Fine-needle liver biopsy in patients with severely impaired coagulation

ABSTRACT— Severe coagulation defects, as reflected by platelet count and prothrombin time, have always been considered a contraindication to needle biopsy of the liver, but there are very limited data on the actual rate of bleeding in patients with such severe alterations and none whatsoever on the bleeding risk associated with newer, fine-gauge needles that produce less trauma to the liver tissue. In addition, there has never been any evidence that platelet count and/or prothrombin time are the most sensitive indices of bleeding risk. This retrospective study of 85 patients, with platelet counts less than 50 000/mm³ and/or prothrombin times less than 50% of controls, subjected to ultrasound-guided fine-needle liver punctures for diagnostic or therapeutic (percutaneous ethanol injection) purposes showed no bleeding episodes after any of the 229 punctures performed. No type of replacement therapy was administered to correct clotting defects prior to the procedure. Correct pathologic diagnoses were obtained in 81.2% of all patients. Ultrasound-guided fine needle puncture appears to be safer than currently believed in patients with severe clotting defects and deserves further evaluation as an alternative to surgical procedures to diagnose and treat liver lesions, even when severe coagulation impairment is present.     

Can cardiorespiratory polygraphy replace portable polysomnography in the assessment of sleep-disordered breathing in heart failure patients?

Purpose

Portable polysomnography (PSG) and cardiorespiratory polygraphy are increasingly being used in the assessment of sleep-disordered breathing (SDB) in heart failure patients. Scoring of SDB from cardiorespiratory polygraphy recordings is based only on respiratory signals, while electroencephalographic, electrooculographic and electromyographic channels are taken into account when using PSG recordings. The aim of this study was to assess the agreement between these two scoring methods.

Methods

An overnight sleep study was performed in 67 heart failure patients using a standard portable polysomnograph. Each recording was scored twice, once using all acquired signals (PSG mode) and, after a median of 64 days, using only respiratory signals (cardiorespiratory mode). Agreement was assessed by Bland–Altman analysis and Cohen’s kappa.

Results

We found that (1) more respiratory events were detected using cardiorespiratory analysis [median (25th percentile, 75th percentile), 75 (39, 200) events] compared to analysis of portable PSG [69 (29, 173) events, p?<?0.0001], the extra events being, for the vast majority, central in origin; (2) the apnea/hypopnea index (AHI) estimated by cardiorespiratory polygraphy [11.9 (5.7, 30.8)/h] showed a negligible negative bias relative to portable PSG [15.1 (5.7, 33.6)/h; bias, ?0.8 (?2.9, 0.4)/h, p?=?0.0002]; (3) limits of agreement between the two systems (?6.2/h, 1.7/h) were much smaller than those previously observed between two nights using the same scoring modality; and (4) the kappa coefficient using categorised AHI was 0.89 (95 % confidence interval (CI) 0.82, 0.96).

Conclusions

We found a high degree of agreement between the AHIs obtained from the two scoring methods, thus suggesting that cardiorespiratory polygraphy may be used as an alternative to portable PSG in the assessment of SDB in heart failure patients.

     

Spontaneous bacterial peritonitis due to carbapenemase-producing Enterobacteriaceae: Etiology and antibiotic treatment

Carbapenem antibiotics were first introduced in the 1980s and have long been considered the most active agents for the treatment of multidrug-resistant gram-negative bacteria. Over the last decade, carbapenem-resistant Enterobacteriaceae (CRE) have emerged as organisms causing spontaneous bacterial peritonitis. Infections caused by CRE have shown a higher mortality rate than those caused by bacteria sensitive to carbapenem antibiotics. Current antibiotic guidelines for the treatment of spontaneous bacterial peritonitis are insufficient, and rapid de-escalation of empiric antibiotic treatment is not widely recognized. This review summarizes the molecular characteristics, epidemiology and possible treatment of spontaneous bacterial peritonitis caused by CRE.     

