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According to the FAO/WHO guidelines, selection of probiotics requires the assessment of survival under gastrointestinal stress and adhesion to human epithelial cells. These attributes were evaluated on Akkermansia muciniphila ATCC BAA-835 simulating the gastrointestinal transit (GIT) immediately followed by adhesion to human intestinal cell lines (CaCo2, HT-29, and HT-29-MTX) as an alternative approach to in vitro methods performed with fresh cells in each trial. The survival rate after GIT, as determined by plate counts and fluorescent probes, was significantly higher for A. muciniphila (about 8 Log CFU/mL) than for the probiotic Lacticaseibacillus rhamnosus GG ATCC 53103 (about 3 Log CFU/mL). The use of Live/Dead assay highlighted that A. muciniphila forms cell aggregates in the gastric phase as protective mechanism, explaining its high viability in the intestine. The rate of adhesion to human cell lines was always lower for strains tested after simulated GIT than for strains that did not undergo simulated GIT. Akkermansia muciniphila exhibited significantly higher adhesion than Lbs. rhamnosus GG, particularly to the mucus-secreting HT-29-MTX cells across a range of concentrations (2–8 Log CFU/mL). Finally, the bioinformatic analysis of A. muciniphila proteome confirmed the Amuc_1434 as a potential factor in binding to the human MUC2 protein.

BACKGROUND Preterm birth (PTB) is hypothesized to be an inflammatory response disease. However, no single factor alone is likely to explain PTB risk. It is more probable that coordinated networks of cytokines affect risk. METHODS Therefore, we examined the relationships between amniotic fluid (AF) cytokines/chemokines and related biomarkers in PTB and normal term deliveries in African Americans and Caucasians. Data were obtained from African American (41 preterm labor and 91 term labor) and Caucasian (105 preterm labor and 100 term labor) pregnant mothers. Pro-inflammatory cytokines and related molecules interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor- (TNF)-α, TNF soluble receptors (sTNFR1 and sTNFR2), and anti-inflammatory cytokine IL-10 that were all previously associated with PTB were studied. Correlations between biomarkers were calculated; differences of correlation coefficients between AF from African American and Caucasian samples in preterm labor and term labor were measured. RESULTS Multiple differences were observed between African American and Caucasian preterm and term birth groups. In term birth the strongest differences were between pro- and anti-inflammatory correlations, whereas in PTB differences were equally distributed between pro-inflammatory/anti-inflammatory and pro-inflammatory/pro-inflammatory correlations. Three correlation patterns differed significantly between AF from PTB African Americans with and without microbial invasion of the intra-amniotic cavity (MIAC); no differences were observed in Caucasians with MIAC. CONCLUSION Correlation analyses of cytokine measurements suggest coordinated interplay during pregnancy; significant differences exist between African Americans and Caucasians. Such analyses can serve as a means of understanding risk factors in these populations. [ABSTRACT FROM AUTHOR]

Importance: The incidence of potentially inappropriate medication (PIM) prescribing among older adults is not as well studied as its prevalence. Estimates of factors associated with PIM incidence, such as patient age, sex, race-ethnicity, medication subsidy support, and comorbidity, are also limited., Objective: To estimate the incidence of PIM prescribing in older adult outpatients, as well as the incidence and predictors for each PIM class, in a large outpatient electronic health records (EHR) cohort., Design: Retrospective study of PIM prescribing among outpatients with encounters leading to prescription orders, 2015-2018, excluding prevalent cases., Setting: Outpatients receiving care from a multi-site health system in western Pennsylvania., Participants: 342,405 patients, contributing 893,754 person-years of follow-up., Main Outcomes and Measures: The incidence of PIM prescribing based on automated coding of 2019 Beers criteria. A multivariable Poisson regression model was estimated to assess the impact of age, sex, race-ethnicity, comorbidity, and medication subsidy (PACE/PACENET) on PIM risk. For each PIM class, the association between predictors and time to PIM prescribing was evaluated using proportional hazard models., Results: The incidence rate (IR) for 1 or more PIM was 193.5 per 1000 person-years, led by short- and intermediate-acting benzodiazepines (37.6), first-generation antihistamines (32.8), and skeletal muscle relaxants (22.0). The incidence of PIM prescribing was 15% higher among white patients and 35% lower among males. High comorbidity (Charlson score ≥ 3) was associated with a 59% higher risk. Participation in the PACE/PACENET program, a medication subsidy program, was associated with an 83% increase in incidence. Each additional year of age was associated with a 1.2% reduction in incidence., Conclusions and Relevance: This study establishes benchmarks for the incidence of PIM prescribing in outpatients and identifies important disparities in PIM risk, which vary by PIM class., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Building on the evidence from the first paper in this Series highlighting the fundamental importance of healthy and nurturing environments for children's growth and development in the next 1000 days (ages 2-5 years), this paper summarises the benefits and costs of key strategies to support children's development in this age range. The next 1000 days build on the family-based and health-sector based interventions provided in the first 1000 days and require broader multisectoral programming. Interventions that have been shown to be particularly effective in this age range are the provision of early childhood care and education (ECCE), parenting interventions, and cash transfers. We show that a minimum package of 1 year of ECCE for all children would cost on average less than 0·15% of low-income and middle-income countries' current gross domestic product. The societal cost of not implementing this package at a national and global level (ie, the cost of inaction) is large, with an estimated forgone benefit of 8-19 times the cost of investing in ECCE. We discuss implications of the overall evidence presented in this Series for policy and practice, highlighting the potential of ECCE programming in the next 1000 days as an intervention itself, as well as a platform to deliver developmental screening, growth monitoring, and additional locally required interventions. Providing nurturing care during this period is crucial for maintaining and further boosting children's progress in