Endoscopic endonasal approach for resection of sellar leiomyosarcoma metastasis: illustrative case.

BACKGROUND: Leiomyosarcoma (LMS) is a rare neoplasm that arises from tissues of embryonic mesodermal origin. Primary tissues of origin can include smooth muscle cells of the abdominopelvic viscera, blood vessels, or arrector pili muscles. LMS is known to metastasize to the lungs, with few reported cases of spread to the central nervous system. OBSERVATIONS: A 66-year-old male with cutaneous LMS of the left forearm with metastases to the lungs and kidney that had been treated with chemoradiation presented with worsening headaches. Magnetic resonance imaging revealed a sellar lesion. An endocrine workup was unremarkable. Imaging over 6 months revealed rapid interval growth. Positron emission tomography demonstrated moderate uptake. Given the rapid growth, the patient was offered an endoscopic endonasal approach for resection. Pathology confirmed LMS. LESSONS: To the authors' knowledge, this is the first documented case of LMS metastasis to the sella. Pituitary carcinoma or metastases to the sellar region should be in the differential among patients with sellar region tumors with a rapid growth rate, bony erosion, or findings of lesions in the upper cervical lymph nodes or soft tissue. Tumors that show significant interval growth should raise suspicion for nonadenomatous lesions, and surgical intervention should be considered even in the absence of endocrinological dysfunction or cranial neuropathies. https://thejns.org/doi/10.3171/CASE2435.

Reducing MRCP Utilization Through a "Surgery First" Approach for Pediatric Choledocholithiasis: A CARES Working Group Retrospective Study.

BACKGROUND: Choledocholithiasis in children is rising and frequently managed with an endoscopy-first (EF) approach that utilizes endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Magnetic resonance cholangiopancreatography (MRCP) is a resource intensive modality that often precedes ERCP to gain further assurance of choledocholithiasis prior to intervention. MRCP can lead to a longer length of stay (LOS) and strain healthcare resources. We hypothesized that the use of MRCP is decreased with a surgery-first (SF) approach. METHODS: The Choledocholithiasis Alliance for Research, Education, and Surgery (CARES) Working Group conducted this retrospective study on pediatric patients with suspected choledocholithiasis. SF patients underwent LC + intraoperative cholangiogram (IOC) ± laparoscopic common bile duct exploration (LCBDE). Imaging studies included ultrasound (US), MRCP, and computed tomography (CT). RESULTS: From seven institutions, 357 pediatric patients were identified. The SF (n = 220) group received fewer imaging studies then EF (n = 137) (1.29 vs. 1.62; p < 0.05). US was more commonly employed and the number of US and CT scans was similar. The SF group had lower MRCP utilization than EF (29% vs. 59%; p < 0.05). EF patients that received an MRCP had the longest LOS (4.0 d [2.4, 6.3]) compared to SF that did not (1.9 d [1.2, 3.2]) (p < 0.05). CONCLUSION: Children with choledocholithiasis managed with an EF approach receive more diagnostic imaging, especially MRCP. While MRCP remains a powerful diagnostic tool, a surgery-first approach can minimize the resource utilization and LOS associated with magnetic resonance imaging. LEVEL OF EVIDENCE: Level III.

Antisense therapy to block the Kallikrein-kinin pathway in COVID-19: The ASKCOV randomized controlled trial.

PURPOSE: To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients. MATERIAL AND METHODS: Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life. RESULTS: From October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 ± 5.2 days for the intervention arm and 7.7 ± 5.1 for the control group; mean difference - 0.65, 95% confidence intervals from -2.95 to 1.36, p = 0.520). CONCLUSION: Antisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020. GOV IDENTIFIER: NCT04549922.

Moving the needle for laparoscopic common bile duct exploration: defining obstacles for the path forward.

