Primitive purine biosynthesis connects ancient geochemistry to modern metabolism.

An unresolved question in the origin and evolution of life is whether a continuous path from geochemical precursors to the majority of molecules in the biosphere can be reconstructed from modern-day biochemistry. Here we identified a feasible path by simulating the evolution of biosphere-scale metabolism, using only known biochemical reactions and models of primitive coenzymes. We find that purine synthesis constitutes a bottleneck for metabolic expansion, which can be alleviated by non-autocatalytic phosphoryl coupling agents. Early phases of the expansion are enriched with enzymes that are metal dependent and structurally symmetric, supporting models of early biochemical evolution. This expansion trajectory suggests distinct hypotheses regarding the tempo, mode and timing of metabolic pathway evolution, including a late appearance of methane metabolisms and oxygenic photosynthesis consistent with the geochemical record. The concordance between biological and geological analyses suggests that this trajectory provides a plausible evolutionary history for the vast majority of core biochemistry.

Life detection in a universe of false positives: Can the Fatal Flaws of Exoplanet Biosignatures be Overcome Absent a Theory of Life?

Astrobiology aims to determine the distribution and diversity of life in the universe. But as the word "biosignature" suggests, what will be detected is not life itself, but an observation implicating living systems. Our limited access to other worlds suggests this observation is more likely to reflect out-of-equilibrium gasses than a writhing octopus. Yet, anything short of a writhing octopus will raise skepticism about what has been detected. Resolving that skepticism requires a theory to delineate processes due to life and those due to abiotic mechanisms. This poses an existential question for life detection: How do astrobiologists plan to detect life on exoplanets via features shared between non-living and living systems? We argue that you cannot without an underlying theory of life. We illustrate this by analyzing the hypothetical detection of an "Earth 2.0" exoplanet. Without a theory of life, we argue the community should focus on identifying unambiguous features of life via four areas: examining life on Earth, building life in the lab, probing the solar system, and searching for technosignatures. Ultimately, we ask, what exactly do astrobiologists hope to learn by searching for life?

Oxidized Phospholipid oxPAPC Alters Regulatory T-Cell Differentiation and Decreases Their Protective Function in Atherosclerosis in Mice.

BACKGROUND: Regulatory T cells (Tregs) are protective in atherosclerosis but reduced during disease progression due to cell death and loss of stability. However, the mechanisms of Treg dysfunction remain unknown. Oxidized phospholipids are abundant in atherosclerosis and can activate innate immune cells, but little is known regarding their impact on T cells. Given Treg loss during atherosclerosis progression and oxidized phospholipid levels in the plaque microenvironment, we investigated whether oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), an oxidized phospholipid associated with atherosclerotic plaques, alters Treg differentiation and function. METHODS: CD4+ T cells were polarized to Treg, T helper (Th) 1, and Th17 cells with or without oxPAPC and assessed by flow cytometry. Gene expression in oxPAPC-treated Tregs was analyzed by bulk RNA sequencing. Functional studies of oxPAPC-induced Tregs were performed by coculturing Tregs with CellTrace Violet-labeled cells in vitro, and by adoptively transferring Tregs to hyperlipidemic Ldlr-/- mice to measure atherosclerosis progression. RESULTS: Compared with controls, oxPAPC-treated Tregs were less viable, but surviving cells expressed higher levels of the Th1-associated markers T-bet, CXCR3, and IFN (interferon)-γ. Th1 and Th17 skewing cultures were unaltered by oxPAPC. IFN-γ is linked to Treg instability, thus Treg polarization experiments were repeated using Ifngr1-/- CD4+ T cells. IFNγR1 (INF gamma receptor 1) deficiency did not improve cell viability in oxPAPC-treated Tregs; however, T-bet and IFN-γ expression was not increased in surviving cells suggesting a role for IFN-γsignaling. OxPAPC-treated Tregs were less suppressive in vitro, and adoptive transfer studies in hyperlipidemic Ldlr-/- mice showed that oxPAPC-induced Tregs possessed altered tissue homing and were insufficient to inhibit atherosclerosis progression. CONCLUSIONS: OxPAPC elicits Treg-specific changes altering Treg differentiation and inducing a Th1-like phenotype in surviving cells partially through IFN-γ signaling. This is biologically relevant as oxPAPC-treated Tregs do not reduce atherosclerosis progression in Ldlr-/- mice. This study supports the role of oxidized phospholipids in negatively impacting Treg differentiation and atheroprotective function.

