The impact of previous endoscopic treatments on functional outcome after cricotracheal resection.

OBJECTIVES: Treatment options for benign subglottic stenosis include endoscopic techniques or open surgery. Although endoscopic treatment is less invasive, a considerable proportion of patients develop recurrent stenosis. Endoscopic pretreatments do not exclude patients from a later surgical repair; however, the impact of previous endoscopic treatment attempts on functional outcome after open surgery is unknown. METHODS: All patients, who received a cricotracheal resection (CTR) between January 2017 and June 2023 at the Department of Thoracic Surgery, Medical University of Vienna, were included in this retrospective study. Patient characteristics, surgical variables and postoperative outcome including a detailed functional assessment were analysed. RESULTS: A total of 65 patients received a CTR during the study period, of which 40 were treatment naïve and 25 had a median of 2 (range 1-9) endoscopic pretreatments. Less-invasive voice-sparing CTR or standard CTR were more often possible in treatment-naïve patients. In contrary, pretreated patients regularly required extended procedures (P = 0.049). Three or more endoscopic treatments resulted in a significantly lower mean fundamental frequency (F0) after open repair (P = 0.048). In addition, a trend towards smaller mean sound pressure levels, a higher voice handicap index, higher impairments in RBH scores (roughness, breathing and hoarseness) and a higher dysphagia severity index was found in pretreated patients. The respiratory outcome after surgery was comparable between both groups. CONCLUSIONS: Multiple endoscopic pretreatments lead to worse voice quality after CTR. The impact of prior endoscopic treatment before surgical repair should be considered when discussing treatment options with patients suffering from subglottic stenosis.

A novel technique of voice-sparing cricotracheal resection.

Background: Cricotracheal resection (CTR) is considered the standard of care for patients suffering from idiopathic subglottic stenosis (iSGS). Although CTR results in permanent restoration of airway patency, it has a mild to moderate impact on voice quality. Here we propose modifications of the standard CTR technique to make it a voice-preserving procedure. Methods: Five women with iSGS underwent voice-sparing CTR between January 2022 and January 2023. In this procedure, through several technical adaptations, the function of the cricothyroid joint was preserved. Outcomes of these voice-sparing CTRs were compared to outcomes in patients who underwent standard CTR in our institution. All patients underwent full functional preoperative and postoperative workups, including spirometry, voice measurements, patient self-assessment, and fiberoptic endoscopic evaluation of swallowing. Results: All 5 patients in the study group suffered from iSGS with high-grade Myer-Cotton III° stenosis (100%); 1 patient had previously undergone endoscopic laser resection. Voice evaluation demonstrated a nearly unchanged fundamental pitch (mean preoperative, 191 ± 73.1 Hz; postoperative, 182 ± 64.2 Hz) and dynamic voice range (preoperative, 24.4 semitones; postoperative, 20.4 semitones). This was in contrast to the control group, in which significantly reduced voice quality was observed. Conclusions: In selected patients suffering from iSGS, excellent functional results can be obtained with voice-sparing CTR.

Persistent Hydrocephalus, Shunt, and Subglottic Stenosis in a Newborn with Plasminogen Deficiency due to Delayed Treatment with Plasminogen Concentrates: A Case Report.

INTRODUCTION: Here we present the case of a newborn baby boy with severe plasminogen deficiency causing occlusive hydrocephalus and ligneous conjunctivitis. CASE PRESENTATION: Shortly after birth, the hydrocephalus was treated with a ventriculoperitoneal shunt implantation. However, the child had to be readmitted soon afterward because of shunt obstruction. Subglottic microtrauma caused by the necessary intubations then led to another life-threatening complication - subglottic stenosis with pseudomembrane formation. Microsurgical removal had to be performed to secure the airway. Initially, regular plasma transfusions achieved slightly elevated plasminogen activity levels and short-term improvement of the respiratory situation. However, shunt dysfunction reoccurred, and alternative treatment options were needed. Since therapy with plasminogen concentrate is already available in the USA with encouraging results, this treatment option was organized in hopes of equally good results for this patient. Fortunately, under short-term substitution with plasminogen concentrates, the implantation of a new ventriculoperitoneal shunt was successful, and respiratory problems resolved. CONCLUSION: Plasminogen concentrates are critically needed in Europe and other parts of the world to improve the care of and prevent complications among patients with plasminogen deficiency.

