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Τρίτη 20 Σεπτεμβρίου 2022

Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study

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imageObjective: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. Background: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. Methods: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. Results: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P
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Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea

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Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea

We assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea. This network meta-analysis demonstrates that intrathecal gadolinium-magnetic resonance cisternography is the most useful diagnostic method to detect CSF rhinorrhea.


Objective

To assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea.

Data Sources

The PubMed, EMBASE, SCOPUS, Web of Science, Cochrane Trials, and Google Scholar databases were searched up to December 2021.

Review Methods

Diagnostic accuracy was compared among seven radiological methods: computed tomography (CT), CT cisternography (CTC), magnetic resonance imaging (MRI), magnetic resonance cisternography (MRC), CT + MRI, radionuclide cisternography, and intrathecal gadolinium (Gd)-MRC. Sensitivity, specificity, and accuracy were used as outcomes of the analysis. Both a traditional pairwise meta-analysis and a network meta-analysis were performed.

Results

Twenty-three trials were included in the analysis. The results of a network meta-analysis performed on a network consisting of seven diagnostic methods showed that all imaging modalities had greater diagnostic accuracy than CT, with the exception of CTC, which had lower sensitivity. Only intrathecal Gd-MRC was significantly superior to other imaging methods with regard to sensitivity and accuracy. Gd-MRC also showed the greatest surface under the cumulative ranking curve values for all of the outcomes (sensitivity: 0.9200; specificity: 0.8364; accuracy: 0.8920).

Conclusion

This network meta-analysis demonstrates that intrathecal Gd-MRC is the most useful diagnostic method to detect CSF rhinorrhea. Laryngoscope, 2022

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Δευτέρα 19 Σεπτεμβρίου 2022

Anti‐SARS‐CoV‐2 Activity of Targeted Kinase Inhibitors: Repurposing Clinically Available Drugs for COVID‐19 Therapy

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Abstract

Purpose

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis.

Methods

We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 varian ts.

Results

Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment.

Conclusions

This work supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.

This article is protected by copyright. All r ights reserved.

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Κυριακή 18 Σεπτεμβρίου 2022

Prevention of the Occupational Silicosis Epidemic

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Abstract
An Australian National Dust Disease Taskforce was established to address the re-emergence of occupational lung disease, in particular silicosis. Exposure to respirable crystalline silica (RCS) occurs in various industries in Australia. We asked occupational hygienists about their practical experiences and perspectives on RCS exposure and regulatory action. A total of 105 members of the Australian Institute of Occupational Hygienists completed an anonymous questionnaire, which addressed individual characteristics, experience, perceived level of employer awareness, effectiveness of current regulation, and recommendations for improvement, across three main industrial sectors. Based on professional experience, 71% were concerned about the potential for RCS over-exposure. Barriers to adequate exposure control included lack of management commitment and financial resources. The employment of specialist occupational hygiene inspectors was considered to b e the most effective regulatory strategy. Given the large number of exposed workers in the construction industry, with only a moderate awareness, there is the potential for significant cost shifting of the burden of occupational lung disease from employers on to individuals and the public health system. A nationally consistent approach to RCS exposure control across all industrial sectors is now recommended, with an increased focus on measuring and controlling exposure.
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The T‐shaped FST pharyngoplasty step‐by‐step closure technique

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Abstract

Pharyngocutaneous fistula is one of the most common and serious complications associated with total laryngectomy. Numerous studies tried to evaluate causative and predisposing factors associated with this complication, but data are considerably variable and there is still no international consensus. Incidence rate varies considerably between studies, with reported rates from 3% to 65%. This 4K video presents our T-shaped four-step technique (FST) for closing the pharyngeal mucosa after total laryngectomy in a step-by-step manner. All sutures were performed by braided absorbable 3/0 26 mm 1/2c (Vicryl plus 3.0; Ethicon, Somerville, NJ, USA). Recordings were performed using a Karl Storz 4K 3D VITOM® exoscope (Karl Storz SE & Co. KG, Tuttlingen, Germany). We have been described this technique through a high-definition video, showing each step, and tips from the authors. Our T-shaped pharyngoplasty closure technique can be divided into four steps: 1. "Key Stitches"; 2. "A rea Refinement Stitches"; 3. "Modified Connell Suture"; 4. "Modified Purse String Suture." Our T-shaped FST closure technique proved to be an effective and reproducible method, which we feel could be the preferred choice for primary pharyngoplasty closure.