Ultrasound-guided pleural biopsy following a non-diagnostic thoracentesis for non-small cell lung cancer.

We report a case of a 65-year-old man with a cavitary lung mass and parietal-based pleural nodules in which a pleural ultrasound-guided approach yielded a definitive diagnosis of stage IV non-small cell lung carcinoma. Computed tomography-guided biopsy is often preferred approach for the majority of United States hospitals for sampling pleural nodules as compared to US. The advantages of an US-guided approach include [1]: increased portability [2]; decreased procedure time [3]; reduced reliance on dedicated ancillary support staff [4]; need for local anesthesia only [5]; lack of ionizing radiation exposure; and [6] cost reduction.

Natural trajectory of recovery of COVID-19 associated olfactory loss.

IMPORTANCE: Prevalence of post-viral olfactory loss has increased dramatically due to the frequency and severity of olfactory dysfunction associated with infection by the SARS-CoV-2 virus. OBJECTIVE: To determine the trajectory of COVID-19 olfactory loss over a six-month period. A key secondary objective is to assess predictive factors associated with the recovery of olfaction. DESIGN: Longitudinal repeated-measures study that enrolled from May 5, 2020 to February 2, 2021, with the last date of data collection on June 15, 2021. SETTING: Barnes-Jewish HealthCare/Washington University School of Medicine facilities (Saint Louis, Missouri, USA). PARTICIPANTS: Individuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction on nasopharyngeal swab and indicated olfactory loss on COVID-19 screening questionnaire. Individuals were excluded if they had previously diagnosed history of olfactory loss, neurodegenerative disorders, <18 years of age, admitted to hospital service, unable to read, write, and understand English, or lacked computer or internet access. INTERVENTIONS/EXPOSURES: Watch and wait for spontaneous recovery. MAIN OUTCOME(S) AND MEASURE(S): Participants completed olfactory assessments every 30 days for six months. Each assessment consisted of the University of Pennsylvania Smell Identification Test (UPSIT), an objective "scratch-and-sniff" test, and Clinical Global Impressions (CGI), a subjective Likert rating scale. RESULTS: The mean age was 41 years old (SD = 16). 39 (80 %) were female and 42 (86 %) white. At baseline assessment of objective olfaction, 18 (36 %) participants had anosmia or severe hyposmia. Subjective, complete recovery at six months was 81 % (95 % CI 74 % to 88 %). Likelihood of recovery was associated with age <50 years (aHR = 8.1 (95 % CI 1.1 to 64.1)) and mild olfactory loss at baseline (UPSIT = 30-33 for males and 31-34 for females) (aHR 6.2 (95 % CI 1.2 to 33.0)). CONCLUSIONS AND RELEVANCE: The trajectory of olfactory recovery among adults with COVID-19 olfactory loss illustrated rapid recovery within 2-3 weeks of infection, and by six months 81 % had recovered based on self-report. Age <50 years old and mild severity of olfactory loss at baseline were associated with increased likelihood of recovery of olfaction. These findings can be used to inform shared decision-making with patients.

Efficacy and Safety of Saline Nasal Irrigation Plus Theophylline for Treatment of COVID-19-Related Olfactory Dysfunction: The SCENT2 Phase 2 Randomized Clinical Trial.

Importance: Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic. Objective: To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19-related OD. Design, Setting, and Participants: This triple-blinded, placebo-controlled, phase 2 randomized clinical trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021. Interventions: Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks. Main Outcomes and Measures: The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19-related questions. Results: A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, -13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, -1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, -2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2 study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, -4% to 52%) in favor of theophylline. Conclusions and Relevance: This randomized clinical trial suggests that the clinical benefit of theophylline nasal irrigations on olfaction in participants with COVID-19-related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully. Trial Registration: ClinicalTrials.gov Identifier: NCT04789499.

An open source computational workflow for the discovery of autocatalytic networks in abiotic reactions.

A central question in origins of life research is how non-entailed chemical processes, which simply dissipate chemical energy because they can do so due to immediate reaction kinetics and thermodynamics, enabled the origin of highly-entailed ones, in which concatenated kinetically and thermodynamically favorable processes enhanced some processes over others. Some degree of molecular complexity likely had to be supplied by environmental processes to produce entailed self-replicating processes. The origin of entailment, therefore, must connect to fundamental chemistry that builds molecular complexity. We present here an open-source chemoinformatic workflow to model abiological chemistry to discover such entailment. This pipeline automates generation of chemical reaction networks and their analysis to discover novel compounds and autocatalytic processes. We demonstrate this pipeline's capabilities against a well-studied model system by vetting it against experimental data. This workflow can enable rapid identification of products of complex chemistries and their underlying synthetic relationships to help identify autocatalysis, and potentially self-organization, in such systems. The algorithms used in this study are open-source and reconfigurable by other user-developed workflows.

