Functional Reconstruction of Forehead and Midface Deficits Using the Endoscopic Technique and Bio-Absorbable Implants.

OBJECTIVES: Functional deficits of the forehead and midface can pose significant problems for patients varying from mild asymmetry to various degrees of functional impairment including total paralysis. Our objectives were to analyse the use of bio-absorbable implants to reconstruct forehead and midface deficits, all of which were for functional (noncosmetic) reasons. METHODS: This study was a retrospective case series between 2008 and 2018. Institutional review board approval was obtained from the Beaumont Health Human Investigation Committee. Surgeries were performed at a tertiary care centre. We evaluated 50 patients who underwent correction of functional deficits of forehead, eyebrow, and midface using the endoscopic technique and bio-absorbable implants. Patient demographics and indicated etiologies and characterization of minor and major complications and their occurrence rates were characterized. RESULTS: Fifty patients were included in the study from 2008 to 2018, with 68% female and 32% male. Combined blepharoplasty and brow lift was the most commonly performed procedure, followed by midface lift and browplasty. The mean follow-up time was 372 days. No major operative complications including stroke, permanent nerve paralysis, or mortality occurred. There was a 4% rate of temporary nerve paresthesia that resolved, 2% rate of infection, and 6% rate of implant migration requiring revision surgery. CONCLUSION: The endoscopic approach and use of bio-absorbable implants to reconstruct functional deficits of the forehead and midface are safe and effective. There were zero major complications and most of the minor complications were temporary. There was a significant association between non-age-related functional impairment and risk of complication.

OBJECTIFS: Les déficits fonctionnels du front et de la région médiofaciale représentent des problèmes importants pour les patients, qui varient entre une légère asymétrie à divers degrés d'atteinte fonctionnelle, y compris la paralysie totale. Les chercheurs visaient à analyser l'utilisation d'implants bioabsorbables pour la reconstruction des déficits du front et de la région médiofacale, dans tous les cas pour des raisons fonctionnelles (non esthétiques). MÉTHODOLOGIE: La présente série rétrospective portait sur les cas observés entre 2008 et 2018. Le comité de recherche sur la santé humaine de Beaumont est le comité d'analyse institutionnel qui a approuvé l'étude. Les opérations étaient exécutées dans un centre de soins tertiaires. Les chercheurs ont évalué 50 patients qui ont fait corriger des déficits fonctionnels du front, des sourcils et de la région médiofaciale par technique endoscopique et implants bioabsorbables. Ils ont colligé la démographie des patients, les étiologies indiquées, les complications mineures et majeures et leur fréquence. RÉSULTATS: Cinquante patients ont participé à l'étude entre 2008 et 2018, pour un pourcentage de 68 % de femmes et de 32 % d'hommes. La principale intervention était une association de blépharoplastie et de redrapage des sourcils, suivie d'un redrapage de la région médiofaciale et d'une plastie des sourcils. Le suivi moyen durait 372 jours. Les chercheurs n'ont constaté aucune complication opératoire majeure, y compris les accidents vasculaires cérébraux, la paralysie nerveuse permanente et la mortalité. Ils ont remarqué un taux de paresthésie nerveuse temporaire qui s'est résorbée de 4 %, un taux d'infection de 2 % et un taux de migration de l'implant exigeant une réintervention chirurgicale de 6 %. CONCLUSION: L'endoscopie et les implants bioabsorbables pour reconstruire les déficits fonctionnels du front et de la région médiofaciale sont à la fois sécuritaires et efficaces. Ils n'ont suscité aucune complication majeure, et la plupart des complications mineures étaient temporaires. Il y avait une association significative entre une atteinte fonctionnelle non liée à l'âge et le risque de complication.

Fellow Selection Protocols in Facial Plastic Surgery: A National Survey of Facial Plastic Surgery Program Directors.

