Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 I. Concept and diagnosis of autoimmune pancreatitis

Background

In response to the proposal of the international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis (AIP) and the Japanese diagnostic criteria in 2011, the 2009 Japanese consensus guidelines for managing AIP required revision.

Methods

Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Fifteen specialists for AIP extracted the specific clinical statements from 1,843 articles published between 1963 and 2012 (obtained from Pub Med and a secondary database, and developed the CQs and statements. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid.

Results

The professional committee created 13 CQs and statements for the current concept and diagnosis of AIP, 6 for extra-pancreatic lesions, 6 for differential diagnosis, and 11 for treatment.

Conclusion

After evaluation by the moderators, amendments to the Japanese consensus guidelines for AIP have been proposed for 2013.     

Impact of hospital volume on outcomes in acute pancreatitis: a study using a nationwide administrative database

Background

Although several population-based studies have shown higher hospital volume (HV) to be associated with better outcomes in acute pancreatitis, they failed to adjust for disease severity and did not take into account the potentially non-linear relationship between HV and outcomes. Using a Japanese nationwide administrative database, this study aimed to evaluate the volume–outcome relationship in acute pancreatitis by means of statistical methods that permitted such considerations.

Methods

In-hospital mortality, length of stay, and total costs for patients with acute pancreatitis were analyzed using multivariate regression models fitted with generalized estimating equations. Adjustment for severity was based on the Japanese Severity Scoring System and other patient characteristics. We used restricted cubic spline functions to examine the potential non-linear relationships between HV and outcomes.

Results

In all, 17,415 eligible patients with acute pancreatitis were identified from 1,032 hospitals between 1 July 2010 and 30 September 2011. The in-hospital mortality rate was 2.6 %, and the median total costs were US $7,740 (interquartile range, 5,150–11,920). The overall and non-linear volume–outcome relationships were not significant either for in-hospital mortality or total costs. The median length of stay was 14 days (interquartile range, 10–22), and high HV was positively associated with shorter hospitalization (overall, P < 0.001; non-linear, P = 0.194).

Conclusions

Despite the shorter hospitalization with higher HV, no inverse volume–outcome relationship was evident for acute pancreatitis. Further evidence is required to justify the volume-based selective referral of acute pancreatitis patients.     

Proposal of a Parameter for OATP1B1 Inhibition Screening at the Early Drug Discovery Stage

It is known that potent inhibition of organic-anion-transporting polypeptide (OATP)1B1 increases exposure to statins, leading to severe adverse effects. The aim of this study was to propose a parameter and its criteria in OATP1B1 inhibition assay at the early drug discovery stage to avoid compounds with the risk of statin-related adverse effects. According to drug label information, most compounds classified as “contraindicated” or “should be avoided” when administered concomitantly with statins increased their AUCs more than 4-fold. Generally, R values where R = 1 + plasma unbound fraction (fu) × maximum inhibitor concentration at the inlet to the liver/IC₅₀ are used to evaluate the extent of clinical drug interaction. However, clinical doses and C_max cannot be determined at the screening stage. Therefore, we estimated the correlations between change in AUC of statins concomitantly administered with OATP1B1 inhibitors and various parameters including fu/IC₅₀. Cyclosporin A, rifampicin, and telaprevir increased the AUC of statins more than 4-fold and fu/IC₅₀ of these compounds was >0.1 L/μmol. On the other hand, fu/IC₅₀ of other compounds was ≤0.03 L/μmol. This study indicates that fu/IC₅₀ is a useful parameter to avoid compounds that seriously affect statin potency through interaction with OATP1B1 at the screening stage.     

Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h

European Journal of Nuclear Medicine and Molecular Imaging - 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous...     

High levels of anti-SSA/Ro antibodies in COVID-19 patients with severe respiratory failure: a case-based review

Clinical Rheumatology - We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither...     

A Low Serum CCL4/MIP-1β Level May Predict a Severe Asthmatic Responsiveness to Mepolizumab

Objective Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, is effective for treating eosinophilic severe asthma. However, there is a need for more biomarkers that can predict the patient response to mepolizumab before starting therapy. This study aimed to identify a new biomarker in the serum that is able to accurately predict the responsiveness to mepolizumab. Methods This study enrolled 11 patients who had all been diagnosed with severe eosinophilic asthma and were then administered mepolizumab every 4 weeks for at least 4 months. Blood samples were collected, and pulmonary function tests and questionnaires were administered at baseline and after 4, 8 and 16 weeks of treatment. The response to mepolizumab was then assessed based on the difference in the Asthma Quality of Life Questionnaire (AQLQ) score after 16 weeks of mepolizumab therapy compared with that at baseline. Patients with an increase in the AQLQ score of more than 0.5 were defined as responders. The cytokine levels in the blood were measured by LUMINEX 200 and ELISA. Results There were 6 responders and 5 non-responders. The responders showed a significantly lower serum level of chemokine (C-C motif) ligand 4/macrophage inflammatory protein-1β (CCL4/MIP-1β) at baseline compared to the non-responders. Receiver operating characteristic curves to distinguish responders from non-responders using the baseline serum CCL4/MIP-1β level showed a good area under the curve of 0.9. The non-responders showed a significant increase in the level of CCL4/MIP-1β after 4 weeks compared to the baseline. Conclusion A low baseline serum CCL4/MIP-1β level may be useful for predicting a good mepolizumab response in severe eosinophilic asthma.     

Non-tuberculous Mycobacterial Pseudo-outbreak of an Intestinal Culture Specimen Caused by a Water Tap in an Endoscopy Unit

Objective Gastrointestinal lesions of non-tuberculous mycobacteria (NTM) are regarded as opportunistic infections. A large number of positive specimens of NTM were identified in an intestinal fluid culture in the endoscopy unit and it was considered to be a pseudo-outbreak. Methods We reviewed the hospital, laboratory, and colonoscopy records of 263 consecutive patients whose intestinal fluids were analyzed for a mycobacterial culture by colonoscopy at St. Marianna University Hospital, between January 2009 and December 2018. The endoscopy reprocessing procedures were reviewed and samples of water used in the endoscopy unit were cultured. Results An intestinal fluid culture of 154 (58.6%) patients tested positive for NTM (M. intracellulare; 125 cases, M. gordonae; 14 cases, M. avium; 4 cases, M. abscessus; 3 cases, and 8 other cases). In 182 cases (69.2%), an intestinal mucosal culture was performed simultaneously with a fluid culture and tested positive for NTM in 2 cases. Next, we examined the endoscopy unit for any possible environmental contamination. NTM were detected in the tap water used to prepare the antifoaming solution in the endoscopy unit. The water faucets in the endoscopy unit were considered to be the source of the contamination of NTMs. Conclusion We observed that a large number of cases tested positive due to contaminated water that had been used in an endoscopy unit, thus leading to a pseudo-outbreak of NTM.