Citations

Study Design Retrospective Cohort Study. Objectives To determine if 3D printed porous titanium (Ti) cages compared to non-porous polyetheretherketone (PEEK) cages predicted improved fusion rate or clinical outcomes after transforaminal lumbar interbody fusion (TLIF). Methods All adult patients who underwent one- and two-level TLIF for degenerative conditions by a single surgeon at an academic center between 2017-2021 were retrospectively identified. Patients were dichotomized into porous Ti and non-porous PEEK interbody cage groups. Fusion status was assessed by at 6-months and 1-year postoperatively by CT Bridwell scale and flexion/extension X-Rays. Postoperative complications (CT-based subsidence, adjacent segment disease, reoperation rates) and interval changes in lumbar radiographic alignment at short- and long-term follow-up were determined. Univariate and multivariate analysis compared patient and surgical factors, fusion rates, alignment, and complications across interbody groups. Results A total of 136 patients with 169 unique fusion levels (125 Ti cages, 44 PEEK cages) met the inclusion/exclusion criteria. Ti relative to PEEK interbodies had significantly decreased surface area and increased height and lordosis. Ti cage use was associated with greater subsidence ( P < 0.001) but did not independently predict maximum subsidence on regression ( P = 0.109). In the overall cohort, there were no significant differences in fusion rates or lumbopelvic alignment between interbody groups. Reoperation (Ti: 10.9% vs PEEK: 28.6%, P = 0.026) and reoperation for pseudoarthrosis (Ti: 2.0% vs PEEK: 11.4%, P = 0.038) was significantly more likely in the PEEK relative to the Ti group. Conclusions Use of 3D printed porous Ti cages relative to non-porous PEEK cages may mitigate pseudoarthrosis related reoperation after TLIF.

Objective Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts. Methods All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non‐RP symptom. Results In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 (31.1%) of 938 patients had a non‐RP initial symptom, most commonly puffy fingers/hands. Black patients had a non‐RP symptom before RP more commonly than patients in other race and ethnicity categories. Non‐RP first patients were more likely than RP first patients to have diffuse cutaneous involvement and joint contractures at enrollment and had a higher prevalence of RNA polymerase III antibody positivity. Conclusion In two large US cohorts, >30% of patients began to manifest SSc with puffy fingers/hands or other symptoms, without the “warning sign” of RP as their initial symptom. These patients presented with more severe skin and musculoskeletal disease on average, highlighting the importance of early recognition. The most common autoantibody associated with this presentation was RNA polymerase III. These results should be considered in efforts to recognize SSc in its earliest stages. Puffy fingers/hands, even in the absence of RP, should prompt consideration of early SSc and testing for ANA and SSc‐associated autoantibodies, including RNA polymerase III.

ABSTRACT Orbitrap (OT) -based mass spectrometer platforms are a gold standard in high-resolution mass spectrometry, where their primary disadvantage is slower-scanning speed in comparison to time-of-flight or linear ion trap mass analyzers. In this study, we utilize long OT transients to extend the precursor dynamic range by modifying the selected ion monitoring method to multiplex several precursor m/z ranges from 400 to 1000 m/z into a single scan called “ M ultiple A ccumulation P recursor M ass S pectrometry” (MAP-MS). Our approach requires no software or hardware modifications and hides the additional ion accumulation steps during the time it takes to make other Orbitrap measurements, producing precursor spectra with nearly 2× dynamic range and essentially no consequences. We collected data using both data-dependent acquisition (DDA) and data-independent acquisition (DIA) methods to evaluate a range of approaches. With DDA, MAP-MS precursor quantification improves with higher quality measurements. At the same time, DIA detection is enhanced by up to 11% when combining precursor and tandem mass spectra for peptide detection.