Background: Despite its popularity among otolaryngology residents, there is currently a paucity of knowledge on the match in facial plastics surgery fellowships and the selection criteria that drive the match process. To increase the understanding of this process and to improve the manner in which candidates are vetted, a survey study was designed. Methods: A 24-question online survey was designed to discern desired qualities regarding fellow selection, interview processes, fellow participation, and program director satisfaction with the current process. This survey was sent to all American Academy of Facial Plastic and Reconstructive Surgery fellowship program directors in the United States. Results: Overall, 40 of the 64 fellowship directors responded to the survey for a total response rate of 62.5%. Most fellowship directors reported that the reputation of an applicant's residency was an important component of the selection criteria with 34 of 40 of those who responded rating it at least "somewhat important." With regard to the otolaryngology trainee examination, nearly all fellowship directors (39/40) reported that there was no minimum cutoff score to be offered an interview. When fellowship directors were asked to rank the academic components of an application that they viewed as most important, they most commonly reported that the strength of an applicant's letters of recommendation were most important. Conclusions: With the increasing popularity of fellowships within the field of otolaryngology, having an understanding of which components of the application process are viewed as most important by fellowship directors is crucial in applicants matching into the fellowship of their choice.

Randomised phase II trial of trofosfamide vs. doxorubicin in elderly patients with untreated metastatic soft-tissue sarcoma.

Doxorubicin represents the standard first-line treatment for metastatic soft-tissue sarcoma. We assessed the efficacy and safety of trofosfamide in elderly patients. In this controlled phase II trial, we randomly (1:2) assigned 120 previously untreated patients with soft-tissue sarcoma, older than 60 years, with an Eastern Cooperative Oncology Group score of 0-2, to receive either doxorubicin for 6 cycles (arm A) or oral trofosfamide (arm B). The primary end-point was a 6-month progression-free rate (PFR) in the experimental arm (clinical trial information: NCT00204568). Between August 2004 and October 2012, forty and 80 patients were randomly assigned to arm A and arm B, respectively, in 16 centres. The median age was 70 years (range, 60-89). The primary study end-point (6-month PFR) was exceeded, with 27.6% in arm B (95% confidence interval [CI], 18.0-39.1) and 35.9% in arm A: (95% CI, 21.2-52.8). Survival data in terms of progression-free survival were 4.3 months (95% CI, 2.2-6.3) and 2.8 months (95% CI, 1.7-3.6) and in terms of overall survival were 9.8 months (95% CI, 6.7-11.6) and 12.3 months (95% CI, 9.6-16.2), respectively. The number of serious adverse event (SAE) was 59% in arm A and 30.3% in arm B (p = 0.005). Trofosfamide caused more often dyspnoea and low-grade fatigue, whereas with doxorubicin, more often leukocytopenia, neutropenia and mucositis were seen. Discontinuation rates for reasons other than disease progression were 15.4% (arm A) vs. 7.9% (arm B). In an elderly population of patients, oral trofosfamide achieved the estimated primary end-point 6-month PFR and was associated with a favourable toxicity profile compared with doxorubicin.

Immuno-Oncological Treatment and Tumor Mass in Non-Small Cell Lung Cancer: Case-Control Analysis of Overall Survival in Routine Clinical Practice.

