Current management of non‐alcoholic steatohepatitis

Non‐alcoholic steatohepatitis (NASH) is the most common cause of liver disease in Western populations, and its prevalence is increasing rapidly. It is part of a multisystem disease affecting other organs such as the kidneys, heart and blood vessels, and is closely associated with the components of the metabolic syndrome. Physicians managing patients with NASH should not only focus on the management of NASH, but also on associated comorbidities in individual patients. The approaches to treatment of NASH include either limiting energy surplus alone, or in combination with targeting of downstream pathways of inflammation and fibrosis. In this mini‐review, we discuss the currently available treatment options for NASH, as well as those in late‐stage clinical trials. We discuss the challenges of managing these patients with a limited number of approved therapies, as well as managing advanced‐stage patients with NASH and cirrhosis. We also discuss the specific management of comorbidities in NASH patients, in particular diabetes, hypertension, dyslipidaemia and cardiovascular diseases. Finally, we present the screening protocols for both hepatocellular carcinoma and extrahepatic malignancies in these patients.     

Computer-aided measurement of mandibular cortical width on dental panoramic radiographs for identifying osteoporosis

Aim: To develop a computer‐aided diagnosis system to continuously measure mandibular inferior cortical width on dental panoramic radiographs and evaluate the system’s efficacy in identifying postmenopausal women with low‐skeletal bone mineral density. Methods: Mandibular inferior cortical width was continuously measured by enhancing the original X‐ray image, determining cortical boundaries, and evaluating all distances between the upper and lower boundaries in the region of interest. The system’s efficacy in identifying osteoporosis at the lumbar spine and the femoral neck was evaluated for 100 women (≥50 years): 50 in the development of the tool and 50 in its validation. Results: The sensitivity and specificity of the cortical measurements for identifying the development patients were 90% (95% confidence interval shown in parentheses) (63.0–87.0) in women with low spinal bone mineral density, and 81.8% (70.1–91.8) and 69.2% (56.2–81.8) in those with low femoral bone mineral density, respectively. Corresponding values in the validation patients were 93.3% (85.9–100) and 82.9% (71.4–92.7) at the lumbar spine, and 92.3% (84.5–99.5) and 75.7% (63.0–87.0) at the femoral neck, respectively. Conclusion: Our new computer‐aided diagnosis system is a useful procedure in triage screening for osteoporosis.     

Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy

Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy.     

Clopidogrel tapering as a strategy to attenuate platelet rebound phenomenon in patients with bare-metal stents

Early clustering of adverse cardiovascular events after abrupt cessation of clopidogrel has been reported in patients with acute coronary syndromes. A platelet rebound phenomenon may contribute to this increased thrombotic risk and a gradual drug tapering may attenuate this proposed platelet effect. Accordingly, we aimed to assess the effect of clopidogrel tapering on platelet reactivity. Twenty patients who underwent elective percutaneous coronary interventions with bare metal stents receiving 3 months of clopidogrel therapy (75 mg daily) were randomized to either of two discontinuation strategies: (1) Off group–abrupt drug cessation or (2) Tapering group–receiving clopidogrel 75 mg every other day for 4 weeks duration. Light transmission aggregometry, induced by ADP (5 and 10 μM) and collagen, was measured at four time-points (at baseline and 2, 4 and 6 weeks after randomization). In the off group, there was an early rise in platelet reactivity at 2 weeks after abrupt drug cessation compared to baseline, as measured by ADP 5 μmol/l (39.6 ± 2.8 vs. 67.9 ± 6.0, P < 0.001). The tapering regimen suppressed this rebound platelet aggregation by ADP 5 μmol/l at 2 weeks (P = 0.001) and 4 weeks (P = 0.001). Similar results were found with ADP 10 μmol/l and collagen agonists. Abrupt cessation of clopidogrel results in an early rise in platelet aggregability in patients with BMS that is attenuated by a tapering regimen. Clopidogrel administration every other day may achieve similar levels of platelet inhibition as full dose therapy. Further investigations evaluating clopidogrel tapering strategies and their potential clinical impact are warranted.     

The first-choice standard of care for an edentulous mandible: A Delphi method survey of academic prosthodontists in the United States

BackgroundIn 2002 and 2009, two consensus statements—one from a symposium in Canada and one from England—were issued that recommended that the first-choice standard of care for an edentulous mandible should be the two implant–retained mandibular overdenture (IRMOD). The authors conducted a survey to determine if, in 2011, U.S. academic prosthodontic experts’ opinions were aligned with those in the two consensus statements.MethodsThe authors administered a Delphi method survey to an expert panel of 16 nationally representative academic prosthodontists to determine if there is consensus on the first-choice standard of care for an edentulous mandible between the IRMOD and a conventional mandibular complete denture (CD). Consensus agreement was defined as a 70 percent agreement level among the panelists.ResultsThe panel attained consensus favoring the IRMOD for nine of the 10 parameters assessed—retention, stability, speech, masticatory efficiency, comfort while eating soft foods and hard foods, confidence in intimate situations, satisfaction and self-esteem. The exception was esthetics for which only a majority (51–69 percent) favored the IRMOD.ConclusionsThe panelists reached consensus that they would recommend an IRMOD instead of a CD as the first-choice standard of care for patients who are healthy or have mild systemic disease, but not for patients with severe systemic disease.Clinical ImplicationsSurveyed academic prosthodontists recommend an IRMOD as the first choice standard of care when restoring an edentulous mandible of a healthy patient or a patient with mild systemic disease.