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Sleep deprivation for one night has been investigated as a treatment for depression since the first publications describing its antidepressant properties almost 30 years ago [Pflug and Tolle, 1971: Int Pharmacopsychiatry 6:187-196]. It remains a field of active research. It is the only intervention consistently demonstrated to produce next-day antidepressant results. This makes sleep deprivation an exciting and unique tool to study the pathophysiology of depressive disorders and to formulate targets for novel antidepressant agents. Importantly, it is also an effective, but underused, clinical treatment for unipolar and bipolar depression. [ABSTRACT FROM AUTHOR]

Key Points: Using 3D modeling, we studied the influence of orbital tumor morphology on post-operative outcomes. Orbital tumor volume did not influence postoperative complication rates. Less spherical tumors may be correlated with a more extensive surgical approach., (© 2024 ARS‐AAOA, LLC.)

Key Points: Penetrating orbital trauma from marine creatures, especially needlefish, should be considered after injuries sustained in open water. Advances in endoscopic sinus surgery have enabled surgeons to remove certain orbital foreign bodies through endoscopic endonasal approaches. 3D segmentation is a valuable pre-operative tool in complex endoscopic orbital cases., (© 2024 ARS‐AAOA, LLC.)

Objectives: The COVID-19 pandemic affected the epidemiology of several diseases. This study aims to compare the incidence of surgically treated odontogenic sinusitis (ODS) before and during the COVID-19 pandemic and identify unique features., Methods: A retrospective chart review of patients who underwent at least maxillary antrostomy at a tertiary referral center was performed. The patients were divided into two cohorts: "pre-COVID" (March 2018 to February 2020) and "COVID" (March 2020 to February 2022). Data on demographics, comorbidities, and treatment interventions were collected and analyzed., Results: Of the 734 patients who underwent maxillary antrostomy, 370 (50.4%) were operated on during the COVID period, with a mean age of 53.1 ± 15.7 years. ODS was found as the etiology of 22 (6%) and 45 (12.2%) of the pre-COVID and COVID cases, respectively (p = 0.006). Although no difference was found in the incidence of diabetes (p = 0.9) or obesity (p = 0.7) between groups, a trend toward higher incidence of immunosuppression was found in the pre-COVID patients (18.2% vs. 0%, p = 0.06). A higher incidence of sphenoid sinus involvement (31.8% vs. 8.9%, p < 0.05) was identified in the pre-COVID group; however, no differences in ethmoid (86.4% vs. 86.7%, p = 0.999) or frontal sinus involvement (54.5% vs. 37.8%, p = 0.3) were found between the groups., Conclusion: There was an increase in the incidence of ODS during the first 2 years of the COVID-19 pandemic compared to the 2 years prior. Similar clinical characteristics were found in both groups. Future studies focusing on specific etiologies to explain ODS preponderance may help determine optimal treatment and prevention strategies., Level of Evidence: 3 Laryngoscope, 134:1597-1602, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Radiofrequency ablation (RFA) reliefs nasal obstruction and improves quality of life (QoL) in patients suffering from inferior turbinate hypertrophy (ITH). A substantial benefit was noted among patients suffering from Rhinitis Medicamentosa (RM), enabling ending decongestant spray abuse. Our aim was to establish the benefit from RFA with respect to QoL in patients suffering from ITH, due to the presence of RM., Study Design: Prospective cohort study., Methods: Prospective Cohort study, including patients suffering from ITH undergoing RFA between 9.2017 and 9.2019 in Tel Aviv Medical Center. The cohort was divided to RM and non-RM (including allergic, non-allergic) patients. The differences between the groups were compared before and after RFA, and included patients' complaints, clinical findings and QoL questionnaires (SNOT-22 & NOSE). In the RM group, the ability to wean from decongestants was also described., Results: Our data demonstrated subjective QoL improvement following RFA (88.9 %, N = 90). All RM patients withdrawaled from nasal decongestant spray. NOSE questionnaire demonstrated a significant improvement in QoL after RFA in the RM group (PV = 0.025). SNOT-22 did not demonstrate significant difference in QoL between RM and the reference group (PV = 0.1). Rates of MCID>8.3 were high, without significant difference between the groups (PV = 0.2)., Conclusion: RFA demonstrated effectiveness in achieving of withdrawal from decongestant spray in RM patients and may be a possible definitive treatment option for this group. The nasal obstruction component in SNOT-22 questionnaire & NOSE questionnaire showed improved QoL in comparison to controls. High QoL after RFA was established in our entire cohort., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The presence of clinically detectable papillary thyroid carcinoma (PTC) metastases in the lateral neck is an indication for neck dissection (ND) and thyroidectomy. Although there is a consensus regarding the importance of therapeutic selective ND of involved levels II to IV in patients with clinically evident locoregional metastatic disease, the prognostic benefit of level V prophylactic ND remains debatable., Methods: All patients who underwent thyroidectomy with ND for metastatic PTC between 2006 and 2019 were included in a single-institution retrospective study. Preoperative characteristics at initial presentation, imaging workup, intraoperative findings, and the final histopathological reports were retrieved from the institutional database., Results: A total of 189 patients with locally advanced PTC were identified, of whom 22 (11.6%) patients underwent therapeutic selective ND at levels II to IV together with level V dissection due to clinical involvement. Comparison of the patients who were operated on level V to those who were not revealed no significant difference. The disease recurrence rate was 20.1% throughout an average follow-up of 5.1±3.1 years. No significant differences in recurrence rate were found between patients who underwent and those who did not undergo level V ND (22.7% vs 19.8%, P = .648). No recurrence at resected level V was detected during follow-up, while recurrence at level V was found in 4 (2.1%) patients who did not undergo level V dissection. Evidence of macroscopic and microscopic extrathyroidal extension was significant predictors of disease recurrence risk., Conclusion: There were no significant associations between level V dissection and risk for recurrence. Recurrence at level V was rare (4/189 patients, 2.1%). Our study's findings suggest a low prophylactic benefit of an elective level V ND. Elective level V ND should not be done routinely when lateral ND is indicated but should rather be considered after careful evaluation in high-risk patients.

