How I do it: hearing preservation in large vestibular schwannomas using vestibular nerve fiber preservation technique.

BACKGROUND: To improve hearing function after resection of large vestibular schwannomas, we describe a strategy of vestibular-nerve-fiber preservation. Anatomical considerations and stepwise dissection are described. METHOD: Steps include locating the vestibular nerve at the brainstem and identifying a dissection plane between nerve fibers and tumor capsule. Using this plane to mobilize and resect tumor reduced manipulation and maintained vascularity of underlying cochlear and facial nerves. CONCLUSION: Preservation of hearing function is feasible in large vestibular schwannomas with vestibular-nerve-fiber preservation. Reducing manipulation and ischemic injury of underlying cochlear and facial nerves thereby helped facilitate hearing preservation, even in large tumors.

Use of a Candida albicans SC5314 PacBio HiFi reads dataset to close gaps in the reference genome assembly, reveal a subtelomeric gene family, and produce accurate phased allelic sequences.

Candida albicans SC5314 is the most-often used strain for molecular manipulation of the species. The SC5314 reference genome sequence is the result of considerable effort from many scientists and has advanced research into fungal biology and pathogenesis. Although the resource is highly developed and presented in a phased diploid format, the sequence includes gaps and does not extend to the telomeres on its eight chromosome pairs. Accurate SC5314 genome assembly is complicated by the presence of extensive repeated sequences and considerable allelic length variation at some loci. Advances in genome sequencing technology provide the tools to obtain highly accurate long-read data that span even the most-difficult-to-assemble genome regions. Here, we describe derivation of a PacBio HiFi data set and creation of a collapsed haploid telomere-to-telomere assembly of the SC5314 genome (ASM3268872v1) that revealed previously unknown features of the strain. ASM3268872v1 subtelomeric distances were up to 19 kb larger than in the reference genome and revealed a family of highly conserved DNA helicase-encoding genes at 10 of the 16 chromosome ends. We also describe alignments of individual HiFi reads to deduce accurate diploid sequences for the most notoriously difficult-to-assemble C. albicans genes: the agglutinin-like sequence (ALS) gene family. We provide a tutorial that demonstrates how the HiFi reads can be visualized to explore any region of interest. Availability of the HiFi reads data set and the ASM3268872v1 comparative guide assembly will streamline research efforts because accurate diploid sequences can be derived using simple in silico methods rather than time-consuming laboratory-bench approaches.

An analysis of the impact of annual cancer genetic testing guideline updates on a past patient population.

Germline genetic testing for cancer predisposition genes has become an essential component of cancer treatment and risk reduction. The National Comprehensive Cancer Network (NCCN) releases annual genetic testing guidelines that identify characteristics of patients that could be affected by a hereditary cancer syndrome. These guidelines have broadened over time and the implications for past patients of cancer genetics clinics are not well understood. This study is a retrospective chart review aimed at determining the percentage and characteristics of past patients that meet updated NCCN guidelines (Breast, Ovarian, and Pancreas [BOP] v1.2022 and Colorectal [CRC] v1.2021), patients that attended a follow-up appointment, and patients who went on to receive genetic testing. Clinical data and characteristics were compared between the study population as a whole and the cohort of patients that met updated NCCN guidelines BOP v1.2022 and CRC v1.2021. The study population consisted of 280 patients with 76 (27.1%) patients meeting updated NCCN guidelines BOP v1.2022 and CRC v1.2021. The year of initial cancer genetic counseling appointment was statistically significant (p = 0.023) with patients more likely to meet NCCN guidelines BOP v1.2022 and CRC v1.2021 with earlier initial cancer genetic counseling appointments. In the cohort that met updated NCCN guidelines BOP v1.2022 and CRC v1.2021, the most common reason was a change in the NCCN guidelines (BOP or CRC) (54/76, 71.1%) with triple-negative breast cancer diagnosed at any age being the most impactful guideline change (19/54, 35.2%). Twenty-one patients attended a follow-up appointment (7.5%) and of those that received genetic testing (17/21, 81%) most received negative results (13/17, 61.9%), with one pathogenic, low penetrance result (1/17, 5.9%, CHEK2 p.I157T). Provider-initiated follow-up was attributed to most follow-up appointments (16/21, 76.2%) implying patients do not tend to follow-up on their own. Education to non-genetics providers as well as targeted implementation of follow-up protocols possibly managed by genetic counseling assistants and utilizing electronic medical record (EMR) patient messaging could lead to improved patient follow-up.

An improved Lodderomyces elongisporus NRRL YB-4239 genome assembly substantiated by its electrophoretic karyotype.