INTRODUCTION: Laparoscopic cholecystectomy is performed very commonly but laparoscopic common bile duct exploration (LCBDE) is performed infrequently. We aimed to determine the most significant barriers to performing LCBDE and to identify the highest yield interventions to facilitate adoption. METHODS AND PROCEDURES: A national survey was designed by content experts, who regularly perform LCBDE. The survey was distributed by email to the Society of American Gastrointestinal and Endoscopic Surgeons and the American Association for the Surgery of Trauma memberships. Non-U.S. surgeon responses were excluded. Descriptive statistics were used to analyze the results. RESULTS: Seven hundred twenty six practicing surgeons responded to the survey, 543 of which were US surgeons who perform laparoscopic cholecystectomy. Only 27% of respondents preferred to manage choledocholithiasis with LCBDE. Their technique of choice was choledochoscopy (70%). Despite this, 36% of surgeons did not have access to a choledochoscope or were unsure if they did. Seventy percent of surgeons who performed LCBDE did not have supplies readily available in a central stocking location. Only 8.5% of surgeons agreed that routine LCBDE would impact their referral relationship with gastroenterology. About half the respondents (47%) considered LCBDE worth the time, but only 25% knew about reimbursement for the procedure. Almost all (85%) of surgeons understood that LCBDE results in shorter length of stay compared to ERCP. CONCLUSIONS: Only a quarter of the surgeons performing cholecystectomy perform LCBDE. Multiple barriers contribute to low LCBDE utilization. Increasing availability of appropriate equipment, a dedicated supply cart, and teaching fluoroscopic LCBDE interventions may address limitations and increase adoption. These efforts may also increase efficiency, minimizing perceived time and skill restraints. Although many surgeons understand LCBDE decreases length of stay, they are unaware of surgeon-specific LCBDE financial benefits. Systematically addressing these barriers may increase LCBDE adoption, improve patient care, and decrease healthcare costs.

Influence of Different Diagnostic Criteria on Alzheimer Disease Clinical Research.

BACKGROUND AND OBJECTIVES: Updates in Alzheimer disease (AD) diagnostic guidelines by the National Institute on Aging-Alzheimer's Association (NIA-AA) and the International Working Group (IWG) over the past 11 years may affect clinical diagnoses. We assessed how these guidelines affect clinical AD diagnosis in a cohort of cognitively unimpaired (CU) and cognitively impaired (CI) individuals. METHODS: We applied clinical and biomarker data in algorithms to classify individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort according to the following diagnostic guidelines for AD: 2011 NIA-AA, 2016 IWG-2, 2018 NIA-AA, and 2021 IWG-3, assigning the following generic diagnostic labels: (1) not AD (nAD), (2) increased risk of developing AD (irAD), and (3) AD. Diagnostic labels were compared according to their frequency, convergence across guidelines, biomarker profiles, and prognostic value. We also evaluated the diagnostic discordance among the criteria. RESULTS: A total of 1,195 individuals (mean age 73.2 ± 7.2 years, mean education 16.1 ± 2.7, 44.0% female) presented different repartitions of diagnostic labels according to the 2011 NIA-AA (nAD = 37.8%, irAD = 23.0%, AD = 39.2%), 2016 IWG-2 (nAD = 37.7%, irAD = 28.7%, AD = 33.6%), 2018 NIA-AA (nAD = 40.7%, irAD = 9.3%, AD = 50.0%), and 2021 IWG-3 (nAD = 51.2%, irAD = 8.4%, AD = 48.3%) frameworks. Discordant diagnoses across all guidelines were found in 512 participants (42.8%) (138 [91.4%] occurring in only ß-amyloid [CU 65.4%, CI 34.6%] and 191 [78.6%] in only tau-positive [CU 71.7%, CI 28.3%] individuals). Differences in predicting cognitive impairment between nAD and irAD groups were observed with the 2011 NIA-AA (hazard ratio [HR] 2.21, 95% CI 1.34-3.65, p = 0.002), 2016 IWG-2 (HR 2.81, 95% CI 1.59-4.96, p < 0.000), and 2021 IWG-3 (HR 3.61, 95% CI 2.09-6.23, p < 0.000), but not with 2018 NIA-AA (HR 1.69, 95% CI 0.87-3.28, p = 0.115). DISCUSSION: Over 42% of the studied population presented discordant diagnoses when using the different examined AD criteria, mostly in individuals with a single positive biomarker. Except for 2018 NIA-AA, all guidelines identified asymptomatic individuals at risk of cognitive impairment. Our findings highlight important differences between the guidelines, emphasizing the necessity for updated criteria with enhanced staging metrics, considering clinical, research, therapeutic, and trial design aspects.

Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: a randomized controlled trial.

BACKGROUND: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1ß play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL. METHODS: In this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20mg/Kg/weight) for 20 days. Group 1 used topical rSm29 (10ug), group 2 a placebo topically applied, and group 3 received only MA. RESULTS: The cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P<0.05). There was a decrease in GzmB and an increase in IFN-γ (P<0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P<0.05) in patients who received rSm29. CONCLUSION: rSm29 associated with MA reduces GzmB levels, is more effective than MA alone and decreases CL healing time. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov under NCT06000514.

