Ashwin N. Ram

Outcomes of pyrolytic carbon arthroplasty for the proximal interphalangeal joint.

Background: Arthritis of the proximal interphalangeal joint is a debilitating condition commonly treated with arthroplasty. The pyrolytic carbon (pyrocarbon) implant has been developed for proximal interphalangeal joint arthroplasty in these patients. This prospective outcomes study evaluated the outcomes and complications of the pyrocarbon implant for the proximal interphalangeal joint. Methods: Consecutive candidates for proximal interphalangeal joint arthroplasty with pyrocarbon implants were evaluated prospectively. Functional measurements and the Michigan Hand Outcomes Questionnaire were administered preoperatively and at 3, 6, and 12 months postoperatively. Preoperative means and 12-month postoperative means for all functional measures were compared using paired t tests and nonparametric Wilcoxon signed rank sum test, and effect size was reported for the Michigan Hand Outcomes Questionnaire. Results: Fourteen patients treated with 21 implants were enrolled in the study. At the 12-month follow-up period, mean active arc of motion was 38 degrees, decreasing slightly from the preoperative value. Mean grip strength improved from 11.3 kg to 15.1 kg, although the difference was not statistically significant. Mean key pinch values improved significantly from 6.6 kg preoperatively to 9.2 kg at the 12-month follow-up (p = 0.03). Jebsen-Taylor test scores showed improvement, although not significantly. Changes in all Michigan Hand Outcomes Questionnaire domains showed a large effect size. Three patients experienced squeaking of the implant and three patients experienced dislocation of the pyrocarbon joint. Conclusion: The pyrocarbon implant for proximal interphalangeal joint arthroplasty shows encouraging results, primarily in patient satisfaction and pain relief, but is associated with complications related to implant dislocations, which required prolonged treatment with external fixators.

Evidence-Based Medicine: The Fourth Revolution in American Medicine?

SUMMARY The use of evidence has become a force in American medicine to improve the quality of health care. Funding decisions from payers will demand studies with high-level evidence to support many of the costly interventions in medicine. Plastic surgery is certainly not immune to this national tidal wave to revamp the health care system by embracing evidence-based medicine in our practices. In scientific contributions of plastic surgery research, application of evidence-based principles should enhance the care of all patients by relying on science rather than opinions. In this article, the genesis of evidence-based medicine is discussed to guide plastic surgery in this new revolution in American medicine.

Cotargeting MAPK and PI3K Signaling with Concurrent Radiotherapy as a Strategy for the Treatment of Pancreatic Cancer

There is an urgent need for the development of novel therapies to treat pancreatic cancer, which is among the most lethal of all cancers. KRAS-activating mutations, which are found in more than 90% of pancreatic adenocarcinomas, drive tumor dependency on the Ras/MAPK and Akt signaling pathways. Radiation is currently being explored as a component of the standard treatment regimen for pancreatic cancer. This studys purpose was to test the hypothesis that MAP kinase kinase (MEK or MAP2K) inhibitors will offer clear therapeutic benefit when integrated into radiotherapy treatment regimens for treatment of this disease. We explored the activation of the mitogen-activated protein kinase (MAPK) and Akt pathways in response to radiation in multiple pancreatic tumor cell lines. Small molecule inhibitors of MEK (PD0325901) and Akt (API-2) were subsequently evaluated for their radiosensitizing potential alone and in combination. In vivo efficacy was tested in subcutaneous MIA-PaCa2 xenografts. Phosphorylated levels of extracellular signal–regulated kinase (ERK)-1/2 and Akt were found to increase in response to radiation treatment in our pancreatic tumor cell line panel. MEK inhibitor–induced radiosensitization was observed in vitro and in vivo. The further addition of an Akt inhibitor to the MEK inhibitor/radiation regimen resulted in enhanced therapeutic gain as determined by increased radiosensitization and tumor cell death. In conclusion, MEK inhibition results in growth arrest, apoptosis, and radiosensitization of multiple preclinical pancreatic tumor models, and the effects can be enhanced by combination with an Akt inhibitor. These results provide rationale for further testing of a treatment regimen in pancreatic cancer that combines MEK inhibition with radiation, optimally in conjunction with Akt inhibition. Mol Cancer Ther; 11(5); 1193–202. ©2012 AACR.

Poland's syndrome: current thoughts in the setting of a controversy.

Summary: Poland’s syndrome is a rare congenital disorder that is characterized by hypoplasia of the pectoralis muscles and ipsilateral webbing of the fingers. The name of this condition pays homage to Dr. Alfred Poland of Guy’s Hospital, who in 1841 described a case of these two deformities during the autopsy of a 27-year-old convict. An exploration of the historical series reveals a clear progression of knowledge about this syndrome, accumulated by scientists across Europe and America. As such, the name “Poland’s syndrome” stands as a point of contention to those who oppose the injudicious use of eponyms in medicine. An analysis of the relevant literature reveals a stepwise understanding of what has come to be known as Poland’s syndrome.