Pacific Biosciences long-read sequencing was used to improve the genome assembly for Lodderomyces elongisporus strain NRRL YB-4239 (ATCC 11503). The new assembly included eight chromosomes that were substantiated by the electrophoretic karyotype. The nuclear genome was 16.1 Mb (37.2% GC) with 5,740 genes predicted.

Genome sequence of Emydomyces testavorans type strain 16-2883 (ATCC TSD-145), an onygenalean fungus associated with freshwater aquatic turtle shell lesions.

Emydomyces testavorans is an onygenalean keratinophilic fungus associated with shell and skin lesions in freshwater aquatic turtles. The genome sequence presented here includes five contigs (ranging in size from 2.8 to 9.8 Mb; 31.8 Mb total; 40% GC) and a 92.2-kb mitochondrial genome. The nuclear genome predicted 7,550 genes.

Diurnal Range and Intra-patient Variability of ACTH Is Restored With Remission in Cushing's Disease.

CONTEXT: Single ACTH measurements have limited ability to distinguish patients with Cushing's disease (CD) from those in remission or with other conditions. OBJECTIVE: To investigate the changes in ACTH levels before and after transsphenoidal surgery (TSS) to identify trends that could confirm remission from CD and help establish ACTH cutoffs for targeted clinical trials in CD. DESIGN: Retrospective analysis of CD patients who underwent TSS from 2005 to -2019. SETTING: Referral center. PATIENTS: CD patients (n = 253) with ACTH measurements before and after TSS. INTERVENTIONS: TSS for CD. MAIN OUTCOME MEASURES: Remission after TSS. RESULTS: Remission was observed in 223 patients after TSS. Those in remission had higher ACTH variability at AM (P = .02) and PM (P < .001) time points compared to nonremission. The nonremission group had a significantly narrower diurnal range compared to the remission group (P = <.0001). A decrease in plasma ACTH of ≥50% from mean preoperative levels predicted CD remission after TSS, especially when using PM values. The absolute plasma ACTH concentration and ratio of preoperative to postoperative values were significantly associated with nonremission after multivariable logistic regression (adj P < .001 and .001, respectively). CONCLUSIONS: Our findings suggest that ACTH variability is suppressed in CD, and remission from CD is associated with the restoration of this variability. Furthermore, a decrease in plasma ACTH by 50% or more may serve as a predictor of remission post-TSS. These insights could guide clinicians in developing rational outcome measures for interventions targeting CD adenomas.

A Chromosome-Level Genome Assembly for Yamadazyma tenuis ATCC 10573.

Pacific Biosciences (PacBio) long-read sequencing was used to generate a chromosome-level genome assembly for Yamadazyma tenuis strain ATCC 10573. The assembly featured 7 chromosomes that matched the electrophoretic karyotype and a 26.5-kb circular mitochondrial genome. The nuclear genome was 10.8 Mb, with a GC content of 43%, and 5,340 predicted genes.

North American genetic counselors' approach to collecting and using ancestry in clinical practice.

Current guidelines from the National Society of Genetic Counselors (NSGC) recommend that patients' ancestry be obtained when taking a family history. However, no study has explored how consistently genetic counselors obtain or utilize this information. The goals of this study included assessing how genetic counselors collect their patients' ancestry, what factors influence this decision, and how they view the utility of this information. Genetic counselors working in a direct patient care setting in the US or Canada were recruited to participate in an anonymous survey via an NSGC email blast. Most participants (n = 115) obtain information about their patients' ancestry (96.5%), with the most common methods being directly asking the patient (91%) and utilizing intake forms (43.2%). Of participants who ask about ancestry directly, 50.5% always ask about the presence of Ashkenazi Jewish ancestry and 70.3% always ask about additional ancestries, suggesting that for most genetic counselors' collection of ancestry is standard practice. However, the clinical utility of ancestry information is highly variable, with the impact on genetic testing choice being particularly low. A slight majority of participants support a reevaluation of current ancestry guidelines (51.3%), with many participants suggesting that the varying utility of ancestry in different clinical indications/specialties should be incorporated into guidelines. Despite being standard practice for most genetic counselors, no unified approach or standard for how ancestral information should be used in genetic counseling practice was identified.

Retrobulbar Hemangioblastomas in von Hippel-Lindau Disease: Clinical Course and Management.

