Vascularised bone transfer: history, blood supply and contemporary problems

Background Since the description of the free fibula flap by Taylor in 1975, many flaps composed of bone have been described. This review documents the history of vascularised bone transfer and reflects on the current understanding of blood supply in an effort to define all clinically described osseous flaps. Methods A structured review of MEDLINE and Google Scholar was performed to identify all clinically described bone flaps in humans. Data regarding patterns of vascularity were collected where available from the anatomical literature. Results Vascularised bone transfer has evolved stepwise in concert with advances in reconstructive surgery techniques. This began with local flaps of the craniofacial skeleton in the late 19th century, followed by regional flaps such as the fibula flap for tibial reconstruction in the early 20th century. Prelaminated and pedicled myo-osseous flaps predominated until the advent of microsurgery and free tissue transfer in the 1960s and 1970s. Fifty-two different bone flaps were identified from 27 different bones. These flaps can be broadly classified into three types to reflect the pedicle: nutrient vessel (NV), penetrating periosteal vessel (PPV) and non-penetrating periosteal vessel (NPPV). NPPVs can be further classified according to the anatomical structure that serves as a conduit for the pedicle which may be direct-periosteal, musculoperiosteal or fascioperiosteal. Discussion The blood supply to bone is well described and is important to the reconstructive surgeon in the design of reliable vascularised bone suitable for transfer into defects requiring osseous replacement. Further study in this field could be directed at the implications of the pattern of bone flap vascularity on reconstructive outcomes, the changes in bone vascularity after osteotomy and the existence of “true” and “choke” anastomoses in cortical bone

A Scoping Review of Quality of Life Questionnaires in Glaucoma Patients

PRECIS: Multiple questionnaires exist to measure glaucoma's impact on quality of life (QoL). Selecting the right questionnaire for the research question is essential, as is patients' acceptability of the questionnaire to enable collection of relevant patient-reported outcomes. PURPOSE: QoL relating to a disease and its treatment is an important dimension to capture. This scoping review sought to identify the questionnaires most appropriate for capturing the impact of glaucoma on QoL. METHODS: A literature search of QoL questionnaires used in glaucoma, including patient-reported outcomes measures, was conducted and the identified questionnaires were analyzed using a developed quality criteria assessment. RESULTS: Forty-one QoL questionnaires were found which were analyzed with the detailed quality criteria assessment leading to a summary score. This identified the top 10 scoring QoL questionnaires rated by a synthesis of the quality criteria grid, considering aspects such as reliability and reproducibility, and the authors' expert clinical opinion. The results were ratified in consultation with an international panel of ophthalmologists (N=49) from the Educational Club of Ocular Surface and Glaucoma representing 23 countries. CONCLUSIONS: Wide variability among questionnaires used to determine vision related QoL in glaucoma and in the responses elicited was identified. In conclusion, no single existing QoL questionnaire design is suitable for all purposes in glaucoma research, rather we have identified the top 10 from which the questionnaire most appropriate to the study objective may be selected. Development of a new questionnaire that could better distinguish between treatments in terms of vision and treatment-related QoL would be useful that includes the patient perspective of treatment effects as well as meeting requirements of regulatory and health authorities. Future work could involve development of a formal weighting system with which to comprehensively assess the quality of QoL questionnaires used in glaucoma

Alerted default mode: functional connectivity changes in the aftermath of social stress

Contains fulltext : 174396.pdf (publisher's version ) (Open Access)Stress affects the brain at a network level: the salience network is supposedly upregulated, while at the same time the executive control network is downregulated. While theoretically described, the effects in the aftermath of stress have thus far not been tested empirically. Here, we compared for the first time resting-state functional connectivity in a large sample of healthy volunteers before and after a mild social stressor. Following the theoretical prediction, we focused on connectivity of the salience network (SN), the executive control network (ECN) and the default mode network (DMN). The DMN exhibited increased resting-state functional connectivity following the cyberball task to the key nodes of the SN, namely the dorsal anterior cingulate cortex (dACC) and the anterior insula, as well as sensorimotor regions and higher-order visual areas. We conclude that this increased connectivity of the DMN with key nodes of the SN and regions responsible for preparatory motor activity and visual motion processing indicates a shift towards an 'alerted default mode' in the aftermath of stress. This brain response may be triggered or aggravated by (social) stress induced by the cyberball task, enabling individuals to better reorient attention, detect salient external stimuli, and deal with the emotional and affective consequences of stress

Pythium insidiosum keratitis confirmed by DNA sequence analysis

Case report/letter detailing identification of the pathogen pythium insidiosum by nucleic acid sequencing

