Salvage carbon dioxide transoral laser microsurgery for laryngeal cancer after (chemo)radiotherapy: a European Laryngological Society consensus statement

Purpose: To provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery (CO2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT]. Methods: Expert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage CO2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision-making were drafted, circulated, and modified or excluded in accordance with the Delphi process. Results: The expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage CO2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up. Conclusion: Management of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage CO2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of CO2 TOLMS for LSCC in the salvage setting is presented

European Laryngological Society position paper on laryngeal dysplasia part II: diagnosis, treatment, and follow-up

Purpose of review To give an overview of the current knowledge regarding the diagnosis, treatment, and follow-up of laryngeal dysplasia (LD) and to highlight the contributions of recent literature. The diagnosis of LD largely relies on endoscopic procedures and on histopathology. Diagnostic efficiency of endoscopy may be improved using videolaryngostroboscopy (VLS) and bioendoscopic tools such as Narrow Band Imaging (NBI) or Storz Professional Image Enhancement System (SPIES). Current histological classifications are not powerful enough to clearly predict the risk to carcinoma evolution and technical issues such as sampling error, variation in epithelial thickness and inflammation hamper pathological examination. Almost all dysplasia grading systems are effective in different ways. The 2017 World Health Organization (WHO) system should prove to be an improvement as it is slightly more reproducible and easier for the non-specialist pathologist to apply. To optimize treatment decisions, surgeons should know how their pathologist grades samples and preferably audit their transformation rates locally. Whether carcinoma in situ should be used as part of such classification remains contentious and pathologists should agree with their clinicians whether they find this additional grade useful in treatment decisions. Recently, different studies have defined the possible utility of different biomarkers in risk classification. The main treatment modality for LD is represented by transoral laser microsurgery. Radiotherapy may be indicated in specific circumstances such as multiple recurrence or wide-field lesions. Medical treatment currently does not have a significant role in the management of LD. Follow-up for patients treated with LD is a fundamental part of their care and investigations may be supported by the same techniques used during diagnosis (VLS and NBI/SPIES).Otorhinolaryngolog

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

The Palomar Testbed Interferometer Calibrator Catalog

The Palomar Testbed Interferometer (PTI) archive of observations between 1998 and 2005 is examined for objects appropriate for calibration of optical long-baseline interferometer observations - stars that are predictably point-like and single. Approximately 1,400 nights of data on 1,800 objects were examined for this investigation. We compare those observations to an intensively studied object that is a suitable calibrator, HD217014, and statistically compare each candidate calibrator to that object by computing both a Mahalanobis distance and a Principal Component Analysis. Our hypothesis is that the frequency distribution of visibility data associated with calibrator stars differs from non-calibrator stars such as binary stars. Spectroscopic binaries resolved by PTI, objects known to be unsuitable for calibrator use, are similarly tested to establish detection limits of this approach. From this investigation, we find more than 350 observed stars suitable for use as calibrators (with an additional $\approx 140$ being rejected), corresponding to $\gtrsim 95$ sky coverage for PTI. This approach is noteworthy in that it rigorously establishes calibration sources through a traceable, empirical methodology, leveraging the predictions of spectral energy distribution modeling but also verifying it with the rich body of PTI's on-sky observations.Comment: 100 pages, 7 figures, 7 tables; to appear in the May 2008ApJS, v176n

No hypoperfusion is produced in the epicardium during application of myocardial topical negative pressure in a porcine model

ABSTRACT: BACKGROUND: Topical negative pressure (TNP), commonly used in wound therapy, has been shown to increase blood flow and stimulate angiogenesis in skeletal muscle. We have previously shown that a myocardial TNP of -50 mmHg significantly increases microvascular blood flow in the myocardium. When TPN is used in wound therapy (on skeletal and subcutaneous tissue) a zone of relative hypoperfusion is seen close to the wound edge. Hypoperfusion induced by TNP is thought to depend on tissue density, distance from the negative pressure source, and the amount negative pressure applied. When applying TNP to the myocardium, a significant, long-standing zone of hypoperfusion could theoretically cause ischemia, and negative effects on the myocardium. The current study was designed to elucidate whether hypoperfusion was produced during myocardial TNP. METHODS: Six pigs underwent median sternotomy. Laser Doppler probes were inserted horizontally into the heart muscle in the LAD area, at depths of approximately, 1-2 mm. The microvascular blood flow was measured before and after the application of a TNP. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium) and after 20 minutes of LAD occlusion (ischemic myocardium). RESULTS: A TNP of -50 mmHg induced a significant increase in microvascular blood flow in normal myocardium (**p = 0.01), while -125 mmHg did not significantly alter the microvascular blood flow. In ischemic myocardium a TNP of -50 mmHg induced a significant increase in microvascular blood flow (*p = 0.04), while -125 mmHg did not significantly alter the microvascular blood flow. CONCLUSION: No hypoperfusion could be observed in the epicardium in neither normal nor ischemic myocardium during myocardial TNP