the first 1000 days, and to allow children to reach optimal developmental trajectories from a socioecological life-course perspective., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Four human acellular dermal matrices (hADMs) were characterized in a nonhuman primate abdominal wall repair model by evaluating host immune response, vascularization, and incorporation into host tissues. AlloDerm™ (electron beam-sterilized hADM [e-hADM]), AlloMax™ (gamma beam-sterilized hADM, freeze-dried [g-hADM-FD]), DermaMatrix™ (hADM, freeze-dried [hADM-FD]), and FlexHD™ (ethanol-treated hADM [EtOH-hADM]) were each implanted in an abdominal wall-bridging defect in nonhuman primates ( n = 3 animals/time point, n = 36 animals). Immunohistochemical and histological assessments were conducted on biopsies from each hADM at 1-, 3-, and 6-months postimplantation to assess vascularization (hematoxylin and eosin [H&E], CD31, alpha smooth muscle actin [αSMA], collagen IV), inflammatory/immune response (H&E, CD3, CD20, CD68), and collagen turnover (H&E, matrix metalloproteinase-9 [MMP-9]). MMP-9 immunolabeling was similar among different hADMs at 1 month; however, hADM-FD and EtOH-hADM showed higher total mean MMP-9-immunopositive areas at approximately 16% compared with <1% for e-hADM and g-hADM at 6 months postimplantation. Cells that stained positively for CD68, CD3, and CD20 were generally higher for hADM-FD and EtOH-hADM compared with other hADMs. The mean CD31-immunopositive area, CD31 vessel density, CD31 vessel diameter, and collagen IV-immunopositive area increased over time. Among all the hADM types, e-hADM had the highest mean (±standard deviation [SD]) CD31-immunopositive area at 1.54% ± 1.01%, vessel density at 7.86 × 10 -5 ± 3.96 × 10 -5 vessels/µm 2 , and collagen IV-immunopositive area at 2.55% ± 0.73% 1-month postimplantation. The pattern of αSMA immunolabeling varied among the hADMs. Histology showed that overall inflammation was mild at 1 month. Overall fibroblast repopulation and collagen remodeling increased over time from 1 to 6 months postimplantation. Fibroblast infiltration was minimal to mild at 1 month, with e-hADM showing the highest mean (±SD) score at 2.00 ± 0.00 compared with other hADMs. Only hADM-FD was not completely replaced by neotissue formation at 6 months postimplantation. All hADMs promoted vascularization, cell infiltration, and incorporation into host tissue, which were associated with acute inflammation and immune responses, within a 6-month period. A trend toward relatively enhanced early vascularization in e-hADM compared with other hADMs was observed. Immunogenic responses among the hADMs in the present study showed a slight distinction toward more quiescent terminally sterilized hADMs (e-hADM, g-hADM-FD) versus aseptically processed hADMs (EtOH-hADM, hADM-FD).

Background: Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be attributed to the use or combination of different therapeutic approaches. Several molecules have been screened as potential treatments in combination with surgical reimplantation of the avulsed roots, the gold standard approach for such injuries. Among the studied molecules, human natural killer-1 (HNK-1) stands out as it is related to the stimulation of motor axon outgrowth. Therefore, we aimed to comparatively investigate the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA), another HNK-1 mimetic, after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB)., Methods: Female mice of the isogenic strain C57BL/6JUnib were divided into five experimental groups: Avulsion, Reimplantation, mp-HNK-1 (in situ), and UA (systemic treatment). Mice were evaluated 2 and 12 weeks after surgery. Functional assessment was performed every four days using the Catwalk platform. Neuronal survival was analyzed by cytochemistry, and glial reactions and synaptic coverage were evaluated by immunofluorescence., Results: Treatment with UA elicited long-term neuroprotection, accompanied by a decrease in microglial reactions, and reactive astrogliosis. The neuroprotective effects of UA were preceded by increased glutamatergic and GABAergic inputs in the ventral spinal cord two weeks after injury. However, a single application of mp-HNK-1 had no significant effects. Functional analysis showed that UA treatment led to an improvement in motor and sensory recovery., Conclusion: Overall, the results indicate that UA is neuroprotective, acting on glial cells and synaptic maintenance, and the combination of these findings led to a better functional recovery., Competing Interests: Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Myeloproliferative neoplasms (MPNs) are associated with immune dysregulation and increased susceptibility to infection, emphasizing the importance of vaccination for patients. This pilot study evaluated immune responses to influenza vaccination in MPN patients compared with healthy donors using mass cytometry and serology. We observed diminished CXCR5+ B-cell, CXCR3+ T-cell, activated CD127+ memory T-cell subsets, and a trend toward lower hemagglutinin inhibition titer in MPN patients. These results indicate that patients with MPN exhibit distinct responses to influenza vaccination suggestive of impaired migration to lymphoid organs and T-cell maturation which may impact the development of protective immunity., Competing Interests: G.H.: Consulting fees from Abbvie, BMS, Moprhosys, CTI, Cogent, Protagonist, Pfizer, Novartis; research support from Incyte; Stock ownership, Regeneron. P.R.: Consulting fees from Merck and PDTx, speaking honoraria from Standard Biotools, member of ImmunoScape scientific advisory board., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

The prospect of creating ferroelectric or high permittivity nanomaterials provides motivation for investigating complex transition metal oxides of the form Ba(Ti, MV)O3, where M = Nb or Ta. Solid state processing typically produces mixtures of crystalline phases, rarely beyond minimally doped Nb/Ta. Using a modified sol-gel method, we prepared single phase nanocrystals of Ba(Ti, M)O3. Compositional and elemental analysis puts the empirical formulas close to BaTi0.5Nb0.5O3-δ and BaTi0.5Ta0.5O3-δ. For both materials, a reversible temperature dependent phase transition (non-centrosymmetric to symmetric) is observed in the Raman spectrum in the region 533-583 K (260-310 °C); for Ba(Ti, Nb)O3, the onset is at 543 K (270 °C); and for Ba(Ti, Ta)O3, the onset is at 533 K (260 °C), which are comparable with 390-393 K (117-120 °C) for bulk BaTiO3. The crystal structure was resolved by examination of the powder x-ray diffraction and atomic pair distribution function (PDF) analysis of synchrotron total scattering data. It was postulated whether the structure adopted at the nanoscale was single or double perovskite. Double perovskites (A2B'B″O6) are