The Practice of Percutaneous Liver Biopsy in a Gastrohepatology Day Hospital: A Retrospective Study on 835 Biopsies

The evolving role of liver biopsy has induced the formulation of several guidelines on its appropriateness. However, the great divergence among hepatologists is still unresolved. We report the 4-year activity of a day hospital of gastrohepatology in northern Italy. Between January 2001 and July 2004, 835 subjects (mean age, 43±12 years) underwent this procedure in our facility. Etiologically, in 465 (56%) and 157 (19%) patients, chronic hepatitis C and nonspecific elevated liver biochemical tests were the first and second indications, followed by chronic hepatitis B and suspected nonalcoholic steatohepatitis. On a purpose basis, procedures requested for staging (n = 578) and/or for diagnosis (n = 217) were identified. Among the former, 80% had the scope of staging chronic hepatitis C, and in 15% of these unsuspected superimposed cirrhosis was detected. Among diagnostic procedures, nonspecific raised liver enzyme level ranked first. Twenty-two percent of patients reported unwanted effects following the procedure. In conclusion, these data accord with indications expressed by international guidelines. The impact of liver biopsy on therapeutic decision-making needs to be studied further.     

Diabetes and metabolic syndrome (MS)

The MS is associated with increased morbidity and mortality for cardiovascular disease (CVD). MS is represented not only by metabolic alteration such as hyperglycemia, and hyperlipemia but also by a chronic pro-inflammatory state. Another responsible in the formation and progression of CVD is the so-called endothelial dysfunction, which is linked to insulin resistance itself. The common denominator of the MS is insulin resistance. The most convincing evidence for the existence of MS comes from the cluster analysis which outlines four main factors: the "metabolic factor", the "pressure factor", the "lipid factor" and the "obesity factor". It is clear that the presence of the MS appears to identify a substantial additional cardiovascular risk on top of the individual risk factors. The studies available in the literature have pointed out the beneficial effects, in terms of cardiovascular mortality, of the treatment with inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins): this reduction of risk has been observed despite the fact that high triglyceride and low high-density lipoprotein (HDL)-cholesterol levels, but not hypercholesterolemia, are the main features of the dyslipidemia observed in patients with MS. Yet, despite a normal low-density lipoprotein (LDL)-cholesterol level, patients with MS are at high risk for future CVD. For this reason, their treatment with statins is mandatory.     

Ketogenic diet: electrophysiological effects on the normal human cortex

PURPOSE: To explore the cortical electrophysiology of the ketogenic diet (KD) in the normal human. KD is effective against refractory epilepsy, but its precise mechanism is obscure. At the transmitter level, an enhancement of GABA inhibition has often been proposed. METHODS: We studied eight healthy volunteers undergoing a "classic" KD for 2 weeks. We measured several biochemical variables at baseline (T0), after 1 week (T1) and 2 weeks (T2) of KD, then 3 months after the KD conclusion (T3). Ketosis was quantified as 24-h ketonuria. At the same time, we studied the motor cortical excitability by means of transcranial magnetic stimulation (TMS). We also quantitatively evaluated the EEG signal in search of frequency shifts over the rolandic areas. RESULTS: Significant (p < 0.05) neurophysiological changes appeared at T2. These consisted of a strengthening of short-latency cortical inhibition (SICI), a TMS index which is thought to reflect GABA-A inhibition in the cortex. Then, there was an enhancement of the beta EEG band over the perirolandic region, similar to that following administration of GABA-A agonists. All changes disappeared at T3. CONCLUSIONS: A standard, short-term KD affected the cortical physiology of the normal human. The main changes were an augmented SICI and an increased perirolandic beta EEG activity, which are compatible with a lower level of neural excitation within the cortex.     

Early and delayed benefits of HIV-1 suppression: timeline of recovery of innate immunity effector cells

OBJECTIVE: The kinetics of recovery for innate immune effectors following antiretroviral therapy are unknown. DESIGN AND METHODS: Multiple sequential cryopreserved samples (viremic and ART-suppressed) from 66 patients enrolled in the Women's Interagency HIV Study or Multicenter AIDS Cohort Study cohorts (median follow-up, 700 days) were analyzed to determine natural killer, dendritic and T-cell changes by flow cytometry. Functional parameters were also measured in a subset of samples. Changes over time were analyzed by mixed-effect modeling based on a linear spline with a single knot at 270 days. RESULTS: Following viral suppression, a rapid rise in CD4 and white blood cell counts and a decline in T-cell activation were confirmed. However, natural killer cell subsets increased after 270 days of therapy, with a negative effect by baseline CD4%. CD123+ plasmacytoid but not myeloid dendritic cells showed a trend to increase during the first 270 days with a positive effect of baseline CD4%; plasmacytoid dendritic cell-induced interferon-alpha production significantly increased by end of follow-up. CONCLUSIONS: The kinetics of natural killer and plasmacytoid dendritic cell recovery are markedly different from those of T-cell subsets, indicative of early and delayed benefits of suppressive regimens.     