Intercomparison Study of Six HTDMAs: Results and Recommendations

We report on an intercomparison of six different hygroscopicity tandem differential mobility analysers (HTDMAs). These HTDMAs are used worldwide in laboratory experiments and field campaigns to measure the water uptake of aerosol particles and have never been intercompared. After an investigation of the different design of the instruments with their advantages and inconveniencies, the methods for calibration, validation and data analysis are presented. Measurements of nebulised ammonium sulphate as well as of secondary organic aerosol generated from a smog chamber were performed. Agreement and discrepancies between the instruments and to the theory are discussed, and final recommendations for a standard instrument are given, as a benchmark for laboratory or field experiments to ensure a high quality of HTDMA data.JRC.H.2-Climate chang

Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks

Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome

A Genome-Wide Association Study of the Metabolic Syndrome in Indian Asian Men

We conducted a two-stage genome-wide association study to identify common genetic variation altering risk of the metabolic syndrome and related phenotypes in Indian Asian men, who have a high prevalence of these conditions. In Stage 1, approximately 317,000 single nucleotide polymorphisms were genotyped in 2700 individuals, from which 1500 SNPs were selected to be genotyped in a further 2300 individuals. Selection for inclusion in Stage 1 was based on four metabolic syndrome component traits: HDL-cholesterol, plasma glucose and Type 2 diabetes, abdominal obesity measured by waist to hip ratio, and diastolic blood pressure. Association was tested with these four traits and a composite metabolic syndrome phenotype. Four SNPs reaching significance level p<5×10−7 and with posterior probability of association >0.8 were found in genes CETP and LPL, associated with HDL-cholesterol. These associations have already been reported in Indian Asians and in Europeans. Five additional loci harboured SNPs significant at p<10−6 and posterior probability >0.5 for HDL-cholesterol, type 2 diabetes or diastolic blood pressure. Our results suggest that the primary genetic determinants of metabolic syndrome are the same in Indian Asians as in other populations, despite the higher prevalence. Further, we found little evidence of a common genetic basis for metabolic syndrome traits in our sample of Indian Asian men

Wound contraction and macro-deformation during negative pressure therapy of sternotomy wounds

<p>Abstract</p> <p>Background</p> <p>Negative pressure wound therapy (NPWT) is believed to initiate granulation tissue formation via macro-deformation of the wound edge. However, only few studies have been performed to evaluate this hypothesis. The present study was performed to investigate the effects of NPWT on wound contraction and wound edge tissue deformation.</p> <p>Methods</p> <p>Six pigs underwent median sternotomy followed by magnetic resonance imaging in the transverse plane through the thorax and sternotomy wound during NPWT at 0, -75, -125 and -175 mmHg. The lateral width of the wound and anterior-posterior thickness of the wound edge was measured in the images.</p> <p>Results</p> <p>The sternotomy wound decreased in size following NPWT. The lateral width of the wound, at the level of the sternum bone, decreased from 39 ± 7 mm to 30 ± 6 mm at -125 mmHg (p = 0.0027). The greatest decrease in wound width occurred when switching from 0 to -75 mmHg. The level of negative pressure did not affect wound contraction (sternum bone: 32 ± 6 mm at -75 mmHg and 29 ± 6 mm at -175 mmHg, p = 0.0897). The decrease in lateral wound width during NPWT was greater in subcutaneous tissue (14 ± 2 mm) than in sternum bone (9 ± 2 mm), resulting in a ratio of 1.7 ± 0.3 (p = 0.0423), suggesting macro-deformation of the tissue. The anterior-posterior thicknesses of the soft tissue, at 0.5 and 2.5 cm laterally from the wound edge, were not affected by negative pressure.</p> <p>Conclusions</p> <p>NPWT contracts the wound and causes macro-deformation of the wound edge tissue. This shearing force in the tissue and at the wound-foam interface may be one of the mechanisms by which negative pressure delivery promotes granulation tissue formation and wound healing.</p