Trends in the Types of Physicians Performing Partial Foot Amputations.

BACKGROUND: Partial foot amputations (PFAs) are often indicated for the treatment of severe infection, osteomyelitis, and critical limb ischemia, which consequently leads to irreversible necrosis. Many patients who undergo PFAs have concomitant comorbidities and generally present with a severe acute manifestation of the condition, such as gangrenous changes, systemic infection, or debilitating pain, which would then require emergency amputation on an inpatient basis. METHODS: The purpose of this study was to track the recent prevalence of PFAs and to investigate the current demographic trends of the physicians managing and performing PFAs, specifically regarding medical degree and specialty. Doctors of podiatric medicine are striving to achieve parity with their allopathic and osteopathic surgical counterparts and become a more prominent part of the multidisciplinary approach to limb salvage and emergency surgical treatment. This study evaluated 4 years (2009-2012) of PFA data from the Pennsylvania state inpatient database in the two most populated areas of Pennsylvania: Philadelphia and Allegheny counties. Statistics on medical schools were obtained directly from the accrediting bodies of allopathic, osteopathic, and podiatric medical schools. The goal of this study was to evaluate the general trends of patients undergoing a PFA and to quantify the upswing of podiatric surgeons intervening in the surgical care of these patients. RESULTS: The number of partial foot amputations in the United States rose from 2006 to 2012. Podiatric surgeons performed 46% of theses procedures for residents of Philadelphia County from 2009 to 2012. In Allegheny County podiatric physicians performed 42% of these procedures during the same time frame. CONCLUSIONS: Partial foot amputations are increasing over time. Podiatric Surgeons perform a significant share of these operations. This share is increasing in the most populated areas of Pennsylvania.

Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw) mice.

BACKGROUND: New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-Abeta28 conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP) transgenic mice (Tg2576). METHODS: Mannan was purified, activated and chemically conjugated to Abeta28 peptide. Humoral immune responses induced by the immunization of mice with mannan-Abeta28 conjugate were analyzed using a standard ELISA. Abeta42 and Abeta40 amyloid burden, cerebral amyloid angiopathy (CAA), astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry. RESULTS: Immunizations with low doses of mannan-Abeta28 induced potent and long-lasting anti-Abeta humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-Abeta antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-Abeta28 prevented Abeta plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant antigen, BSA (mannan-BSA) or non-immunized mice. Of note, mice immunized with mannan-Abeta28 showed a trend toward elevated levels of CAA in the neocortex and in the leptomeninges compared to that in mice of both control groups. CONCLUSION: Mannan conjugated to Abeta28 provided sufficient adjuvant activity to induce potent anti-Abeta antibodies in APP transgenic mice, which have been shown to be hyporesponsive to immunization with Abeta self-antigen. However, in old Tg2576 mice there were increased levels of cerebral microhemorrhages in mannan-Abeta28 immunized mice. This effect was likely unrelated to the anti-mannan antibodies induced by the immunoconjugate, because control mice immunized with mannan-BSA also induced antibodies specific to mannan, but did not have increased levels of cerebral microhemorrhages compared with non-immunized mice. Whether these anti-mannan antibodies increased the permeability of the blood brain barrier thus allowing elevated levels of anti-Abeta antibodies entry into cerebral perivascular or brain parenchymal spaces and contributed to the increased incidence of microhemorrhages remains to be investigated in the future studies.