalization datasets are useful resources to estimate and monitor the burden of MA-NGE in a population over time. [ABSTRACT FROM AUTHOR]

The author reflects on the suggestions of a reader regarding the need to focus on giving knowledge about perioperative care .Topics include the growing interest in education and training in perioperative care, professional development, and the significance of perioperative care in the surgical robotics, oncology settings, and multimodal therapy.

Objective: To compare preoperative chlorhexidine-alcohol topical antiseptic agent with povidone-iodine in patients undergoing abdominal hysterectomy for benign indications.Methods: A retrospective cohort study of patients undergoing abdominal hysterectomy from July 2012 to February 2015 in the Michigan Surgical Quality Collaborative was performed. The primary exposure was the use of chlorhexidine-alcohol or povidone-iodine. The primary outcome was surgical site infection within 30 days. Multivariable logistic regression and propensity score matching analysis were done to estimate the independent association of skin antiseptic choice on the rate of surgical site infection.Results: Of the total 4,259 abdominal hysterectomies included, chlorhexidine-alcohol was used in 70.5% (n=3,005) and povidone-iodine in 29.5% (n=1,254) of surgeries. The overall unadjusted rate of any surgical site infection was 2.9% (95% CI 2.5-3.5; n=124). The unadjusted rate of surgical site infection 2.6% (95% CI 2.1-3.3; n=79) for chlorhexidine-alcohol and 3.6% (95% CI 2.7-4.8; n=45; P=.09) for the povidone-iodine group. Using multivariate logistic regression and adjusting for differences between populations in patient demographic factors (age and body mass index), medical comorbidities (American Society of Anesthesiologists class and diabetes status), perioperative variables (estimated blood loss, surgical time, intraoperative adhesions, and antibiotic categories), and hospital characteristics (bed size and teaching status), we estimate that patients receiving chlorhexidine-alcohol had 44% lower odds of developing a surgical site infection (adjusted odds ratio 0.56, 95% CI 0.37-0.85, P=.01). Propensity score matching (one to one) yielded 808 patients in the chlorhexidine-alcohol group and 845 patients in the povidone-iodine group. In the matched groups, the rate of surgical site infection was 1.5% (95% CI 0.8-2.6; n=12) for the chlorhexidine-alcohol group and 4.7% (95% CI 3.5-6.4; n=40) for the povidone-iodine group (P<.001).Conclusion: In abdominal hysterectomy performed for benign indications, chlorhexidine-alcohol-based skin antisepsis is associated with overall lower odds of surgical site infection compared with povidone-iodine. [ABSTRACT FROM AUTHOR]

The Vitiligo Global Issues Consensus Conference ( VGICC), through an international e-Delphi consensus, concluded that 'repigmentation' and 'maintenance of gained repigmentation' are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e-surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus. [ABSTRACT FROM AUTHOR]

Background: Terminology and classifications are the vehicles by which pathologic conditions are identified and understood. It is critically important for the patient admitted with suspected blunt thoracic aortic injury that admitting physicians have a thorough knowledge of acute traumatic aortic tear and its natural history. Objectives: The objectives of this review were as follows: (1) to introduce a pathology-based terminology and classification of acute traumatic aortic injuries that unambiguously defines each, and (2) to emphasize the clinical relevance of acute traumatic tear to post-hospital admission deaths in blunt thoracoabdominally injured patients. Methods: This is a literature review of 32 refereed articles pertaining to acute traumatic thoracic aortic injury published from 1957 to the present. Results: The terminology used to describe aortic injury is inconsistent. Several terms are often loosely interchanged: tear, laceration, transection, and rupture. Furthermore, classifications of aortic injuries have been proposed based on microscopic or gross pathologic or computed tomography scan results. While microscopically-based classifications have little or no clinical application, a classification based on gross pathology provides information useful for aortic injury prognosis and management. Conclusion: Reduction of post-hospital death caused by acute aortic tear requires knowledge and understanding of the pathology of acute traumatic aortic tear and its natural history. Such understanding of pathology of acute traumatic aortic tear and its natural history is enhanced by terminology that defines the aortic injury. Therefore, we present our proposed terminology and classification of acute traumatic injuries. [ABSTRACT FROM AUTHOR]

The article offers information on a study to develop international consensus over a core outcome set for vitiligo trials that is acceptable to healthcare professionals, patients and their caregivers. Topics discussed include use of Delphi technique for the study, patients' views on the effectiveness of a treatment for vitiligo, and quality of life of patients with vitiligo.

Vitiligo is a common autoimmune disease of the skin that results in disfiguring white spots. There are no Food and Drug Administration (FDA)-approved treatments, and current treatments are time-consuming, expensive, and of low efficacy. We sought to identify new treatments for vitiligo, and first considered repurposed medications because of the availability of safety data and expedited regulatory approval. We previously reported that the IFN-γ-induced chemokine CXCL10 is expressed in lesional skin from vitiligo patients, and that it is critical for the progression and maintenance of depigmentation in our mouse model of vitiligo. We hypothesized that targeting IFN-γ signaling might be an effective new treatment strategy. Activation of signal transducer and activator of transcription 1 (STAT1) is required for IFN-γ signaling and recent studies revealed that simvastatin, an FDA-approved cholesterol-lowering medication, inhibited STAT1 activation in vitro. Therefore, we hypothesized that simvastatin may be an effective treatment for vitiligo. We found that simvastatin both prevented and reversed depigmentation in our mouse model of vitiligo, and reduced the number of infiltrating autoreactive CD8+ T cells in the skin. Treatment of melanocyte-specific, CD8+ T cells in vitro decreased proliferation and IFN-γ production, suggesting additional effects of simvastatin directly on T cells. Based on these data, simvastatin may be a safe, targeted treatment option for patients with vitiligo. [ABSTRACT FROM AUTHOR]

Abstract: MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds. [Copyright &y& Elsevier]