BACKGROUND: Immuno-oncological (IO) therapies such as PD-1 and PD-L1 antibodies have been introduced in the treatment of advanced non-small cell lung cancer (NSCLC) since 2015 based on randomized trials showing unprecedented advantages in overall survival (OS) with hazard ratios (HRs) between 0.5 and 0.7. The impact of these treatments on OS in routine clinical practice and the role of tumor mass have not been studied. METHODS: 557 consecutive patients with inoperable stage III or stage IV NSCLC diagnosed in our certified lung cancer center from 2006 to 2018 were included if they had received at least one line of systemic treatment. OS of immuno-oncologically treated patients (IO patients, n = 144) who received treatment with a PD-1 antibody (nivolumab [n = 77] or pembrolizumab [n = 51]) or a PD-L1 antibody (atezolizumab [n = 4] or durvalumab [n = 12]) was compared to historic controls treated before availability of IO treatment (n = 413) using case-control analysis. IO patients and historic controls were individually matched for stage, performance state, histology, smoking status, gender, age, and initial treatment mode (palliative vs. definitive radio-chemotherapy). RESULTS: Case-control analysis of 91 matched pairs showed significantly longer OS in IO patients compared to historic controls (21.2 vs. 10.9 months, HR 0.526, CI 0.373-0.723). The benefit was more pronounced in patients with lower tumor stage (HR 0.48 [stage III], 0.40 [IVA], 0.63 [IVB]) or smaller tumor size (HR 0.38 [RECIST ≤57 mm], 0.40 [RECIST 58-94 mm], 0.59 [RECIST 95-141 mm], 0.75 [RECIST ≥142 mm]). CONCLUSIONS: IO patients showed significant benefit in OS with HRs comparable to those reported in phase III trials. The benefit tended to be greater in patients with lower tumor mass.

Second malignancy in non-small cell lung cancer (NSCLC): prevalence and overall survival (OS) in routine clinical practice.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and a prior or synchronous second malignancy are generally excluded from clinical trials. Therefore, little is known on prevalence and prognosis of these patients. METHODS: 1252 patients diagnosed with NSCLC in our center from 2006 to 2017 were studied. Overall survival (OS) of patients with a prior or synchronous malignancy was compared to controls including case-control analysis. RESULTS: 158 patients (12.6%) had a prior malignancy. The most common sites were prostate (17%), breast (16%), gastrointestinal tract (12%), head and neck (11%), bladder (10%), and lung (8%). Compared to controls, patients with prior malignancy were older (71.3 vs. 67.5 years), but had otherwise better prognostic characteristics (stage I-III 63 vs. 53%). Survival was identical compared to controls [hazard ratio (HR) 1.017, CI 0.776-1.333]. A further 3.5% of patients had a synchronous malignancy including 34% prior lung cancer. Patients with a synchronous malignancy had an earlier stage (I-III 84%), and had longer median OS in unselected patients (38.6 vs. 16.2 months, p = 0.021). However, the case-control analysis showed similar OS [hazard ratio (HR) 0.899, CI 0.497-1.621]. CONCLUSIONS: Prior or synchronous second malignancies are common at diagnosis of NSCLC. The sites reflect the high proportion of smokers in the population. The earlier stage of NSCLC with a second malignancy might be attributed to chance finding of NSCLC during follow-up. The second malignancy does not affect OS of NSCLC. Therefore, the exclusion of patients with second malignancies from NSCLC trials should be reconsidered.

Effect of ABCG2, OCT1, and ABCB1 (MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. MATERIALS AND METHODS: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated. RESULTS: The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (‰) was retained as the only significant variable (P = .02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P = .04). Patients with an ABCG2/GUSB transcript level >4.5‰ (n = 93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (≤4.5‰; n = 39) had a 12-month TFR rate of 72% (95% CI, 55%-82%). CONCLUSION: In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation.

Oncogenic driver mutations, treatment, and EGFR-TKI resistance in a Caucasian population with non-small cell lung cancer: survival in clinical practice.