characterized by the type and extent of cation ordering, which gives rise to higher symmetry crystal structures. PDF analysis was used to examine all likely candidate structures and to look for evidence of higher symmetry. The feasible phase space that evolves includes the ordered double perovskite structure Ba2(Ti, MV)O6 (M = Nb, Ta) Fm-3m, a disordered cubic structure, as a suitable high temperature analog, Ba(Ti, MV)O3Pm-3m, and an orthorhombic Ba(Ti, MV)O3Amm2, a room temperature structure that presents an unusually high level of lattice displacement, possibly due to octahedral tilting, and indication of a highly polarized crystal., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Study Design: Systematic review., Objective: The purpose of this review is to identify modifiable risk factors in patients undergoing adult spinal deformity surgery and compile literature recommendations for the preoperative optimization of these risk factors., Summary of Background Data: Optimization of modifiable risk factors not only benefits the patient but also lessens resource and cost burdens on the health care system, allowing for better quality and value-based care. There is limited but applicable literature discussing preoperative optimization in adult spinal deformity surgery patients specifically., Methods: We searched PubMed for studies that looked at one of the variables of interest (eg, osteoporosis, prehabilitation and functional status, multidisciplinary preoperative screening, infection, obesity, nutrition, smoking, diabetes, blood loss, chronic opioid use, and psychosocial factors) in adult patients with spinal deformity according to Preferred Reporting Items for Systematic Reviews and Meta-Analyse guidelines., Results: Seventy studies were included in the final review and synthesis of information. Guidelines and recommendations from these studies were compared and compiled into evidence-based action items for preoperative optimization of modifiable risk factors before adult spinal deformity surgery., Conclusions: While the approach of preoperative optimization of modifiable risk factors may incur additional planning efforts and patient care time, it has the potential to significantly reduce perioperative complications and reduce morbidity and mortality during surgery, thus allowing for improved outcomes, increased quality of life, and satisfaction from this patient population., Level of Evidence: 3., Competing Interests: Z.S. has received consulting fees from Medtronic. J.L. has received consulting fees from Medtronic. The remaining authors (P.K., J.R., and J.C.) declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Microbial pathogens local to prosthetic breast devices may promote infection, inflammation, and capsular contracture. Although antimicrobial solutions have been used, their effects on human acellular dermal matrix (HADM) incorporation when used with prosthetic devices are unknown. The authors' objective was to histologically assess the effect of 10% povidone iodine (PI)-saturated tissue expander (TE) exposure on HADM biological response in a primate model. They hypothesized that PI exposure would not negatively affect the HADM biological response., Methods: Samples (1.5 × 1.5 cm) from smooth silicone TEs were saturated in saline or PI for 2 minutes and sutured to HADM to create HADM/TE constructs. Primates implanted subcutaneously with saline ( n = 9) and PI-treated HADM/TE ( n = 9) construct pairs were evaluated histologically for biological response after 2 or 4 weeks by means of a host response scoring scale (1 to 9), including recellularization, neovascularization, and inflammation. Inflammatory cells (eosinophils, lymphocytes, neutrophils, histiocytes, foreign-body giant cells) and evidence of HADM remodeling (fibroblasts, vessels) were further evaluated by means of a cell-specific scoring scale (0 to 4) and corroborated by immunostaining (CD3, CD20, CD68, FSP-1, collagen type IV)., Results: Mean histology scores were similar between saline- and PI-exposed HADM at 2 weeks (5.3 ± 0.9 and 5.6 ± 0.5; P = 0.52) and 4 weeks (4.6 ± 1.0 and 4.2 ± 0.9; P = 0.44). There was no difference in inflammatory cell presence at 2 and 4 weeks between groups. Fibroblast infiltration differences were insignificant between groups but exhibited trends toward an increase between time points for saline (1.6 ± 0.7 to 1.8 ± 0.8) and PI (1.3 ± 0.8 to 1.8 ± 1.0) groups, suggesting HADM incorporation over time., Conclusion: Data suggest that HADM exposure to PI-treated TEs does not negatively affect inflammation, vascularization, recellularization, incorporation, or host response to HADM in this model., Clinical Relevance Statement: PI is a surgical pocket irrigant used to address bacterial colonization, but its impact on ADM incorporation is unknown. This study demonstrates similar biologic response to ADMs adjacent to PI- or saline-saturated TEs in a primate model., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Biosensors with high selectivity, high sensitivity, and real-time detection capabilities are of significant interest for diagnostic applications as well as human health and performance monitoring. Graphene field-effect transistor (GFET) based biosensors are suitable for integration into wearable sensor technology and can potentially demonstrate the sensitivity and selectivity necessary for real-time detection and monitoring of biomarkers. Previously reported DC-mode GFET biosensors showed a high sensitivity for sensing biomarkers in solutions with a low salt concentration. However, due to Debye length screening, the sensitivity of the DC-mode GFET biosensors decreases significantly during operation in a physiological fluid such as sweat or interstitial fluid. To overcome the Debye screening length limitation, we report here alternating current (AC) mode heterodyne-based GFET biosensors for sensing neuropeptide-Y (NPY), a key stress biomarker, in artificial sweat at physiologically relevant ionic concentrations. Our AC-mode GFET biosensors show a record ultralow detection limit of 2 × 10 -18 M with an extensive dynamic range of 10 orders of magnitude in sensor response to target NPY concentration. The sensors were characterized for various carrier frequencies (ranging from 30 kHz to 2 MHz) of the applied AC voltages and various salt concentrations (10, 50, and 100 mM). Contrary to DC-mode sensing, the AC-mode sensor response increases with an increase in salt concentration in the electrolyte. The sensor response can be further enhanced by tuning the carrier frequency of the applied AC voltage. The optimum response frequency of our sensor is approximately 400-600 kHz for salt concentrations of 50 and 100 mM, respectively. The salt-concentration- and frequency-dependent sensor response can be explained by an electrolyte-gated capacitance model.

