The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low‐dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti‐inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non‐fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at‐risk groups include an HIV test, a QuantiFERON‐TB Gold test and a chest X‐ray. In patients without complications, repeat the FBC at 2–4 weeks, then every 3–6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low‐dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment‐emergent liver toxicity is related to underlying metabolic syndrome and non‐alcoholic fatty liver disease or non‐alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: ‘20 mg/day’ has been corrected to ‘20 gm/day’.] Although MTX is a potential teratogen post‐conception, there is little evidence for this pre‐conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri‐surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti‐tumour necrosis factor biologics.     

Use of the Falciform Ligament Flap for Closure of the Esophageal Hiatus in Giant Paraesophageal Hernia

OBJECTIVES: Laparoscopic repair of a giant paraesophageal hiatal hernia remains a challenging procedure. Several techniques have been developed in efforts to achieve tension-free reconstruction of the esophageal hiatus. In this report, we describe a technique whereby the falciform ligament is used as an autologous onlay flap to achieve tension-free closure of the crural defect of a giant paraesophageal hernia (GPEH). DISCUSSION: Use of the falciform ligament as a vascularized autologous onlay flap is a safe and effective procedure to obtain closure of the crural defect of a GPEH. The falciform ligament should be adequately mobilized from the anterior abdominal wall to prevent lateral tension on the flap, but care must be taken to avoid devascularization. Interrupted vertical mattress sutures are used to fix the falciform ligament to the left and right hiatal crurae.     

Measuring the double-drift illusion and its resets with hand trajectories

If a Gabor pattern drifts in one direction while its internal texture drifts in the orthogonal direction, its perceived position deviates further and further away from its true path. We first evaluated the illusion using manual tracking. Participants followed the Gabor with a stylus on a drawing tablet that coincided optically with the horizontal monitor surface. Their hand and the stylus were not visible during the tracking. The magnitude of the tracking illusion corresponded closely to previous perceptual and pointing measures indicating that manual tracking is a valid measure for the illusion. This allowed us to use it in a second experiment to capture the behavior of the illusion as it eventually degrades and breaks down in single trials. Specifically, the deviation of the Gabor stops accumulating at some point and either stays at a fixed offset or resets toward the veridical position. To report the perceived trajectory of the Gabor, participants drew it after the Gabor was removed from the monitor. Resets were detected and analyzed and their distribution matches neither a temporal nor a spatial limit, but rather a broad gamma distribution over time. This suggests that resets are triggered randomly, about once per 1.3 seconds, possible by extraneous distractions or eye movements.     

Evaluation of sE-Selectin and sICAM-1 as Parameters for Renal Function

Introduction. In order to monitor acute renal failure, intensive care patients were examined, and routine as well as specialized parameters were compared. Materials and Methods. Thirty-three patients at the Surgical Intensive Care Unit (ICU) were examined daily over the entire period for which they stayed in the ICU. The patients were retrospectively classified as being either with or without acute renal failure. Group 1 consisted of 22 patients who resided in the ICU for 11–15 (median 14) days without ARF. Group 2 consisted of 11 patients who developed an ARF during their stay of 13–18 (median 16) days in the ICU. In addition to the routine parameters of diuresis, serum creatinine/urea, and clearance of creatinine, specialized parameters for kidney function, including the excretion rates of α1-microglobulin, N-acetyl-β-D-glucosaminidase, and total protein, were compared with the excretion rate of soluble ICAM-1 and sE-Selectin. Results. Diuresis, serum creatinine, urea, and enzyme elimination were pathological among patients with ARF. Already on the day of admission, raised elimination rates of sICAM-1 were found in the urine of patients who had developed an ARF. While high values were still shown upon discharge, levels kept falling among patients without ARF. Clearly raised values were also shown for sE-Selectin compared to patients without ARF. Conclusions. sICAM-1 and sE-Selectin as supplementary parameters indicating renal function revealed early signs of kidney damage. These parameters may play a major role in the development of novel therapeutic approaches for ARF (antibodies against ICAM-1 or sE-Selectin).     

Paraganglioma-like dermal melanocytic tumor: a case report with particular features

Childhood dermal tumors with melanocytic features is an unusual tumor that can create diagnostic confusion. Among them, paraganglioma-like melanocytic tumors- previous included in melanocytic tumors of uncertain malignant potential- has some particular histopathologic and immunohistochemical features. We describe a case of 13 years old girl with a paraganglioma-like dermal melanocytic tumor of the left leg.     

Tissue saturation measurement - exciting prospects,but standardisation and reference data still needed

Sepsis and shock result in disturbances in microcirculatory perfusion and tissue oxygen utilisation that may not be reflected in global measures of haemodynamics. Near-infrared spectroscopy enables measurement of tissue oxygen saturation (StO₂) and provides information on local microvascular and mitochondrial function. This measure could be incorporated with existing targets of goal-directed therapy to provide an integrated approach to haemodynamic resuscitation of both the macro- and microcirculation in various shock states. However, key methodological factors must be addressed before widespread clinical application.     

The amino terminus of the salmonid alphavirus capsid protein determines subcellular localization and inhibits cellular proliferation

Salmonid alphavirus (SAV) is the most divergent member of the family Togaviridae and constitutes a threat to farming of salmonid fish in Europe. Here, we report cloning, expression and preliminary functional analysis of the capsid protein of SAV, confirming it to be expressed as an approximately 31-kDa protein in infected cells. The protein localizes strictly to the cytoplasm in Chinook salmon embryo cells, and either to the nucleus or cytoplasm in bluegill fry cells. An expression study of full-length and different truncated versions of the SAV capsid fused to the enhanced green fluorescent protein demonstrated that the localization is independent of other viral components in both cell lines, and controlled by the N-terminal 82 aa, which include a conserved, predicted helix and a downstream positively charged region. Thus, the results suggest that the SAV capsid possesses a cell-type-dependent potential for nuclear import and export. Moreover, the SAV capsid and its N-terminal 82 aa were shown to be associated with inhibition of cellular proliferation, a hallmark of the cytopathic effect caused by SAV. These results highlight that the SAV capsid is a multifunctional protein with possible importance for pathogenesis.