BACKGROUND: Retrobulbar hemangioblastomas involving the optic apparatus in patients with von Hippel-Lindau disease (VHL) are rare, with only 25 reported cases in the literature. OBJECTIVE: To analyze the natural history of retrobulbar hemangioblastomas in a large cohort of VHL patients in order to define presentation, progression, and management. METHODS: Clinical history and imaging of 250 patients with VHL in an ongoing natural history trial and 1774 patients in a neurosurgical protocol were reviewed. The clinical course, magnetic resonance images, treatment, and outcomes were reviewed for all included patients. RESULTS: A total of 18 patients with retrobulbar hemangioblastoma on surveillance magnetic resonance imaging met the inclusion criteria for this study. Of the 17 for whom clinical information was available, 10 patients presented with symptoms related to the hemangioblastoma, and 7 were asymptomatic. The mean tumor volume was larger for symptomatic (810.6 ± 545.5 mm3) compared to asymptomatic patients (307.6 ± 245.5 mm3; P < .05). A total of 5 of the symptomatic patients were treated surgically and all experienced improvement in their symptoms. All 3 symptomatic patients that did not undergo intervention had continued symptom progression. Long-term serial imaging on asymptomatic patients showed that these tumors can remain radiographically stable and asymptomatic for extended periods of time (101.43 ± 71 mo). CONCLUSION: This study suggests that retrobulbar hemangioblastomas may remain stable and clinically asymptomatic for long durations. Recent growth and larger tumor volume were associated with symptom occurrence. Surgical treatment of symptomatic retrobulbar hemangioblastomas can be safe and may reverse the associated symptoms.

Coagulation Profile as a Significant Risk Factor for Short-Term Complications and Mortality after Anterior Cervical Discectomy and Fusion.

BACKGROUND: Cervical degenerative disc disease is the most common indication for anterior cervical discectomy and fusion. Given the possible complications, patients are stratified before anterior cervical discectomy and fusion by preoperative risk factors to optimize treatment. One preoperative factor is a patient's coagulation profile. METHODS: The American College of Surgeons-National Surgical Quality Improvement Database was used to identify patient preoperative coagulation profile and postoperative complications. By generating binary logistic regression models, each of the 4 abnormal coagulation categories (bleeding disorder, low platelet count, high partial thromboplastin time, and high international normalized ratio [INR]) were analyzed for their independent impact on increased risk for complications compared with the control cohort. RESULTS: A total of 61,977 patients were assessed. The most common abnormal coagulation was abnormal platelet count (n = 2149). The most common postoperative outcome was an extended length of hospital stay among patients with an abnormal coagulation profile relative to the control cohort. After multivariate analysis, patients with an abnormal INR (odds ratio, 2.2 [1.3-3.8]; P = 0.003) or abnormal platelet count (odds ratio, 1.5 [1.2-2.1]; P = 0.003) had a higher chance of having an extended length of hospital stay relative to patients having a normal coagulation profile. Having an abnormal INR was found to be associated with an increased risk for having "Any complication." CONCLUSIONS: Our results show significant differences in the incidence rates of a multitude of complications among the 5 groups based on univariate analysis. Patients with any abnormal coagulation disorder had increased rates of developing any complication or having an extended length of hospital stay.

A minimally invasive surgical approach for the treatment of piriformis syndrome: a case series.

BACKGROUND: Piriformis syndrome accounts for approximately 6% of patients who present with sciatic pain. There are many treatment options ranging from physical therapy, to trigger point injections, to surgical intervention. We discuss a surgical method that represents a minimally invasive technique for the treatment of piriformis syndrome. METHODS: We describe a novel operative approach and technique for release of the piriformis muscle in the treatment of piriformis syndrome. Described are the preoperative planning, incision and approach, and technique for identifying and releasing the piriformis muscle. RESULTS: Three patients were treated for piriformis syndrome using the described technique. Each patient displayed successful relief of their symptoms immediately following the surgical procedure and at delayed follow-up. CONCLUSION: Early experience with our method of piriformis release suggests that it is well suited for the treatment of piriformis syndrome. The novel integration of pre-operative trigger point localization coupled with intraoperative neuromonitoring allows effective pain relief with minimal morbidity.

Cold Atmospheric Plasma as an Adjunct to Immunotherapy for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer in adults. GBM carries a dismal prognosis because of its proliferative, invasive, and angiogenic capabilities and because of its ability to downregulate the immune system. Immune-based therapies under investigation for GBM have been unsuccessful in vivo because of this downregulation. Cold atmospheric plasma (CAP) is a high-energy state of matter that can be applied directly or indirectly to tumor tissue to serve as an adjunct to immunotherapy in the treatment of GBM because it upregulates the immune system by the induction of reactive oxygen species. CAP has the potential to improve the efficacy of existing and investigative immunotherapies for GBM.

An anatomical study of the foramen of Monro: implications in management of pineal tumors presenting with hydrocephalus.