Prefrontal Cortex Activated Bilaterally by a Tilt Board Balance Task: A Functional Near-Infrared Spectroscopy Study in a Semi-Immersive Virtual Reality Environment

The aim of this study was to assess the prefrontal cortex (PFC) oxygenation response to a 5-min incremental tilt board balance task (ITBBT) in a semi-immersive virtual reality (VR) environment driven by a depth-sensing camera. It was hypothesized that the PFC would be bilaterally activated in response to the increase of the ITBBT difficulty, given the PFC involvement in the allocation of the attentional resources to maintain postural control. Twenty-two healthy male subjects were asked to use medial–lateral postural sways to maintain their equilibrium on a virtual tilt board (VTB) balancing over a pivot. When the subject was unable to maintain the VTB angle within ±35° the VTB became red (error). An eight-channel fNIRS system was employed for measuring changes in PFC oxygenated-deoxygenated hemoglobin (O₂Hb-HHb, respectively). Results revealed that the number of the performed board sways and errors augmented with the increasing of the ITBBT difficulty. A PFC activation was observed with a tendency to plateau for both O₂Hb-HHb changes within the last 2 min of the task. A significant main effect of the level of difficulty was found in O₂Hb and HHb (p < 0.001). The study has demonstrated that the oxygenation increased over the PFC while the subject was performing an ITBBT in a semi-immersive VR environment. This increase was modulated by the task difficulty, suggesting that the PFC is bilaterally involved in attention-demanding tasks. This task could be considered useful for diagnostic testing and functional neurorehabilitation given its adaptability in elderly and in patients with movement disorders.     

IL‐4‐induced gene 1 maintains high Tob1 expression that contributes to TCR unresponsiveness in human T helper 17 cells

Human Th17 cells have a limited proliferative capacity compared to other T‐cell subsets. We have shown that human Th17 cells display impaired IL‐2 production due to IL‐4‐induced gene 1 (IL4I1) upregulation. Here, we show that in human Th17 cells, IL4I1 also maintains high levels of Tob1, a member of the Tob/BTG (B‐cell traslocation gene) antiproliferative protein family, which prevents cell‐cycle progression mediated by TCR stimulation. Indeed, Th17 cells exhibited higher levels of Tob1 than Th1 cells in both resting and TCR‐activated conditions. Accordingly, the expression of positive regulators of the cell cycle (cyclin A, B, C, and E and Cdk2), as well as of Skp2, which promotes Tob1 degradation, was lower in Th17 cells than in Th1 cells. Tob1 expression in human Th17 cells correlated with both RAR (retinoic acid receptor)‐related orphan receptor C (RORC) and IL4I1 levels. However, RORC was not directly involved in the regulation of Tob1 expression, whereas IL4I1 silencing in Th17 cells induced a substantial decrease of Tob1 expression. These data suggest that IL4I1 upregulation in human Th17 cells limits their TCR‐mediated expansion not only by blocking the molecular pathway involved in the activation of the IL‐2 promoter, but also by maintaining high levels of Tob1, which impairs entry into the cell cycle.     

Search for Neuro-Endocrine Markers (Chromogranin A,Synaptophysin and VGF) in Breast Cancers. An integrated Approach Using Immunohistochemistry and Gene Expression Profiling

Discordant data are reported in the literature on the definition, incidence and clinical features of neuroendocrine (NE) carcinomas of the breast. This tumour entity is currently assessed by immunohistochemistry (IHC) detecting “general” NE markers such as chromogranin A (CHGA) and synaptophysin (SYP), but other markers have been considered as well. In the present study, in addition to CHGA and SYP, we investigated the expression of VGF, a neurotrophin-inducible gene, which is emerging as a new specific NE marker. In order to evaluate the differential expression of these neuro-endocrine markers in breast cancers, we conducted parallel immunohistochemical and gene expression analyses, using PCR, gene array and real-time quantitative PCR procedures. Data obtained in 28 cases were further validated with a meta-analysis of published datasets of 103 breast cancer cases. The value of IHC positivity (irrespective of the percentage of positive cells) was confirmed by over-expression of the related gene. However, the genetic approach emerged as more sensitive, showing over-expression of NE markers in a subset of IHC-negative carcinomas. In conclusion, the present study confirms, by a novel approach, the occurrence of NE differentiation in breast cancers. Over-expression of one or more NE marker (CHGA and/or SYP and/or VGF) characterizes a significant fraction (approximately 10 %) of infiltrative breast cancers.