Short-chain fatty acids (SCFAs), the end products of gut microbial fermentation of dietary fibers and non-digestible polysaccharides, act as a link between the microbiome, immune system, and inflammatory processes. The importance of accurately quantifying SCFAs in plasma has recently emerged to understand their biological role. In this work, a sensitive and reproducible LC-MS/MS method is reported for SCFAs quantification in three different matrices such as human, rat and mouse plasma via derivatization, using as derivatizing agent O-benzylhydroxylamine (O-BHA), coupled with liquid-liquid extraction. First, the instrumental parameters of the mass spectrometer and then the chromatographic conditions were optimized using previously SCFAs derivatives synthetized and used as standards. After that, the best conditions for derivatization and extraction from plasma were studied and a series of determinations were performed on human, rat, and mouse plasma aliquots to validate the overall method (derivatization, extraction, and LC-MS/MS determination). The method showed good performance in terms of recovery (> 80%), precision (RSD <14%), accuracy (RE < ± 10%) and sensitivity (LOQ of 0.01 µM for acetic, butyric, propionic and isobutyric acid) in all plasma samples. The method thus developed and validated was applied to the quantification of major SCFAs in adult and aged mice, germ-free mice and in germ-free recipient mice subjected to fecal transplant from adult and aged donors. Results highlighted how plasma concentrations of SCFAs are correlated with age further highlighting the importance of developing a method that is reliable for the quantification of SCFAs to study their biological role., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Study Design: Retrospective Cohort Study., Objectives: Using natural language processing (NLP) in combination with machine learning on standard operative notes may allow for efficient billing, maximization of collections, and minimization of coder error. This study was conducted as a pilot study to determine if a machine learning algorithm can accurately identify billing Current Procedural Terminology (CPT) codes on patient operative notes., Methods: This was a retrospective analysis of operative notes from patients who underwent elective spine surgery by a single senior surgeon from 9/2015 to 1/2020. Algorithm performance was measured by performing receiver operating characteristic (ROC) analysis, calculating the area under the ROC curve (AUC) and the area under the precision-recall curve (AUPRC). A deep learning NLP algorithm and a Random Forest algorithm were both trained and tested on operative notes to predict CPT codes. CPT codes generated by the billing department were compared to those generated by our model., Results: The random forest machine learning model had an AUC of .94 and an AUPRC of .85. The deep learning model had a final AUC of .72 and an AUPRC of .44. The random forest model had a weighted average, class-by-class accuracy of 87%. The LSTM deep learning model had a weighted average, class-by-class accuracy 0f 59%., Conclusions: Combining natural language processing with machine learning is a valid approach for automatic generation of CPT billing codes. The random forest machine learning model outperformed the LSTM deep learning model in this case. These models can be used by orthopedic or neurosurgery departments to allow for efficient billing.

Various tissue origins and manufacturing processes can differentially affect the retention of native properties of acellular dermal matrices (ADMs); however, comparative studies are limited. Head-to-head comparisons between different configurations of porcine-derived Strattice (Allergan Aesthetics, an AbbVie Company, Irvine, CA) and bovine-derived SurgiMend (Integra LifeSciences, Billerica, MA) ADMs were performed to evaluate mechanical integrity and host tissue biologic response. Thermodynamic profile and morphology, which affect retention of mechanical strength, were evaluated through differential scanning calorimetry, scanning electron microscopy, and histology. Mechanical strength was assessed through tensile testing following collagenase exposure in vitro and following subcutaneous implantation in a rodent model. Host biologic response was evaluated through histopathology. Compared with respective native tissues, reductions in onset melting temperature following tissue processing were smaller for Strattice Firm versus SurgiMend 1.0 (Δ0.79°C vs. Δ5.77°C), Strattice Extra Thick versus SurgiMend 3.0 (Δ1.57°C vs. Δ4.79°C), and Strattice Perforated versus SurgiMend Microperforated (Δ1.18°C vs. Δ7.76°C), with similar trends for peak melting temperature. Strattice maintained native dermal architecture versus compacted collagen with process-induced interstices observed for SurgiMend. Strattice Firm, Extra Thick, and Perforated retained 33.44%, 65.65%, and 17.20% of initial strength after 48 h exposure to excess collagenase, while the SurgiMend ADMs were completely digested by 48 h. At 6 weeks postimplantation, both Strattice and SurgiMend showed minimal inflammatory response, but greater fibroblast repopulation was evident for Strattice. Strattice Firm had higher maximum load (145.85 ± 33.05 N/cm vs. 24.29 ± 12.35 N/cm, p  ≤ 0.01), maximum stress (8.20 ± 1.91 MPa vs. 2.24 ± 1.27 Mpa, p  ≤ 0.01), and stiffness (7491.00 ± 1981.32 N/cm vs. 737.56 ± 292.55 N/cm, p  ≤ 0.01) than SurgiMend 1.0. Strattice Extra Thick had lower maximum load (198.54 ± 58.79 N/cm vs. 303.08 ± 76.76 N/cm, p  < 0.05) than SurgiMend 3.0, but similar maximum stress (6.96 ± 1.78 Mpa vs. 8.73 ± 2.15 Mpa) and stiffness (13386.11 ± 3123.28 N/cm vs. 9389.02 ± 4860.67 N/cm). Strattice Perforated had higher maximum load (72.65 ± 41.44 N/cm vs. 10.23 ± 4.67 N/cm, p  < 0.05) and maximum stress (4.08 ± 2.08 Mpa vs. 0.44 ± 0.19 p  < 0.05) than SurgiMend Microperforated. Maximum load retention rates following implantation were higher for Strattice Firm versus SurgiMend 1.0 (37.85% vs. 8.03%), Strattice Extra Thick versus SurgiMend 3.0 (45.03% vs. 37.80%), and Strattice Perforated versus SurgiMend Microperforated (28.04% vs. 6.21%). Similar results were obtained for maximum stress and stiffness. In conclusion, Strattice retained greater mechanical strength in vitro and in vivo , while exhibiting greater fibroblast cell infiltration. Impact statement Acellular dermal matrix (ADM)-derived surgical meshes are used in abdominal wall reconstruction procedures, such as hernia repair. Comparative studies evaluating the mechanical properties of ADMs and how they integrate with host tissue are essential because these properties impact performance in a clinical setting. This study compared the maintenance of mechanical integrity and host tissue biologic response of two commercially available ADMs, Strattice and SurgiMend, using in vitro and in vivo techniques. A better understanding of the properties of ADMs is expected to impact mesh selection and help to minimize the incidence of herniation recurrence and need for revisional surgery.

