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Background Temporary arterial occlusion (TAO) is valuable for minimizing intraoperative rupture risk during intracranial aneurysm microsurgery; however, it may be associated with ischemic injury. This study aims to identify surgical and intraoperative neurophysiologic monitoring factors that predict perioperative stroke risk after TAO. Methods We performed a retrospective chart review of 177 intracranial aneurysm surgeries at our institution in which TAO was performed before placement of a permanent clip under monitoring with somatosensory evoked potentials (SSEPs) and electroencephalography. Perioperative stroke was defined as a new-onset neurologic deficit that developed within 24 hours postoperatively that was correlated with hypodensity on postoperative computed tomography. Results Ten (6%) patients developed perioperative stroke in the vascular territory of TAO. SSEP changes were observed in 50% (5/10) of patients with perioperative stroke and in 14% (24/167) of patients without stroke ( P = 0.003). Mean maximum single-episode TAO duration for patients who developed perioperative stroke was 12.6 minutes (95% confidence interval 8.1–17.1) and TAO duration for patients without stroke was 8.0 minutes (95% confidence interval 7.3–8.7; P = 0.026). In patients with SSEP changes, risk of stroke was particularly elevated with unruptured aneurysms ( P = 0.013) compared with patients with ruptured aneurysms. Temporary clip location, number of occlusive episodes, onset and duration of intraoperative neurophysiologic monitoring changes, and rupture status were not predictive of perioperative stroke. Conclusions SSEP changes and increased single-episode TAO duration are independently associated with increased perioperative stroke risk. SSEP changes are most predictive for perioperative stroke in unruptured cases. [ABSTRACT FROM AUTHOR]

Skull base chordoma is a rare and locally destructive malignancy which presents unique therapeutic challenges. While achieving gross total resection (GTR) confers the greatest survival advantage, the role of adjuvant radiotherapy (RT) for patients who receive GTR remains unclear in the absence of prospective trials. Here, we aim to assess the effect of RT on survival outcomes in skull base chordoma patients who receive GTR by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Patients with diagnostic, primary site, and resection codes specific for chordoma, skull base, and GTR, respectively, were queried in the SEER database (2000–2018). Kaplan-Meier curves (log-rank test) were constructed and Cox proportional hazards models were used to assess survival outcomes. A total of 115 skull base chordomas undergoing GTR were identified, of which 37 (32%) received no RT and 78 (68%) received RT. Median follow-up was 55.00 months (range: 0.00–227.00). Overall survival (OS) of patients with GTR was 85% and 70% at 5 and 10 years, respectively. Multivariate Cox proportional hazard analysis among chordoma patients undergoing GTR found age ≥65 (P < 0.01) was associated with poorer OS outcomes. RT appeared to trend toward offering benefit in terms of OS in patients after GTR, however this did not achieve statistical significance in the adjusted model (HR = 0.51, CI = 0.23–1.16, P = 0.09). When comparing, disease-specific survival was also not improved in patients undergoing RT (HR = 0.58, CI = 0.23–1.46, P = 0.25). It remains unclear whether RT after GTR of chordoma improved survival outcomes among SEER database patients. [ABSTRACT FROM AUTHOR]

Background: Acromegaly is a disease of growth hormone excess that results in enlargement of extremities, abnormal glucose and lipid metabolism, and gonadal disruption. Manifestations of the disease are insidious and typically lead to a diagnostic delay of 7–10 years. Classically the polycystic ovary syndrome (PCOS) phenotype is described in women with irregular menses, clinical or biochemical evidence of androgen excess, and/or multiple ovarian follicles on pelvic ultrasonography. Women with acromegaly may present with some or all of these symptoms. Our objective was to evaluate the prevalence of PCOS in patients with acromegaly and to determine if diagnosis of PCOS results in a delay in diagnosing acromegaly. Methods: Using patient databases at two academic health centers, we identified 97 premenopausal women aged 18–49 years old presenting with acromegaly. Data were collected regarding pelvic sonography and reproductive history, including the diagnosis of PCOS. Patients carrying the diagnosis of PCOS before their diagnosis of acromegaly were identified and the remaining patients were screened using the Rotterdam criteria to identify additional patients meeting the criteria for PCOS prior to their diagnosis of acromegaly. Results: Mean age of the population (n = 97) at the time of diagnosis of acromegaly was 33.4 ± 7.5 years (SD). Thirty-three percent of patients (n = 32) either carried a diagnosis of PCOS or met diagnostic criteria for PCOS before their diagnosis of acromegaly. In the subset of patients in whom data on symptom onset were available, those who met criteria for PCOS were diagnosed with acromegaly a median of 5 years [4, 9] after the onset of symptoms compared to 2 years [0.92, 3] (p = 0.006) in the patients who did not meet criteria for PCOS. Conclusions: Our data demonstrate a high prevalence of signs and symptoms of PCOS in reproductive-aged women with acromegaly and a longer time to diagnosis in women who meet the clinical criteria for PCOS. As screening for acromegaly is relatively simple and done with measurement of a random, non-fasting IGF-1 level that can be drawn at any time during the menstrual cycle, screening patients with PCOS for acromegaly may lessen the delay in diagnosis for reproductive-aged women with this disease. [ABSTRACT FROM AUTHOR]

