Cerebellar granular neuron progenitors exit their germinative niche via BarH-like1 activity mediated partly by inhibition of T-Cell Factor.

Cerebellar granule neuron progenitors (GNP) originate from the upper rhombic lip (URL), a germinative niche whose developmental defects produce human diseases. T-Cell Factors (TCF) responsiveness and Notch dependence are hallmarks of self-renewal in neural stem cells. TCF activity together with transcripts coding for proneural genes repressors hairy and enhancer of split (hes/hey), are detected in the URL. However, their functions and regulatory modes are undeciphered. Here we established amphibian as a pertinent model to study vertebrate URL development. Amphibians long-lived URL is Tcf active, while the External Granular layer (EGL) is non-proliferative and expresses hes4/5 genes. Using functional and transcriptomic approaches, we show that Tcf activity is necessary for URL emergence and maintenance. We establish that the transcription factor Barhl1 controls GNP exit from the URL acting partly through direct Tcf inhibition. Identification of Barhl1 target genes argues that besides Tcf, Barhl1 inhibits transcription of hes5 genes independently of Notch signaling. Observations in amniotes suggest a conserved role of a Barhl in maintenance of the URL/EGL via coregulation of TCF and hes/hey genes.

Accuracy of Salivary Circulating Tumor Human Papillomavirus DNA in Detecting Oropharyngeal Cancer: A Systematic Review and Meta-analysis.

Importance: Circulating tumor human papillomavirus DNA (ctHPV DNA) has shown potential as a biomarker capable of improving outcomes in patients with HPV-related oropharyngeal (OP) cancer. It can be isolated from plasma or saliva, with the latter offering reduced invasiveness and theoretic reduction of lead time. Objective: To perform a systematic review and meta-analysis on the accuracy of salivary ctHPV DNA for detecting HPV-associated OP cancer. Data Sources: Cochrane Library, Embase, PubMed, and Web of Science databases were searched from inception through October 2023. Study Selection: All patients who underwent salivary ctHPV DNA testing at presentation for possible or diagnosed HPV-related OP cancer were included. Non-English and review publications were excluded. Two authors independently voted on article inclusion with a third resolving conflicting votes. Data Extraction and Synthesis: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, multiple authors independently abstracted data and assessed bias of included articles. Bivariate random-effects meta-analysis was performed with I2 to assess for study heterogeneity. Main Outcomes and Measures: Sensitivities, specificities, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) with 95% CIs alongside area under the curve (AUC) of a summary receiver operating characteristic (SROC) curve were calculated. The initial analysis took place throughout December 2023. Results: Of 440 initially identified articles, 6 met inclusion criteria and demonstrated moderate heterogeneity (I2 = 36%) with low risk of bias and low applicability concerns. Overall, 263 total patients were included with a median (range) age of 58 (39-86) years, and 228 (87%) were male patients. Per updated prognostic staging criteria, localized tumors (ie, stages 1 or 2) comprised most cancers at 139 (77%), whereas advanced ones (ie, stages 3 or 4) comprised the remaining 41 (23%). Pooled sensitivity, specificity, PLR, NLR, and DOR values were 64% (95% CI, 36%-85%), 89% (95% CI, 46%-99%), 11.70 (95% CI, 0.37-77.00), 1.21 (95% CI, 0.08-7.00), and 139.00 (95% CI, 0.05-837.00), respectively. The AUC of the SROC curve was 0.80. Conclusions and Relevance: This study supports salivary ctHPV DNA as an acceptably specific test in detecting HPV-associated OP cancer that would benefit from testing in clinical trials prior to real-time implementation.

Microsurgical resection of a large petroclival meningioma through an extended retrosigmoid approach: how I do it.

BACKGROUND: Petroclival meningiomas are challenging tumors. Several skull base approaches have been proposed in the last decades, with variable rates of postoperative morbidity and extent of resection. METHODS: We herein reported the step-by-step microsurgical resection of a large petroclival meningioma through an extended retrosigmoid approach. Detailed surgical technique has been accompanied by a 2D operative video. CONCLUSION: The extended retrosigmoid approach allowed for a safe gross total resection of the tumor, as confirmed by the postoperative MRI. The patient did not experience any new postoperative deficit, despite a transient diplopia, and was discharged on postoperative day 7.