Background: The presence of cervical lymph node (LN) metastasis at the initial presentation of papillary thyroid carcinoma (PTC) constitutes an independent risk factor for disease recurrence, increases the risk for mortality, and impacts overall outcome. The 2016 American Joint Committee on Cancer raised the age cutoff for PTC staging from 45 to 55 years for better prediction of overall survival. Age > 55 years is considered a significant risk factor for a more aggressive and advanced disease with worse outcomes. We identified histopathological factors for disease recurrence in PTC patients younger and older than 55 years of age., Methods: Data on all patients who underwent thyroid surgery due to PTC between 2006 and 2018 in the Tel Aviv Sourasky Medical Center were retrieved for this retrospective cohort study. Patients with lymph node (LN) metastases were further investigated for preoperative presentation, pathological characteristics, and recurrence. A multivariate analysis was used to detect predictors for recurrence and patient outcome for each age-group., Results: Twenty-two of the 183 patients (12%) with PTC who met the inclusion criteria and had sufficient follow-up period sustained recurrence. The predictors of recurrence varied between the two age-groups. The size of thyroid lesions (p = 0.003) was identified as a risk factor in the older group, while the number of metastatic cervical LNs (p = 0.001) and the ratio of metastatic-to-total dissected cervical LNs (p = 0.027) were the main predictors of recurrence for the younger group., Conclusion: The histopathological factors predictive for disease recurrence differed among PTC patients younger and older than 55 years of age., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Objectives: Inferior turbinate hypertrophy (ITH) and nasal septum deviation are leading causes of chronic nasal obstruction. Radiofrequency ablation (RFA) of hypertrophic inferior turbinates is effective for improving quality of life (QOL). We aim to assess QOL among patients with nasal obstruction associated with ITH and major deviated nasal septum., Methods: A prospective cohort study comparing the difference in improved QOL among patients with and without septal deviation following RFA treatment between March 2016 and June 2019. The patients formed two groups according to their grade of septal deviation. Patients participating filled in QOL questionnaires (Sino-Nasal Outcome Test-22 [SNOT-22] and Nasal Obstruction Symptom Evaluation [NOSE]) Pre- and 2 months postprocedure., Results: All patients demonstrated QOL improvement with no significant difference between those with and those without any degree of deviated septum, as demonstrated by their responses to the SNOT-22 questionnaire ( p  = .29), the NOSE questionnaire ( p  = .93), and the degree of nasal obstruction (question 22 in the SNOT-22 questionnaire) ( p  = .14)., Conclusion: We conclude that septal deviation to certain degree does not preclude treatment of ITH with RFA nor does it negatively affect subjective improvement of the patient's QOL. Both those with and those without septal deviation will benefit similarly with regards to subjective QOL improvement., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: After diagnosing well-differentiated thyroid cancer (WDTC), assessment of the risk for disease-specific recurrence is essential for deciding between hemi-thyroidectomy (HT) and total thyroidectomy (TT). The American Thyroid Association (ATA) 2015 guidelines suggest that patients with 1-4 cm WDTC without suspicious features may be suitable for HT. Patients' preoperatively determined risk levels are re-stratified according to surgical and final histopathological findings. The incidence and clinical implications of high-risk features discovered postoperatively in patients with preoperatively determined low-risk WDTC are yet to be better defined., Methods: Thyroidectomies performed in the Tel-Aviv Sourasky Medical Center (TASMC) [2006-2018] were included. Patients with 1-4 cm WDTC without evidence of positive cervical lymph nodes, invasion to adjacent structures, or high-risk cytology were considered at low risk for disease-specific recurrence-suitable for lobectomy. Patients were stratified according to their risk for disease-specific recurrence, pre- and postoperatively, and the rate of completion thyroidectomy was determined., Results: In total, 301 (21%) patients were preoperatively stratified as low risk. Forty-six of them (15%) were re-stratified postoperatively as intermediate-to-high-risk. There were no significant differences in the characteristics of the patients who maintained their original stratification to patients who were upscaled to a higher risk level postoperatively., Conclusions: We report a 15% rate of postoperative risk escalation of patients who required completion thyroidectomy according to current ATA guidelines. In our opinion, this rate of postoperative WDTC upscaling of risk requiring more radical surgery than originally planned, is acceptable. Meticulous preoperative personalized evaluation by an experienced multidisciplinary dedicated team is essential., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-105). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Objective  Reconstruction after open surgery of anterior skull base lesions is challenging. The fascia lata graft is our workhorse for achieving dural sealing and preventing cerebrospinal fluid leak and meningitis. This study seeks to analyze the donor and recipient site complication rates after fascia lata reconstruction. Methods  This is a retrospective review of all open anterior skull base operations in which a double-layer fascia lata graft was used for the reconstruction of the defect from 2000 to 2016 at the Tel-Aviv Sourasky Medical Center, a tertiary referral center in Israel. Results  Of the 369 patients operated for skull base lesions, 119 underwent open anterior skull base surgery and were reconstructed with a fascia lata graft. The patients' mean age was 47.1 years, and 68 (57.1%) were males. The overall postoperative early and late donor site complication rates were 6.7% ( n  = 8) and 5.9% ( n  = 7), respectively. Multivariate analysis found minor comorbidities and persistent/recurrent disease as being predictors for early-term complications. The overall postoperative early central nervous system (CNS) complication rate was 21.8% ( n  = 26), while 12.6% ( n  = 15) of the patients had late postoperative CNS complications. Conclusion  Reconstruction of open anterior skull base lesions with fascia lata grafting is a safe procedure with acceptable complication and donor site morbidity rates., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Surgery is the preferred treatment of benign parotid lesions, but it carries a risk of complications. Therefore, the approach toward the surgery of these lesions should seek to avoid complications. There are no guidelines or recommendations for when not to operate. Integration of comorbidities and other factors shift the scales from surgery toward observation in a small subset of patients presenting with parotid tumors. When observation is chosen, the patient should be followed frequently and cautiously, and the surgeon should be prepared to change strategy to surgical excision if in doubt., Competing Interests: Conflict of Interest Disclosures The authors have no funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction  Endoscopic endonasal surgery (EES) has become the preferred approach for pituitary tumor resection. Nevertheless, research on quality of life related to pituitary adenoma surgery is scarce. Objective  The aim of the study is to evaluate short-term quality of life in patients after endoscopic endonasal resection of pituitary tumors and to find predictors for poor quality of life (QOL) outcome. Materials and Methods  A prospective cohort study was conducted, including all patients who underwent EES for pituitary tumors in a tertiary medical referral center. Recruited patients completed the Anterior Skull Base Disease-Specific QOL (ASBS-Q) questionnaire and the Sinonasal Outcome Test 22 (SNOT-22) questionnaire before surgery, 2 and 4 to 6 months after surgery. Demographic and clinical data was collected. Results  Our study included 49 patients. The overall ASBS-Q scores significantly improved 4 to 6 months after surgery (4.46 vs. 4.2, p  < 0.05). We found a significant improvement in QOL related to emotional state 2 months post surgery (4.41 vs. 3.87, p  < 0.05), which became borderline significant 4 to 6 months post surgery. There was a significant improvement in pain (4.5 vs. 4.08, p  < 0.05) and vitality (4.43 vs. 4.16, p  < 0.05) domains 4 to 6 months post surgery. SNOT-22 scores did not change significantly postoperatively. Factors such as secreting and non-secreting tumors, tumor size, intraoperative cerebrospinal fluid leak, gross tumor resection, endocrine remission, and the use of nasoseptal flap reconstruction did not have a significant effect on QOL. Conclusion  We found that patients after EES reported improved QOL 4 to 6 months post surgery. Specific improvement was noted in the QOL related to pain and vitality., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Introduction  Isolated nasal obstruction (INO) is a common complaint of multiple etiology. The preoperative evaluation of patients presenting with nasal obstruction and deviated nasal septum (DNS) does not typically include imaging. The benefits of performing computed tomography (CT) in the preoperative setting are inconclusive. Objective  Assessing the contribution of preoperative CT to the surgical treatment of non-sinusitis patients presenting with INO and DNS. Methods  A retrospective cohort study on patients referred to surgery for nasal obstruction due to DNS or turbinate hypertrophy between 2006 and 2015. Data was retrieved from patients' medical charts. The CT scans and clinical data were reassessed by a second surgeon blinded to the patients' clinical course. Results  Seventy of the 843 patients (8.06%) who underwent endoscopic sinonasal procedures during the study period had presented with INO and met the inclusion criteria. Thirty-eight (55.88%) of them underwent CT scans during their preoperative assessment. Modification of the initial preoperative planning based on the radiological findings was required in 32 cases (84.2%). When reassessed by a second blinded surgeon, 58% of cases required surgical modification rather than classical submucosal resection of nasal septum and turbinate reduction ( P  = 0.048). Conclusion  Computed tomography was found beneficial in the preoperative planning for patients with INO. The original surgical plan based upon physical examination findings was modified based on radiological findings in 84.2% of the patients., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Papillary thyroid cancer (PTC) usually metastasizes via lymphatic channels in a sequential fashion, first to the central compartment, followed by the lateral neck. PTC patients diagnosed with lateral neck disease (N1b) without proof for central involvement traditionally undergo prophylactic central neck dissection (pCND). However, substantial evidence on outcomes to support this approach is lacking., Materials and Methods: We conducted a dual center retrospective study to compare the rate of central neck recurrence between N1b PTC patients undergoing pCND and those spared pCND. All patients diagnosed with N1b PTC who underwent total thyroidectomy and lateral neck dissections with or without pCND between January 1998 and December 2015 were included in this study. The rates of central neck recurrences were compared between the groups., Results: The 111 patients who met the inclusion criteria were 44 females (39.6%) and 67 males (60.4%), with a mean age of 50.2 ± 17.7 years, and a mean follow-up of 10.2 ± 5.3 years. Sixty patients (54.1%) underwent a pCND and 51 patients (45.9%) did not (non-pCND). During follow-up, 18 patients (16.2%) had level VI recurrences, 13 in the pCND group and 5 in the non-pCND group. Cox-regression models with propensity scoring did not reveal any inclination or an advantage for performing pCND., Conclusion: The present study demonstrated no advantage in performing pCND to prevent central neck recurrence among PTC patients with lateral neck involvement only. These findings question the need for pCND in patients without clinical evidence of central neck disease., (© 2020 Wiley Periodicals LLC.)