INTRODUCTION: Oncogenic driver mutations activating EGFR, ALK, or BRAF in NSCLC predict sensitivity to specific tyrosine-kinase inhibitors (TKIs). We provide data on prevalence, treatment and survival of driver-mutation positive NSCLC in a predominantly Caucasian population in routine clinical practice. PATIENTS AND METHODS: NSCLC patients diagnosed from 2006-2015 with an EGFR-test result were included (n=265). Testing for EGFR, ALK, or BRAF was performed if specific TKI therapy was considered. Case-control analyses of overall survival (OS) comparing driver-mutation positive and negative patients were performed. RESULTS: 44 sensitizing EGFR mutations (17%), 8 ALK translocations (7%, n=111) and 3 BRAF mutations (8%, n=39) were detected in adenocarcinoma or adenosquamous carcinoma. We did not find mutations in tumors without an adenocarcinoma-component. More than 90% of inoperable driver-mutation positive patients received TKI-therapy. Case-control analysis revealed improved OS of driver-mutation positive patients (39.6 vs. 19.4 months, HR 0.51). OS was improved in stage IV patients but not in stage I-III patients.OS of EGFR-TKI treated patients was similar for 1st and 2nd-line EGFR-TKI treatment. Patients not treated with EGFR-TKI had no benefit in OS. Re-biopsies obtained at progression revealed an EGFR-T790M mutation in 73% (n=11). These patients responded to the 3rd-generation EGFR-TKI osimertinib. DISCUSSION: Testing guided by predictive clinical parameters resulted in twice as high rates of mutation-positive patients than expected, and TKI treatment resulted in a strong long-term OS advantage. CONCLUSION: Testing for driver mutations is feasible in routine clinical practice, and identifies patients who benefit from TKI-therapy. OS compares favorably with OS in clinical studies.

Trauma patterns, symptoms, and complications associated with external auditory canal fractures.

OBJECTIVES/HYPOTHESIS: External auditory canal (EAC) trauma, although rare, can have significant long-term adverse outcomes. This study aims to investigate the frequency, treatment, and complications of external ear canal injury in association with mandibular and temporal bone trauma. STUDY DESIGN: Retrospective chart review. METHODS: Computed tomography images with mandibular or temporal bone trauma were reviewed for EAC fractures. Patient data were collected from initial presentation and subsequent follow-up clinic visits. RESULTS: Thirty-nine percent of temporal bone fractures and 3.3% of mandible trauma involved the EAC. In particular, 10% of condylar or subcondylar trauma included an EAC fracture (P = 0.0006). One patient sustained bilateral EAC fractures despite an isolated, unilateral condylar fracture. The most common presenting sign was blood in the external auditory canal. Two patients underwent exam under anesthesia and removal of debris and stenting as treatment, whereas 42% of the patients were placed on otic drops and 5% received packing or a stent. Follow-up data were only available for 16% of the patients. Hearing loss from otic capsule involvement or ossicular chain disruption were follow-up complaints, and one patient had persistent canal stenosis. CONCLUSIONS: External auditory canal trauma is present in a significant proportion of mandibular and temporal bone trauma, including both condylar and noncondylar fractures with a higher incidence of condylar fractures. One case was seen with bilateral EAC fractures despite a unilateral mandibular fracture. Complications of these fractures can include hearing loss and canal stenosis; however, additional outpatient follow-up is needed to further elucidate long-term complications and shape treatment recommendations.

Comprehensive analysis of the whole transcriptomes from two different pig breeds using RNA-Seq method.

Next-generation sequencing RNA-Seq technology is a powerful tool that creates new possibilities for whole-transcriptome analysis. In our study, the RNA-Seq method was applied to analyze global changes in transcriptome from muscle tissue (m. semimembranosus) in two pig breeds (Pietrain and Polish Landrace, PL). The breeds differ in terms of muscularity, growth rate and reproduction traits. Using three different approaches (deseq, cufflinks and edger) and taking into account the most restrictive criteria, 35 genes differentially expressed between Pietrain and PL pigs were identified. In both breeds, the most abundant were transcripts encoding ribosomal and cytoskeletal proteins (TPM3, TCAP, TMOD4, TPM2, TNNC1) and calcium-binding proteins involved in muscle contraction, calcium-mediated signaling or cation transport (CASQ1, MLC2V, SLC25A4, MYL3). In PL pigs, we identified up-regulation of several genes that play crucial roles in reproduction: female gamete generation (BDP1, PTPN21, USP9X), fertilization (EGFR) and embryonic development (CPEB4). In the Pietrain breed, only seven genes were over-expressed (CISH, SPP1, TUBA8, ATP6V1C2, IGKC, predicted LOC100510960 and LOC100626400), and they play important roles in, for example, negative regulation of apoptosis, immune response, cell-cell signaling, cell growth and migration as well as the metabolic process. The functions of the majority of selected genes were consistent with phenotypic variation in investigated breeds; thus, we proposed a new panel of candidate genes that can be associated with economically important pig traits.