Assessing the Knowledge and Attitudes of Breastfeeding During the COVID-19 Pandemic.

Background It is generally accepted that breastfeeding is a practice that provides valuable health benefits to both mother and baby. However, the COVID-19 pandemic unveiled questions regarding the safety of breastfeeding, leading to potential hesitation among the public. Our study seeks to appreciate the public's understanding and attitudes toward breastfeeding during the COVID-19 pandemic. Methods An anonymous survey was distributed online through social media platforms. Demographic information was collected with questions specifically analyzing the knowledge and attitude of each participant. Calculations were performed using Spearman's rho correlations to determine significant differences. Results Thirty-nine women were recruited. The average overall knowledge score was 93% correct. 87% of participants believe breastfeeding is better than formula feeding, and 92% stated they would breastfeed their infant if they knew it could protect their child from COVID-19. Discussion The results of our study indicated that although overall knowledge of breastfeeding during the COVID-19 pandemic was well understood, higher levels of education may play a role in the depth of one's knowledge. In addition, while participants were reporting high levels of education about breastfeeding from their healthcare providers, few were receiving data specific to the pandemic. The data gathered from this study may help to target future educational initiatives.

The role of preoperative [11C]methionine PET in defining tumor-related epilepsy and predicting short-term postoperative seizure control in temporal lobe low-grade gliomas.

OBJECTIVE: Surgery is the mainstay of treatment for low-grade glioma (LGG)-related epilepsy. However, the goal of achieving both oncological radical resection and seizure freedom can be challenging. PET with [11C]methionine (MET) has been recently introduced in clinical practice for the management of patients with LGGs, not only to monitor the response to treatments, but also as a preoperative tool to define the metabolic tumor extent and to predict tumor grading, type, and prognosis. Still, its role in defining tumor-related epilepsy and postoperative seizure outcomes is limited. The aim of this preliminary study was to investigate the role of MET PET in defining preoperative seizure characteristics and short-term postoperative seizure control in a cohort of patients with newly diagnosed temporal lobe low-grade gliomas (tLGGs). METHODS: Patients with newly diagnosed and histologically proven temporal lobe grade 2/3 gliomas (2021 WHO CNS tumor classification) who underwent resection at the authors' institution between July 2011 and March 2021 were included in this retrospective study. MET PET images were acquired, fused with MRI scans, and qualitatively and semiquantitatively analyzed. Any eventual PET/MRI involvement of the temporomesial area, seizure characteristics, and 1-year seizure outcomes were reported. RESULTS: A total of 52 patients with tLGGs met the inclusion criteria. MET PET was positive in 41 (79%) patients, with a median metabolic tumor volume of 14.56 cm3 (interquartile range [IQR] 6.5-28.2 cm3). The median maximum and mean tumor-to-background ratio (TBRmax, TBRmean) were 2.24 (IQR 1.58-2.86) and 1.53 (IQR 1.37-1.70), respectively. The metabolic tumor volume was found to be related to the presence of seizures at disease onset, but only in noncodeleted tumors (p = 0.014). Regarding patients with uncontrolled seizures at surgery, only the temporomesial area PET involvement showed a statistical correlation both in the univariate (p = 0.058) and in the multivariate analysis (p = 0.030). At 1-year follow-up, seizure control was correlated with MET PET-derived semiquantitative data. Particularly, higher TBRmax (p = 0.0192) and TBRmean (p = 0.0128) values were statistically related to uncontrolled seizures 1 year after surgery. CONCLUSIONS: This preliminary study suggests that MET PET may be used as a preoperative tool to define seizure characteristics and outcomes in patients with tLGGs. These findings need to be further validated in larger series with longer epileptological follow-ups.

Reassessing the Utility of Surgical Intervention for Skull Base Osteomyelitis: A 16-Year Experience.