Purpose: The skull base inventory (SBI) was developed to better assess health-related quality of life (HR-QOL) in patients with anterior and central skull base neoplasms treated by endoscopic and open approaches. The primary objective of this study was to prospectively assess the psychometric properties of the SBI., Methods: This study is part of a multi-center study of patients undergoing endoscopic and open procedures completed between 2012 and 2018. Participants were eligible if they were over 18 years of age; had benign or malignant anterior, antero-lateral, or central skull base tumors; and required either an open or endoscopic skull base surgical approach. In order to assess the psychometric properties of the SBI, patients completed the instrument at six time points (preoperative, 2 weeks, 3 months, 6 months, 12 months postoperative). Patients also completed the Anterior Skull Base (ASB) questionnaire and the Sinonasal Outcome Test (SNOT-22) to allow comparison to the SBI., Results: One hundred and eighty-seven patients were included across five centers, with 121 having an endoscopic procedure. Internal consistency (Cronbach's alpha = 0.95) and test-retest at 12 months and 12 months plus 2 weeks (intraclass correlation > 0.90) were excellent. Concurrent validity was demonstrated by very strong correlation between total SBI scores and ASB scores (r = 0.810 to 0.869, p < 0.001) and moderate correlation between nasal domain SBI scores and SNOT-22 scores (r = - 0.616 to - 0.738, p < 0.001). Convergent validity was demonstrated by moderate correlation between change in SBI scores and global QOL change (r s  = 0.4942, p < 0.001). The minimally important clinical difference (global HR-QOL change of "a little better" or "a little worse") was 6.0., Conclusion: The SBI questionnaire is reliable and valid for patients treated by both endoscopic and open approaches and can be used for assessment of HR-QOL in these settings.