BACKGROUND: For pineal tumors presenting with hydrocephalus, simultaneous endoscopic third ventriculostomy (ETV) and tumor biopsy is commonly used as the initial step in management. To analyze the restriction which the foramen of Monro poses to this procedure, one must start with a detailed description of the microsurgical anatomy of the foramen in living subjects. However, the orientation and shape of the foramen of Monro make this description difficult with conventional imaging techniques. METHOD: Virtual reality technology was applied on MRIs on living subject without hydrocephalus, as well as patients with hydrocephalus, to generate precise anatomical models with sub-millimeter accuracy. The morphometry of the foramen of Monro was studied in each group. In addition, displacement of the margins of the foramen was studied in detail for simultaneous ETV and pineal tumor biopsy through a single burr hole. RESULTS: In 30 normal subjects, the foramen of Monro had oval-shaped openings averaging 5.23 mm2. The foramen was larger in people above age 55 (p = 0.007) and on the left side compared to the right (p = 0.002). For patients with clinical presentation of hydrocephalus, the average opening was 32.6 mm2. Simulated single burr hole simultaneous ETV and pineal tumor biopsy was performed in 10 specimens. Average displacement of the posterior and anterior margins of the foramen was 5.71 mm and 5.76 mm, respectively. However, maximum displacement reached 9.3 mm posteriorly and 10 mm anteriorly. CONCLUSIONS: The foramen of Monro is an oval-shaped cylinder that changes in size and orientation in the hydrocephalic patient. If universally applied to all patients regardless of foramen and tumor size, ETV/biopsy can displace structures around the Foramen of Monro up to 1 cm, which can potentially lead to neurological damage. Careful pre-operative assessment is critical to determine if a single burr hole approach is safe.

Building evidence around ghost gear: Global trends and analysis for sustainable solutions at scale.

Abandoned, lost or discarded fishing gear (ALDFG) comprises a significant amount of global marine debris, with diverse impacts to marine environments, wildlife, and the fishing industry. Building evidence on ALDFG is critical to holistically understand the marine debris issue, and to inform the development of solutions that reduce amounts of ALDFG sources and recover existing gear. Substantial work has been and continues to be undertaken around the world to collect data on ALDFG, much of which remains unpublished. To provide a global picture of data on ALDFG, we organized a technical session that brought together seven ALDFG leaders to share their expertise in data collection, retrieval, and awareness-raising. This paper summarizes the technical session to highlight: 1) case studies that feature innovative approaches to ALDFG data collection and retrieval; 2) examples of opportunities to fill data gaps and improve our understanding of wildlife ingestion of and entanglement in ALDFG; and 3) awareness-raising through the development of a publicly accessible global ALDFG database.

Clinical Management of Prostate Cancer Metastasis to Pineal Gland: Case Report and Review of Literature.

BACKGROUND: Prostate cancer is the most common cancer among American men, with an incidence of approximately 233,000 cases per year. Intracranial metastases are rare and, specifically, metastasis to the pineal gland has only been reported in 2 postmortem cases in the literature. CASE DESCRIPTION: We present the first documented case of confirmed prostate cancer metastasis to the pineal gland in a living patient. The patient underwent an endoscopic third ventriculostomy and pineal lesion biopsy with complete resolution of his hydrocephalus and presenting symptoms. His biopsy results confirmed the prostate origin of the metastasis, and he subsequently underwent stereotactic radiosurgery for treatment of this lesion. CONCLUSIONS: This is the first report of the clinical management of metastatic prostate cancer to the pineal region and description of the clinical outcome. Although prostate cancer is the most common cancer in American men, metastasis to the pineal has only been reported twice from autopsy examinations. Overall, pineal tumors in the geriatric population are exceedingly rare and the age and comorbidities in this patient made management quite unique.

The Practice of Electroconvulsive Therapy in US Correctional Facilities: A Nationwide Survey.