Validation of the revised 2018 AAST-OIS classification and the CT severity index for prediction of operative management and survival in patients with blunt spleen and liver injuries.

OBJECTIVES: Non-operative management (NOM) is increasingly utilised in blunt abdominal trauma. The 1994 American Association of Surgery of Trauma grading (1994-AAST) is applied for clinical decision-making in many institutions. Recently, classifications incorporating contrast extravasation such as the CT severity index (CTSI) and 2018 update of the liver and spleen AAST were proposed to predict outcome and guide treatment, but validation is pending. METHODS: CT images of patients admitted 2000-2016 with blunt splenic and hepatic injury were systematically re-evaluated for 1994/2018-AAST and CTSI grading. Diagnostic accuracy, diagnostic odds ratio (DOR), and positive and negative predictive values were calculated for prediction of in-hospital mortality. Correlation with treatment strategy was assessed by Cramer V statistics. RESULTS: Seven hundred and three patients were analysed, 271 with splenic, 352 with hepatic and 80 with hepatosplenic injury. Primary NOM was applied in 83% of patients; mortality was 4.8%. Comparing prediction of mortality in mild and severe splenic injuries, the CTSI (3.1% vs. 10.3%; diagnostic accuracy = 75.4%; DOR = 3.66; p = 0.006) and 1994-AAST (3.3% vs. 10.5%; diagnostic accuracy = 77.9%; DOR = 3.45; p = 0.010) were more accurate compared with the 2018-AAST (3.4% vs. 8%; diagnostic accuracy = 68.2%; DOR = 2.50; p = 0.059). In hepatic injuries, the CTSI was superior to both AAST classifications in terms of diagnostic accuracy (88.7% vs. 77.1% and 77.3%, respectively). CTSI and 2018-AAST correlated better with the need for surgery in severe vs. mild hepatic (Cramer V = 0.464 and 0.498) and splenic injuries (Cramer V = 0.273 and 0.293) compared with 1994-AAST (Cramer V = 0.389 and 0.255; all p < 0.001). CONCLUSIONS: The 2018-AAST and CTSI are superior to the 1994-AAST in correlation with operative treatment in splenic and hepatic trauma. The CTSI outperforms the 2018-AAST in mortality prediction. KEY POINTS: • Non-operative management of blunt abdominal trauma is increasingly applied and correct patient stratification is crucial. • CT-based scoring systems are used to assess injury severity and guide clinical decision-making, whereby the 1994 version of the American Association of Surgery of Trauma Organ Injury Scale (AAST-OIS) is currently most commonly utilised. • Including contrast media extravasation in CT-based grading improves management and outcome prediction. While the 2018-AAST classification and the CT-severity-index (CTSI) better correlate with need for surgery compared to the 1994-AAST, the CTSI is superior in outcome-prediction to the 2018-AAST.

Early effects of cigarette smoke extract on human oral keratinocytes and carcinogenesis in head and neck squamous cell carcinoma.

BACKGROUND: Cigarette smoking is a major risk factor for head and neck squamous cell carcinoma. Still, the effect of cigarette smoke on the molecular level is unclear. The aim of the present study was to investigate the early effects of cigarette smoke on carcinogenesis of head and neck squamous cell carcinoma. METHODS: Human oral keratinocytes were exposed for 1 week to standardized cigarette smoke extract, and subsequently RT-quantitative PCR array was performed. Protein expression of dysregulated genes was determined by immunohistochemistry in tissue samples of oral squamous cell carcinoma, oral leukoplakia, and tonsil mucosa. RESULTS: RT-PCR revealed upregulation of ITGA-2 and MMP-1, whereas TEK receptor tyrosine kinase was downregulated in human oral keratinocytes. ITGA-2 and MMP-1 were significantly overexpressed in tissue samples of oral squamous cell carcinoma in comparison to normal mucosa (P <.01 in all experiments). CONCLUSION: Upregulation of ITGA-2 and MMP-1 induced by cigarette smoke contributes significantly to oral carcinogenesis.

Progenitor Cells from the Adult Human Inner Ear.