Objective: Lateral and central compartments cervical lymph nodes metastases are common among patients with papillary thyroid carcinoma (PTC). Elective level VI neck dissection during thyroidectomy and lateral neck dissection (LND) for the treatment of PTC with lateral compartment lymph node metastases is controversial because of the uncertain benefit in clinical outcomes and increased risks of surgical morbidity. We aimed to determine the potential benefit of elective level VI neck dissection in patients with cN1 papillary thyroid carcinoma (PTC) by investigating the rate and pattern of locoregional recurrence in PTC patients who underwent total thyroidectomy and therapeutic lateral node dissection (LND; levels II-IV) without elective level VI dissection., Methods: A retrospective cohort study. Data on demographics, clinical presentation and workup, intraoperative and pathological report, postoperative course, adjuvant therapy, recurrence patterns, and overall survival were retrieved from the medical charts of patients who underwent thyroid surgery in our hospital between January 2006 and December 2017., Results: A total of 1415 thyroidectomies were performed during the study period, of which 802 (56.67%) were for PTC. Of those PTC patients, 228 (28.42%) also underwent LND (levels II-VI) during the same thyroidectomy procedure. Thirty-four (14.91%) of those 228 patients, underwent total thyroidectomy with therapeutic lateral ND II-IV without elective level VI ND. During the follow-up period, five (14.7%) of the latter cohort were diagnosed with recurrence in central neck (level VI) lymph nodes, and four of them (11.7%) were diagnosed with ipsilateral recurrence at level VI., Conclusion: Our results revealed 11.7% rate of clinically significant recurrent disease in ipsilateral level VI which, in our opinion, does not justify routine prophylactic level VI ND dissection when the ipsilateral lateral neck is operated for metastases.

Objectives: Reconstruction of surgical defects by free tissue transfer following resection of head and neck tumors in children are sparse. This study aims to assess the feasibility and safety of free flap reconstruction following surgical ablation of head and neck and skull base tumors in children based on our experience and the recent literature., Methods: Data from medical files of all children and adolescents <18 years of age who underwent free flap reconstruction following resection of head and neck and skull base tumors at our tertiary center between 2000 and 2018 were retrospectively reviewed. Data on early and late complications at the primary and donor sites, functional and aesthetic outcome, and tumor control were analyzed., Results: Twenty-four children (mean age 11.3 ± 5.1 years) were enrolled. Early complications occurred in 14 (56%) and late complications occurred in 8 (32%) of the procedures, with surgical intervention required in 4 (16%). Prior chemoradiation, sarcoma, non-reanimation procedures, and the use of rectus abdominis free flaps were associated with higher complication rates. The final functional and cosmetic outcomes, including mastication, deglutition, and speech, were satisfactory in all patients with one exception., Conclusions: Free flap transfer is a safe and feasible technique for reconstructing head and neck and skull base defects following surgical excision of tumors in children. Early identification and precautionary measures against the effects of potential causes of complications may improve outcome. Larger international cohort studies are warranted., (Copyright © 2020. Published by Elsevier B.V.)

Objective  Despite its technical feasibility, anterior skull base surgery still carries the risk of severe postoperative complications, morbidity, and mortality. The reported rate of complications has diminished over the past two decades, but they continue to pose various challenges. This study aims to report late complications in a relatively large series of patients who underwent open anterior skull base surgery, and to propose methods for averting such complications. Methods  Retrospective chart review of all patients who underwent anterior open skull base surgery between 2000 and 2016 in a university-affiliated tertiary referral cancer center. Results  There were 301 operations, of which 198 (65.8%) were for benign disease and 103 (34.2%) were for malignant tumors. The male-to-female ratio was 1.4:1, and the mean age was 44.8 years. Delayed complications occurred in 85 patients (28.2%): 31 (10.3%) involved wounds, 18 (13.9%) involved the central nervous system, and 14 (4.6%) involved the orbit. Multivariate analysis found malignant pathology, intracranial extension, and previous radiochemotherapy as predictors for the development of a delayed complication. The patients who were operated in the later study period (after 2007) had lower rates of all three types of complications compared with the earlier study period. Conclusion  Delayed complications following skull base surgery are in decline. This is mainly due to the advancement in imaging studies, surgical techniques, development of sophisticated reconstructive procedures, and the cooperation of multidisciplinary teams. We attribute the reduction in our department to our revised treatment protocol which is presented herein, with emphasis on averting the occurrence of these complications. Level of Evidence  The level of evidence is 4., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Purpose: Acute supraglottitis (SG) can potentially lead to rapid airway obstruction. The last few decades have witnessed a shift towards a more conservative approach in airway management of adult SG. This study aims to evaluate this watchful approach based on a large case series combined with a high-level meta-analysis of all reports in the English literature., Methods: Retrospective case series and meta-analysis. The medical records of all adult patients diagnosed as having SG who were hospitalized in a large-volume tertiary referral center between January 2007 and December 2018 were reviewed. A meta-analysis was conducted on all English literature published between 1990 and 2018., Results: A total of 233 patients (median age 49.1 years, 132 males), were admitted due to acute SG during the study period. No airway intervention was required in 228 patients (97.9%). Five patients (2.1%) required preventive intubation, and two of them (0.9%) were later surgically converted to a tracheotomy. Patients who required airway intervention had higher rates of diabetes (P = .001), cardiovascular diseases (P = .036) and other comorbidities (P = .022). There was no mortality. The meta-analysis revealed that the overall intubation rates random effects model was 8.8% [95% confidence interval (CI) 4.6%-14.0%] and that the tracheotomy random effects model was 2.2% (95% CI; 0.5%-4.8%). The overall mortality rate was 0.89%., Conclusions: This study provides evidence of low rates of surgical airway intervention in patients diagnosed with SG worldwide. A conservative approach in adult SG is safe and should be advocated., Level of Evidence: 2., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Several surgical procedures have been described for the treatment of respiratory distress secondary to vocal fold immobility (VFI), but the contribution of posterior cordotomy (PC) to tracheostomy weaning or prevention has not been studied in depth, particularly in the acute setting. The objective of this study was to show the effectiveness of PC to relieve dyspnea, prevent the need for tracheostomy, and enable decannulation in patients with VFI., Methods: We conducted a retrospective study and reviewed the medical records of all patients whose dyspnea warranted surgical intervention from January 2013 to January 2018. Data were retrieved on epidemiology, etiology, and duration of VFI, tracheostomy dependence, success in decannulation from tracheostomy or respiratory relief, number of procedures until decannulation, and complications., Results: Twelve suitable patients were identified of whom eleven had bilateral VFI and one had unilateral VFI. Five were tracheostomy-dependent. Ten patients underwent unilateral PC, and two patients underwent bilateral PC. All the patients experienced respiratory relief, eleven after a single PC and one after two PCs. All tracheostomy-dependent patients were decannulated. The mean follow-up after PC was 24.55 months during which none of the patients required a re-tracheostomy and three patients required revision of the PC. There were no surgical complications. Postoperatively, eight patients (67%) experienced a breathy voice and three patients (25%) had dysphagia for fluids. No patient had aspiration pneumonia., Conclusions: We conclude that PC is an easy, safe, and effective procedure for tracheostomy weaning and respiratory relief in patients with VFI. A revision PC may be indicated in some patients. A breathy voice is to be expected, and a few patients will experience dysphagia to fluids that may be addressed by instructing the patient to use a fluid thickener and take small sips., Competing Interests: Conflict of interest: The authors declare that they have no competing interests. The Alma Pixel CO2 laser was on loan to our department from Alma Lasers., (©Copyright: the Author(s).)

