XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome(APS)

Cardiogenic shock is a high-acuity, potentially complex, and hemodynamically diverse state of end-organ hypoperfusion that is frequently associated with multisystem organ failure. Despite improving survival in recent years, patient morbidity and mortality remain high, and there are few evidence-based therapeutic interventions known to clearly improve patient outcomes. This scientific statement on cardiogenic shock summarizes the epidemiology, pathophysiology, causes, and outcomes of cardiogenic shock; reviews contemporary best medical, surgical, mechanical circulatory support, and palliative care practices; advocates for the development of regionalized systems of care; and outlines future research priorities.

Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association

There are more than half a million incident cases of squamous-cell carcinoma of the head and neck worldwide each year, primarily affecting the oropharynx, oral cavity, hypopharynx, and larynx. This review considers the biologic features of these tumors, including the role of human papillomavirus as a risk factor for cancer of the oropharynx. New therapies are considered, along with management approaches.

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Recent Advances in Head and Neck Cancer

We have identified a new role for the matrix enzyme lysyl oxidase-like-2 (LOXL2) in the creation and maintenance of the pathologic microenvironment of cancer and fibrotic disease. Our analysis of biopsies from human tumors and fibrotic lung and liver tissues revealed an increase in LOXL2 in disease-associated stroma and limited expression in healthy tissues. Targeting LOXL2 with an inhibitory monoclonal antibody (AB0023) was efficacious in both primary and metastatic xenograft models of cancer, as well as in liver and lung fibrosis models. Inhibition of LOXL2 resulted in a marked reduction in activated fibroblasts, desmoplasia and endothelial cells, decreased production of growth factors and cytokines and decreased transforming growth factor-beta (TGF-beta) pathway signaling. AB0023 outperformed the small-molecule lysyl oxidase inhibitor beta-aminoproprionitrile. The efficacy and safety of LOXL2-specific AB0023 represents a new therapeutic approach with broad applicability in oncologic and fibrotic diseases.

http://basicmed.med.ncku.edu.tw/admin/up_img/0325-1.pdf

Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment.

Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs); however, SSI after hepatobiliary and pancreatic surgery (HBPS) has not been well investigated in a large cohort of patients. This study analyzed the factors associated with SSI following HBPS in Japan, using a Japanese national database. Data on HBPS performed between 2012 and 2014 were extracted from a national monitoring system for HAI: The Japan Nosocomial Infections Surveillance. Using multivariate logistic regression, I assessed the factors associated with SSI. The cumulative incidence of SSI following HBPS was 15.6% (2873/18,398). The incidence of SSI after pancreatoduodenectomy was 28.0%, which was significantly higher than that after liver resection and other types of HBPS (8.8 and 15.5%, respectively). Among the four traditional risk factors, the American Society of Anesthesiologists score was ineffective for predicting SSI in the final model of all three types of surgery. Additional risk factors were identified, including age and male gender. The incidence of and factors associated with SSI after the three types of HBPS analyzed differed significantly. To accurately compare hospital performance in relation to SSI following HBPS, the operative procedure category in the surveillance system must be divided into three types.

Epidemiology and risk factors associated with surgical site infection after different types of hepatobiliary and pancreatic surgery

Background/Aims : Duodenum-preserving resection of the head of the pancreas has been performed for benign and, sometimes, malignant diseases of the pancreas. We propose a new procedure of duodenum-preserving subtotal pancreatectomy of the pancreas according to the precise anatomy of the pancreatoduodenal region, especially of the pancreaticoduodenal arteries which provide blood to the duodenum. Material and Methods : After a complete Kocher's maneuver is performed, the pancreas is cut above the portal vein and removed from the third portion of the duodenum, followed by the removal of the posterior surface of the pancreas head from a connective tissue membrane. The main pancreatic duct is identified at its junction with the terminal portion of the bile duct from the posterior surface of the head of the pancreas and is cut at the junction. The pancreas is cut in the line of the ASPD. This line is almost the same as the left side of the common bile duct. The ASPD and the common bile duct should be preserved in this procedure. Results : The reason for leaving part of the pancreas between the duodenum and the anterior superior pancreaticoduodenal artery and the common bile duct is that the artery toward the papilla of Vater runs along the right side of the common bile duct and would be difficult to be preserved with the removal of this part of the pancreas. The most important technique of this procedure is in keeping the connective tissue membrane of the posterior surface of the pancreas intact so as to preserve pancreaticoduodenal arteries and veins, because all the pancreaticoduodenal arteries and veins are situated on this membrane. Complete Kocher's maneuver should cause no problem in this procedure. Conclusions : Benign lesions as well as low-grade malignancy of the head of the pancreas may possibly be the indication of this procedure.