Prolonged Emesis Causing Esophageal Perforation: A Case Report.

Transmural esophageal rupture or Boerhaave syndrome carries a high mortality rate due to delayed diagnosis and treatment. The heterogeneity of symptoms, age, comorbidities, and the severity of illness in this group of patients add to the difficulty of the management of Boerhaave syndrome. It generally occurs in the distal part of the esophagus and may result in the leakage of gastric contents into the thoracic cavity leading to mediastinal necrosis and bacterial infection. The management relies on prompt detection and intervention with conservative care and/or surgical repair. Early recognition within 24 hours followed by primary repair of the esophagus with mediastinal and chest drainage is associated with a 90% survival rate.

Accessory Spleen Masquerading as an Intrapancreatic Tumor: A Case Report.

The finding of splenic tissue within the pancreas, also known as splenosis or intrapancreatic accessory spleen (IPAS), is a relatively uncommon condition that presents as an intrapancreatic mass. The discovery of an intrapancreatic mass often prompts a thorough diagnostic workup for a primary pancreatic malignancy, often exposing patients to unnecessary risks associated with invasive testing and even surgery. The benign, asymptomatic nature of this finding places emphasis on utilizing non-invasive techniques for confirmation of the diagnosis, reducing risks of morbidity and mortality in this patient population. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) will display near-identical signal intensities (SI) between the spleen and the intrapancreatic mass, as well as identical contrast-enhancement patterns. Nuclear medicine evaluation with Tc-99m heat-damaged red blood cells (HDRBCs) is often used as a confirmatory test and allows for differentiation from malignancies.

An Evaluation of Annual Adherence to Lung Cancer Screening in a Large National Cohort.

INTRODUCTION: Lung cancer screening reduces mortality in large RCTs where adherence is high. Unfortunately, recently published adherence rates do not replicate those seen in trials. Previous publications support a centralized approach to ensure patient eligibility and improve adherence. METHODS: Investigators reviewed a large, geographically diverse cohort of patients from 14 health systems, with 73 centers across the U.S. Lung cancer screening patients were screened from 2015 to 2019 and tracked utilizing a commercial system. Data were analyzed in 2019-2021. Demographics, eligibility, imaging results, and cancer diagnosis were collected. Overall return was calculated for 2 years (Time 0-Time 1 and Time 1-Time 2) on the basis of follow-up through March 31, 2020. Only U.S. Preventive Services Task Force-eligible patients with a normal or benign result (Lung-Reporting and Data System 1 or 2) at baseline (Time 0) were included in annual adherence calculations. RESULTS: A total of 30,166 patients were screened; 50% were male, with a mean age of 65 years. Most individuals currently smoked (58.3%), with an average of 48.3 pack years. A total of 58% were White, 6% were Black, and 34% had race information unavailable. U.S. Preventive Services Task Force eligibility criteria were not met by 10.6%. Of the 26,958 patients eligible at baseline, 76% were Lung-Reporting and Data System 1 or 2. Annual adherence at Year 1 (Time 0-Time 1) was 48.4%. Adherence at Year 2 (Time 1-Time 2) was 44.4%. A total of 93 U.S. Preventive Services Task Force‒eligible patients were diagnosed with lung cancers, mostly during the first annual follow-up. CONCLUSIONS: In this large cohort screened and managed primarily using a commercial tracking platform, most patients were U.S. Preventive Services Task Force eligible. However, annual adherence was poor despite this resource, suggesting that additional interventions are needed to recognize the full mortality benefit from screening programs.

Surgical management of chronic scrotal pain: a review of the current literature.

Chronic scrotal pain (CSP) may be due to an identifiable cause, may be multifactorial, or may be idiopathic. Successful treatment often requires multimodal therapy with a multidisciplinary approach. Conservative options may be offered initially, but if symptoms fail to improve with conservative interventions, more invasive therapies may be required. A nerve block may be attempted and patients who experience improvement in pain following nerve blocks may be good candidates for surgical denervation of the spermatic cord. Alternative surgical treatment options including proximal nerve blocks, neuromodulation, cryoablation, vasectomy reversal, varicocelectomy, and even orchiectomy have been described. The aim of this review is to discuss the treatment options for CSP with a focus on surgical treatment options.