Objective: Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to address certain shortcomings of traditional, or legacy patient-reported outcome measures (PROMs). Because the use of PROMIS across orthopedic populations continues to increase, the purpose of this study was to provide a comprehensive overview of the use and validation of PROMIS in spine surgery., Methods: PubMed and Google Scholar were searched for relevant articles reporting on the use and validation of PROMIS in spine surgery. The PROMIS formats and individual domains used by investigators were noted. Additionally, psychometric properties reported in validation studies were evaluated., Results: Both individual studies and systematic reviews have demonstrated the convergent validity of PROMIS domains, reporting moderate-to-strong correlations with legacy measures in a variety of spine patient populations. Across spine surgery patient populations, PROMIS instruments are consistently efficient, demonstrating decreased question burden compared with legacy PROMs. PROMIS domains overall exhibit responsiveness comparable with legacy measures, and the normalization of PROMIS scores to a general population allows for broad coverage, resulting in acceptable floor and ceiling effects. Despite the many strengths of PROMIS, there remain some populations where PROMIS is not suited to be used in isolation., Conclusions: PROMIS is widely used as an outcome measure in spine surgery and has been validated in a range of patient populations. Although PROMIS domains cannot fully replace legacy measures in spine patients, they can be used in certain settings to provide an efficient and psychometrically sound PROM., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A931)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Visinin-like protein 1 (VILIP-1) belongs to the group of emerging biomarkers with the potential to support the early diagnosis of Alzheimer's disease (AD). However, studies investigating the differential diagnostic potential in cerebrospinal fluid (CSF) are rare and are not available for blood., Methods: We set up a novel, sensitive single molecule array (Simoa) assay for the detection of VILIP-1 in CSF and serum. In total, paired CSF and serum samples from 234 patients were investigated: 73 AD, 18 behavioral variant frontotemporal dementia (bvFTD), 26 parkinsonian syndromes, 20 amyotrophic lateral sclerosis (ALS), 22 Creutzfeldt-Jakob disease (CJD), and 75 non-neurodegenerative control (Con) patients. The differential diagnostic potential of CSF and serum VILIP-1 was assessed using the receiver operating characteristic curve analysis and findings were compared to core AD biomarkers., Results: CSF and serum VILIP-1 levels correlated weakly (r=0.32 (CI: 0.20-0.43), p<0.0001). VILIP-1 concentrations in CSF and serum were elevated in AD compared to Con (p<0.0001 and p<0.01) and CJD (p<0.0001 for CSF and serum), and an increase in CSF was observed already in early AD stages (p<0.0001). In the discrimination of AD versus Con, we could demonstrate a strong diagnostic potential for CSF VILIP-1 alone (area under the curve (AUC): 0.87), CSF VILIP-1/CSF Abeta 1-42 (AUC: 0.98), and serum VILIP-1/CSF Abeta 1-42 ratio (AUC: 0.89)., Conclusions: We here report on the successful establishment of a novel Simoa assay for VILIP-1 and illustrate the potential of CSF and serum VILIP-1 in the differential diagnosis of AD with highest levels in CJD., (© 2022. The Author(s).)