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Effectiveness of root canal treatment for vital pulps compared with necrotic pulps in the presence or absence of signs of periradicular pathosis: a systematic review and meta‐analysis

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Abstract

Background

Pre-operative pulpal status may influence the outcomes of root canal treatment (RCTx) according to various measures used.

Objectives

To compare effectiveness of RCTx of teeth with a vital pulp versus a necrotic pulp using a range of clinical and patient-related outcomes, for the development of S3-Level clinical practice guidelines.

Methods

A search was conducted in the PubMed-MEDLINE, Scopus, EMBASE, Google scholar databases and available repositories, followed by hand searches, until 29 March 2022. Clinical studies published in English language comparing the stipulated outcomes of RCTx of teeth with vital versus necrotic pulp were included. The Newcastle-Ottawa Scale was adapted to assess study quality. Effects of pulpal status were estimated and expressed as risk ratio (RR) using fixed- and random-effect meta-analyses. The quality of evidence was assessed through the Grading of Recommendations Assessment, Development, and Evaluation tool.

Results

Twenty-eight studies published between 1961 and 2021 were included. Five studies have investigated the 'tooth survival' outcome, four reported pulpal status was not a significant predictor, consistent with meta-analysis finding (RR: 1.00; 95% CI: 1.00, 1.00; n=3). Seven studies reported pulpal status had no significant influence on post-operative pain, regardless of duration after treatment. Sixteen studies have analysed 'periapical health', eleven revealed pulpal status had no significant influence. Meta-analyses revealed the influence was not significant if pre-operative periapical radiolucency was absent (RR: 0.95; 95% CI: 0.90, 1.00; n=9) but significant if it was present (RR: 1.12; 95% CI: 1.05, 1.19; n=11). Most studies were classified as 'some concerns' (n=16) to 'low' (n=10) risk of bias (RoB).

Discussion

Evidence is limited and only available for three outcomes when comparing the effectiveness of RCTx in permanent teeth with vital pulp versus pulp necrosis. Nevertheless, the quality of available evidence was moderate to high. The 'periapical health' data heterogeneity could be explained by pre-operative radiolucency, thus RCTx was found more effective for prevention than resolution of apical periodontitis.

Conclusions

There was no significant difference in the 'tooth survival', 'post-operative pain' and 'evidence of apical radiolucency' outcomes of RCTx in teeth with vital or necrotic pulps.

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Hyperkalaemia and potassium binders: Retrospective observational analysis looking at the efficacy and cost effectiveness of calcium polystyrene sulfonate and sodium zirconium cyclosilicate

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Hyperkalaemia and potassium binders: Retrospective observational analysis looking at the efficacy and cost effectiveness of calcium polystyrene sulfonate and sodium zirconium cyclosilicate

Both CPS and SZC are equally effective at lowering acutely raised potassium concentrations with a cost analysis that favours CPS. Any claims of benefits of newer agents over established medications need to be explored in randomized trials.


Abstract

What is Known and Objective

Hyperkalaemia is a common medical emergency in patients admitted to hospital. There is a limited evidence base supporting some of the commonly applied treatment strategies. Although, NICE has recommended the use of sodium zirconium cyclosilicate (SZC) (TA599) and patiromer (TA623) in both acute and chronic hyperkalaemia, there is a limited evidence base for their use in acute hyperkalaemia in the hospital setting, particularly when compared to the present standard of care calcium polystyrene sulfonate (CPS).