Expression and imprinting analysis of the NESP55 gene in pigs.

Most imprinted genes play important roles in a mammalian development. One of them is GNAS complex locus which codes for several imprinted or biallelically expressed transcripts. The function of some of them are well understood (for example GSα-guanine nucleotide binding, α -stimulating protein is essential element of cell signaling), whereas the others are little known. The function of NESP55 (Neuroendocrine secretory protein 55) remains elusive, although there are suggestions about its role in brain development. Imprinted genes are currently being studied as potential candidate genes for quantitative trait loci (QTLs) in farm animals. In our study, we analyzed tissue distribution of NESP55 mRNA in pigs and established imprinting status of this gene in the brain stem, muscle, kidney and liver at several developmental stages. NESP55 mRNA was most abundant in central nervous system (CNS) and pituitary. Substantial expression was also noticed in the kidney, testis and muscle. Moreover, we identified a 12-nucleotides deletion within the coding region of NESP55 (accession number ss#342570450) which was used in imprinting analysis. The deletion was very rare in the analyzed populations and present only in heterozygous form. The imprinting analysis showed that NESP55 is maternally expressed in young and adult pigs, similar to what was obtained in humans, mice and cattle.

Benefit of erlotinib in patients with non-small-cell lung cancer is related to smoking status, gender, skin rash and radiological response but not to histology and treatment line.

BACKGROUND: Erlotinib is a standard of treatment for metastatic non-small-cell lung cancer after failure of initial therapy. Patient selection based on clinical factors is under discussion. METHODS: We analyzed the outcome in relation to clinical factors of 121 consecutive Caucasian patients treated with erlotinib in a routine clinical setting in a comprehensive cancer center and 2 regional oncology centers. RESULTS: For patients with erlotinib treatment at the 1st/2nd/3rd/> or = 4th line, progression-free survival (PFS) was 4.5/3.5/2.5/3.0 months, and overall survival (OS) was 8.0/8.5/7.8/6.5 months. Patients with adenocarcinoma had an improved PFS, but a similar OS. Never-smokers had longer PFS (7 months) and OS (13 months) than smokers and ex-smokers. Male patients had a slightly longer survival than female patients (PFS 3.0 vs. 2.5 months, OS 8.5 vs. 7.0 months). After adjustment for smoking and histology, the gender difference in OS was significant (adjusted hazard ratio 0.57). Patients with clinically relevant skin toxicity (grade 2, 3) had a significantly prolonged PFS and OS. Patients with partial response on 1st radiological evaluation had a significantly prolonged PFS and OS. CONCLUSION: Among clinical factors, never-smoking status and male gender predicted a prolonged survival. During treatment, skin toxicity and radiological response were related to better survival.

Solar power wires based on organic photovoltaic materials.

Organic photovoltaics in a flexible wire format has potential advantages that are described in this paper. A wire format requires long-distance transport of current that can be achieved only with conventional metals, thus eliminating the use of transparent oxide semiconductors. A phase-separated, photovoltaic layer, comprising a conducting polymer and a fullerene derivative, is coated onto a thin metal wire. A second wire, coated with a silver film, serving as the counter electrode, is wrapped around the first wire. Both wires are encased in a transparent polymer cladding. Incident light is focused by the cladding onto to the photovoltaic layer even when it is completely shadowed by the counter electrode. Efficiency values of the wires range from 2.79% to 3.27%.