Effect of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19.

OBJECTIVE: To investigate the effect of a single oral dose of 200,000 IU of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in Sao Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D3 (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-ß2-Glycoprotein-I (aß2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)]. RESULTS: Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m2), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D3 [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies. CONCLUSION: These findings do not support the use of a single oral dose of 200,000 IU of vitamin D3 to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Jump Squat Vs. Resisted Sprint Training Programs Applied to Elite Youth Soccer Players: Effects on Sprint and Power-Related Performance.

ABSTRACT: Loturco, I, Pereira, LA, Mercer, VP, Oliveira, LP, Zanetti, V, Lima, L, Bastos, T, Moura, TBMA, and McGuigan, MR. Jump squat vs. resisted sprint training programs applied to elite youth soccer players: effects on sprint and power-related performance. J Strength Cond Res XX(X): 000-000, 2024-This study examined the effectiveness of 2 different and widely used training programs on the sprint and power-related performance of youth soccer players. Two distinct training strategies-vertically oriented jump squats (JSs) or horizontally oriented resisted sprints (RSs)-were executed under the same absolute loading conditions (i.e., 30% of the athletes' body mass [BM]) during a 4-week preseason period. Training schemes, loading intensities (based on %BM), and the number of experimental sessions were designed in conjunction with the soccer club's coaching staff, considering the calendar, available resources, and regular training programs. Twenty-five under-17 soccer players performed a series of speed, power, and jump tests before and after 10 resisted training sessions, consisting solely of loaded JS or RS. Overall, neither group (i.e., JS or RS training groups) exhibited any improvement in linear sprint and change-of-direction (COD) speed. Conversely, vertical jumping ability and peak velocity in the loaded JS increased significantly only in the JS group, which may positively affect players' performance and training prescription during short soccer preseasons. Given the challenges in enhancing sprint speed among soccer players during preseasons (and even over the competitive season), coupled with the limited effectiveness of RS in improving sprinting, COD, and jumping capabilities within congested and short training phases (i.e., ≤4 weeks), the regular use of RS training methods during these phases may be highly questionable. Coaches should carefully consider these critical limitations and potential disadvantages when designing neuromuscular training programs for soccer players during the preparatory phases of the annual training season.

Can human sex be estimated based on the dimensions of the maxillary sinuses? A systematic review of the literature on cone-beam and multi-slice computed tomography.

PURPOSE: To critically appraise and summarize the potential of linear and/or volumetric dimensions of the maxillary sinuses obtained with cone-beam and multi-slice computed tomography. METHODS: A bibliographic search was conducted in seven databases in August 2023. Cross-sectional retrospective studies using linear and volumetric measurements of the maxillary sinuses obtained with cone-beam and multi-slice computed tomography for sex estimation and presenting numerical estimation data were included. Narrative or systematic reviews, letters to the editor, case reports, laboratory studies in animals, and experimental studies were excluded. The critical appraisal and certainty of evidence were assessed using the guidelines described by Fowkes and Fulton and GRADE, respectively. RESULTS: A total of 656 studies were found, 32 of which were included. A total of 3631 individuals were analyzed and the overall sex estimation rate ranged from 54.9 % to 95 %. When compared with isolated measurements, combined linear measurements of the right and left maxillary sinuses, such as width, length, and height, provided a higher rate of sex estimation (54.9-95 %). In most of the studies (62.5 %), all measurements were higher in men than in women. Multiple methodological problems were found in the studies, especially distorting influences in 84.4 % of the answers. The certainty of evidence varied from very low to low. CONCLUSIONS: The combination of height, width, and length measurements of the right and left maxillary sinuses from cone-beam and multi-slice computed tomography can be useful in the estimation of sex of humans. Further primary studies are needed to increase the certainty of evidence. PROSPERO REGISTER: CRD42020161922.

Extracellular vesicles from primary human macrophages stimulated with VIP or PACAP mediate anti-SARS-CoV-2 activities in monocytes through NF-κB signaling pathway.

