Topical vascular endothelial growth factor reverses delayed wound healing secondary to angiogenesis inhibitor administration

The prevention of new blood vessel growth is an increasingly attractive strategy to limit tumor growth. However, it remains unclear whether anti-angiogenesis approaches will impair wound healing, a process thought to be angiogenesis dependent. Results of previous studies differ as to whether angiogenesis inhibitors delay wound healing. We evaluated whether endostatin at tumor-inhibiting doses delayed excisional wound closure. C57/BL6J mice were treated with endostatin or phosphate-buffered solution 3 days prior to the creation of two full-thickness wounds on the dorsum. Endostatin was administered daily until wound closure was complete. A third group received endostatin, but also had daily topical vascular endothelial growth factor applied locally to the wound. Wound area was measured daily and the wounds were analyzed for granulation tissue formation, epithelial gap, and wound vascularity. Endostatin-treated mice showed a significant delay in wound healing. Granulation tissue formation and wound vascularity were significantly decreased, but reepithelialization was not effected. Topical vascular endothelial growth factor application to wounds in endostatin-treated mice resulted in increased granulation tissue formation, increased wound vascularity, and wound closure approaching that of control mice. This study shows that the angiogenesis inhibitor endostatin delays wound healing and that topical vascular endothelial growth factor is effective in counteracting this effect.     

The Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) collaborative quality improvement initiative in percutaneous coronary interventions

The past decade has been characterized by increased scrutiny of outcomes of surgical and percutaneous coronary interventions (PCIs). This increased scrutiny has led to the development of regional, state, and national databases for outcome assessment and for public reporting. This report describes the initial development of a regional, collaborative, cardiovascular consortium and the progress made so far by this collaborative group. In 1997, a group of hospitals in the state Michigan agreed to create a regional collaborative consortium for the development of a quality improvement program in interventional cardiology. The project included the creation of a comprehensive database of PCIs to be used for risk assessment, feedback on absolute and risk-adjusted outcomes, and sharing of information. To date, information from nearly 20,000 PCIs have been collected. A risk prediction tool for death in the hospital and additional risk prediction tools for other outcomes have been developed from the data collected, and are currently used by the participating centers for risk assessment and for quality improvement. As the project enters into year 5, the participating centers are deeply engaged in the quality improvement phase, and expansion to a total of 17 hospitals with active PCI programs is in process. In conclusion, the Blue Cross Blue Shield of Michigan Cardiovascular Consortium is an example of a regional collaborative effort to assess and improve quality of care and outcomes that overcome the barriers of traditional market and academic competition.     

Clinical outcomes and risk factors for severe COVID-19 in patients with haematological disorders receiving chemo- or immunotherapy

Haematology patients receiving chemo- or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP). COVID-19 diagnosis coincided with a new diagnosis of a haematological malignancy in four patients. Among patients, 82% were on systemic anti-cancer therapy (SACT) at the time of COVID-19 diagnosis. Of hospitalised patients, 37% (19/51) died while all four outpatients recovered. Risk factors for severe disease or mortality were similar to those in other published cohorts. Raised C-reactive protein at diagnosis predicted an aggressive clinical course. The majority of patients recovered from COVID-19, despite receiving recent SACT. This suggests that SACT, where urgent, should be administered despite intercurrent COVID-19 infection, which should be managed according to standard pathways. Delay or modification of therapy should be considered on an individual basis. Long-term follow-up studies in larger patient cohorts are required to assess the efficacy of treatment strategies employed during the pandemic.     

Mechanical strain alters gene expression in an in vitro model of hypertrophic scarring

Fibroblasts represent a highly mechanoresponsive cell type known to play key roles in normal and pathologic processes such as wound healing, joint contracture, and hypertrophic scarring. In this study, we used a novel fibroblast-populated collagen lattice (FPCL) isometric tension model, allowing us to apply graded biaxial loads to dermal fibroblasts in a 3-dimensional matrix. Cell morphology demonstrated dose-dependent transition from round cells lacking stress fibers in nonloaded lattices to a broad, elongated morphology with prominent actin stress fibers in 800-mg-loaded lattices. Using quantitative real-time RT-PCR, a dose dependent induction of both collagen-1 and collagen-3 mRNA up to 2.8- and 3-fold, respectively, as well as a 2.5-fold induction of MMP-1 (collagenase) over unloaded FPCLs was observed. Quantitative expression of the proapoptotic gene Bax was down-regulated over 4-fold in mechanically strained FPCLs. These results suggest that mechanical strain up-regulates matrix remodeling genes and down-regulates normal cellular apoptosis, resulting in more cells, each of which produces more matrix. This "double burden" may underlie the pathophysiology of hypertrophic scars and other fibrotic processes in vivo.     

Glioblastoma multiforme in a child with acute lymphoblastic leukemia: case report and review of literature

An 11-year-old boy with acute lymphoblastic leukemia had received prophylactic cranial irradiation (1800 cGy /10 fractions) and intrathecal methotrexate. Five years later, he developed a glioblastoma multiforme in the right frontal region while the leukemia was in remission. It is possible that the glioma may have been induced by radiation and /or chemotherapy.     

Rituximab maintenance in relapsed or refractory follicular non-Hodgkin's lymphoma: the evidence of its therapeutic value

INTRODUCTION: Non-Hodgkin's lymphoma (NHL) is the sixth most common malignancy, and follicular lymphoma (FL) is the second most common form of NHL. FL is generally considered to be incurable, and is characterized by periods of remission followed by episodes of relapse, with median survival of 8-10 years. Maintenance treatment is aimed at improving quality of life and survival. AIMS: To review the current evidence for maintenance rituximab in patients with FL. EVIDENCE REVIEW: Two randomized studies of rituximab maintenance or observation after induction therapy with single-agent rituximab, which were performed mainly in patients with relapsed/refractory disease, have demonstrated a two- to three-fold improvement in median progression-free survival (PFS) in the maintenance arm. Two further studies of rituximab maintenance or observation following induction chemotherapy with or without rituximab performed in patients with relapsed/refractory FL have shown a two- to four-fold increase in median PFS in the maintenance arm. In one of these studies an overall survival benefit has also been demonstrated. An additional study, this time in previously untreated patients, has demonstrated a four-fold improvement in median PFS as well as a significant overall survival benefit with rituximab maintenance following induction with chemotherapy alone. PLACE IN THERAPY: Currently rituximab maintenance can be considered to be appropriate therapy for patients with relapsed/refractory disease who have not received rituximab previously and who are not suitable for autologous stem cell transplantation, and for patients who receive first-line therapy with chemotherapy without rituximab.     

Free transverse rectus abdominis myocutaneous flap reconstruction of a massive lumbosacral defect using superior gluteal artery perforator vessels

Despite significant advances in reconstructive surgery, the repair of massive lumbosacral defects poses significant challenges. When the extent of soft tissue loss, tumor resection, and/or radiation therapy preclude the use of traditional local options, such as gluteal advancement flaps or pedicled thigh flaps, then distant flaps are required. We report a case of a 64-year-old male who presented with a large sacral Marjolin's ulcer secondary to recurrent pilonidal cysts and ulcerations. The patient underwent wide local composite resection, which resulted in a wound measuring 450 cm(2) with exposed rectum and sacrum. The massive defect was successfully covered with a free transverse rectus abdominis myocutaneous flap, providing a well-vascularized skin paddle and obviating the need for a latissimus flap with skin graft. The free-TRAM flap proved to be a very robust flap in this situation and would be one of our flaps of choice for similar defects.