B cells in systemic sclerosis: from pathophysiology to treatment

Clinical Rheumatology - Systemic sclerosis is a debilitating autoimmune disease with unknown pathogenesis. The clinical phenotype of fibrosis is preceded by vascular and immunologic aberrations....     

Textbook outcomes in hepatobiliary and pancreatic surgery

The concept of textbook outcome (TO) has recently gained popularity in surgical research and has been used to evaluate the quality or success of different surgical procedures, including hepatopancreatobiliary (HPB) operations. TO consists of individual outcome parameters that each reflect different domains of care including structure, process, and individual outcomes; in turn, the composite TO metric represents the optimal course after a surgical episode. TO can be used to assess patient-level outcomes, hospital performance, center designation and quality metrics. In addition to being an outcome measurement, TO may also be linked to healthcare costs. Future efforts should be directed towards establishing a universal definition of TO in HPB surgery so that surgeons and hospitals can assess and compare outcomes, identify shortcomings and improve real world patient outcomes.     

Neuromuscular diseases and their cardiac manifestations under the spectrum of cardiovascular imaging

Heart Failure Reviews - Neuromuscular diseases (NMDs) include a broad spectrum of disorders that affect motor unit in every possible site, extending from the cell body of peripheral nerves to the...     

Locoregional immunochemotherapy in primary and metastatic liver disease: meta-analysis and review of literature

BACKGROUND/AIMS: Primary and metastatic liver tumors are the most common malignancies that resist conventional chemotherapy and radiotherapy. Several immunotherapies have been attempted for cancer treatment on the basis of stimulating host immune response to tumors and recent development of combined targeting locoregional immunochemotherapy reported with promising results. However, the efficacy of this therapeutic modality is not yet widely established. METHODOLOGY: We reviewed the medical literature for publications dealing with the value of locoregional immunochemotherapy in patients with primary or metastatic liver tumors. RESULTS: We found that 5 and 7 studies have been controlled and inadequately controlled, respectively. Among 131 patients with primary liver cancer, 40 were treated with combined locoregional immunochemotherapy, and 20 with systemic immunochemotherapy, and 71 with systemic chemotherapy served as two control groups. Complete or partial response was observed in 32 out of 40 (80%) patients who received combined locoregional therapy, and in 10 out of 20 (50%) systemic immunochemotherapy controls (P = 0.03). Survival was three times higher in the patients who received combined locoregional therapy compared with systemic chemotherapy controls (18 vs. 5.6 months). Recurrence of tumor was higher in systemic immunochemotherapy controls (P = 0.003). Among 286 patients with metastatic liver disease, 180 patients were treated with combined locoregional immunochemotherapy and 106 patients with systemic immunochemotherapy. Response (complete or partial) was observed in 65 out of 98 (66.3%) patients who received combined therapy, and in 4 out of 26 (15.4%) controls (P < = 0.001). Survival was two-fold higher in the patients treated with combined therapy (21 vs. 10.5 months). Tumor recurrence was higher in the systemic immunochemotherapy controls (P < = 0.001). CONCLUSIONS: The observational studies indicate a plausible therapeutic rationale for the introduction of locoregional immunotherapy in patients with primary and metastatic liver disease.     

Mechanisms of Action and Resistance of Somatostatin Analogues for the Treatment of Hepatocellular Carcinoma: A Message Not Well Taken

Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.     

Ultrasensitive Amplification Refractory Mutation System Real-Time PCR (ARMS RT-PCR) Assay for Detection of Minority Hepatitis B Virus-Resistant Strains in the Era of Personalized Medicine

Resistance to antiviral treatment for chronic hepatitis B virus (HBV) has been associated with mutations in the HBV polymerase region. This study aimed at developing an ultrasensitive method for quantifying viral populations with all major HBV resistance-associated mutations, combining the amplification refractory mutation system real-time PCR (ARMS RT-PCR) with a molecular beacon using a LightCycler. The discriminatory ability of this method, the ARMS RT-PCR with molecular beacon assay, was 0.01 to 0.25% for the different HBV resistance-associated mutations, as determined by laboratory-synthesized wild-type (WT) and mutant (Mut) target sequences. The assay showed 100% sensitivity for the detection of mutant variants A181V, T184A, and N236T in samples from 41 chronically HBV-infected patients under antiviral therapy who had developed resistance-associated mutations detected by direct PCR Sanger sequencing. The ratio of mutant to wild-type viral populations (the Mut/WT ratio) was >1% in 38 (63.3%) of 60 samples from chronically HBV-infected nucleos(t)ide analogue-naive patients; combinations of mutations were also detected in half of these samples. The ARMS RT-PCR with molecular beacon assay achieved high sensitivity and discriminatory ability compared to the gold standard of direct PCR Sanger sequencing in identifying resistant viral populations in chronically HBV-infected patients receiving antiviral therapy. Apart from the dominant clones, other quasispecies were also quantified. In samples from chronically HBV-infected nucleos(t)ide analogue-naive patients, the assay proved to be a useful tool in detecting minor variant populations before the initiation of the treatment. These observations need further evaluation with prospective studies before they can be implemented in daily practice.