Primary and secondary small cell neuroendocrine carcinoma of the larynx: a review

Primary laryngeal small cell neuroendocrine carcinoma (SCNC) is an unusual malignancy accounting for <0.5% of laryngeal carcinomas. To date, approximately 200 cases of primary and 5 of secondary SCNC of the larynx have been reported. This tumor most often presents in the sixth and seventh decades in men who are heavy cigarette smokers. The lesion may be associated with different paraneoplastic syndromes (ectopic adrenocorticotropic hormone syndrome, Schwartz-Bartter syndrome or syndrome of inappropriate secretion of antidiuretic hormone, and Eaton-Lambert myasthenic syndrome) or with ectopic hormone production. The diagnosis is based essentially on the histologic appearance of the tumor, confirmed by immunocytochemical investigations. Concurrent chemoradiotherapy regimens offer potential for long-term survival. This tumor is biologically aggressive, and the extent of the disease is the most significant independent prognostic factor of survival. The survival rate is similar to that with pulmonary SCNC.     

Recent changes in the treatment of patients with advanced laryngeal cancer

Since the original data from the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated that nonsurgical therapy could achieve survival rates comparable to total laryngectomy in selected cases, there has been a progressive increase in employment of nonsurgical therapy for the management of advanced laryngeal cancer. Both neoadjuvant chemotherapy followed by conventionally fractionated or hyperfractioned radiotherapy for chemotherapy responders, or simultaneously administered chemoradiation has resulted in a significant number of patients who achieved cure while preserving their larynges. Nevertheless, combined chemotherapy and external beam radiation is associated with a variety of acute and chronic sequelae that can have a debilitating impact on function and quality of life. Although no therapeutic option is without risk, the decision regarding the modality of therapy for a patient with advanced laryngeal cancer should prompt a careful review of the current surgical techniques available for treatment. Data on quality of life and aging, as well as advances in minimally invasive surgical techniques, are available today that were not available at the time of the Veterans study. Selection of optimal therapy is often complex and raises the question whether the pendulum may have swung too far in the direction of nonsurgical therapy for advanced laryngeal cancer. This article reviews the current options available for a patient with advanced laryngeal cancer and discusses the impact of therapy.     

Second-tier test for quantification of alloisoleucine and branched-chain amino acids in dried blood spots to improve newborn screening for maple syrup urine disease (MSUD)

BACKGROUND: Newborn screening for maple syrup urine disease (MSUD) relies on finding increased concentrations of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine by tandem mass spectrometry (MS/MS). d-Alloisoleucine (allo-Ile) is the only pathognomonic marker of MSUD, but it cannot be identified by existing screening methods because it is not differentiated from isobaric amino acids. Furthermore, newborns receiving total parenteral nutrition often have increased concentrations of BCAAs. To improve the specificity of newborn screening for MSUD and to reduce the number of diet-related false-positive results, we developed a LC-MS/MS method for quantifying allo-Ile. METHODS: Allo-Ile and other BCAAs were extracted from a 3/16-inch dried blood spot punch with methanol/H2O, dried under nitrogen, and reconstituted into mobile phase. Quantitative LC-MS/MS analysis of allo-Ile, its isomers, and isotopically labeled internal standards was achieved within 15 min. To determine a reference interval for BCAAs including allo-Ile, we analyzed 541 dried blood spots. We also measured allo-Ile in blinded samples from 16 MSUD patients and 21 controls and compared results to an HPLC method. RESULTS: Intra- and interassay imprecision (mean CVs) for allo-Ile, leucine, isoleucine, and valine ranged from 1.8% to 7.4%, and recovery ranged from 91% to 129%. All 16 MSUD patients were correctly identified. CONCLUSIONS: The LC-MS/MS method can reliably measure allo-Ile in dried blood spots for the diagnosis of MSUD. Applied to newborn screening as a second-tier test, it will reduce false-positive results, which produce family anxiety and increase follow-up costs. The assay also appears suitable for use in monitoring treatment of MSUD patients.