The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

An overview of the self-organizing map algorithm, on which the papers in this issue are based, is presented in this article.

The Self-Organizing Map

In this paper we develop new Newton and conjugate gradient algorithms on the Grassmann and Stiefel manifolds. These manifolds represent the constraints that arise in such areas as the symmetric eigenvalue problem, nonlinear eigenvalue problems, electronic structures computations, and signal processing. In addition to the new algorithms, we show how the geometrical framework gives penetrating new insights allowing us to create, understand, and compare algorithms. The theory proposed here provides a taxonomy for numerical linear algebra algorithms that provide a top level mathematical view of previously unrelated algorithms. It is our hope that developers of new algorithms and perturbation theories will benefit from the theory, methods, and examples in this paper.

http://www-math.mit.edu/~edelman/publications/geometry_of_algorithms.pdf

The Geometry of Algorithms with Orthogonality Constraints

结节病易误诊,据王洪武等~([1])收集国内18篇关于此病误诊的文献,误诊率高达63.2%,当然有误诊就会有误治,如孙永昌等~([2])报道26例结节病在影像学检查诊断的第一印象中拟诊结核5例,其中就有2例完成规范的抗结核治疗,为此应引起临床对本病诊治的重视。

Sarcoidosis

Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.

Type 2 diabetes mellitus.

Snoring is a very common phenomenon with both social and clinical effects. The need for a reliable and effective monitoring and analyzing system, for the snoring signal, stems from the recent awareness of the severity of the problem and from the fact that surgical correction procedures are now available. A preliminary analysis of the snoring signal is presented. Some features, describing the signal are presented. The airway area model is suggested as one of the means to estimate the source and location of the obstruction. The preliminary analysis is demonstrated on a signal recorded from a patient suffering from laryngomalacia. It is shown that the suggested analysis describes the special characteristics of the signal.

Analysis and classification of snoring signals

Giant cell arteritis is a systemic autoimmune disorder which involves inflammation of medium to large vessels. The association between giant cell arteritis and autoimmune thyroid disorders has been investigated numerous times in the literature with inconsistent results. Our objective was to evaluate whether a genuine association exists between giant cell arteritis and thyroid dysfunction, which is often due to immune-mediated thyroid disease. Utilizing the medical database of Clalit Health Services, we compared the proportion of hypo and hyperthyroidisim between patients with giant cell arteritis and age-matched and gender-matched controls in a cross-sectional study. Univariate analysis was performed using Chi-square and student t-test and a multivariate analysis was performed using a logistic regression model. Five thousand six hundred and sixty three giant cell arteritis patients and 23,308 age-matched and gender-matched controls were included in the study. The proportion of hypothyroidism amongst giant cell arteritis patients was increased in comparison with controls (18.2 vs. 6.91%, respectively, p-value < 0.001), as was hyperthyroidism (2.56 and 1.19% respectively, p-value < 0.001). Giant cell arteritis demonstrated an independent association with hypothyroidism on multivariate analysis (Odd Ratios 1.297, 95% Confidence Intervals 1.19–1.42), yet not with hyperthyroidism. Giant cell arteritis patients have a higher proportion of hypothyroidism in comparison with matched controls. Physicians treating giant cell arteritis patients should consider screening for thyroid dysfunction on a regular basis.

Association between giant cell arteritis and thyroid dysfunction in a "real life" population.

AIM: To combine community and hospital services in order to enable improvements in patient management, an integrated gastroenterology service (IGS) was established.

METHODS: Referral patterns to specialist clinics were optimized; open access route for endoscopic procedures (including esophago-gastro-duodenoscopy, sigmoidoscopy and colonoscopy) was established; family physicians’ knowledge and confidence were enhanced; direct communication lines between experts and primary care physicians were opened. Continuing education, guidelines and agreed instructions for referral were promoted by the IGS. Six quality indicators were developed by the Delphi method, rigorously designed and regularly monitored. Improvement was assessed by comparing 2010, 2011 and 2012 indicators.

