Low Incidence of Community-Acquired Pneumonia among Human Immunodeficiency Virus-Infected Patients after Interruption of Pneumocystis carinii Pneumonia Prophylaxis

We compared the incidence of bacterial pneumonia among 336 patients who discontinued trimethoprim-sulfamethoxazole (TMP-SMX) as prophylaxis against Pneumocystis carinii pneumonia (PCP) with that among 75 patients who fulfilled the criteria for discontinuation but continued receiving prophylaxis. The difference in the overall incidence rates for the 2 groups (1.2 events per 100 person-years) was not statistically significant. Discontinuation of TMP-SMX prophylaxis against PCP is not associated with a significant increase in the incidence of bacterial pneumonia among patients with a sustained CD4 cell count increase to >200 cells/μ

Pulmonary Arterial Hypertension Related to HIV Infection: Improved Hemodynamics and Survival Associated with Antiretroviral Therapy

This study aimed to assess the long-term course of pulmonary arterial hypertension related to infection with human immunodeficiency virus (PAHRH) and the influence of antiretroviral therapy (ART) on its characteristics. We retrospectively analyzed all 47 patients in the Swiss HIV Cohort Study in whom PAHRH was diagnosed. Among 35 patients who underwent follow-up Doppler echocardiography, the right ventricular systolic pressure over right atrial pressure gradient increased by a median of 25 mm Hg in 9 patients who had not received ART, decreased by a median of 3 mm Hg in 12 patients who had received nucleoside analogs, and decreased by a median of 21 mm Hg in 14 patients who had received highly active ART (HAART) (P < .005). Among all 47 patients, median duration of survival after PAHRH diagnosis was 2.7 years. HAART significantly decreased mortality due to PAHRH as well as other causes. This study suggests a beneficial effect of combination ART in patients with PAHR

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

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

Intralesional PV-10 for the treatment of in-transit melanoma metastases-Results of a prospective, non-randomized, single center study

Background: Patients with in-transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi-center study, PV-10 treatment was continued at our institution for patients with in-transit disease. Methodology: An open-label, non-randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV-10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions. Results: Forty-five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV-10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow-up duration was 22 months and the median overall survival was 25 months from first PV-10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response (P = 0.03). Conclusions: Intralesional PV-10 provided rapid lesion-specific ablation of melanoma metastases with well-tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume

Protocol for the BONE-RECON trial: a single-arm feasibility trial for critical sized lower limb BONE defect RECONstruction using the mPCL-TCP scaffold system with autologous vascularised corticoperiosteal tissue transfer

Introduction Reconstruction of critical bone defects is challenging. In a substantial subgroup of patients, conventional reconstructive techniques are insufficient. Biodegradable scaffolds have emerged as a novel tissue engineering strategy for critical-sized bone defect reconstruction. A corticoperiosteal flap integrates the hosts’ ability to regenerate bone and permits the creation of a vascular axis for scaffold neo-vascularisation (regenerative matching axial vascularisation—RMAV). This phase IIa study evaluates the application of the RMAV approach alongside a custom medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold (Osteopore) to regenerate bone sufficient to heal critical size defects in lower limb defects.Methods and analysis This open-label, single-arm feasibility trial will be jointly coordinated by the Complex Lower Limb Clinic (CLLC) at the Princess Alexandra Hospital in Woolloongabba (Queensland, Australia), the Australian Centre for Complex Integrated Surgical Solutions (Queensland, Australia) and the Faculty of Engineering, Queensland University of Technology in Kelvin Grove (Queensland, Australia). Aiming for limb salvage, the study population (n=10) includes any patient referred to the CLLC with a critical-sized bone defect not amenable to conventional reconstructive approaches, after discussion by the interdisciplinary team. All patients will receive treatment using the RMAV approach using a custom mPCL-TCP implant. The primary study endpoint will be safety and tolerability of the reconstruction. Secondary end points include time to bone union and weight-bearing status on the treated limb. Results of this trial will help shape the role of scaffold-guided bone regenerative approaches in complex lower limb reconstruction where current options remain limited.Ethics and dissemination Approval was obtained from the Human Research Ethics Committee at the participating centre. Results will be submitted for publication in a peer-reviewed journal.Trial registration number ACTRN12620001007921

Migrants from Sub-Saharan Africa in the Swiss HIV Cohort Study: access to antiretroviral therapy, disease progression and survival

OBJECTIVE: To examine the proportion of migrants from Sub-Saharan Africa entering the Swiss HIV Cohort Study (SHCS) and to compare these participants with participants from Northwestern Europe for access to antiretroviral therapy, progression to AIDS and survival. DESIGN: Prospective national cohort study of HIV-1-infected adults from seven HIV centres in Switzerland. METHODS: Trends in the proportion of participants from Sub-Saharan Africa were followed in 11 872 HIV-infected adults entering the SHCS from 1984 to 2001. Survival methods were used to compare uptake of antiretroviral therapy, survival and progression to AIDS in the 2684 participants from Sub-Saharan Africa and Northwest Europe enrolled from 1997-2001. RESULTS: There was a steady increase in the proportion of Sub-Saharan African participants over time, reaching 11.9% in 1997-2001. These participants were more likely to be younger, female, to have been infected by heterosexual intercourse and had lower CD4 cell counts at presentation. There were no differences between Sub-Saharan Africans and Northwest Europeans in uptake of triple antiretroviral therapy, progression to AIDS or survival up to 48 months after starting treatment. Tuberculosis was the most frequent AIDS-defining event in Sub-Saharan African patients. CONCLUSIONS: There is no evidence that access to potent antiretroviral therapy is influenced by geographic origin of participants. The prognosis of Sub-Saharan African patients on triple therapy is equivalent to that of Northwest European patients. Future research should address wider issues about access to specialist health services for HIV-infected people from Sub-Saharan Africa

Assessment of morbidity following regional nodal dissection in the axilla and groin for metastatic melanoma

BackgroundThis study assessed and compared the morbidity of nodal dissection in the axilla and groin including sentinel lymph node biopsy (SLNB), completion lymph node dissection for a positive SLNB (CLND) and therapeutic lymph node dissection (TLND) with and without adjuvant radiotherapy (RT)

Pectus excavatum camouflage : a new technique using a tissue engineered scaffold

Pectus excavatum is the most common congenital chest wall deformity. Customised silicone implants have been used to camouflage this deformity with good short-term outcomes. In the long term, permanent implants have a significant risk of capsular contracture, migration and extrusion. Scaffold-guided tissue engineering provides an alternative autologous solution which avoids issues associated with permanent implants. We implanted a 3D-printed, custom-made, biodegradable and highly porous scaffold filled with autologous fat graft. We were able to sustain autologous fat in the construct. There was an excellent aesthetic outcome and the highly porous polycaprolactone implant was well tolerated by the patient. This case illustrates the first-in-human trial of soft tissue engineering to camouflage a pectus excavatum defect not reconstructable by conventional techniques. Level of evidence: Level V, therapeutic study.</p