Methods

A retrospective review of the electronic patient record system across our hospital over a 6-month period identified 138 patients who received either SZC (65 patients) or CPS (73 patients) to manage hyperkalaemia, investigating their efficacy and cost effectiveness. Results were analysed using simple descriptive statistics. Based on the results a naïve cost comparison between the two drugs was made.

Results and Discussion

CPS and SZC both effectively reduced plasm potassium concentrations in patients with hyperkalaemia (6.07 and 6.03 mmol/L respectively) by 1.17 mmol/L and 1.24 mmol/L taking a similar amount of time to work (2.97 days vs. 3 days). The principle causes of hyperkalaemia identified were acute kidney injury, medication, and chronic kidney disease. Cost comparison analysis which took into account raw product price and time needed to dispense medications revealed that CPS has slightly better cost effectiveness compared to SZC albeit at a cost of increased staff input.

What is New and Conclusion

Both CPS and SZC were equally effective at lowering acutely raised potassium concentrations. The cost difference between the two products appears to be small. Claims regarding the benefits of newer agents over older established medications need to be properly explored in randomized trials rather than being based on small scale non-comparative studies.

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Extracapsular dissection with a transparotid facial nerve dissection approach versus partial superficial parotidectomy for benign tumours in the tail of the parotid gland: a single-centre retrospective study of 89 patients

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The aims of this study were (1) to evaluate the transparotid facial nerve dissection approach (TFND), in which the intraparotid cervicofacial or temporofacial division is identified first through a superficial lobe incision; and (2) to compare extracapsular dissection with a TFND (ECD-TFND) with partial superficial parotidectomy with a retrograde approach (PSP) for benign tumours in the tail of the parotid gland with respect to surgical outcomes. Eighty-nine patients underwent PSP or ECD-TFND for benign tumours in the tail of the parotid gland: 49 were treated surgically with PSP and 40 with ECD-TFND. (Source: International Journal of Oral and Maxillofacial Surgery)
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Πέμπτη 15 Σεπτεμβρίου 2022

Dupilumab use is associated with protection from COVID-19 mortality: A retrospective analysis

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Abstract
We previously found that type 2 immunity promotes COVID-19 pathogenesis in a mouse model. To test relevance to human disease we used electronic health record databases and determined that patients on dupilumab (anti-IL-4R monoclonal antibody that blocks IL-13 and IL-4 signaling) at the time of COVID-19 infection had lower mortality.
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Inhibition of kidney potassium channels by fluoxetine: in vivo and in vitro studies

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Abstract

In vitro studies have demonstrated that fluoxetine, a commonly used antidepressant drug, can modulate the activity of K+ channels. In the present study, we investigated the in vivo effect of acute and sub-chronic treatment of rats with fluoxetine on K+ renal transport. Furthermore, OK cells, a kidney epithelial cell line, was used in order to evaluate the in vitro effect of fluoxetine on K+ currents. In the sub-chronic study, fluoxetine was administrated daily (10 mg/kg, p.o.) for 15 days to male adult Wistar rats. In the acute study, rats were given increasing doses of fluoxetine (1, 3, 10, 30 and 50 mg/kg, p.o.) for 24 hours. Results from the sub-chronic study show that urinary K+ content (in mmol/L) was markedly reduced in the fluoxetine-treated animals (fluoxetine: 83±9; control: 131±10; P<0.001). K+ fractional renal excretion (in %) was also significantly lower in the fluoxetine group (fluoxetine : 6±1; control: 13±2; P<0.001). No significant changes was observed in creatinine clearance and on renal tubular Na+,K+-ATPase activity. Results obtained from the acute study demonstrate that, after a 24-hour administration, fluoxetine produced a dose-dependent decrease in urinary K+, with an ED50 (in mg/kg) of 4.2 (2.8; 5.5) and a maximal effect of 62% reduction. In vitro, fluoxetine produced a concentration-dependent inhibition of K+ currents in OK cells, with an EC50 of 107 (84.8; 129.5) μM. In conclusion, fluoxetine produces a marked reduction on urinary K+ excretion; this effect constitutes an in vivo evidence for the inhibitory action of fluoxetine on kidney epithelial K+ channels.

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