Purpose: Acute supraglottic laryngitis (ASL) is manifested by supraglottic inflammation that has the potential for rapid and fatal airway obstruction. Complete/incomplete vocal fold immobility (VFIm) in the setting of ASL may contribute to airway obstruction. The rate of VFIm complicating ASL is not known, and it is not clear whether its occurrence alters the course and the management of ASL, particularly the need to secure the airway (by endotracheal intubation/tracheostomy). This study seeks to describe the natural history of VFIm associated with ASL (ASLIm) and to determine the added effect of VFIm on ASL severity, management, and the need for intervention to secure the airway., Methods: This is a retrospective cohort study in a tertiary referral center. The medical records of all patients hospitalized due to ASL between January 2007 and December 2016 were reviewed., Results: Of the 214 patients admitted due to ASL, VFIm was identified in 9 (4.2%). The VFIms resolved within 1-90 days in all 8 patients with available follow-up of 1-3 months. One patient required endotracheal intubation. The 9 ASLIm patients had significantly higher rates of hoarseness and a history of diabetes mellitus. There was no group difference in the need to secure the airway., Conclusions: VFIm is an apparently uncommon finding among patients with ASL. It appears to be usually transient, short-lasting, and full recovery can be expected. VFIm did not alter the ASL course, nor did it put our patients at increased risk for the need for intervention to secure the airway., Level of Evidence: 4.

Objectives/hypothesis: Anterior skull base operations pose the risk for postoperative cerebrospinal fluid (CSF) leak. Routine lumbar continuous drainage catheter (LD) placement is intended to decrease CSF leaks and central nervous system (CNS) complications, but there are no sound evidence-based data on its efficacy. The primary goal of this study was to review CNS complications following anterior open skull base surgery and their association with LD placement. The secondary goal was to define predictors for the development of early CNS complications., Study Design: Retrospective case series., Methods: We conducted a retrospective analysis of all patients who underwent anterior skull base surgery between 2000 and 2016 at the Tel Aviv Sourasky Medical Center, an Israeli tertiary referral center., Results: A total of 226 patients underwent open skull base surgery, of whom 118 had elective perioperative continuous LD insertion and 108 did not. Delayed complications were defined as those occurring more than 30 days after the index operation. Thirty-one (26%) patients in the LD group had early CNS complications compared with only two (1.6%) in the non-LD group, whereas 13 (11%) of the former patients had late CNS complications compared with four (3%) of the latter patients. Early systemic and late wound complications were also significantly more numerous in the LD group. On multivariate analysis, elective LD insertion and intracranial tumor extension were found to be predictors for developing early CNS complications., Conclusions: The placement of continuous LDs might increase the risk of developing early and late CNS complications after open anterior skull base surgery., Level of Evidence: 4 Laryngoscope, 128:2702-2706, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction  The steady increase in average life expectancy has led to a rise in the number of referrals of elderly patients for major operations. It is not clear whether age itself is a risk factor for morbidity and mortality after skull base operations. We investigated a possible link among a cohort of patients older than 80 years of age who underwent those surgeries in our department. Methods  We conducted a retrospective analysis of all patients who underwent skull base surgery at the TASMC (Tel Aviv Sourasky Medical Center) between 2000 and 2016. Results  A total of 369 patients underwent open skull base surgeries in our institution, and 13 were patients older than 80 years. The median age of the octogenarians was 83.4 (range 80-89), and the male-to-female ratio was 7:6. Twelve patients had major systemic comorbidities. Four patients had major complications associated with surgery: three had early wound complications, and one each had early central nervous system complications, early and late systemic complications, and late orbital complications. This complication rate is comparable to that of our younger group of 356 patients. The overall survival rate was measured for 30 days, 1 year, and 3 years, and it was not significantly different between the octogenarians and that of the younger patients. Further comparison of the elderly group with 13 matched younger patients revealed no difference of morbidity and mortality between the two groups. Conclusions  Despite their systemic comorbidities, the morbidity and mortality rates associated with skull base surgery in octogenarians appear to be comparable to that of younger patients undergoing the same procedures.

Objective  The endoscopic endonasal approach is being increasingly used for the resection and reconstruction of anterior skull base (ASB) lesions. Vascularized nasoseptal flaps (NSF) have become the workhorse for the reconstruction of ASB defects, resulting in a significant decrease in the incidence of cerebrospinal fluid (CSF) leaks. The objective of this study was to investigate the efficacy and safety of NSF in children. Methods  This is a retrospective analysis of the medical records of all patients under the age of 18 years who underwent endoscopic repair of ASB lesions with the use of NSF at our tertiary medical center between 1/2011 and 8/2016. Results  Twelve children underwent ASB defect repair for both benign and malignant neoplasms using the endoscopic endonasal NSF technique. Four children had previously undergone ASB surgery. The male-to-female ratio was 1:1, the average age was 12.3 years, the average hospitalization time was 8.3 days, and the maximum follow-up period was 24 months, during which craniofacial growth appeared to be unimpaired. A lumbar drain was used postoperatively in six cases. Crust formation and synechia were observed in two cases. There was one case of a major long-term complication (a CSF leak followed by meningitis). Conclusions  Endoscopic endonasal NSF was both an effective and a safe technique for ASB defect reconstruction in 12 children for both benign and malignant neoplasms. It had a high success rate and a low complication rate. No apparent negative influence on craniofacial growth was observed in our series.