Objectives: The COVID-19 pandemic has placed unprecedented strain on healthcare systems and may have consequential impacts on patient safety incidents (PSIs). The primary objective of this study was to examine the impact of the COVID-19 pandemic on PSIs reported in Niagara Health., Methods: Flexible Farrington models were used to retrospectively detect weeks from January to September 2020 where PSI counts were significantly above expected counts. Incident counts were adjusted to weekly inpatient-days. Outcomes included overall incident numbers, incidents by category, and incidents by ward type., Results: The overall number of PSIs across Niagara Health did not increase during the first wave of the COVID-19 pandemic. However, significant increases in falls were observed, suggesting that other types of incidents decreased. Falls increased by 75% from February to March 2020, coinciding with the onset of the first wave of the pandemic. Further investigation by unit type revealed that the number of falls increased specifically on internal medicine and complex continuing care wards., Conclusions: Despite no observed changes in overall number, significant composition shifts in PSIs occurred during the first wave of the COVID-19 pandemic, with increased falls on internal medicine and complex continuing care wards. Possible explanations include restrictions on patient visitation, reduced patient contact/supervision, and/or personal protective equipment requirements. Providers should maintain a particularly high vigilance for patient falls during pandemic outbreaks, and hospitals should consider targeting resources to higher-risk locations. The results of this study reinforce the need for ongoing pandemic PSI monitoring and rapidly adaptive responses to new patient safety concerns., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Synaptosomal-associated protein 25 (SNAP-25) in cerebrospinal fluid (CSF) is an emerging synaptic biomarker for the early diagnosis of Alzheimer's disease (AD). However, comprehensive studies investigating the marker in Creutzfeldt-Jakob disease (CJD) and in the differential diagnosis of neurodegenerative diseases are still lacking., Methods: We developed a novel, sensitive ELISA for the measurement of SNAP-25 in CSF. In total, we analysed 316 patients from 6 diagnostic groups comprising patients with AD (n=96), CJD (n=55), Parkinson's disease spectrum (n=41), frontotemporal lobar degeneration (n=25) and amyotrophic lateral sclerosis (n=24) and non-neurodegenerative control patients (n=75). Using receiver operating characteristic curve analysis, we analysed the differential diagnostic potential and compared the results with core AD biomarkers., Results: SNAP-25 CSF concentrations were elevated in AD and CJD (p<0.0001) but not in the other neurodegenerative diseases. Increased levels were observed already at early AD and CJD stages (p<0.0001). In CJD, SNAP-25 levels correlated negatively with survival time (r=-0.33 (95% CI -0.57 to -0.04, p=0.02). For the discrimination of AD from all other diseases except CJD, we observed a good diagnostic performance for CSF SNAP-25 (area under the curve (AUC) 0.85) which was further improved by applying the ratio with CSF amyloid-β 1-42 (AUC 0.95). For CJD, we could demonstrate a strong differential diagnostic potential against all other groups including AD (AUC 0.97)., Conclusion: Using the novel established CSF SNAP-25 ELISA, we here demonstrate the applicability of SNAP-25 as an early synaptic biomarker for both AD and CJD with a possible prognostic value in patients with CJD., Competing Interests: Competing interests: SHa, PS, SHe, PO, SAR, SA-S, JL, CAFVA, AG and ACL report no competing interests. MO gave scientific advice for Fujirebio, Roche, Biogen and Axon., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

We sought to assess the safety of adding ixazomib, an oral proteasome inhibitor, to a multi-agent treatment regimen for older adults with acute lymphoblastic leukemia (ALL). Patients 51 to 75 years of age with newly diagnosed ALL were screened. Induction consisted of prednisone (P), vincristine (V), and doxorubicin (D). For BCR-ABL1+ patients, dasatinib was added. On Days 1, 8, 15 of induction, ixazomib was given orally. After induction patients received 1 cycle of consolidation in which ixazomib was given on Days 1, 8, 15. After consolidation, patients in remission (CR) were offered stem cell transplantation. Among the 19 patients treated, 15 (79%) [90% CI, 58-92%] achieved CR or CRi. At 2 years, the overall survival was 47% [95%CI, 29-72%]. In this study the dose of 2.3 mg of ixazomib in combination was the MTD for older patients with ALL and is the recommended dose for future phase 2 studies.

Aims: At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there were no clinically-tested medications for the effective treatment of coronavirus disease. In this context, on 5 March 2020, the French Public Health Council issued several recommendations for the therapeutic management of this new disease, including the use of hydroxychloroquine (HCQ). An unexpected cardiovascular safety signal was quickly identified as being more frequent than expected thanks to the reports of adverse drug reactions (ADRs) submitted to French regional pharmacovigilance centres (RPVC). The objective of this study was to compare all ADRs reported with HCQ used in its usual indication, collected before the pandemic period (1985 to 31 December, 2019) with those reported with the coronavirus disease 2019 (COVID-19) indication (1 January to 21 July, 2020)., Methods: For this purpose, reports were extracted from the French pharmacovigilance database and analysed for these two periods., Results: Our study showed a different safety profile in COVID-19 patients with more cardiac disorders (57% of ADRs versus 5% before the pandemic period), especially QT interval prolongation, resulting from an interaction with azithromycin in more than 20% of cases. Hepatobiliary disorders were also significantly more frequent., Conclusions: These observations could be associated with the effect of the virus itself on the various organs, the profile of the patients treated, and concomitant drug treatments., (Copyright © 2021. Published by Elsevier Masson SAS.)

Study Design: Consecutively collected cases., Objective: To determine if a machine-learning (ML) program can accurately predict the postoperative thoracic kyphosis through the uninstrumented thoracic spine and pelvic compensation in patients who undergo fusion from the lower thoracic spine (T10 or T11) to the sacrum., Methods: From 2015 to 2019, a consecutive series of adult (≥18 years old) patients with adult spinal deformity underwent corrective spinal fusion from the lower thoracic spine (T10 or T11) to the sacrum. Deidentified data was processed by a ML system-based platform to predict the postoperative thoracic kyphosis (TK) and pelvic tilt (PT) for each patient. To validate the ML model, the postoperative TK (T4-T12, instrumented thoracic, and uninstrumented thoracic) and the pelvic tilt were compared against the predicted values., Results: A total of 20 adult patients with a minimum 6-month follow-up (mean: 22.4 ± 11.3 months) were included in this study. No significant differences were observed for TK (predicted 37.6° vs postoperative 38.3°, P = .847), uninstrumented TK (predicted 33.9° vs postoperative 29.8°, P = .188), and PT (predicted 23.4° vs postoperative 22.7°, P = .754). The predicted PT and the TK of the uninstrumented thoracic spine correlated well with postoperative values (uninstrumented TK: R 2 = 0.764, P < .001; PT: R 2 = 0.868, P < .001). The mean error with which kyphosis through the uninstrumented thoracic spine can be measured was 4.8° ± 4.0°. The mean error for predicting PT was 2.5° ± 1.7°., Conclusion: ML algorithms can accurately predict the spinopelvic compensation after spinal fusion from the lower thoracic spine to the sacrum. These findings suggest that surgeons may be able to leverage this technology to reduce the risk of proximal junctional kyphosis in this population.