OBJECTIVE: The role of surgery in lateral skull base osteomyelitis (SBO) is controversial. Surgical intervention is often requested by consulting services in the interest of additional culture data to inform medical management. However, whether surgery alters subsequent antibiotic treatment or modifies disease outcome remains unknown. The aim of this study was to investigate the role of surgical intervention in the treatment of SBO by (1) comparing nonsurgical and surgical culture data and (2) assessing clinical outcomes and treatment course following surgical intervention. STUDY DESIGN: Retrospective. SETTING: Tertiary care center. METHODS: The electronic record was queried for all patients with SBO who presented to a single institution over a 16-year period (2007-2023). Information recorded included history and exam, bedside and intraoperative culture data, antibiotic course, and disease outcomes. Primary outcome measures included change in medical management based on intraoperative cultures, recurrence rates, and mortality rates. RESULTS: Forty patients (41 ears, average age 73 ± 13 years) met inclusion criteria. Out of 13 (32%) patients who underwent surgical intervention, one intraoperative culture changed the antibiotic course due to identification of resistance to the original antibiotic used. Surgery did not demonstrate a benefit in overall mortality (23% vs 18%, P = 0.36) or facial nerve function (33% vs 50%, P = 0.56) compared to medical management, and was associated with increased recurrence rates (54% vs 11%, P = 0.05). CONCLUSION: Surgical cultures rarely changed antibiotic selection. Surgical debridement in treatment-refractory SBO was also not associated with improvement in recurrence or mortality rates, though this may reflect underlying differences in disease severity.

A randomized prospective comparative study on sinonasal morbidity and quality of life of transsphenoidal endoscopic surgery for pituitary adenomas: endonasal versus trans-septal approach.

PURPOSE: Endoscopic endonasal transsphenoidal approach (Endonasal approach) is commonly used to treat pituitary adenomas. The extent of dissection possibly changes the anatomy and the physiology of the nasal cavities and could give rise to post-operative morbidity and the quality of life (QoL). The purpose of this study was to investigate sinonasal morbidity and general QoL in patients who underwent surgery for treatment of pituitary adenoma, comparing Endonasal and endoscopic trans-septal transsphenoidal approach (Trans-septal approach). METHODS: A prospective observational study, recruiting 40 patients undergoing surgery for pituitary adenoma, 20 via Endonasal approach and 20 via Trans-septal approach at our institution. Surveys with Sinonasal Outcome Test-22 (SNOT-22), Chronic Sinusitis Survey (CSS), and Short Form Health Survey 36 version 2 (SF-36v2) were obtained to collect QoL data pre- and postoperatively. RESULTS: All the 40 patients completed the questionnaires. At 6 months postoperatively, the SNOT-22 and CSS score shows significant improvements both in Endonasal approach (p = 0.01) and in Trans-septal approach (p = 0.02). No significant difference in sinonasal morbidity is observed between the two groups for SNOT-22 (p = 0.13) and CSS scores, except for sinus headache (p = 0.49), with a better score in Endonasal approach. The mean SF-36v2 scores remain the same in pre- and post-operative periods, but an improvement in time is seen in general health (p = 0.027), and general health compared to one year ago (p < 0.001). CONCLUSIONS: Endoscopic transsphenoidal surgery has negligible morbidity and does not negatively affect the nasal function in the long term. Endonasal approach and Trans-septal approach are comparable in terms of morbidity outcomes and general QoL, leaving the choice of the approach to the surgeon preference.

The fragility index: how robust are the outcomes of head and neck cancer randomised, controlled trials?

BACKGROUND: The fragility index represents the minimum number of patients required to convert an outcome from statistically significant to insignificant. This report assesses the fragility index of head and neck cancer randomised, controlled trials. METHODS: Studies were extracted from PubMed/Medline, Scopus, Embase and Cochrane databases. RESULTS: Overall, 123 randomised, controlled trials were included. The sample size and fragility index medians (interquartile ranges) were 103 (56-213) and 2 (0-5), respectively. The fragility index exceeded the number of patients lost to follow up in 42.3 per cent (n = 52) of studies. A higher fragility index correlated with higher sample size (r = 0.514, p < 0.001), number of events (r = 0.449, p < 0.001) and statistical significance via p-value (r = -0.367, p < 0.001). CONCLUSION: Head and neck cancer randomised, controlled trials demonstrated low fragility index values, in which statistically significant results could be nullified by altering the outcomes of just two patients, on average. Future head and neck oncology randomised, controlled trials should report the fragility index in order to provide insight into statistical robustness.

Home Sleep Testing versus Traditional Polysomnography: Pros and Cons.