ZFC3H1 and U1-70K promote the nuclear retention of mRNAs with 5' splice site motifs within nuclear speckles.

Quality control of mRNA represents an important regulatory mechanism for gene expression in eukaryotes. One component of this quality control is the nuclear retention and decay of misprocessed RNAs. Previously, we demonstrated that mature mRNAs containing a 5' splice site (5'SS) motif, which is typically found in misprocessed RNAs such as intronic polyadenylated (IPA) transcripts, are nuclear retained and degraded. Using high-throughput sequencing of cellular fractions, we now demonstrate that IPA transcripts require the zinc finger protein ZFC3H1 for their nuclear retention and degradation. Using reporter mRNAs, we demonstrate that ZFC3H1 promotes the nuclear retention of mRNAs with intact 5'SS motifs by sequestering them into nuclear speckles. Furthermore, we find that U1-70K, a component of the spliceosomal U1 snRNP, is also required for the nuclear retention of these reporter mRNAs and likely functions in the same pathway as ZFC3H1. Finally, we show that the disassembly of nuclear speckles impairs the nuclear retention of reporter mRNAs with 5'SS motifs. Our results highlight a splicing independent role of U1 snRNP and indicate that it works in conjunction with ZFC3H1 in preventing the nuclear export of misprocessed mRNAs by sequestering them into nuclear speckles.

Severe Post-prandial Pain: A Case Report.

Median arcuate ligament syndrome (MALS) is a rare cause of post-prandial abdominal pain due to compression of the celiac artery and celiac plexus. Associated symptoms include nausea, vomiting, diarrhea, and weight loss. The incidence of radiologic compression of the celiac axis is reported to be between 10% and 24%; however, symptomatic compression is noted to be found in about half of the population. MALS is considered a diagnosis of exclusion due to its tendency to present with nonspecific symptoms that mimic other common causes of abdominal pain. Radiologic evidence from angiography with breathing maneuvers is the gold standard for diagnosis. Surgical division of the median arcuate ligament to decompress the celiac artery is an effective treatment proving to provide up to 60-70% of symptomatic relief.

Natural Trajectory of Recovery of COVID-19 Associated Olfactory Loss.

IMPORTANCE: Prevalence of post-viral olfactory loss has increased dramatically due to the frequency and severity of olfactory dysfunction associated with infection by the SARS-CoV-2 virus. OBJECTIVE: To determine the trajectory of COVID-19 olfactory loss over a six-month period. A key secondary objective is to assess predictive factors associated with the recovery of olfaction. DESIGN: Longitudinal repeated-measures study that enrolled from May 5, 2020 to February 2, 2021, with the last date of data collection on June 15, 2021. SETTING: Barnes-Jewish HealthCare/Washington University School of Medicine facilities (Saint Louis, Missouri, USA). PARTICIPANTS: Individuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction on nasopharyngeal swab and indicated olfactory loss on COVID-19 screening questionnaire. Individuals were excluded if they had previously diagnosed history of olfactory loss, neurodegenerative disorders, less than 18 years of age, admitted to hospital service, unable to read, write, and understand English, or lacked computer or internet access. INTERVENTIONS/EXPOSURES: Watch and wait for spontaneous recovery. MAIN OUTCOMES AND MEASURES: Participants completed olfactory assessments every 30 days for six months. Each assessment consisted of the University of Pennsylvania Smell Identification Test (UPSIT), an objective "scratch-and-sniff" test, and Clinical Global Impressions (CGI), a subjective Likert rating scale. RESULTS: The mean age was 41 years old (SD = 16). 39 (80%) were female and 42 (86%) white. At baseline assessment of objective olfaction, 18 (36%) participants had anosmia or severe hyposmia. Subjective, complete recovery at six months was 81% (95% CI 74% to 88%). Likelihood of recovery was associated with age less than 50 years (aHR = 8.1 (95% CI 1.1 to 64.1)) and mild olfactory loss at baseline (UPSIT = 30-33 for males and 31-34 for females) (aHR 6.2 (95% CI 1.2 to 33.0)). CONCLUSIONS AND RELEVANCE: The trajectory of olfactory recovery among adults with COVID-19 olfactory loss illustrated rapid recovery within 2-3 weeks of infection, and by six months 81% had recovered based on self-report. Age less than 50 years old and mild severity of olfactory loss at baseline were associated with increased likelihood of recovery of olfaction. These findings can be used to inform shared decision-making with patients.

Development and Validation of a Novel At-home Smell Assessment.