Study Design: Retrospective review., Objective: Identify surgical complex adult spine deformity patients who are at increased risk for an unplanned postoperative 90-day readmission and/or reoperation., Methods: A total of 227 consecutive records of complex adult (≥18 years old) spine deformity surgeries from 2015 to 2018 were reviewed. Demographics, comorbidities, operative details, and postoperative complication data was collected. Chi-square/Fisher's exact test and t tests were used for bivariate analysis. To determine independent predictors for readmissions/reoperations, stepwise multivariate logistic regressions were employed. The C-statistic and Hosmer-Lemeshow (HL) value was used to measure concordance and goodness of fit., Results: Average age was 50.5 ± 17.8 years and 67.8% were female. Ninety-day readmission and reoperation rates were 7.0% and 5.3%, respectively. Median number of days after index discharge date resulting in readmission and reoperation were 16.5 and 28, respectively. The multivariate regression for 90-day readmissions included pulmonary comorbidity, depression, history of deep vein thrombosis/pulmonary embolism (DVT/PE), and gastrointestinal comorbidity (C-statistic = 0.82; HL = 0.79). Pulmonary comorbidity, depression, and history of DVT/PE increased risk for 90-day readmission by 5-, 3.5-, and 10.2-fold, respectively. The multivariate regression for 90-day reoperations was similar to readmissions (C-statistic = 0.89; HL = 0.31). Operative time>7 hours and history of DVT/PE increased risk for early reoperation by 5.8- and 8.7-fold, respectively., Conclusions: An emphasis on medically optimizing patients with preexisting pulmonary comorbidities, depression, and history of DVT/PE may have a substantial impact on improving short-term outcomes in this population. The present study provides benchmark data and may serve as an initial model to predict unplanned reoperations and readmissions.

Lyme disease is the fastest growing vector-borne disease in the United States. However, current testing modalities are ill suited to detection of Lyme disease, leading to the diagnosis of many cases after treatment is effective. We present an improved, direct method Lyme disease diagnosis, where the Lyme specific biomarker Outer Surface Protein A (OspA) in clinical serum samples is identified using a diagnostic platform combining surface enhanced Raman scattering (SERS) and aptamers. Employing orthogonal projections to latent structures discriminant analysis, the system accurately identified 91% of serum samples from Lyme patients, and 96% of serum samples from symptomatic controls. In addition, the OspA limit-of-detection, determined to be 1 × 10 -4 ng/mL, is greater than four orders of magnitude lower than that found in serum samples from early Lyme disease patients. The application of this platform to detect this difficult-to-diagnose disease suggests its potential for detecting other diseases that present similar difficulties., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We conducted a single-center, open-label, dose escalation, and expansion phase I trial of the antiangiogenic multikinase inhibitor regorafenib in patients with advanced myeloid neoplasms. We enrolled 16 patients with relapsed/refractory acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia (CMML), or myelodysplastic syndrome (MDS). A 3 + 3 dose escalation design was used with two planned dose levels (120 or 160 mg daily) and one de-escalation level (80 mg daily). An additional 10 patients were treated on an expansion cohort. The recommended phase two dose of regorafenib was 160 mg daily, with no dose-limiting toxicities. The best overall disease response by International Working Group criteria included one partial and stable disease in 11 patients. Tissue studies indicated no change in Ras/mitogen-activated protein kinase (MAPK) pathway activation in responders. Pharmacodynamic changes in plasma VEGF, PlGF, and sVEGFR2 were detected during treatment. Baseline proinflammatory and angiogenic cytokine levels were not associated with clinical response. Single-agent regorafenib demonstrated an acceptable safety profile in relapsed/refractory myeloid malignancy patients. Most patients achieved stable disease, with modest improvements in cell counts in some MDS patients. Biomarker studies were consistent with on-target effects of regorafenib on angiogenesis. Future studies should investigate the role of regorafenib in combination therapy approaches., Competing Interests: Amir T. Fathi: Consulting: Foghorn, Amgen, Celgene, BMS, Agios, Novartis, Ipsen, Forma, Abbvie, Genentech, Morphosys, and Takeda. Donna Neuberg: Stock ownership in Madrigal Pharmaceuticals, and received research funding from Pharmacyclics. Yi‐Bin Chen: Consulting: Daiichi, Abbvie, Equilium, Incyte, Jasper, Celularity, and Actinium; clinical trial support: Abbvie, Celgene, BMS, Agios, and Servie; Dan G. Duda received consultant fees from Simcere, Surface Oncology, Sophia Bioscience, Innocoll and BMS, and research grants from Exelixis, BMS, and Surface Oncology. Dan G. Duda's research is supported by National Institutes of Health (NIH) (grant numbers: R01CA260857, R01CA247441, R01CA254351, R03CA256764, and P01CA261669) and Department of Defense PRCRP (grant numbers: #W81XWH‐19‐1‐0284 and W81XWH‐21‐1‐0738). Gabriela Hobbs: Consulting fees from Abbvie, Incyte, Blueprint, Novartis, and Keros; research support from Bayer, Incyte and Constellation; grants: ECOR PSDA Award and ASH‐AMFDP award. The other authors declare no potential conflict of interest. Result of this study has previously been reported as an abstract at the 2020 American Society of Hematology Annual Meeting (Virtual). The funders had no role in data analysis or the preparation of this article., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Although a growing amount of literature that suggests robots are safe and can achieve comparable outcomes to conventional techniques, much of this literature is limited by small sample sizes and single-surgeon or single center series. Furthermore, it is unclear what the impact of robotic technology has made