Obstructive sleep apnea (OSA) is associated with long-term cardiovascular and respiratory comorbidities and increased burden on the health-care system. Early and accurate diagnosis is essential to reduce physical and financial implications of the disease. Polysomnography uses neurophysiologic channels as well as basic respiratory and sleep parameters to best estimate the presence and/or severity of OSA. Although home sleep testing may have the potential for more variable results, it is a viable alternative to increase access to diagnosis of OSA and facilitate initiation of positive airway pressure.

Platelet inventory management with demand and supply uncertainty and variable pricing considerations.

Managing the inventory of blood is a crucial operation in hospitals owing to its significance in medical treatment. At the same time, blood is characterized by unique attributes, such as perishability and the unpredictable nature of its supply and demand. While models have been developed to optimize the said process, gaps in literature exist in terms of considering the possibility of variable pricing and extensively accounting for uncertainties in the supply chain. In this light, the present study proposes a stochastic multi-period mixed integer linear programming cost minimization model that determines the optimal inventory plan for a hospital purchasing platelets, assuming that prices fluctuate along with the blood center's supply. To implement uncertain supply and demand, the model considers a discrete set of scenarios for each parameter. A study was performed, and the results indicate a promising direction as inventory costs decreased relative to models without the new considerations.

Using injectable fillers for chin and jawline rejuvenation.

Objective: As the population ages, facial plastic providers must remain aware of the treatments to prevent and reverse the external signs of aging. In the mandibular region, skin laxity and soft tissue sagging in the jawline may lead to jowling and chin ptosis along with reduced chin projection. While surgical procedures, including chin implantation, may be performed, nonsurgical procedures are becoming increasingly popular due to their temporary, noninvasive, yet effective methods. This review covers the use of hyaluronic acid, calcium hydroxylapatite, poly-l-lactic acid, and polymethyl methacrylate in the jawline. Methods: PubMed was searched for data on the mechanism of action, pertinent anatomy, indications, contraindications, technique, and evidence supporting the safety and efficacy of the fillers. Results: There are a wide variety of fillers available for use in the lower face with unique characteristics and application methods. While the advantages of injectable fillers include relatively affordable cost, minimal patient discomfort, and limited recovery times, taking measures to prevent short- and long-term complications is necessary for optimal results. Conclusions: Understanding the benefits and limitations of injectable fillers in the jawline can help providers appropriately counsel and treat patients.

Prevalence of opioid dependence in New South Wales, Australia, 2014-16: Indirect estimation from multiple data sources using a Bayesian approach.

AIMS: To estimate the prevalence of, and number of unobserved people with opioid dependence by sex and age group in New South Wales (NSW), Australia. DESIGN: We applied a Bayesian statistical modelling approach to opioid agonist treatment records linked to adverse event rate data. We estimated prevalence from three types of adverse event separately: opioid mortality, opioid-poisoning hospitalizations and opioid-related charges. We extended the model and produced prevalence estimates from a 'multi-source' model based on all three types of adverse event data. SETTING, PARTICIPANTS AND MEASUREMENTS: This study was conducted in NSW, Australia, 2014-16 using data from the Opioid Agonist Treatment and Safety (OATS) study, which included all people who had received treatment for opioid dependence in NSW. Aggregate data were obtained on numbers of adverse events in NSW. Rates of each adverse event type within the OATS cohort were modelled. Population data were provided by State and Commonwealth agencies. FINDINGS: Prevalence of opioid dependence among those aged 15-64 years in 2016 was estimated to be 0.96% (95% credible interval [CrI] = 0.82%, 1.12%) from the mortality model, 0.75% (95% CrI = 0.70%, 0.83%) from hospitalizations, 0.95% (95% CrI = 0.90%, 0.99%) from charges and 0.92% (95% CrI = 0.88%, 0.96%) from the multi-source model. Of the estimated 46 460 (95% CrI = 44 680, 48 410) people with opioid dependence in 2016 from the multi-source model, approximately one-third (16 750, 95% CrI = 14 960, 18 690) had no record of opioid agonist treatment within the last 4 years. From the multi-source model, prevalence in 2016 was estimated to be 1.24% (95% CrI = 1.18%, 1.31%) in men aged 15-44, 1.22% (95% CrI = 1.14%, 1.31%) in men 45-64, 0.63% (95% CrI = 0.59%, 0.68%) in women aged 15-44 and 0.56% (95% CrI = 0.50%, 0.63%) in women aged 45-64. CONCLUSIONS: A Bayesian statistical approach to estimate prevalence from multiple adverse event types simultaneously calculates that the estimated prevalence of opioid dependence in NSW, Australia in 2016 was 0.92%, higher than previous estimates.