Pseudomonas syringae pv. actinidiae (Psa), the causal agent of kiwifruit canker, is one of the most devastating plant diseases of recent times. We have generated two mini-Tn5-based random insertion libraries of Psa ICMP 18884. The first, a ‘phenotype of interest’ (POI) library, consists of 10,368 independent mutants gridded into 96-well plates. By replica plating onto selective media, the POI library was successfully screened for auxotrophic and motility mutants. Lipopolysaccharide (LPS) biosynthesis mutants with ‘Fuzzy-Spreader’-like morphologies were also identified through a visual screen. The second, a ‘mutant of interest’ (MOI) library, comprises around 96,000 independent mutants, also stored in 96-well plates, with approximately 200 individuals per well. The MOI library was sequenced on the Illumina MiSeq platform using Transposon-Directed Insertion site Sequencing (TraDIS) to map insertion sites onto the Psa genome. A grid-based PCR method was developed to recover individual mutants, and using this strategy, the MOI library was successfully screened for a putative LPS mutant not identified in the visual screen. The Psa chromosome and plasmid had 24,031 and 1,236 independent insertion events respectively, giving insertion frequencies of 3.65 and 16.6 per kb respectively. These data suggest that the MOI library is near saturation, with the theoretical probability of finding an insert in any one chromosomal gene estimated to be 97.5%. However, only 47% of chromosomal genes had insertions. This surprisingly low rate cannot be solely explained by the lack of insertions in essential genes, which would be expected to be around 5%. Strikingly, many accessory genes, including most of those encoding type III effectors, lacked insertions. In contrast, 94% of genes on the Psa plasmid had insertions, including for example, the type III effector HopAU1. These results suggest that some chromosomal sites are rendered inaccessible to transposon insertion, either by DNA-binding proteins or by the architecture of the nucleoid. [ABSTRACT FROM AUTHOR]

Objectives To determine the risk factors associated with cerebrospinal fluid (CSF) leak following endoscopic endonasal surgery (EES) for pediatric skull base lesions. Methods Retrospective chart review of pediatric patients (ages 1 month to 18 years) treated for skull base lesions with EES from 1999 to 2014. Five pathologies were reviewed: craniopharyngioma, clival chordoma, pituitary adenoma, pituitary carcinoma, and Rathke's cleft cyst. Fisher's exact tests were used to evaluate the different factors to determine which had a statistically higher risk of leading to a post-operative CSF leak. Results 55 pediatric patients were identified who underwent 70 EES's for tumor resection. Of the 70 surgeries, 47 surgeries had intraoperative CSF leaks that were repaired at the time of surgery. 11 of 47 (23%) surgeries had post-operative CSF leaks that required secondary operative repair. Clival chordomas had the highest CSF leak rate at 36%. There was no statistical difference in leak rate based on the type of reconstruction, although 28% of cases that used a vascularized flap had a post-operative leak, whereas only 9% of those cases not using a vascularized flap had a leak. Post-operative hydrocephalus and perioperative use of a lumbar drain were not significant risk factors. Conclusions Pediatric patients with an intra-operative CSF leak during EES of the skull base have a high rate of post-operative CSF leaks. Clival chordomas appear to be a particularly high-risk group. The use of vascularized flaps and perioperative lumbar drains did not statistically decrease the rate of post-operative CSF leak. [ABSTRACT FROM AUTHOR]