Infection by SARS-CoV-2 is associated with uncontrolled inflammatory response during COVID-19 severe disease, in which monocytes are one of the main sources of pro-inflammatory mediators leading to acute respiratory distress syndrome. Extracellular vesicles (EVs) from different cells play important roles during SARS-CoV-2 infection, but investigations describing the involvement of EVs from primary human monocyte-derived macrophages (MDM) on the regulation of this infection are not available. Here, we describe the effects of EVs released by MDM stimulated with the neuropeptides VIP and PACAP on SARS-CoV-2-infected monocytes. MDM-derived EVs were isolated by differential centrifugation of medium collected from cells cultured for 24 h in serum-reduced conditions. Based on morphological properties, we distinguished two subpopulations of MDM-EVs, namely large (LEV) and small EVs (SEV). We found that MDM-derived EVs stimulated with the neuropeptides inhibited SARS-CoV-2 RNA synthesis/replication in monocytes, protected these cells from virus-induced cytopathic effects and reduced the production of pro-inflammatory mediators. In addition, EVs derived from VIP- and PACAP-treated MDM prevented the SARS-CoV-2-induced NF-κB activation. Overall, our findings suggest that MDM-EVs are endowed with immunoregulatory properties that might contribute to the antiviral and anti-inflammatory responses in SARS-CoV-2-infected monocytes and expand our knowledge of EV effects during COVID-19 pathogenesis.

Wolbachia impacts microbiome diversity and fitness-associated traits for Drosophila melanogaster in a seasonally fluctuating environment.

The microbiome contributes to many different host traits, but its role in host adaptation remains enigmatic. The fitness benefits of the microbiome often depend on ecological conditions, but theory suggests that fluctuations in both the microbiome and environment modulate these fitness benefits. Moreover, vertically transmitted bacteria might constrain the ability of both the microbiome and host to respond to changing environments. Drosophila melanogaster provides an excellent system to investigate the impacts of interactions between the microbiome and the environment. To address this question, we created field mesocosms of D. melanogaster undergoing seasonal environmental change with and without the vertically transmitted bacteria, Wolbachia pipientis. Sampling temporal patterns in the microbiome revealed that Wolbachia constrained microbial diversity. Furthermore, Wolbachia and a dominant member of the microbiome, Commensalibacter, were associated with differences in two higher-order fitness traits, starvation resistance and lifespan. Our work here suggests that the interplay between the abiotic context and microbe-microbe interactions may shape key host phenotypes that underlie adaptation to changing environments. We conclude by exploring the consequences of complex interactions between Wolbachia and the microbiome for our understanding of eco-evolutionary processes that shape host-microbiome interactions.

Emerging athletes' career transitions in professional sport: an existential multi-case perspective.

Introduction: This article examines athletes preparing for, transitioning into, or going through the developmental stages of a professional sports career, referred to as the emerging athlete career transition. This transition includes events such as selections, Junior-to-Senior promotions, contracting, migration, and early exits. The article presents the collective findings of a multi-case study in three professional sports: rugby league, basketball, and boxing. Method: Consistent with pragmatic qualitative research methodology, a stratified data set was collected and analysed, incorporating researcher-practitioner fieldwork, interviews, documents and artefacts for these cases. This article explores unique events and the demographic and cultural implications of navigating emergent transitions along professional sporting pathways in New Zealand. Findings: These findings highlight the importance of building self-efficacy as a pre-condition for coping through preparation and experience. Recommendations: Recommendations include fostering collaborative cultures and authentic support relationships to facilitate better coping alongside athletic and personal development in these high-pressured environments. Furthermore, understanding existential perspectives of meaning, choice, and responsibility provides insights for developing the resources that allow emerging athletes to thrive in life beyond sport.

Correction: Boia-Ferreira et al. TCTP from Loxosceles Intermedia (Brown Spider) Venom Contributes to the Allergic and Inflammatory Response of Cutaneous Loxoscelism. Cells 2019, 8, 1489.

In the original publication [...].

Neurosurgical Management of Patients with Alpha-Gal Syndrome.

Alpha-gal syndrome (AGS) is an immunoglobulin E-mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate mammalian products. Initial exposure to alpha-gal most often occurs through a tick bite, most commonly the lone star tick in the United States. Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis. The allergy restricts dietary intake and may significantly impact perioperative risk, as many medications, anesthetics, and intraoperative surgical products utilize bovine or porcine-derived agents, including those containing magnesium stearate, glycerol, and gelatin. Here, we review the perineurosurgical care of two individuals with AGS and highlight pertinent clinical practices and perioperative management of these patients.

Birds optimize fruit size consumed near their geographic range limits.

