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

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.25762

The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

H. pylori is one of the most common bacterial infections in human beings, and its discovery 20 years ago altered the diagnosis and treatment of gastroduodenal disease. This review considers current knowledge about the epidemiology and transmission of H. pylori, as well as the role of this infectious agent in the pathogenesis of upper gastrointestinal tract disease. Diagnostic approaches, indications for therapy, and measures of therapeutic efficacy are reviewed.

Helicobacter pylori infection.

Several infectious agents are considered to be causes of cancer in humans. The fraction of the different types of cancer, and of all cancers worldwide and in different regions, has been estimated using several methods; primarily by reviewing the evidence for the strength of the association (relative risk) and the prevalence of infection in different world areas. The estimated total of infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of the global cancer burden. The principal agents are the bacterium Helicobacter pylori (5.5% of all cancer), the human papilloma viruses (5.2%), the hepatitis B and C viruses (4.9%), Epstein-Barr virus (1%), human immunodeficiency virus (HIV) together with the human herpes virus 8 (0.9%). Relatively less important causes of cancer are the schistosomes (0.1%), human T-cell lymphotropic virus type I (0.03%) and the liver flukes (0.02%). There would be 26.3% fewer cancers in developing countries (1.5 million cases per year) and 7.7% in developed countries (390,000 cases) if these infectious diseases were prevented. The attributable fraction at the specific sites varies from 100% of cervix cancers attributable to the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide) caused by liver flukes.

/pdf/the-global-health-burden-of-infection-associated-cancers-in-4oe8mapm0f.pdf

The global health burden of infection-associated cancers in the year 2002.

https://www.commed.vcu.edu/Chronic_Disease/2012/cochranrvwrschbias.pdf

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

Tratamiento de la anemia en la enfermedad inflamatoria intestinal

BACKGROUND
Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Treatment effectiveness remains a subject of debate considering bacterial antimicrobial resistance. Our aim was to analyze the diagnostic methods and eradication treatments for H. pylori infection in Serbia.


METHODS
An observational multicenter prospective study was conducted in Serbia, as part of the European Registry on H. pylori Management (Hp-EuReg). Demographics, treatment indication, diagnostic methods, previous eradication attempts, and treatment were collected at AEG-REDCap e-CRF. Modified intention-to-treat (mITT) and per-protocol (PP) effectiveness analyses were performed. Safety, compliance, and bacterial antimicrobial resistance rates were reported. Data were quality checked.


RESULTS
Overall, 283 patients were included, with a mean age of 55 ± 15 years. Dyspepsia (n = 214, 77%) was the most frequent treatment indication, and histology (n = 144, 51%) was the most used diagnostic method. Overall eradication rate was 95% (PP) and 94% (mITT). Most prevalent first-line therapy was quadruple PPI + clarithromycin + amoxicillin + metronidazole, with a 96% effectiveness (p < 0.001). Second-line main treatment choice was triple amoxicillin + levofloxacin, with a 95% effectiveness (p < 0.05). Single-capsule Pylera® was the most prescribed third-line therapy, with 100% effectiveness (p < 0.05). Longer treatment duration was associated with a higher eradication rate in first-line therapy (p < 0.05). Clarithromycin and quinolone resistance rates in first-line were 24% and 8.3%, respectively. The overall adverse events' incidence rate was 13.4%, and therapy compliance was 97%.


CONCLUSIONS
Considering the high eradication rate, 14-day non-bismuth quadruple concomitant therapy is a reasonable first-line choice, while quinolone-based therapy and single-capsule Pylera® should be considered as rescue therapy options.

Current Trends in the Management of Helicobacter pylori Infection in Serbia: Preliminary Results from the European Registry on H. pylori Management.

We appreciate the considerations of Hsu et al about the recommendation of empiric firstline therapies in our Maastricht VI/Florence consensus report for the management of Helicobacter pylori. 2 We fully agree that H. pylori eradication therapy should aim at a cure rate of ≥90%. This also meets the expectation of patients as referred by the authors from a realworld expectation survey of the AsiaPacific region. However, we disagree that the cutoff for clarithromycin resistance, at least for now, is too high at 15% for triple therapy consisting of proton pump inhibitor (PPI), amoxicillin and clarithromycin used as empirical firstline option. Hsu et al suggest a cutoff for clarithromycin resistance at or below 5 % for the empirical use of PPIamoxicillinclarithromycin and base their claim on a recent systematic review. However, this review has several relevant limitations: ► First, the review was limited to the analysis of randomized controlled trials (RCTs) with a small number of studies included. This represents just a minor piece of information regarding the influence of clarithromycin resistance on the eradication efficacy with standard triple therapy. ► Second, the sample size of the included RCTs was small. Only 104 patients harboring clarithromycinresistant strains received 14day triple standard therapy. ► Third, many observational studies on the efficacy of H. pylori therapies have included information on clarithromycin resistance. In these studies, the efficacy with 14day standard triple therapy was higher than the 46% reported in the analysis of Shih et al . The higher eradication rate in several studies is likely to be attributed to the contribution of an increased amoxicillin efficacy if combined with adequate acid suppression. The high efficacy of amoxicillin in eradication regimens is well documented when administered in combination with potent acid suppression. ► Fourth, it remains implausible from studies included in the analysis of Shih et al that patients harbouring clarithromycinsusceptible strains treated with 7day triple standard therapy had a higher eradication rate (92.5%) than those receiving 14day triple standard therapy (eradication rate of 90.2%). ► Finally, recent data from the European Registry on H. pylori management showed that the eradication rate in clarithromycinsusceptible and resistant strains was of 92% and 75%, respectively. This allows to calculate an eradication rate of 90% if the clarithromycin resistance rate in a specific geographical area is of 15% (85 × 92 + 15 × 75 = 90%). Furthermore with the recommended 14 days treatment duration instead of 7–10 days the cure rate can be expected to be even higher. Similar conclusions on the 15% cutoff point for clarithromycin resistance using standard triple therapy for 14 days were made in other reviews. 8 We also consider the WHO recommendations that, although not strictly related to the effectiveness of H. pylori eradication therapy, the threshold to define an area as low clarithromycin resistance is 15%. In summary, there are insufficient evidence and arguments at present to change the cutoff point for clarithromycin resistance from 15% to 5%. The use of reverse hybrid therapy for H. pylori eradication as an empirical first line suggested by Hsu et al l is effective but with limited data compared with other treatment options. Furthermore the reverse hybrid therapy because of the complexity and difficult patient adherence is not considered an option in the European consensus report. Looking forward, there is a need to improve the current practice in management of H. pylori infection and overcome the challenge of antibiotic resistance. Options consist in dissemination and implementation of new insights, the consideration of new molecular methods for H. pylori susceptibility testing and treatment modifications with the inclusion of more potent acid suppressants.

Javier P. Gisbert

Papers

Tratamiento de la anemia en la enfermedad inflamatoria intestinal

Current Trends in the Management of Helicobacter pylori Infection in Serbia: Preliminary Results from the European Registry on H. pylori Management.

Empiric use of standard triple therapy in Helicobacter pylori eradication does not require readjustment in the clarithromycin resistance cut-off point

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Response to Chao and Mulani