The literature includes many studies examining the genetic abnormalities that influence pituitary adenomas (PAs). We aimed to state the collective knowledge on the genetic underpinnings of PAs by organizing, summarizing, and consolidating the literature to serve as a comprehensive review for scientists and clinicians of the most up-to-date information underlying the genetic landscape of PAs. The PubMed and Google Scholar databases were searched using multiple key words and combined Medical Subject Headings terms; only articles published in English between January 2000 and January 2022 were included. Articles in which the focus did not relate to genetics, that included mainly anecdotal evidence, or that were single case studies were eliminated. PAs are one of the most common intracranial neoplasms. However, the genetic underpinnings for these tumors are not yet fully elucidated. There are several categories of PAs: clinically significant versus not clinically significant, functional versus nonfunctional, and germline-derived versus sporadic origin. Each of these disease subcategories is characterized by unique genetic aberrations. Recently, more genes and other types of genetic aberrations have been identified as possible causes of PAs, such as copy number variations and altered levels of microRNAs. This review serves to consolidate and summarize the literature discussing the genetic motifs of PAs to help physicians and scientists deliver patient-centered therapies. [ABSTRACT FROM AUTHOR]

Transcranial removal of the anterior clinoid process (ACP) provides access to the clinoidal segment of the internal carotid artery as well as superolateral decompression of the optic canal. Endoscopic endonasal approaches (EEAs) can access the entire medial and inferior portions of the optic canal, but no data exist to support what proportion of the anterior clinoid could be safely resected via an EEA. A cadaveric anatomical study was performed with removal of the ACP in 3 major steps in order of difficulty and risk. At each step, the removal was stopped when no more bone of the ACP could be seen without traction on neural structures. After each step, a CT scan was performed to allow volumetric measurement of the remaining ACP. Twenty ACPs in 10 cadaveric heads were removed to various degrees using the described stepwise technique. The mean portion of the ACP resected by each step was 21%, 46%, and 27%, respectively. Cumulated ACP removal at the end of step 3 was 94%, with complete removal achieved in 35% of the specimens. Using the safe route above the optic canal, removal of 21% of the ACP can be achieved via EEA. Although substantially more of the ACP can be drilled by accessing the optic strut, the benefits of pursuing additional removal must be weighed against the significant risks of drilling in this narrow corridor bordered by the internal carotid artery, the third cranial nerve, and the optic nerve. [ABSTRACT FROM AUTHOR]

Introduction  The application of cranial tissue sealants to assist with postoperative closure is widespread, but data are lacking regarding its utility in endoscopic endonasal surgery (EEA). A prospective study was conducted to assess the effect of sealant usage on postoperative cerebrospinal fluid (CSF) leak rate following standard reconstruction. Methods  A prospective trial of sealant usage after endoscopic endonasal skull base surgery was performed from May 2016 to June 2019 at a tertiary referral cranial base center. This study enrolled 300 consecutive adult and pediatric patients with skull base pathology who underwent EES in which an intraoperative CSF leak occurred. Patients were sequentially stratified into equally sized groups who did or did not receive sealant as part of their reconstruction. Results  Three hundred consecutive adult and pediatric patients were enrolled in the study and had a confirmed intraoperative CSF leak. The intervention cohort with sealant (first 150 patients) had 21 postoperative CSF leaks (14% rate) compared with 9 postoperative CSF leaks (6% rate) in the control group without sealant (p  = 0.02). On multivariate analysis, sealant usage was associated with a higher rate of postoperative CSF leak (odds ratio [OR] = 2.7; p  = 0.025). Male gender (OR = 2.4; p  = 0.04) and high-flow intraoperative CSF leak (OR = 3.1; p  = 0.038) were also found to be associated with postoperative CSF leak. Conclusion  Among all patients undergoing EES with an intraoperative CSF leak, the addition of sealant to standard closure techniques did not reduce the rate of postoperative CSF leaks. [ABSTRACT FROM AUTHOR]