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma

BACKGROUNDIn-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction

Patients with in-transit melanoma metastases have comparable survival outcomes following isolated limb infusion or intralesional PV-10-A propensity score matched, single center study

Isolated limb infusion (ILI) and intralesional PV-10 are well described locoregional therapies for in-transit melanoma. The objective of this study was to assess the effect of these treatments on survival outcomes within a cohort matched for key characteristics.Patients were treated using ILI or intralesional PV-10 at a single institution and the data prospectively recorded. Propensity score matching was performed using key covariates within a logistic regression model. The primary outcome was the melanoma-specific survival.Seventy-two patients nonrandomized were successfully matched. Both treatments produced similar best overall responses. The median melanoma-specific survival (MSS) was 74.4 months from ILI and 36.4 months from PV-10 treatments (P = 0.164). Within the ILI subgroup, the 12-, 24-, 36- and 60-month MSS rates were 85.3%, 75.3%, 60.1%, and 60.1%, respectively. From the time of PV-10 the corresponding 12-, 24-, 36-, and 60-month MSS rates were 82.6%, 70.0%, 53.9%, and 35.9%. On multivariate analysis, there was a significant difference in survival comparing completely with noncomplete responders ( P = 0.031).These findings demonstrate that ILI and PV-10 treatments for in-transit disease produce comparable long-term survival. Both therapies have reproducible response rates and predominantly localized and tolerable side-effects

Switching from protease inhibitors to efavirenz: differences in efficacy and tolerance among risk groups: a case-control study from the Swiss HIV Cohort

OBJECTIVES: Many patients have simplified their therapy by replacing protease inhibitors (PI) with efavirenz. In a large cohort study representative of clinical practice, we compared outcomes in patients who replaced PI with efavirenz (switchers), with patients who continued on PI (non-switchers). We investigated the likelihood of virological failure in switchers and non-switchers, and the tolerance of efavirenz-containing regimens in different transmission risk groups. DESIGN, SETTING, AND METHODS: Using the database of the Swiss HIV Cohort Study, we identified patients who switched from PI-containing to efavirenz-containing highly active antiretroviral therapy for reasons of tolerance, toxicity, or convenience. Switchers were matched to non-switchers on the basis of calendar time, CD4 cell count, and viral load. RESULTS: The probability of virological failure was less in patients who switched to efavirenz values after one year: 9.4% [95% confidence interval (CI) 5.5-15.9] versus 27.2% (95% CI 21.5-34.1), odds ratio (OR) for failure 0.34. The effect was more pronounced when injection drug users (IDU) were omitted from the analysis (OR 0.19, 95% CI 0.09-0.43); it was absent in IDU (OR 0.95, 95% CI 0.44-2.04). IDU stopped efavirenz more frequently during the first 2 months of treatment than non-IDU [22.6% (95% CI 11.5-41.6) versus 6.6% (95% CI 3.6-11.8) at 2 months]. No difference between IDU and non-IDU was evident when the frequency of stopping indinavir or nelfinavir was measured. CONCLUSION: Switchers had less virological failure and less chance of further treatment changes than non-switchers. However, efavirenz was less successful in IDU than in other transmission categories

Protocol for the TIDAL Melanoma Study: topical imiquimod or diphenylcyclopropenone for the management of cutaneous in-transit melanoma metastases-a phase II, single centre, randomised, pilot study

Patients with in-transit melanoma metastases present a therapeutic challenge. Complete surgical excision of localised disease is considered as the gold standard; however, surgery is not always acceptable and alternatives are required. Treatment results reported using imiquimod and diphenylcyclopropenone (DPCP) suggest that topical immunotherapies can be used to successfully treat select patients with melanoma metastases. A phase II, randomised, single centre, pilot study was designed to assess the clinical efficacy and safety of DPCP and imiquimod for the treatment of superficial, cutaneous in-transit melanoma metastases.This is an open-label, non-superiority, pilot study with no treatment cross-over. Eligible patients are randomised in a 1:1 ratio to receive topical therapy for up to 12 months with a minimum follow-up period of 12 months. The target sample size is 30 patients, with 15 allocated to each treatment arm. The primary endpoint is the number of patients experiencing a complete response of treated lesions as determined clinically using Response Evaluation Criteria in Solid Tumours. This trial incorporates health-related quality of life measures and biological tissue collection for further experimental substudies. The study will also facilitate a health economic analysis.Approval was obtained from the Human Research Ethics Committee at the participating centre, and recruitment has commenced. The results of this study will be submitted for formal publication within a peer-reviewed journal.Prospectively registered on 16 October 2015 with the Australian New Zealand Clinical Trials Registry (ACTRN12615001088538). This study conforms to WHO Trial Registration Data Set