OBJECTIVES: There are little data regarding the practice of electroconvulsive therapy (ECT) in correctional settings in the United States. A survey was conducted to study the current practice of ECT in US prisons. We hypothesize that ECT is underutilized in the correctional setting. We also review the ethical aspects of using ECT for the treatment of mental illness in the prison population. METHODS: A 12-question survey via a Survey Monkey link was emailed to chiefs of psychiatry, or the equivalent, of each state's department of corrections. We examined the frequency of Likert-type responses, tabulated individual comments for qualitative review, and grouped for comparison. RESULTS: Email contacts for chiefs of psychiatry, or the equivalent, for the department of corrections in 45 states (90%) were obtained and a survey link was sent. Thirty-one (68.9%) of 45 responded to the survey. Respondent estimates of the number of inmates with mental illness in 31 prison systems varied from less than 500 to more than 4500. Of these 31, 12 (38.7%) had more than 4500 inmates with mental illness. Four systems reported the use of ECT within the last 5 years. Of those, one reported use in the last 1 to 6 months, and 3 reported use in the last 2 to 5 years. Of these 4 prison systems, all felt that they had up to 10 patients who would benefit if ECT continued to be offered or became available in the future. None of these systems provided ECT within the prison. The inmates were referred to a local state psychiatric facility, a university hospital, or other institutions. The reasons for not using ECT as reported by the respondents are grouped under subheadings of stigma, ethical concerns, logistical concerns, and others. CONCLUSIONS: Considering the high prevalence of mental illness in prisons, one might expect a high prevalence of ECT responsive mental illness and, hence, provision of ECT to some prisoners with mental illness. However, our survey suggests that the use of ECT in prisons in the United States is low. Stigma, ethical concerns, and logistical concerns were the main hindrances for providing ECT to prisoners with mental illness. Given that ECT is the standard of care in certain clinical scenarios, physicians are obligated to offer such treatment to inmates when necessary. It can be argued that failure of the prison to offer the standard of care is unethical and unconstitutional.

Elevated insulin-like growth factor 2 expression may contribute to the hypermuscular phenotype of myostatin null mice.

OBJECTIVES: Myostatin (Mstn) inhibits while insulin-like growth factors 1 and 2 (Igf1 and Igf2) increase skeletal muscle growth. However, there is little known regarding Mstn regulation of Igf1 and Igf2 expression. Therefore, the objective of this study was to quantify the expression of IGF family members in skeletal muscle and liver throughout the growth phase of Mstn null (MN) mice. Further, differences between male and female mice were investigated. METHODS: Male and female wild type (WT) and MN mice were euthanized at birth (0 d), 7 days (7 d), weaning (21 d), sexual maturity (42 d), and 70 d. For the neonatal periods, 0 d and 7 d, all muscles from the hind limbs were compiled for RNA extraction. At 21 d, 42 d, and 70 d, biceps femoris (BF), tibialis anterior, triceps brachii (TB), and gastrocnemius-soleus complex were collected. RESULTS: As expected, muscle weights were up to 90% greater in MN mice compared with WT mice at 21 d, 42 d and 70 d. However, Igf1 expression was reduced (P ≤ 0.04) at 7d and 21 d in MN mice compared to WT mice. Expression of Igf2 did not differ between genotypes at 0 d and 7d, but, at 21 d, 42 d and 70 d in BF and TB muscles, Igf2 expression was 1.9-2.9 fold greater (P<0.01) in MN compared to WT mice. Hepatic Igf1 and Igf2 levels were minimally affected by genotype; with the exception of a 1.4-fold reduction (P=0.04) in Igf1 expression in 21 d MN mice compared with WT mice. Though male mice were heavier than females starting at 21 d of age, expression differences in Igf1, Igf2, their receptors and binding proteins do not account for growth differences. In every case, when expression was different between sexes, female expression was increased despite increased growth in male mice. CONCLUSION: This study is the first to provide evidence that Mstn may negatively regulate Igf2 expression to control postnatal skeletal muscle growth, however differences in growth between male and female mice are not readily explained by changes in expression of Igf family members.

The Chiari malformations: a review with emphasis on anatomical traits.

Hindbrain herniations come in many forms and have been further subdivided as their original descriptions. For cerebellar tonsillar ectopia, they can be divided into two categories, acquired and congenital. Acquired hindbrain herniations are due to increased intracranial pressure caused by certain conditions such as trauma or brain tumor. Although the mechanism for their formation is not clear, congenital hindbrain herniation makes up the majority of these congenital malformations. Furthermore, these malformations are often found to harbor additional anatomical derailments in addition to the hindbrain herniation whether it be the cerebellar tonsils (Chiari I malformation) or the cerebellar vermis (Chiari II malformation). This article reviews these forms of cerebellar ectopia and describes the details of their anomalous anatomy. Moreover, this article compares and contrasts the differing embryological theories found in this literature.

Blood supply to the human spinal cord: part I. Anatomy and hemodynamics.

The arterial network that supplies the human spinal cord, which was once thought to be similar to that of the brain, is in fact much different and more extensive. In this article, the authors attempt to provide a comprehensive review of the literature regarding the anatomy and known hemodynamics of the blood supply to the human spinal cord. Additionally, as the medical literature often fails to provide accurate terminology for the arteries that supply the cord, the authors attempt to categorize and clarify this nomenclature. A complete understanding of the morphology of the arterial blood supply to the human spinal cord is important to anatomists and clinicians alike.