The microscopic transciliary SupraOrbital keyhole (mtSO) approach has been used for a wide variety of anterior and middle fossa pathologies, including aneurysms, meningiomas, craniopharyngiomas, and other skull-base tumors. Several clinical series have proven its efficacy and safety, but detailed anatomical demarcations of the anterior and middle cranial base exposure are lacking. Our aim was to define the surgical limitations of the mtSO approach to the ipsilateral and contralateral anterior and middle skull base. Five cadaveric specimens (10 sides) were studied with image guidance to illustrate the limits of the surgical exposure. In addition, 30 dry skulls were used to measure the working distances between the craniotomy and key bony landmarks of the mtSO approach. Surgical exposure at the anterior skull base covered the area between the medial half of the contra- and the medial two-thirds of the ipsilateral sphenoid wing including both optic nerves and interoptic space. The anterior limit at the midline was the sphenoethmoidal suture. Ipsilateral anterior clinoidectomy permitted exposure of the superior orbital fissure, which defined the anteromedial limit at the middle fossa, whereas the anterolateral limit was defined by the ophthalmic branch of the trigeminal nerve. Moreover, the posteromedial and posterolateral limits were the posterior clinoid process and the petrous ridge, respectively. Our findings define the surgical limitations of the mtSO approach for the treatment of anterior and middle cranial base pathologies. These limits can be reliably identified on imaging studies allowing assessment of exposure to guide preoperative case selection. [ABSTRACT FROM AUTHOR]

Prealbumin levels correlate with overall nutritional status, and low values are associated with poor wound healing. We investigated whether low preoperative prealbumin levels predict risk of endoscopic endonasal skull base surgery (EESBS) reconstruction failure, as demonstrated by postoperative cerebrospinal fluid (CSF) leak and/or infection. Between October 2018 and February 2020, 98 patients with documented preoperative prealbumin levels were prospectively followed. The incidence of CSF leak and infection in patients with low prealbumin levels (≤20 mg/dL) was compared with those with normal prealbumin levels (>20 mg/dL). Numerous factors previously shown to influence CSF leak rates were assessed. Both univariate and multivariable analyses were performed to identify independent predictive factors. Within this prospectively gathered patient cohort composed of >95% "high-risk" expanded EESBS, 14 of 98 patients (14.3%) experienced a postoperative CSF leak. Factors univariately associated with postoperative complications at the 0.2 level of significance were used in a multivariable model. Low prealbumin levels (≤20 mg/dL) proved to be a strong independent predictive factor associated with a 5-fold increased risk of postoperative CSF leak (odds ratio 5.01, P = 0.01), and postoperative surgical-site infection (P = 0.0009). These associations remained after controlling for multiple other factors, including body mass index, surgical pathology, previous EESBS, risk assessment index, and high- versus low-flow intraoperative CSF leaks. Preoperative prealbumin levels are an independent predictor of EESBS associated CSF leak and infection. Future studies are needed to investigate the utility of screening and correcting prealbumin levels to limit postoperative complications. [ABSTRACT FROM AUTHOR]

Background As the importance of non-coding RNAs becomes more evident, the need for computational methods for ncRNAs grows. Predicting the secondary structure is of great importance, and combining this with multiple alignment yields a useful tool for researchers. The exact solution to the problem of simultaneous multiple alignment and structure prediction for RNA sequences was described by Sankoff, but to date only pairwise implementations (e.g. Foldalign, Dynalign) or heuristics for multiple sequences (e.g. FoldalignM, LocARNA, RNA Sampler) exist. Methods We present a novel approach to the problem: Using Markov chain Monte Carlo in a simulated annealing framework, we sample multiple alignments and secondary structures. The sampling is based on a scoring system that combines a sequence measure with a structure measure: The sequence alignment is scored using the log-likelihood, and the structure is scored using basepair probabilities and a covariation term. The sampling procedure itself uses simple local moves to optimize the solution. These moves either act on the sequence alignment or the predicted structure. The input to the program can be unaligned sequences or an alignment obtained using e.g. Clustal. The structure can be constrained by indicating e.g. basepairs or unpaired positions in one of the sequences. The program MASTR (Multiple Alignment of STructural RNAs) is implemented in C++. Results MASTR is compared to LocARNA, FoldalignM, RNA Sampler and Clustal+RNAalifold on various RNA families. The datasets are unaligned and of varying average pairwise identities ranging from 30% to 100%. The sequence alignments are consistently better than or comparable to all other methods, the running time is significantly faster than FoldalignM and RNA Sampler, and MASTR can handle larger datasets than both these programs. RNA Sampler is best on datasets with identities between 30% and 45%, but MASTR is better than all other programs tested from 45% ID up to 80% ID, where the structure predictions deteriorate due to the poor covariation signal. [ABSTRACT FROM AUTHOR]