RESULTS: An integrated delivery system in a specific medical field may provide a solution to a fragmented healthcare system impaired by a lack of coordination. In this paper we describe a new integrated gastroenterology service established in April 2010. Waiting time for procedures decreased: 3 mo in April 30th 2010 to 3 wk in April 30th 2011 and stayed between 1-3 wk till December 30th 2012. Average cost for patient’s visit decreased from 691 to 638 NIS (a decrease of 7.6%). Six health indicators were improved significantly comparing 2010 to 2012, 2.5% to 67.5%: Bone densitometry for patients with inflammatory bowel disease, preventive medications for high risk patients on aspirin/NSAIDs, colonoscopy following positive fecal occult blood test, gastroscopy in Barrett’s esophagus, documentation of family history of colorectal cancer, and colonoscopy in patients with a family history of colorectal cancer.

CONCLUSION: Establishment of an IGS was found to effectively improve quality of care, while being cost-effective.

Establishing an integrated gastroenterology service between a medical center and the community.

Rheumatoid arthritis (RA) is the most common inflammatory joint disorder presenting also with extra-articular manifestations. As many other autoimmune diseases, it has been suggested that infectious diseases might contribute to its emergence. Hepatitis viruses were suggested by several reports as a trigger of RA onset. We aimed to assess the association between RA and chronic hepatitis B viral infection (HBV). Patients with RA were compared with age- and sex-matched controls regarding the proportion of chronic HBV infection in a case-control study. The chi-square and t tests were used for univariate analysis, whereas a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. There was a significantly higher proportion of chronic HBV infection in RA patients compared with controls (1.19% vs 0.63%, respectively; p < 0.001). In a multivariate logistic regression analysis, RA was significantly associated with chronic HBV infection (OR = 1.89, 95%CI 1.55–2.29, p < 0.001). Patients with RA have a greater proportion of chronic HBV infection than matched controls. Screening for HBV infection among RA patients may be warranted.

Chronic hepatitis B viral infection among RA patients-a cross-sectional control study.

Ankylosing spondylitis (AS) is a chronic progressive and debilitating form of arthritis with associated extra-articular features including uveitis , intestinal and lung apical inflammation and psoriasis . Putative associations between AS and neurologic disorders has been relatively overlooked. The purpose of this study is to assess the link between AS and major neurologic disorders and whether treatment with Tumor-Necrosis-Factor inhibitors (TNFi) has an impact on that association. A retrospective cross-sectional study was carried out based on the Clalit Health Services (CHS) computerized database. AS patients were compared to age- and gender-matched controls with respect to the proportion of Alzheimer’s disease (AD), Parkinson's disease (PD), epilepsy , and multiple sclerosis (MS). The impact of AS therapy (biologic vs conventional therapy) was assessed as well. 4082 AS patients and 20,397 age- and gender-matched controls were identified. AS was associated with a higher prevalence of AD (odds-ratio(OR) 1.46 [95%Confidence-interval(CI) 1.13–1.87], p = 0.003), epilepsy (OR 2.33 [95%CI 1.75–3.09] p < 0.0001) and PD (OR 2.75 [95%CI 2.04–3.72], p < 0.0001), whereas no statistically significant association was found for MS. Association with PD remained significant in the multivariate analysis (OR 1.49 [95%CI 1.05–2.13],p = 0.027). Within AS patients, the use of TNFi (OR 0.10 [95%CI 0.01–0.74], p = 0.024) were associated with a lowered risk of developing AD. AS is positively associated with AD, PD, and epilepsy but not MS. AS patients treated with TNFi have lower rates of AD. 

Arnon D. Cohen

Papers

Analysis and classification of snoring signals

Association between giant cell arteritis and thyroid dysfunction in a "real life" population.

Establishing an integrated gastroenterology service between a medical center and the community.

Chronic hepatitis B viral infection among RA patients-a cross-sectional control study.

TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study.