Abstract Background Robotic Whipple holds the promise to overcome safety concerns associated with laparoscopy, paving the way for widespread implementation of minimal-invasive surgery in this complex procedure. However, randomized data comparing robot vs. open Whipple demonstrate more pancreas-specific complications and R1-resections in the robotic arm. Recent international consensus identified establishing benchmarks as critical to ensure safe adoption of the robot. Benchmarking is a validated quality improvement tool, enabling comparison of surgical performance. Aims The aim was to define benchmarks for outcome parameters in robotic Whipple. Methods We analyzed consecutive patients undergoing robotic Whipple from January 2020 until December 2023 in 11 centers across 4 continents, with a minimum one-year follow-up. Centers had to perform ≥15 cases/year and have mounted their learning curve. Benchmark criteria included benign or resectable malignant disease without neoadjuvant therapy, arterial resection, major co-morbidities, or significant previous abdominal surgery. Medians across centers represented benchmark cutoffs. Results Eleven centers performed 1’037 Whipple procedures, of which 603 (58%) were benchmark cases. One third (n=192) were pancreatic ductal adenocarcinoma (PDAC) patients. Key benchmarks at 6 months included ≤1.2% mortality, ≤24.2% major complications, and ≤ 8.7 points Comprehensive Complication Index®. Pancreas-specific cutoffs included ≤13.0% postoperative pancreatic fistula (POPF) B/C and ≤3.4% post-pancreatectomy hemorrhage B/C, with 100% R0-resection and ≥19 harvested lymph nodes in PDAC patients. One-year actuarial overall and recurrence-free survival was 87% and 77%. In the entire cohort POPF B/C occurred in 16% (n=195). Independent POPF predictors included duct diameter ≤4mm (OR 1.79 95%CI [1.27-2.55]), anticoagulation (OR 3.68 95%CI [2.14-6.24]), and indication other than PDAC (OR 3.17, 95%CI [2.13-4.85]). Conclusion This study establishes benchmarks for key outcomes in robotic Whipple, demonstrating oncologic adequacy and morbidity comparable to open surgery. Risk factors for POPF in open surgery also hold true in the robotic approach.

Fusobacterium nucleatum and Prevotella loescheii are anaerobic gram-negative rods that exist in the oral cavity. To our knowledge, pediatric central nervous system complications with these pathogens have not been well described. An 11-year-old previously healthy vaccinated female child presented for 2 weeks of sinusitis that progressed to left arm and leg hemiplegia. Initial neuroimaging demonstrated a superior sagittal sinus thrombosis and a right hemispheric subdural empyema with midline shift, necessitating surgical evacuation. Culture of the subdural accumulation demonstrated coinfection of Fusobacterium nucleatum and Prevotella loescheii . Within 24 hours of evacuation, the patient progressed to have right hemispheric electrographic status epilepticus, with neuroimaging demonstrating reaccumulation of the empyema and a moderate right middle cerebral artery vasospasm. Transcranial doppler ultrasonography of the right middle cerebral artery territory demonstrated mean flow velocities up to 148 cm/s with a Lindengaard ratio of 3.44. The patient underwent repeat subdural evacuation and was managed with intravenous fluids, permissive hypertension, oral nimodipine, and intravenous milrinone. Electrographic status epilepticus was treated with intravenous lacosamide and levetiracetam. Repeat neuroimaging demonstrated improvement in subdural collection size and resolution of vasospasms. She was discharged after 16 days with continued lacosamide and levetiracetam for seizures, and enoxaparin (Lovenox) for the superior sagittal sinus thrombosis. We present a novel pediatric case of Fusobacterium nucleatum and Prevotella loescheii manifesting with rapid subdural empyema reaccumulation after surgical evacuation, status epilepticus, cerebrovascular vasospasms, and cerebral sinus venous thrombosis. Further work is needed to understand the potential neurologic complications of this condition.

ABSTRACT Objective There is limited consensus on endoscopic skull base surgery (ESBS) reconstruction principles. This study aims to generate comprehensive themes regarding ESBS reconstruction by pooling the experiences of ESBS experts, with comparison to a literature review of current published evidence. Methods Structured qualitative interviews of ESBS experts regarding postoperative management and reconstruction of various defect locations were conducted. Results A total of 68 experts comprising 40 academic teams across 13 countries with an average of 18 years of ESBS experience were included. We propose 10 stepwise algorithms for common skull base reconstruction scenarios based on these expert interviews. When available, the nasoseptal flap is used for all high_flow cerebrospinal leak defects. Multilayered reconstruction is favored at all anatomical subsites with increasing number of layers for increasing defect size and complexity. Heterogeneity exists in terms of inlay technique and materials, free grafting versus various pedicled flap options for low‐flow defects or in the absence of a nasal septum, nasal packing, tissue sealant, lumbar drain use, and postoperative management. Commonalities and discrepancies between experts were summarized. Conclusion Skull base reconstruction and post‐ESBS management is highly complex with a wide variety of practice patterns and expert strategies. Further research of higher quality evidence is warranted to identify optimal management patterns, though the current work aims to inform surgeons on these controversial areas by drawing from numerous experiences.