IMPORTANCE: Current tools for diagnosis of olfactory dysfunction (OD) are costly, time-consuming, and often require clinician administration. OBJECTIVE: To develop and validate a simple screening assessment for OD using common household items. DESIGN, SETTING, AND PARTICIPANTS: This fully virtual diagnostic study included adults with self-reported OD from any cause throughout the US. Data were collected from December 2020 to April 2021 and analyzed from May 2021 to July 2021. MAIN OUTCOMES AND MEASURES: Participants with self-reported olfactory dysfunction took a survey assessing smell perception of 45 household items and completed the Clinical Global Impression-Severity (CGI-S) smell questionnaire, the University of Pennsylvania Smell Identification Test (UPSIT), and the 36-item Short Form Survey (SF-36). Psychometric and clinimetric analyses were used to consolidate 45 household items into 2 short Novel Anosmia Screening at Leisure (NASAL) assessments, NASAL-7 (range, 0-14; lower score indicating greater anosmia) and NASAL-3 (range, 0-6; lower score indicating greater anosmia). RESULTS: A total of 115 participants were included in the study, with a median (range) age of 42 (19-70) years, 92 (80%) women, and 97 (84%) White individuals. There was a moderate correlation between the UPSIT and NASAL-7 scores and NASAL-3 scores (NASAL-7: ρ = 0.484; NASAL-3: ρ = 0.404). Both NASAL-7 and NASAL-3 had moderate accuracy in identifying participants with anosmia as defined by UPSIT (NASAL-7 area under the receiver operating curve [AUC], 0.706; 95% CI, 0.551-0.862; NASAL-3 AUC, 0.658; 95% CI, 0.503-0.814). Scoring 7 or less on the NASAL-7 had 70% (95% CI, 48%-86%) sensitivity and 53% (95% CI, 43%-63%) specificity in discriminating participants with anosmia from participants without. Scoring 2 or less on the NASAL-3 had 57% (95% CI, 36%-76%) sensitivity and 78% (95% CI, 69%-85%) specificity in discriminating participants with anosmia from participants without. There was moderate agreement between UPSIT-defined OD categories and those defined by NASAL-7 (weighted κ = 0.496; 95% CI, 0.343-0.649) and those defined by NASAL-3 (weighted κ = 0.365; 95% CI, 0.187-0.543). The agreement with self-reported severity of olfactory dysfunction as measured by CGI-S and the NASAL-7 and NASAL-3 was moderate, with a weighted κ of 0.590 (95% CI, 0.474-0.707) for the NASAL-7 and 0.597 (95% CI, 0.481-0.712) for the NASAL-3. CONCLUSION AND RELEVANCE: The findings of this diagnostic study suggest that NASAL-7 and NASAL-3, inexpensive and brief patient-reported assessments, can be used to identify individuals with OD. As the burden of COVID-19-associated OD increases, these assessments may prove beneficial as screening and diagnostic tools. Future work will explore whether the NASAL assessments are sensitive to change and how much of a change is clinically important.

Guideline-Recommended Lung Cancer Screening Adherence Is Superior With a Centralized Approach.

BACKGROUND: To recognize fully the benefit of lung cancer screening (LCS), annual adherence must approach the high levels seen in the National Lung Screening Trial. Emerging data suggest that annual adherence is poor and that a centralized approach to screening improves adherence. RESEARCH QUESTIONS: Do differences in adherence exist between a centralized and decentralized approach to LCS within a hybrid program and what are predictors of adherence? STUDY DESIGN AND METHODS: A retrospective evaluation of a single-center hybrid LCS program was conducted to compare outcomes including patient eligibility and adherence between the centralized and decentralized approaches. Patient demographics and outcomes were compared between those screened with a centralized and decentralized approach and between adherent and nonadherent patients using two-sample t tests, χ 2 tests, or analyses of variance, as appropriate. Annual adherence analysis was conducted using data from patients who remained eligible for screening with a baseline Lung CT Screening Reporting and Data System (Lung-RADS) score of 1 or 2. Logistic regression was used to estimate the association between adherence and the primary exposure, adjusting for potential confounders. RESULTS: A cohort of 1,117 patients underwent baseline low-dose CT imaging. Two hundred eleven patients (19%) were ineligible by United States Preventative Services Task Force criteria and most (90%) were screened with the decentralized approach. After exclusions, 765 patients with Lung-RADS score of 1 or 2 remained eligible for annual screening. Overall adherence was 56%; however, adherence in the centralized program was 70%, compared with 41% with the decentralized approach (P < .001). Individuals screened in a decentralized approach were 73% less likely to be adherent (OR, 0.27; 95% CI, 0.19-0.37). A greater proportion of patients with three or more comorbidities were screened outside the centralized program. INTERPRETATION: Those screened using a centralized approach were more likely to meet eligibility criteria for LCS and more likely to return for annual screening than those screened using a decentralized approach.