Objective  The jugular foramen is one of the most challenging surgical regions in skull base surgery. With the development of endoscopic techniques, the endoscopic endonasal approach (EEA) has been undertaken to treat some lesions in this area independently or combined with open approaches. The purpose of the current study is to describe the anatomical steps and landmarks for the EEA to the jugular foramen and to compare it with the degree of exposure obtained with the lateral infratemporal fossa approach. Materials and Methods  A total of 15 osseous structures related to the jugular foramen were measured in 33 adult dry skulls. Three silicone-injected adult cadaveric heads (six sides) were dissected for EEA and three heads (six sides) were used for a lateral infratemporal fossa approach (Fisch type A). The jugular foramen was exposed, relevant landmarks were demonstrated, and the distances between relevant landmarks and the jugular foramen were obtained. High-quality pictures were obtained. Results  The jugular foramen was accessed in all dissections by using either approach. Important anatomical landmarks for EEA include internal carotid artery (ICA), petroclival fissure, inferior petrosal sinus, jugular tubercle, and hypoglossal canal. The EEA exposed the anterior and medial parts of the jugular foramen, while the lateral infratemporal fossa approach (Fisch type A) exposed the lateral and posterior parts of the jugular foramen. With EEA, dissection and transposition of the facial nerve was avoided, but the upper parapharyngeal and paraclival ICA may need to be mobilized to adequately expose the jugular foramen. Conclusion  The EEA to the jugular foramen is anatomically feasible but requires mobilization of the ICA to provide access to the anterior and medial aspects of the jugular foramen. The lateral infratemporal approach requires facial nerve transposition to provide access to the lateral and posterior parts of the jugular foramen. A deep understanding of the complex anatomy of this region is paramount for safe and effective surgery of the jugular foramen. Both techniques may be complementary considering the different regions of the jugular foramen accessed with each approach. [ABSTRACT FROM AUTHOR]

Background  High-flow skull base dural defects are associated with an increased risk of postoperative cerebrospinal fluid (CSF) leaks. Objective  This study aimed to identify the risk factors for persistent postoperative CSF leak after endoscopic endonasal surgery (EES) and determine the ideal reconstruction strategy after initial failed repair. Methods  Patients with CSF leak after intradural EES between October 2000 and February 2017 were identified. Cases with persistent CSF leak were compared with patients with similar pathologic diagnosis without a persistent leak to identify additional risk factors. Results  Two hundred and twenty-three out of 3,232 patients developed postoperative CSF leak. Persistent leaks requiring more than one postoperative repair occurred in 7/223 patients (3.1%). All seven had undergone intradural approach to the posterior fossa for resection of recurrent/residual clival chordomas. This group was matched with 25 patients with recurrent/residual clival chordoma who underwent EES without postoperative CSF leak (control group). Age, gender, history of diabetes, smoking, or radiotherapy were not statistically different between the groups. Obesity (body mass index > 30) was significantly more common in the group with persistent leak (86%) compared with controls (36%) (p  = 0.02). All patients with a persistent CSF leak developed meningitis (p  = 0.001). Five patients with persistent leak required a pericranial flap to achieve definitive repair. Conclusion  Multiple recurrent CSF leak after EES primarily occurs following resection of recurrent/residual posterior fossa chordoma. Obesity is a major risk factor and meningitis is universal with persistent leak. Flap necrosis may play a role in the development of persistent CSF leaks, and the use of secondary vascularized flaps, specifically extracranial–pericranial flaps, should be considered as an early rescue option in obese patients. [ABSTRACT FROM AUTHOR]