Introduction  Skull base lesions in children and adolescents are rare, and comprise only 5.6% of all skull base surgery. Anterior skull base lesions dominate, averaging slightly more than 50% of the cases. Until recently, surgery of the anterior skull base was dominated by open procedures and endoscopic skull base surgery was reserved for benign pathologies. Endoscopic skull base surgery is gradually gaining popularity. In spite of that, open skull base surgery is still considered the "gold standard" for the treatment of anterior skull base lesions, and it is the preferred approach in selected cases. Objective  This article reviews current concepts and open approaches to the anterior skull base in children in the era of endoscopic surgery. Materials and Methods  Comprehensive literature review. Results  Extensive intracranial-intradural invasion, extensive orbital invasion, encasement of the optic nerve or the internal carotid artery, lateral supraorbital dural involvement and involvement of the anterior table of the frontal sinus or lateral portion of the frontal sinus precludes endoscopic surgery, and mandates open skull base surgery. The open approaches which are used most frequently for surgical resection of anterior skull base tumors are the transfacial/transmaxillary, subcranial, and subfrontal approaches. Reconstruction of anterior skull base defects is discussed in a separate article in this supplement. Discussion  Although endoscopic skull base surgery in children is gaining popularity in developed countries, in many cases open surgery is still required. In addition, in developing countries, which accounts for more than 80% of the world's population, limited access to expensive equipment precludes the use of endoscopic surgery. Several open surgical approaches are still employed to resect anterior skull base lesions in the pediatric population. With this large armamentarium of surgical approaches, tailoring the most suitable approach to a specific lesion in regard to its nature, location, and extent is of utmost importance.

Aims/hypothesis: The determinants and mechanisms of the development of diabetic sensorimotor polyneuropathy as a painful (DSPN+p) or painless (DSPN-p) entity remain unclear. We examined the degree of cutaneous nerve fibre loss and regeneration in individuals with type 2 diabetes with DSPN+p or DSPN-p compared with individuals with recent-onset type 2 diabetes and corresponding healthy volunteers., Methods: In this cross-sectional study, skin biopsies taken from the distal lateral calf were obtained from individuals with recent-onset type 2 diabetes (n = 32) from the German Diabetes Study, with DSPN+p (n = 34) and DSPN-p (n = 32) from the PROPANE study, and volunteers with normal glucose tolerance (n = 50). Double immunofluorescence staining for protein gene product 9.5 (PGP9.5) (pan-neuronal marker) and growth-associated protein 43 (GAP-43) (nerve regeneration marker) was applied to assess intraepidermal nerve fibre density (IENFD) and length (IENFL) and dermal nerve fibre length (DNFL). DSPN was diagnosed using the modified Toronto Consensus (2011) criteria, while neuropathic pain was assessed using an 11-point Numerical Rating Scale., Results: After adjustment for age, sex, BMI and HbA 1c , IENFD and IENFL were reduced for both markers in individuals with recent-onset diabetes and both DSPN groups compared with control participants (all p < 0.05), but did not differ between the DSPN groups. The DNFL GAP-43/PGP9.5 ratio was higher in the DSPN+p and DSPN-p groups compared with control participants (1.18 ± 0.28 and 1.07 ± 0.10 vs 1.02 ± 0.10; p ≤ 0.05) and in the DSPN + p group compared with DSPN-p (p < 0.05). Correlation analyses showed distinct inverse associations between the DNFL GAP-43/PGP9.5 ratio and PGP9.5 positive IENFD as well as DNFL (IENFD: β = -0.569, DNFL: β = -0.639; both p < 0.0001) in individuals with type 2 diabetes, but not in the control group. A similar pattern was found for correlations between the DNFL GAP-43/PGP9.5 ratio and peripheral nerve function tests., Conclusions/interpretation: Dermal nerve fibre regeneration is enhanced in DSPN, particularly in DSPN+p, and increases with advancing intraepidermal nerve fibre loss. These data suggest that, despite progressive epidermal fibre loss, dermal nerve repair is preserved, particularly in DSPN+p, but fails to adequately counteract epidermal neurodegenerative processes.

Chronic obstructive pulmonary disease (COPD) occurs typically in current or former smokers, but only a minority of people with smoking history develops the disease. Besides environmental factors, genetics is an important risk factor for COPD. However, the relationship between genetics, environment and phenotypes is not well understood. Sample sizes for genome-wide expression studies based on lung tissue have been small due to the invasive nature of sample collection. Increasing evidence for the systemic nature of the disease makes blood a good alternative source to study the disease, but there have also been few large-scale blood genomic studies in COPD. Due to the complexity and heterogeneity of COPD, examining groups of interacting genes may have more relevance than identifying individual genes. Therefore, we used Weighted Gene Co-expression Network Analysis to find groups of genes (modules) that are highly connected. However, module definitions may vary between individual data sets. To alleviate this problem, we used a consensus module definition based on two cohorts, COPDGene and ECLIPSE. We studied the relationship between the consensus modules and COPD phenotypes airflow obstruction and emphysema. We also used these consensus module definitions on an independent cohort (TESRA) and performed a meta analysis involving all data sets. We found several modules that are associated with COPD phenotypes, are enriched in functional categories and are overrepresented for cell-type specific genes. Of the 14 consensus modules, three were strongly associated with airflow obstruction (meta p ≤ 0.0002), and two had some association with emphysema (meta p ≤ 0.06); some associations were stronger in the case-control cohorts, and others in the cases-only subcohorts. Gene Ontology terms that were overrepresented included "immune response" and "defense response." The cell types whose type-specific genes were overrepresented in modules (p < 0.05) included natural killer cells, dendritic cells, and neutrophils. Together, this is the largest investigation of gene blood expression in COPD with 469 cases in COPDGene, ECLIPSE and TESRA combined, with 6267 genes common to all data sets. Additional, we have 42 and 83 controls in COPDGene and ECLIPSE, respectively.

Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) length and density (CNFL, CNFD) in patients with diabetes, but the spatial pattern of CNF loss has not been studied. We aimed to determine whether spatial analysis of the distribution of corneal nerve branching points (CNBPs) may contribute to improving the detection of early CNF loss. We hypothesized that early CNF decline follows a clustered rather than random distribution pattern of CNBPs. CCM, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed in a cross-sectional study including 86 patients recently diagnosed with type 2 diabetes and 47 control subjects. In addition to CNFL, CNFD, and branch density (CNBD), CNBPs were analyzed using spatial point pattern analysis (SPPA) including 10 indices and functional statistics. Compared to controls, patients with diabetes showed lower CNBP density and higher nearest neighbor distances, and all SPPA parameters indicated increased clustering of CNBPs (all P<0.05). SPPA parameters were abnormally increased >97.5th percentile of controls in up to 23.5% of patients. When combining an individual SPPA parameter with CNFL, ≥1 of 2 indices were >99th or <1st percentile of controls in 28.6% of patients compared to 2.1% of controls, while for the conventional CNFL/CNFD/CNBD combination the corresponding rates were 16.3% vs 2.1%. SPPA parameters correlated with CNFL and several NCS and QST indices in the controls (all P<0.001), whereas in patients with diabetes these correlations were markedly weaker or lost. In conclusion, SPPA reveals increased clustering of early CNF loss and substantially improves its detection when combined with a conventional CCM measure in patients with recently diagnosed type 2 diabetes.

Aims/hypothesis: Oxidative stress and microvascular damage have been implicated in the pathogenesis of diabetic neuropathy, with manganese superoxide dismutase 2 (SOD2) responsible for superoxide detoxification in mitochondria. We hypothesised that patients with recently diagnosed type 2 diabetes would show an altered cutaneous expression of SOD2 and endothelial cell area., Methods: In this cross-sectional study, we assessed skin biopsies using immunohistochemistry, peripheral nerve function and heart rate variability in 69 participants of the German Diabetes Study with recently diagnosed type 2 diabetes and 51 control individuals., Results: Subepidermal SOD2 area in the distal leg was increased by ~60% in the diabetic group vs the controls (0.24 ± 0.02% vs 0.15 ± 0.02%; p = 0.0005) and was correlated with an increasing duration of diabetes (r = 0.271; p = 0.024) and with the low frequency/high frequency ratio (β = 0.381; p = 0.002) as an indicator of sympathovagal balance. The area of the subepidermal endothelial cells (measured by CD31 staining) did not differ between the groups., Conclusions/interpretation: Cutaneous antioxidative defence is enhanced in relation to the duration of diabetes and is linked to a cardiac sympathovagal imbalance towards a sympathetic predominance in individuals with recently diagnosed type 2 diabetes without evidence of endothelial cell damage. Whether cutaneous SOD2 levels can predict the development of diabetic neuropathy remains to be determined in prospective studies.

The Dauer larva is a non-feeding alternative larval stage of some nematodes specialized for long-term survival and dispersal. In this study we compared proteome maps obtained from Dauer larvae with those from the corresponding third larval stage (L3) of the feeding life cycle of C. elegans wild-type strain N2. We demonstrate at the protein level that altered metabolism may participate in longevity determination of Dauers. We detected huge amounts of alcohol dehydrogenase (CE12212) and aldehyde dehydrogenase (CE29809) in Dauer animals, indicating highly active fermentative pathways. Inorganic pyrophosphatase (CE05448) that enables to metabolize pyrophosphate as a high-energy source was over-expressed in Dauers. An interesting differentially expressed protein was phosphatidylethanolamine-binding protein (CE38516) that was found in high abundance in samples from Dauer larvae. Protein synthesis may be lowered in Dauer animals by the reduced expression of splicing factor rsp-3 (CE31089) and methionyl-tRNA synthase (CE34219). We observed significantly lower amounts of the pepsin-like aspartyl protease 1 (CE21681) in non-feeding Dauers, which is in agreement with reduced nutrient digestion. Finally, the hypothetical protein R08E5.2 (CE33294) was present in high abundance in L3 animals.

A proteomic approach has been used to establish a proteome map and differentiate between the protein composition of tonsils from patients with chronic tonsillitis (CT) and that of tonsils with hyperplasia (HPL). Two-dimensional gel analysis was performed with material from four patients with HPL and five patients with CT. An average of approximately 600 spots were detected in each gel. A total of 127 different proteins were identified in 158 spots analyzed by mass spectrometry. Our study revealed disease-associated differences between protein abundance for two protein spots, an HSP27 isoform and UMP-CMP kinase. Both protein spots were more abundant in the CT group. HSP27 ELISA was performed for 32 patients, 12 belonging to the HPL group and 20 to the CT group. ELISA could not be used to differentiate HSP27 isoforms nor to distinguish CT from HPL. HSP27 was found to migrate to two further protein spots in the 2D gels. The differently expressed HSP27 isoform migrated as the most acidic of all the HSP27 isoforms detected, indicating the highest degree of phosphorylation. The sum of all three HSP27 abundances in the gels from the CT group was not different from that of the HPL group, consistent with the ELISA results. Our results suggest that phosphorylation differences caused the observed migration differences of HSP27. Together with the UMP-CMP kinase abundance differences, we conclude that kinase and/or phosphatase activity are different in CT and HPL.