Animals can adjust their diet to maximize energy or nutritional intake. For example, birds often target fruits that match their beak size because those fruits can be consumed more efficiently. We hypothesized that pressure to optimize diet-measured as matching between fruit and beak size-increases under stressful environments, such as those that determine species' range edges. Using fruit-consumption and trait information for 97 frugivorous bird and 831 plant species across six continents, we demonstrate that birds feed more frequently on closely size-matched fruits near their geographic range limits. This pattern was particularly strong for highly frugivorous birds, whereas opportunistic frugivores showed no such tendency. These findings highlight how frugivore interactions might respond to stressful conditions and reveal that trait matching may not predict resource use consistently.

A Novel Taxonomy of Intraoperative Cholangiograms in Suspected Choledocholithiasis: A Tool for Advancing Laparoscopic Common Bile Duct Exploration Outcomes Research.

BACKGROUND: Cholangiography for visualization of the biliary tree during laparoscopic cholecystectomy is an important diagnostic roadmap in the context of suspected choledocholithiasis (CDL). The renewed interest in transcystic laparoscopic common bile duct exploration (LCBDE) necessitates a general description of the range of CDL presentations. Our aim was to establish a novel classification system of intraoperative cholangiograms (IOCs) to advance research efforts in this field. METHODS: A novel cholangiogram classification system, featuring 8 distinct presentations of choledocholithiasis, was applied to a data set of 80 preintervention IOCs for suspected choledocholithiasis. The classification system is as follows: A (no common bile duct stones, duodenal filling present, and concern for air bubbles), B (no common bile duct stones, no duodenal filling, and concern for sludge), C1 (stone(s) < 2x size of cystic duct with duodenal filling), C2 (stone(s) < 2x size of cystic duct without duodenal filling), D1 (stone(s) ≥ 2x size of cystic duct with duodenal filling), D2 (stone(s) ≥ 2x size of cystic duct without duodenal filling), E1 (congenital anatomical variant and/or common duct stricture), and E2 (surgically altered biliary anatomy). RESULTS: Cholangiogram review yielded preintervention classifications for 6 of 8 variants (A-E): A (7.5%), B (3.75%), C1 (23.75%), C2 (42.5%), D1 (15%), and D2 (7.5%). Analysis of cystic duct diameter yielded no significant differences among classification groups, indicating no predominant pattern of cystic duct anatomy within a given classification. DISCUSSION: An IOC classification system for suspected choledocholithiasis is foundational to answering key clinical questions for transcystic laparoscopic common bile duct exploration.

Vertical root fracture diagnosis in teeth with metallic posts: Impact of metal artifact reduction and sharpening filters.

Purpose: This study examined the influence of a metal artifact reduction (MAR) tool, sharpening filters, and their combination on the diagnosis of vertical root fracture (VRF) in teeth with metallic posts using cone-beam computed tomography (CBCT). Materials and Methods: Twenty single-rooted human premolars - 9 with VRF and 11 without - were individually placed in a human mandible. A metallic post composed of a cobalt-chromium alloy was inserted into the root canal of each tooth. CBCT scans were then acquired under the following parameters: 8 mA, a 5×5 cm field of view, a voxel size of 0.085 mm, 90 kVp, and with MAR either enabled or disabled. Five oral and maxillofacial radiologists independently evaluated the CBCT exams under each MAR mode and across 3 sharpening filter conditions: no filter, Sharpen 1×, and Sharpen 2×. The diagnostic performance was quantified by the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. These metrics were compared using 2-way analysis of variance with a significance level of α=5%. Intra- and inter-examiner agreement were assessed using the weighted kappa test. Results: Neither MAR nor the application of sharpening filters significantly impacted AUC or specificity (P>0.05). However, sensitivity increased when MAR was combined with Sharpen 1× and Sharpen 2× (P=0.015). The intra-examiner agreement ranged from fair to substantial (0.34-0.66), while the inter-examiner agreement ranged from fair to moderate (0.27-0.41). Conclusion: MAR in conjunction with sharpening filters improved VRF detection; therefore, their combined use is recommended in cases of suspected VRF.

Anatomical Step-by-Step Dissection of Complex Skull Base Approaches for Trainees: Surgical Anatomy of the Frontotemporal and Orbitozygomatic Craniotomies.