A synthetic lethal screen for Snail-induced enzalutamide resistance identifies JAK/STAT signaling as a therapeutic vulnerability in prostate cancer.

Despite substantial improvements in the treatment landscape of prostate cancer, the evolution of hormone therapy-resistant and metastatic prostate cancer remains a major cause of cancer-related death globally. The mainstay of treatment for advanced prostate cancer is targeting of androgen receptor signaling, including androgen deprivation therapy plus second-generation androgen receptor blockade (e.g., enzalutamide, apalutamide, darolutamide), and/or androgen synthesis inhibition (abiraterone). While these agents have significantly prolonged the lives of patients with advanced prostate cancer, is nearly universal. This therapy resistance is mediated by diverse mechanisms, including both androgen receptor-dependent mechanisms, such as androgen receptor mutations, amplifications, alternative splicing, and amplification, as well as non-androgen receptor-mediated mechanisms, such as lineage plasticity toward neuroendocrine-like or epithelial-mesenchymal transition (EMT)-like lineages. Our prior work identified the EMT transcriptional regulator Snail as critical to hormonal therapy resistance and is commonly detected in human metastatic prostate cancer. In the current study, we sought to interrogate the actionable landscape of EMT-mediated hormone therapy resistant prostate cancer to identify synthetic lethality and collateral sensitivity approaches to treating this aggressive, therapy-resistant disease state. Using a combination of high-throughput drug screens and multi-parameter phenotyping by confluence imaging, ATP production, and phenotypic plasticity reporters of EMT, we identified candidate synthetic lethalities to Snail-mediated EMT in prostate cancer. These analyses identified multiple actionable targets, such as XPO1, PI3K/mTOR, aurora kinases, c-MET, polo-like kinases, and JAK/STAT as synthetic lethalities in Snail+ prostate cancer. We validated these targets in a subsequent validation screen in an LNCaP-derived model of resistance to sequential androgen deprivation and enzalutamide. This follow-up screen provided validation of inhibitors of JAK/STAT and PI3K/mTOR as therapeutic vulnerabilities for both Snail+ and enzalutamide-resistant prostate cancer.

Combined telovelar posterolateral (far lateral) approach for the resection of a large posterior fossa ependymoma: how I do it.

BACKGROUND: Ependymomas are glial cell tumors whose recommended treatment, according to the recent European guidelines, is surgical. Patient outcomes, in terms of progression-free survival and overall survival, are strongly related to the extent of resection. However, in some cases, critical locations and/or large dimensions could make a gross total resection challenging. In this article, we describe the surgical anatomy and technique of a combined telovelar-posterolateral approach for the resection of a giant posterior fossa ependymoma. METHODS: A 24-year-old patient who presented to our institution complaining of a 3-month history of headache, vertigo, and imbalance. Preoperative MRI scans showed a large mass within the fourth ventricle, extending towards the left cerebellopontine angle and perimedullary space through the homolateral Luschka foramen. Surgical treatment was proposed with the aims of releasing the preoperative symptoms, obtaining the tumor's histopathological and molecular definition, and preventing any future neurological deterioration. The patient gave his written consent for surgery and consented to the publication of his images. A combined telovelar-posterolateral approach was then performed to maximize the tumor's exposure and resection. Surgical technique and anatomical exposure have been extensively described, and a 2-dimensional operative video has been included. RESULTS: The postoperative MRI scan demonstrated an almost complete resection of the lesion, with only a millimetric tumor remnant infiltrating the uppermost portion of the inferior medullary velum. Histo-molecular analysis revealed a grade 2 ependymoma. The patient was discharged home neurologically intact. CONCLUSIONS: The combined telovelar-posterolateral approach allowed to achieve a near total resection of a giant multicompartimental mass within the posterior fossa in a single surgical stage.