Objective  Though microvascular free tissue transfer is well established for open skull base reconstruction, normative data regarding flap design and inset after endoscopic endonasal skull base surgery (ESBS) is lacking. We aim to describe anatomical considerations of endoscopic endonasal inset of free tissue transfer of transclival (TC) and anterior cranial base resection (ACBR) defects. Design and Setting  Radial forearm free tissue transfer (RFFTT) model. Participants  Six cadaveric specimens. Main Outcome Measures  Pedicle orientation, pedicle length, and recipient vessel intraluminal diameter. Results  TC and ACBR defects averaged 17.2 and 11.7 cm 2 , respectively. Anterior and lateral maxillotomies and endoscopic medial maxillectomies were prepared as corridors for flap and pedicle passage. Premasseteric space tunnels were created for pedicle tunneling to recipient facial vessels. For TC defects, the RFFTT pedicle was oriented cranially with the flap placed against the clival defect (mean pedicle length 13.1 ± 0.6 cm). For ACBR defects, the RFFTT pedicle was examined in three orientations with respect to anterior–posterior axis of the RFFTT: anteriorly, posteriorly, and laterally. Lateral orientation offered the shortest average pedicle length required for anastomosis in the neck (11.6 ± 1.29 cm), followed by posterior (13.4 ± 0.7cm) and anterior orientations (14.4 ± 1.1cm) (p  < 0.00001, analysis of variance). Conclusions  In ACBR reconstruction using RFFTT, our data suggests lateral pedicle orientation shortens the length required to safely anastomose facial vessels and protects the frontal sinus outflow anteriorly while limiting pedicle exposure through a maxillary corridor within the nasal cavity. With greater understanding of anatomical factors related to successful preoperative flap planning, free tissue transfer may be added to the ESBS reconstruction ladder. [ABSTRACT FROM AUTHOR]

Objectives  The aim of this study was to describe the anatomical nuances, feasibility, limitations, and surgical exposure of the parapharyngeal space (PPS) through a novel minimally invasive keyhole endoscopic-assisted transcervical approach (MIKET). Design  Descriptive cadaveric study. Setting  Microscopic and endoscopic high-quality images were taken comparing the MIKET approach with a conventional combined transmastoid infralabyrinthine transcervical approach. Participants  Five colored latex-injected specimens (10 sides). Main Outcome Measures  Qualitative anatomical descriptions in four surgical stages; quantitative and semiquantitative evaluation of relevant landmarks. Results  A 5 cm long inverted hockey stick incision was designed to access a corridor posterior to the parotid gland after independent mobilization of nuchal and cervical muscles to expose the retrostyloid PPS. The digastric branch of the facial nerve, which runs 16.5 mm over the anteromedial part of the posterior belly of the digastric muscle before piercing the parotid fascia, was used as a landmark to identify the main trunk of the facial nerve. MIKET corridor was superior to the crossing of the accessory nerve over the internal jugular vein within 17.3 mm from the jugular process. Further exposure of the occipital condyle, vertebral artery, and the jugular bulb was achieved. Conclusion  The novel MIKET approach provides in the cadaver straightforward access to the upper and middle retrostyloid PPS through a natural corridor without injuring important neurovascular structures. Our work sets the anatomical nuances and limitations that should guide future clinical studies to prove its efficacy and safety either as a stand-alone procedure or as an adjunct to other approaches, such as the endonasal endoscopic approach. [ABSTRACT FROM AUTHOR]

Objectives To identify the prevalence and risk factors for nasal deformities after endoscopic endonasal surgery (EES) of the skull base. Design Retrospective case series. Setting Tertiary referral academic center. Participants EES patients from January 2011 to October 2013. Main Outcome Measures Surgical approach, method of skull base reconstruction, and postoperative nasal deformities. Results Of 328 patients, 19 patients (5.8%) had nasal dorsum collapse, 3 (0.9%) with new septal perforations and 2 (0.6%) with septal deviations requiring surgical correction. Postoperative deformities were only found in the setting of nasoseptal flap reconstruction (p = 0.0001) and were most common in patients who had undergone an approach involving more than one anatomical subsite (p = 0.0021). Patients with nasal deformities were on average 6 years younger (p = 0.08) and were more likely to have a malignant pathology (p = 0.08). Conclusions All deformities were associated with use of a nasoseptal flap for reconstruction and were most common in combined approaches, suggesting that flap size may play a role in the development of nasal deformities. The mechanism of nasal dorsum collapse is unclear but does not appear to be related to septal cartilage necrosis. These findings warrant a prospective analysis to identify risk factors for postoperative nasal deformities and data for counseling of patients. [ABSTRACT FROM AUTHOR]