Introduction Although many neuroanatomic atlases have been published, few have detailed complex cranial approaches and pertinent anatomic considerations in a stepwise fashion intended for rapid comprehension by neurosurgery students, residents, and fellows. Methods Five sides of formalin-fixed latex-injected specimens were dissected under microscopic magnification. The frontotemporal and orbitozygomatic approaches were performed by neurosurgical residents and fellows at different training levels with limited previous experience in anatomical dissection mentored by the senior authors (M.P.C. and M.J.L.). Meticulous surgical anatomic dissections were performed until sufficient visual and technical completion was attained, with parameters of effectively demonstrating key surgical steps for educational training purposes. Following the completion of dissection and three-dimensional photography, illustrative case examples were reviewed to demonstrate the relative benefits and optimal applications of each approach. Results The frontotemporal and orbitozygomatic approaches afford excellent access to anterior and middle skull base pathologies, as well as the exposure of the infratemporal fossa. Key considerations include head positioning, skin incision, scalp retraction, fat pad dissection and facial nerve protection, true or false MacCarty keyhole fashioning, sphenoid wing drilling and anterior clinoidectomy, completion of the craniotomy and accessory orbital osteotomy cuts, dural opening, and intradural neurovascular access. Conclusion The frontotemporal and orbitozygomatic approaches are core craniotomies that offer distinct advantages for complex cranial operations. Learning and internalizing their key steps and nuanced applications in a clinical context is critical for trainees of many levels. The orbitozygomatic craniotomy in particular is a versatile but challenging approach; operative-style laboratory dissection is an essential component of its mastery and one that will be powerfully enhanced by the current work.

INVESTIGATING THE RELATIONSHIP BETWEEN BLEEDING, CLOTTING, AND COAGULOPATHY DURING AUTOMATED PARTIAL REBOA STRATEGIES IN A HIGHLY LETHAL PORCINE HEMORRHAGE MODEL.

ABSTRACT: Background: Death due to hemorrhagic shock, particularly, noncompressible truncal hemorrhage, remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently, whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer. In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared with pREBOA due to more oscillatory flow. Methods: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 min of automated pREBOA, iREBOA, or no balloon support (control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., eight key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 min). Citrated kaolin heparinase assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between the iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R time: P < 0.001; K time: P < 0.001) and clot strength (MA: P = 0.01; G: P = 0.02) over the duration of the experiment. Conclusions: Despite observing acute differences in peak proximal pressures between the iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.

Candida parapsilosis: Heterogeneous and strain-specific expression of secreted aspartic proteases (Sapp1 and Sapp2).

The increasing prevalence of Candida parapsilosis as a causative agent of fungal infections underscores the need to comprehensively understand its virulence factors. Secreted aspartic proteases (Saps) play a significant role in adhesion events, promoting biofilm formation, causing tissue damage and evading the host's immune response. In C. parapsilosis, three Saps have been identified: Sapp1, Sapp2 and Sapp3. The present study investigates the production dynamics of Sapp1 and Sapp2 across 10 clinical isolates of C. parapsilosis using various approaches. Each fungal isolate demonstrated the capability to utilize bovine serum albumin (BSA) as the sole nitrogen source, as evidenced by its degradation in a cell-free culture medium, forming low molecular mass polypeptides. Interestingly, the degradation of different proteinaceous substrates, such as BSA, human serum albumin (HSA), gelatin and hemoglobin, was typically isolate-dependent. Notably, higher proteolysis of HSA compared to BSA, gelatin and hemoglobin was observed. A quantitative assay revealed that the cleavage of a peptide fluorogenic substrate (cathepsin D) was isolate-specific, ranging from 44.15 to 270.61 fluorescence arbitrary units (FAU), with a mean proteolysis of 150.7 FAU. The presence of both Sapp1 and Sapp2 antigens on the cell surface of these fungal isolates was confirmed through immunological detection employing specific anti-Sapp1 and anti-Sapp2 antibodies. The surface levels of Sapp1 were consistently higher, up to fourfold, compared to Sapp2. Similarly, higher levels of Sapp1 than Sapp2 were detected in fungal secretions. This study provides insights into the dynamic expression and regulation of Sapps in C. parapsilosis, highlighting a known virulence factor that is considered a potential target for drug development against this increasingly prominent pathogen.

The fungal pathogen Candida parapsilosis can secrete aspartic proteases (Sapps) as part of its arsenal of virulence factors. We demonstrated that Sapps were able to cleave key host proteins, and the production of Sapp1 and Sapp2 antigens was typically dependent on the fungal isolate when grown in both planktonic- and biofilm-forming cells.