ImportanceVestibular migraine has no established treatments.ObjectiveTo test the efficacy of rizatriptan for treating vestibular migraine attacks.Design, Setting, and ParticipantsThis double-blind, randomized clinical trial of rizatriptan vs placebo was conducted from December 2014 through July 2020 (data analyses in 2021 and sensitivity analyses in 2022 and 2024) at 2 tertiary neurotologic centers. Adults with vestibular migraine were included.InterventionAll participants underwent prospective observation to confirm diagnosis and illness activity and were then randomized in a 2:1 ratio to receive rizatriptan 10 mg or placebo to treat up to 3 vestibular migraine attacks per participant.Main Outcomes and MeasuresParticipants rated symptoms as absent, mild, moderate, or severe at scheduled intervals. Primary outcomes were the percentage of attacks with reductions in vertigo and unsteadiness/dizziness from moderate or severe to absent or mild at 1 hour. Secondary outcomes were the percentage of attacks with complete resolution of vestibular symptoms at 1 hour; reductions in headache and associated symptoms at 1 hour; use of rescue medications after 1 hour; reductions in vestibular, headache, and associated symptoms at 24 hours without rescue medications; treatment satisfaction and quality of life at 48 hours; and rates of serious adverse effects and discontinuation due to adverse effects.ResultsOf 222 total participants (mean [SD] age, 42.3 [11.7] years; 70.7% were women), 134 (60.4%) with active illness treated 307 attacks. Efficacy was tested using 240 attacks with vestibular symptoms rated as moderate or severe when participants took study drug. At 1 hour, rizatriptan did not differ from placebo for reducing vertigo (73/151 [48.3%] vs 50/88 [56.8%] attacks; odds ratio [OR], 0.71 [95% CI, 0.42-1.21]), unsteadiness/dizziness (29/151 [19.2%] vs 11/89 [12.4%] attacks; OR, 1.69 [95% CI, 0.80-3.57]), or any secondary outcomes. Similar percentages of participants in rizatriptan and placebo groups (26.4% for both groups) added rescue remedies after 1 hour. At 24 hours, rizatriptan had medium effects over placebo for unsteadiness/dizziness (OR, 2.65) and motion sensitivity (OR, 3.58). Post hoc analyses of all treated attacks found a medium effect favoring rizatriptan for headache and photophobia or phonophobia at 24 hours. Treatment satisfaction was equivocal. Quality of life was mixed. No participants experienced serious adverse effects or discontinued treatment for adverse effects.Conclusions and RelevanceIn this study, rizatriptan was ineffective at 1 hour for treating vestibular migraine attacks and had limited benefit on symptoms at 24 hours. Findings do not support using rizatriptan for vestibular migraine attacks.Trial RegistrationClinicalTrials.gov Identifier: NCT02447991

ABSTRACT Aims To discuss the use of urodynamic testing for female stress urinary incontinence and provide a narrative review of the current evidence regarding the utility of urodynamics across the spectrum of clinical presentations. Methods A nonsystemic, extensive literature review via PubMed was performed on the use of urodynamics for female stress urinary incontinence. Results Findings from several large multicenter trials and subsequent secondary analyses have significantly influenced treatment patterns away from the routine use of urodynamics in female patients with uncomplicated stress urinary incontinence. Much of the current literature focuses on selected patients with uncomplicated stress urinary incontinence that are subsequently treated with midurethral sling placement. These studies comprise the foundational evidence supporting multiple national and international guidelines on the topic. In uncomplicated patients, these guidelines do not support the routine use of urodynamics. However, in more complicated presentations, urodynamic studies are more often valuable for diagnosis and management. Conclusions Routine use of urodynamic testing is not currently recommended in guidelines for evaluating uncomplicated female stress urinary incontinence. It is important to recognize that much of the evidence supporting these recommendations is derived from a select population of uncomplicated patients, which may limit generalizability to more complex cases. In such cases, urodynamic testing may be more useful to guide diagnosis and management, though further research is needed to identify which findings have the greatest impact on clinical outcomes.