Loss of inner ear hair cells leads to incurable balance and hearing disorders because these sensory cells do not effectively regenerate in humans. A potential starting point for therapy would be the stimulation of quiescent progenitor cells within the damaged inner ear. Inner ear progenitor/stem cells, which have been described in rodent inner ears, would be principal candidates for such an approach. Despite the identification of progenitor cell populations in the human fetal cochlea and in the adult human spiral ganglion, no proliferative cell populations with the capacity to generate hair cells have been reported in vestibular and cochlear tissues of adult humans. The present study aimed at filling this gap by isolating colony-forming progenitor cells from surgery- and autopsy-derived adult human temporal bones in order to generate inner ear cell types in vitro. Sphere-forming and mitogen-responding progenitor cells were isolated from vestibular and cochlear tissues. Clonal spheres grown from adult human utricle and cochlear duct were propagated for a limited number of generations. When differentiated in absence of mitogens, the utricle-derived spheres robustly gave rise to hair cell-like cells, as well as to cells expressing supporting cell-, neuron-, and glial markers, indicating that the adult human utricle harbors multipotent progenitor cells. Spheres derived from the adult human cochlear duct did not give rise to hair cell-like or neuronal cell types, which is an indication that human cochlear cells have limited proliferative potential but lack the ability to differentiate into major inner ear cell types. Anat Rec, 303:461-470, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Non-operative management of blunt hepatic and splenic injury: a time-trend and outcome analysis over a period of 17 years.

Background: A widespread shift to non-operative management (NOM) for blunt hepatic and splenic injuries has been observed in most centers worldwide. Furthermore, many countries introduced safety measures to systematically reduce severe traffic and leisure sports injuries. This study aims to evaluate the effect of these nationwide implementations on individual patient characteristics and outcomes through a time-trend analysis over 17 years in an Austrian high-volume trauma center. Methods: A retrospective review of all emergency trauma patients admitted to the Medical University of Innsbruck from 2000 to 2016. Injury severity, clinical data on admission, operative and non-operative treatment parameters, complications, and in-hospital mortality were evaluated. Results: In total, 731 patients were treated with blunt hepatic and/or splenic injuries. Among these, 368 had a liver injury, 280 splenic injury, and 83 combined hepatic/splenic injury. Initial NOM was performed in 82.6% of all patients (93.5% in hepatic and 71.8% in splenic injuries) with a success rate of 96.7%. The secondary failure rate of NOM was 3.3% and remained consistent over 17 years (p = 0.515). In terms of injury severity, we observed a reduction over time, resulting in an overall mortality rate of 4.8% and 3.5% in the NOM group (decreasing from 7.5 to 1.9% and from 5.6 to 1.3%, respectively). These outcomes confirmed an improved utilization of the NOM approach. Conclusion: Our cohort represents one of the largest Central European single-center experiences available in the literature. NOM is the standard of care for blunt hepatic and splenic injuries and successful in > 96% of all patients. This rate was quite constant over 17 years (p = 0.515). Overall, national and regional safety measures resulted in a significantly decreased severity of observed injury patterns and deaths due to blunt hepatic or splenic trauma. Although surgery is nowadays only applied in about one third of splenic injury patients in our center, these numbers might further decrease by intensified application of interventional radiology and modern coagulation management.

Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines.

BACKGROUND AND PURPOSE: Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. MATERIALS AND METHODS: Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. RESULTS: Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. CONCLUSION: Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation.

Intranasal submucosal bevacizumab for epistaxis in hereditary hemorrhagic telangiectasia: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: The purpose of this study was to investigate the efficacy of bevacizumab ("Avastin") for the treatment of epistaxis in hereditary hemorrhagic telangiectasia (HHT). METHODS: In this double blind, placebo controlled trial, 15 adult patients with HHT with a minimum of 2 epistaxis episodes per week were randomized. A history of thromboembolic events or recent or planned surgery led to exclusion. Patients received a single intranasal submucosal injection (10 mL) of 100 mg bevacizumab or placebo. The primary outcome was the relative reduction of average daily epistaxis visual analog score (VAS). RESULTS: Average daily posttreatment VAS scores decreased by 27% in the bevacizumab group and by 3% in the placebo group (p = .57). The reduction in HHT epistaxis severity scores was -0.61 greater in the bevacizumab group compared to the placebo group (p = .34). CONCLUSION: Results show a trend toward reduced epistaxis with bevacizumab. This further supports the use of bevacizumab in HHT. Clincial Trials. gov number: NCT01314274