Abstract B43: Co-targeting MAPK and PI3K signaling with concurrent radiotherapy as a strategy for the treatment of pancreatic cancer.

There is an urgent need for the development of novel therapies to treat pancreatic cancer, which is among the most lethal of all cancers. KRAS activating mutations, which are found in >90% of pancreatic adenocarcinomas, drive tumor dependency on the Ras/MAPK and Akt signaling pathways. Radiation is currently being explored as a component of the standard treatment regimen for pancreatic cancer. This study9s purpose was to test the hypothesis that MEK inhibitors will offer clear therapeutic benefit when integrated into radiotherapy treatment regimens for treatment of this disease. We explored the activation of the MAPK and Akt pathways in response to radiation in multiple pancreatic tumor cell lines. Small molecule inhibitors of MEK (PD0325901) and Akt (API-2) were subsequently evaluated for their radiosensitizing potential alone and in combination. In vivo efficacy was tested in subcutaneous MIA-PaCa2 xenografts. Phosphorylated levels of ERK-1/2 and Akt were found to increase in response to radiation treatment in our pancreatic tumor cell line panel. MEK inhibitor-induced radiosensitization was observed in vitro and in vivo. The further addition of an Akt inhibitor to the MEK inhibitor/radiation regimen resulted in enhanced therapeutic gain as determined by increased radiosensitization and tumor cell death. In conclusion, MEK inhibition results in growth arrest, apoptosis, and radiosensitization of multiple preclinical pancreatic tumor models, and the effects can be enhanced by combination with an Akt inhibitor. These results provide rationale for further testing of a treatment regimen in pancreatic cancer that combines MEK inhibition with radiation, optimally in conjunction with Akt inhibition. Citation Format: Terence M. Williams, Athena Flecha, Paul Keller, Ashwin Ram, David Karnak, Brian Ross, Theodore Lawrence, Alnawaz Rehemtulla, Judith Sebolt-Leopold. Co-targeting MAPK and PI3K signaling with concurrent radiotherapy as a strategy for the treatment of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B43.

Abstract 5090: Targeted inhibition of MEK and AKT pathways in combination with radiation as a novel treatment paradigm in pancreatic cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL There is an urgent need for the development of novel therapies to treat pancreatic cancer, which is among the most lethal of all cancers. KRAS activating mutations, which are found in >90% of pancreatic adenocarcinomas, drive tumor dependency on the RAS/MAPK and AKT signaling pathways. Radiation is currently being explored in both the post-operative and inoperable settings as a component of the standard treatment regimen for pancreatic cancer. The purpose of this study was to test the hypothesis that MEK inhibitors will offer clear therapeutic benefit when integrated into radiotherapy treatment regimens for treatment of this disease. We explored the activation of the MAPK and AKT pathways in response to radiation in multiple pancreatic tumor cell lines. Small molecule inhibitors of MEK (PD0325901) and AKT (API-2) were subsequently evaluated for their radiosensitizing potential alone and in combination. In vivo efficacy was tested in subcutaneous MiaPaCa2 xenografts and diffusion MRI (dMRI) was explored as a surrogate biomarker of response. Phosphorylated levels of ERK and AKT were found to increase in response to radiation treatment in our pancreatic tumor cell line panel. MEK inhibitor-induced radiosensitization was observed in vitro as well as in vivo, where changes in dMRI strongly correlated with changes in tumor burden. The further addition of an AKT inhibitor to the MEK inhibitor/radiation regimen resulted in enhanced therapeutic gain as measured by radiosensitization and tumor cell death. In conclusion, MEK inhibition results in growth arrest, apoptosis, and radiosensitization of multiple preclinical pancreatic tumor models and the effects can be enhanced by combination with an AKT inhibitor. These results provide rationale for further testing of a treatment regimen in pancreatic cancer that combines MEK inhibition with radiation, optimally in conjunction with AKT inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5090. doi:10.1158/1538-7445.AM2011-5090

Study of Hand Signs in Judeo-Christian Art

Hand gestures play a crucial role in religious art. An examination of Judeo-Christian art finds an ecclesiastical language that is concealed in metaphors and expressed by unique hand gestures. Many of these hand signs convey messages that are not familiar to most people admiring these paintings. Investigating the history and classifying some of the predominant hand signs found in Judeo-Christian art might serve to stimulate discussion concerning the many nuances of symbolic art. This presentation examines the meaning behind 8 common hand signs in Judeo-Christian art.