Decision Making for Active Surveillance in Vestibular Schwannoma.

Objective: To describe the experiences of patients who elected for the active surveillance treatment option for their vestibular schwannoma (VS). Study Design: Twenty-two patients participated in semistructured patient interviews. Setting: Interviews were conducted between March and April 2021 via telephone with audio recordings and notes taken during each interview. Patients: Adults diagnosed with a VS and at any point after their diagnosis underwent a period of active surveillance were recruited based on the diagnosis made by MRI. Patients were excluded if they chose to undergo treatment immediately, had a diagnosis of neurofibromatosis type 2, or if they had a confirmed alternative diagnosis. Intervention: This intervention was a qualitative interview to assess patient experiences with their VS treatment decision. Main Outcome Measures: Identifying abstract categories that represent many of the stories told by the participants that produces a theory grounded in the data with explanatory power. Results: Factors that influenced patients' treatment decisions were perceived physician bias, selfeducation, and personal accounts of VS patients through support groups, and side effects/complications of the various treatment options. Conclusion: Patients who opted for active surveillance as a treatment option reported high satisfaction with their decision and greater confidence in future treatments that would be necessary based on tumor growth. Future work should be done to increase shared decision making between the physician and patient to arrive at a treatment plan that aligns with their goals of care as well as potentially reducing overtreatment of VS.

Clinical Staging to Estimate the Probability of Severe Postoperative Complications in Patients With Vestibular Schwannoma.

Importance: Vestibular schwannomas have long been treated as a homogeneous entity. Clinical symptoms at presentation may help elucidate the underlaying pathophysiologic characteristics of tumor subtypes. Describing the heterogeneity of these benign tumors may assist in predicting clinical outcomes associated with their treatment. Objective: To create a tumor staging system that incorporates symptoms at presentation and tumor size to predict severe surgical complications. Design, Setting, and Participants: A retrospective cohort of patients at a single-center tertiary referral center from January 1, 1998, to October 13, 2020, was studied. Patients diagnosed with sporadic vestibular schwannoma surgically treated at Washington University in St Louis, Missouri, were included. Main Outcomes and Measures: Severe surgical complications within 30 days of surgery as determined by the Clavien-Dindo classification system. Patients experiencing a complication of grade 3 or above were determined to have a severe complication. Results: Of 185 patients evaluated, 40 (22%) had severe postoperative complications. Twenty of the 40 patients (50%) were women; mean (SD) age was 46 (13) years. Patients with severe complications were more likely to have large tumors (>2.5 cm in largest diameter), vestibular symptoms, and recent hearing loss at presentation. Using conjunctive consolidation, a 4-stage clinical severity staging system that incorporates clinical symptoms and tumor size at presentation was created to predict severe complications. The clinical severity staging system demonstrated an improvement in the ability to discriminate severe complications (C index, 0.754; 95% CI, 0.67-0.84) from a model of tumor size alone (C index, 0.706; 95% CI 0.62-0.79). Conclusions and Relevance: This cohort study found that, among patients with vestibular schwannoma, symptoms present at initial evaluation, in addition to tumor size, served as predictors of severe postoperative complications. A new clinical severity staging system incorporating symptoms at presentation can be helpful for clinicians to identify patients at high risk for severe postoperative complications.

Spine surgery complexity score predicts outcomes in 671 consecutive spine surgery patients.

BACKGROUND: The spine surgery complexity score (SSCS), previously reported by us, is a simple grading system to predict postoperative complications and hospital length of stay (LOS). This scale is based on the technical difficulty of the spinal procedures being performed. METHODS: We performed a retrospective chart review to validate SSCS in 671 consecutive patients undergoing spine procedures at a quaternary academic hospital. RESULTS: The SSCS was predictive of the hospital LOS and postoperative complications (defined by the ClavienDindo score), based on linear regression analysis (P < 0.001 for both). CONCLUSION: Categorizing procedures according to the SSCS may enable neurosurgeons to assess surgical risk and predict longer LOS courses after spine surgery. Thus, it may prove useful in preoperative patient evaluation/ education and determining a prognosis based on surgical complexity.