A new method of duodenum-preserving subtotal resection of the head of the pancreas based on the surgical anatomy.

We established a model of orthotopic injection of a syngeneic pancreatic tumor cell line in C57BL/6 mice and evaluated the effects of organ site on induction of immunity to a tumor-specific antigen, MUC1. Mice were challenged with a syngeneic pancreatic adenocarcinoma cell line that expressed MUC1 (Panc02-MUC1) by orthotopic injection into the pancreas, or by subcutaneous injection. Tumor cells injected into the pancreas grew much faster than those injected subcutaneously. Mice challenged subcutaneously with Panc02-MUC1 rejected tumors or developed slowly growing tumors that were negative for MUC1 expression. In contrast, mice challenged orthotopically into the pancreas developed progressive tumors that were positive for MUC1 expression. Sera from mice that rejected PancO2-MUC1 (tumor-immune mice) showed no detectable IgG1 and IgM titers against the MUC1 tandem-repeat peptide, whereas mice with progressive tumor growth had significant titers of IgG1 and IgM specific for MUC1. This suggests that the humoral immune response was ineffective in mediating tumor rejection. The results show that the growth properties and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.

Organ-specific pancreatic tumor growth properties and tumor immunity

Infection Control in Healthcare Settings in Japan

We investigated the influence of organ-specific parameters on tolerance and immunity to human MUC1. C57Bl/6 mice (wild-type) and C57Bl/6 transgenic for MUC1 (MUC1.Tg) were challenged in the pancreas with Panc02-MUC1, a C57Bl/6-syngeneic pancreatic cancer cell line expressing human MUC1. Wild-type mice produced immune responses to MUC1 when presented on tumor cells growing in the pancreas; however, the responses to tumors in the pancreas were less effective than responses produced by tumor challenge at the s.c. site. Tumor immunity specific for MUC1 was produced in wild-type mice by two different procedures: (i) s.c. immunization of wild-type mice with a low dose of Panc02-MUC1 or (ii) adoptive transfer of spleen and lymph node cells harvested from wild-type mice previously immunized s.c. with Panc02-MUC1. This demonstrates that immune responses to MUC1 presented at the s.c. site can be detected and adoptively transferred. MUC1.Tg mice were immunologically tolerant to MUC1; however, some immunological protection against orthotopic challenge with Panc02-MUC1 was conferred by adoptive transfer of CD4+ and CD8+ T cells from wild-type mice. These results show that it is more difficult to produce immune responses to tumors growing at the pancreatic site than the s.c. site. Panc02-MUC1 cells growing in the pancreas were accessible to the immune system, and immune responses evoked by s.c. presentation of this molecule in wild-type mice were effective in rejecting tumor cells in the pancreas of both wild-type and MUC1.Tg mice. No effective anti-tumor immune responses against MUC1 were produced in MUC1.Tg mice.

/pdf/influence-of-organ-site-and-tumor-cell-type-on-muc1-specific-2jhgyrxyji.pdf

Keita Morikane

Papers

Epidemiology and risk factors associated with surgical site infection after different types of hepatobiliary and pancreatic surgery

A new method of duodenum-preserving subtotal resection of the head of the pancreas based on the surgical anatomy.

Organ-specific pancreatic tumor growth properties and tumor immunity

Infection Control in Healthcare Settings in Japan

Influence of organ site and tumor cell type on MUC1-specific tumor immunity.