A quiet place: The impact of the word "quiet" on clinical workload.

Purpose: This study aimed to determine the impact of uttering the word "quiet" on clinical workload during the overnight otolaryngology call shift and understand the factors contributing to resident busyness. Materials and Methods: A multicenter, single-blind, randomized-controlled trial was conducted. A total of 80 overnight call shifts covered by a pool of 10 residents were randomized to the quiet or to the control group. At the start of shift, residents were asked to state aloud, "Today will be a quiet night" (quiet group) or "Today will be a good night" (control group). Clinical workload, as measured by number of consults, was the primary outcome. Secondary measures included number of sign-out tasks, unplanned inpatient and operating room visits, number of phone calls and hours of sleep, and self-perceived busyness. Results: There was no difference in the number of total (P = 0.23), nonurgent (P = 0.18), and urgent (P = 0.18) consults. Tasks at signout, total phone calls, unplanned inpatient visits, and unplanned operating room visits did not differ between the control and quiet groups. While there were more unplanned operating room visits in the quiet group (29, 80.6%) compared to the control group (34, 94.4%), this was not found to be significant (P = 0.07). The majority of residents reported feeling "not busy" during control nights (18, 50.0%) compared to feeling "somewhat busy" during quiet nights (17, 47.2%; P = 0.42). Conclusion: Contrary to popular belief, there is no clear evidence that uttering the word "quiet" significantly increases clinical workload.

Cerebellar Ischemic Stroke Secondary to Rotational Non-Dominant Vertebral Artery Occlusion (RVAO): A Rare Complication Following Supratentorial Surgery.

Non-traumatic vertebrobasilar stroke syndrome is rare. Many etiological mechanisms have been described over the years, with the dynamic occlusion of one vertebral artery following head rotation (RVAO) being one of them. We report the case of a patient undergoing surgery for supratentorial metastasis, who postoperatively developed a cerebellar ischemic stroke secondary to RVAO. Postoperative imaging showed a right hypoplastic VA; so, a transient occlusive mechanism was thought to be responsible for the postoperative cerebellar stroke. Although rare, RVAO can occur following head rotation during patient positioning for neurosurgical procedures.

The Use of Endonasal Spreader Grafts in Preservation Rhinoplasty.

SUMMARY: Rhinoplasty is a complicated procedure that requires surgical finesse and precision to sculpt a framework that suits each patient's unique anatomical needs. Extensive resection may lead to nasal valve incompetence, causing obstructive symptoms associated with reduced quality of life. Numerous techniques have been described to help preserve and open the nasal airway, thereby mitigating valvular obstructive problems. In particular, the endonasal spreader graft is a common technique used to widen the internal nasal valve cross-sectional area while limiting external incisions and preserving local nasal structures. Preservation rhinoplasty is a variation of the traditional rhinoplasty that can lower the nasal dorsum without causing major disruption to the nasal keystone area, the junction between the middle and upper thirds of the nose. This study describes the successful and safe combination of these two surgical operations, demonstrating three case examples in which all patients reported improved postoperative nasal obstruction symptoms. Using endonasal spreader grafts in preservation rhinoplasty allows providers to manage the nasal valve and nasal dorsum similarly to the external approach without extensive deconstruction and reconstruction.

Minimally invasive microsurgical decompression of the lumbar spine using a novel robotised digital microscope: A preliminary experience.

BACKGROUND: The operative microscope (OM) represents, to date, the standard for neurosurgical procedures. However, new technologies have been proposed during the latest years to overcome its limitations, from high-quality exoscopes to complex robotised visualisation systems. We report our preliminary experience with a novel digital robotised microscope, the BHS RoboticScope (RS), for minimally invasive spinal surgery. METHODS: We employed the RS in five consecutive patients who underwent bilateral lumbar spine decompression through a monolateral approach. Patient outcomes, device technical characteristics and the surgeon's personal perspectives have been evaluated. RESULTS: No complications occurred. All procedures were concluded without switching to the microscope. Image quality, lightning, depth perception and freedom of movement were judged satisfactory as compared to the standard microscope. CONCLUSION: The easy maneuverability and the high quality of pictures provided by the RS device improve the surgeon's comfort in deep fields, representing an effective option for minimally invasive spinal procedures.