Abstract Rationale: Ongoing healthcare staffing shortages have prompted new care paradigms that incorporate remote care delivery to support timely detection of patient physiological deterioration through mechanisms other than clinician bedside evaluations. In partnership with institutional Information Technology, our team has developed a unique clinical informatics environment, known as the Advanced Medical Practice (AMP) platform, that incorporates data from multiple sources and platforms and supports remote observation of patients from the electronic intensive care unit(eICU). AMP takes advantage of technologies outside of vendor-supported EHRs, and its advanced user-interface design reduces information overload while incorporating real-time data from novel devices and sensors. We partnered with the hospital practice to co-develop a score within the AMP platform(Clinical Events Detection and Response[CEDAR]) that incorporates heart rate, blood pressure, respiratory rate, and SpO2 to stratify patient risk and generate deterioration alerts for the electronic ICU(eICU) team. This formative evaluation employed an implementation science approach to refine CEDAR and ensure it is acceptable to users and can be feasibly implemented in practice. Methods: The study team conducted this pilot work in the eICU at Mayo Clinic (Rochester, MN). We observed the eICU workflow and documented feedback from eICU staff in fieldnotes. eICU staff were asked to log issues in a tracking file during shifts. Issues were reviewed daily and discussed at multidisciplinary team meetings weekly. Observation and tracking data were coded to constructs in the Consolidated Framework for Implementation Research(CFIR 2.0) framework and mapped to Expert Recommendations for Implementation Change(ERIC) strategies that targeted key determinants. Results: Between 9/23/24 and 10/25/24 we completed 25 days of observations. Most identified issues related to technical/design issues like unclear vital trigger alerts (CFIR: Innovation trialability and design); staff knowledge of CEDAR functionality and attitudes about functionality, complexity, or relative advantage compared to current systems (CFIR: Inner setting access to knowledge and information and relative advantage); and difficulties incorporating CEDAR into workflow(CFIR: Inner setting/compatibility). Implementation strategies mapped to CFIR determinants included promoting adaptability of customized interface features; staging implementation scale-up with iterative improvements; providing local technical assistance; assessing for readiness and identifying facilitators and barriers; and conducting educational outreach visits. Conclusions: Formative evaluation during pilot studies are a critical step in the process of intervention development and testing. User engagement and frameworks from implementation science can identify issues of feasibility and inform strategies to ensure acceptability prior to intervention scale-up in clinical practice and readiness for conducting larger implementation studies.

Abstract Rationale Immune checkpoint inhibitors (ICI) have become standard care for many cancers. Their mechanism of action mediates immune related adverse events including ICI pneumonitis. Diagnosis of this is difficult to differentiate from infectious and radiation pneumonitis as it is a diagnosis of exclusion often requiring bronchoscopy and imaging interpreted by expert radiologists. This study investigates the use of CALIPER, a computer-aided lung informatics program, in identifying differences between Computed Tomography (CT) patterns in ICI, radiation, and infectious pneumonitis that may aid in diagnosis noninvasively. Methods CT images of ten patients with ICI pneumonitis, ten patients with infectious pneumonitis, and nine patients with radiation pneumonitis, all diagnosed by clinical expertise and evaluation with bronchoalveolar lavage, were analyzed with CALIPER. CALIPER classified each CT voxel into either vessel-related structures (VRS), normal, mild low-attenuation area (LAA), moderate LAA, severe LAA, reticular (R), honeycomb (HC) or ground-glass (GG) features. Each lung was divided into upper, middle, and lower lobes. Exploratory analyses explored the relationship between CALIPER components and diagnosis, comparing ICI and radiation pneumonitis with infectious pneumonitis. Diagnosis was analyzed using multinomial logistic regression adjusted for presence of pleural effusion. Additionally, diagnosis was assessed as infectious versus a pooled group of radiation and ICI pneumonitis and analyzed using logistic regression adjusted for pleural effusion. Due to the exploratory nature of analysis, no correction was applied for multiplicity of testing. Results Twenty-nine patients were analyzed. ICI pneumonitis patients had less moderate low attenuation in the left upper (p = 0.016) and middle peripheral lung (p = 0.038), and radiation pneumonitis patients had less moderate low attenuation in the left upper peripheral lung (p = 0.031). When comparing the pooled group of ICI and radiation pneumonitis images with infectious pneumonitis, there was more moderate LAA in left upper (0.012) and middle (0.034) peripheral lung in the pooled group compared to infectious pneumonitis. There was no association with VRS, GG, HC, R, mild, or severe LAA patterns. Conclusions Although areas of moderate low attenuation were more prevalent for infectious pneumonitis, these results taken in the context of low sample size, exploratory analysis, and lack of clinical reasoning to support these findings make them likely insignificant. Based on this limited exploratory analysis, it is unlikely that we can solely use CALIPER as noninvasive evaluation to differentiate radiation and ICI pneumonitis from infectious pneumonitis. This highlights the need for a more robust program to aid in noninvasive diagnosis.