Haptoglobin belongs to the major constituents of plasma and acts as hemoglobin-binding and acute-phase protein. Due to the occurrence of three major allelic variants and further structural modifications, the alpha chains of haptoglobin form varying spot patterns in two-dimensional gel electrophoresis (2-DE) gels, which is generally observed in differential proteome analyses using plasma or related body fluids of humans. In the present study plasma samples from 10 donors of initially unknown haptoglobin phenotype were separated by 2-DE and tryptic digests of excised haptoglobin alpha chain spots were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and MALDI-quadrupole ion trap TOF-MS. Haptoglobin alpha1S, alpha1F, as well as alpha2 chains were found to occur each with at least three structurally differing protein species: (i) the unmodified form, which corresponds to the sequence database entries; (ii) derivatives, in which asparagine at position five is deamidated to aspartic acid; and (iii) derivatives with an additional C-terminal arginine residue. These structural variants account for the most commonly observed spot patterns of haptoglobin alpha chains in Coomassie-stained gels. Additionally, a minor derivative of the haptoglobin alpha2 chain carrying both modifications, deamidation at position five and the C-terminal arginine residue, was identified. Theoretical pI values of the characterized structural variants are, consistent with their observed migration in the 2-DE gels.

Proteome maps and differences of protein patterns of the synchronized larval stage L4 of the temperature-sensitive Caenorhabditis elegans (C. elegans) glp-1 mutant (e2144ts) were investigated after cultivation at 15 degrees C (developing a normal phenotype) or 25 degrees C (developing a mutated phenotype) by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. From the 183 identified protein spots six proteins were found differently expressed. The Vit-6 vitellogenin (CE28594), the hypothetical 17.2 protein (CE25224), the hypothetical 17.4 protein (CE16999), and the heat shock protein 16 kDa (CE14249) were more abundant when growing worm cultures at 25 degrees C. By contrast, the nucleoside diphosphate kinase (CE09650) was found increased at 15 degrees C. Most notably, the eukariotic initiation factor 5A-1 (CE00503), highly abundant at 15 degrees C, was not present in cultures grown at 25 degrees C. Its absence at 25 degrees C can not be attributed to lack of the enzymatic machinery that is necessary for hypusinylation. Instead, a direct downstream effect of the lack of functionality of GLP-1 may cause the expression of this protein. The yolk proteins 115 kDa and 88 kDa were attributed by mass spectrometric protein structure analysis as C-terminal and N-terminal fragments of the Vit-6 vitellogin protein (CE28594), respectively. The cleavage site between both derivatives was located between R764 and A768. A conflict in the database sequences at amino acid positions 1622 and 1623 of vitellogenin-6 was solved by mass spectrometric sequence analysis. The combination of 2-DE with mass spectrometry enabled the identification of mutation-associated differences on somatic gonadal cell and germ line cell development-associated proteins.

New experimental approaches of molecular medicine such as transcriptome and proteome analysis have been implemented in rheumatology research. Two-dimensional gel electrophoresis in combination with mass spectrometry was used to visualize and to identify proteins in synovial fluid (SF) and plasma samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The small calcium binding protein S100A9 (MRP14) was identified as a discriminatory marker protein in SF by global proteomic analysis. To confirm these results and to examine the reproducibility and the applicability as a diagnostic marker, levels of the S100A8 (MRP8)/A9 (MRP14) heterocomplex in plasma and in synovial fluid were validated from patients with RA, OA, and other inflammatory joint diseases using enzyme immunoassay techniques. It was found that plasma levels of the S100A8/A9 heterocomplex correlate well with levels in SF, and hence, determination of plasma levels can be used to distinguish RA patients from patients with other inflammatory joint diseases, as well as from OA patients and controls. Initial studies on RA patients also indicate that plasma levels of the S100A8/A9 heterocomplex are a useful marker in monitoring anti TNFalpha therapy.

We investigated the effect of cultivation temperatures on the protein expression levels in the fourth larval stage of the postembryonic development of wild-type Caenorhabditis elegans by mass spectrometric proteome analysis. From the 64 protein spots that were investigated, 5 spots were found reproducibly differently expressed when proteome maps derived from animals kept at 15 degrees C and at 25 degrees C, respectively, were compared. Spots of heat shock proteins HSP 70 (CE18679 or CE09682) and HSP 16 (CE14249) were present only in gels from protein extracts when worms were grown at 15 degrees C. Spots of two metabolic enzymes, the isocitrate dehydrogenase (CE10345) and the aspartic proteinase (CE21681) were detected only in cultures grown at the lower temperature as well. A protein with still unknown function (CE05036) was present only in gels from worm samples grown at 25 degrees C. We show for the first time by proteome analyses that cultivation of worms at the lowest temperature of the known physiological range (15 degrees C) already triggers a (weak) stress response in wild-type animals. This work led to the identification of "internal control proteins" in the wild-type strain for further characterization of temperature-sensitive strains using a proteomics approach.

Proteome maps obtained by synchronization of the wild-type Caenorhabditis elegans development reflected stage-dependent molecular differences and revealed dynamic cytoskeletal processes during ontogenesis. Distinct protein spots that may function as molecular markers for the corresponding developmental stages were mass spectrometrically identified. The amount of the Cu(2+)- Zn(2+) superoxide dismutase (CE23550) and an aspartyl proteinase (CE21681) was highest in the first larval stage (L1) and decreased during the ontogenesis from the first larval stage to the adult. Tropomyosin III (CE29059) was prominently present in the first and second larval stage (L1/L2). Abundances of actin 1 or 4 (CE12358 or CE13148) and tropomyosin I (CE28782) were particularly high in multiple spots in the third larval stage (L3). Interestingly, the amount of DIM-1 protein (CE27706), reflected by two spots, was the lowest in this stage. A particular splicing factor (CE31089) was detected only in the fourth larval stage (L4), whereas a spot with high abundance representing the cuticle collagen (CE02272) was only found highly expressed in adult animals (A). In addition, a Ca(2+)-binding protein (CE12368) and one protein spot which has not yet been identified, both reached their maximal spot intensities in the adult stage (A). Moreover, the ASP-1, CCT-5, GPD-1, GPD-2, HSP-6, HSP-16.2, IFB-2, LEC-2, LIN-53, LMN-1, MDH-1, NUD-1, RPA-0, RSP-12, SOD-1, TBB-1, TBB-2, TMY-1, UNC-60, and VIT-2 proteins for which mutants are available and two still unidentified protein spots which were present in all developmental stages, have been reproducibly localized in proteome maps of distinct ontogenesis states.