on operative and clinical outcomes over time. This is the first and largest multicenter study to examine the trends in outcomes and complications after robot-assisted spine surgery over a 5-year period., Methods: Adult (≥18 years old) patients who underwent spine surgery with robot-assistance between 2015 and 2019 at four unique spine centers. The robotic systems used included the Mazor Renaissance, Mazor X, and Mazor Stealth Edition. Patients with incomplete data were excluded from this study. The minimum follow-up was 90 days., Results: A total of 722 adult patients were included (117 Renaissance, 477 X, 128 Stealth). Most patient and operative factors (e.g., sex, tobacco status, total instrumented levels, and pelvic fixation,) were similar across the years. Mean ± standard deviation Charlson comorbidity index (CCI) was 1.5±1.5. The most commonly reported diagnoses included high grade spondylolisthesis (40.6%), degenerative disc disease (18.4%), and degenerative scoliosis (17.6%). Mean (standard deviation) number of instrumented levels was 3.8±3.4. From 2015 to 2019, average robot time per screw improved from 7.2 to 5.5 minutes (P=0.004, R 2 =0.649). Average fluoroscopy time per screw improved from 15.2 to 9.4 seconds (P=0.002). Rates of both intraoperative screw exchange for misplaced screw (2015-2016: 2.7%, 2019: 0.8%, P=0.0115, R 2 =0.1316) and robot abandonment (2015-2016: 7.1%, 2019: 1.1%, P=0.011, R 2 =0.215) improved significantly over time. The incidence of other intraoperative complications (e.g., dural tear, loss of motor/sensory function, blood transfusion) remained consistently low, but similar throughout the years. The length of stay (LOS) decreased by nearly 1 day from 2015 to 2019 (P=0.007, R 2 =0.779). 90-day reoperation rates did not change significantly., Conclusions: At four institutions among seven surgeons, we demonstrate robot screw accuracy, reliability, operative efficiency, and radiation exposure improved significantly from 2015 to 2019. 90-day complication rates remained low and LOS decreased significantly with time. These findings further validate continued usage of robot-assisted spine surgery and the path toward improved value-based care., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-21-102/coif). SZ serves as an unpaid editorial board member of Journal of Spine Surgery. EJ reports consulting fees from Stryker, Medtronic, and Innovasis outside the submitted work. CH reports personal fees from Medtronic, Globus Medical, Spineart, and Innovasis outside the submitted work. CRG reports royalties from Stryker/K2M and Medtronic; consulting fees from Stryker/K2M, Medtronic; educational grant support from Medtronic, is on an advisory board for Stryker/K2M, Medtronic, and Augmedics, and owns stock in Augmedics and NSite. The other authors have no conflicts of interest to declare., (2022 Journal of Spine Surgery. All rights reserved.)

Objective: This study examined how the COVID-19 pandemic differently affected households of children with versus without special healthcare needs. We compared caregivers' and children's emotional well-being (Aim 1), the utilization of preventive healthcare services for young children (Aim 2), and the promotive effects of social support on well-being outcomes (Aim 3) during the pandemic between the two groups., Methods: Data were drawn from an ongoing, large, longitudinal, and national survey that assessed the pandemic impact on households of young children (0-5). Analyses for Aims 1 and 2 were based on 10,572 households, among which 10.96% had children with special healthcare needs. Analyses for Aim 3 were based on a subsample of 821 families, among which 12.54% had children with special healthcare needs., Results: Caregivers of children with special healthcare needs exhibited more emotional distress and reported higher levels of household children's behavioral problems during the pandemic. The percentages of missed preventive healthcare visits and vaccinations were also higher in families of children with special healthcare needs due to structural barriers. Lastly, emotional social support was indirectly related to children's decreased behavioral problems through caregivers' reduced emotional distress, only among households of children without special healthcare needs. In other words, social support alone was not sufficient in promoting caregivers' and children's better well-being outcomes among households of children with special healthcare needs., Conclusions: The pandemic has caused extensive burdens on families of children with special healthcare needs. Actions from policymakers and early intervention service providers are urgently needed to mitigate these impacts., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA)., Objective: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA., Method: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture. Data from 204 patients (68 svPPA, 85 nfvPPA, and 51 lvPPA) and 33 healthy controls were analyzed., Results: Controls completed both tasks with >90% accuracy. Patients with svPPA had high scores in repetition (mean=9.2±1.32) but low scores in pointing (mean=6±2.52). In contrast, patients with nfvPPA and lvPPA performed comparably in both tasks with lower scores in repetition (mean=7.4±2.7 for nfvPPA and 8.2±2.34 for lvPPA) but higher scores in pointing (mean=8.9±1.41 for nfvPPA and 8.6±1.62 for lvPPA). The R&P Test had high accuracy discriminating svPPA from nfvPPA (83% accuracy) and lvPPA (79% accuracy). However, there was low accuracy discriminating nfvPPA from lvPPA (<60%)., Conclusion: The R&P Test helps to differentiate svPPA from 2 nonsemantic variants (nfvPPA and lvPPA). However, additional tests are required for the differentiation of nfvPPA and lvPPA., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The behavioral variant of frontotemporal dementia (bvFTD) is a rare neurodegenerative disease. Reliable predictors of disease progression have not been sufficiently identified. We investigated multivariate magnetic resonance imaging (MRI) biomarker profiles for their predictive value of individual decline., Methods: One hundred five bvFTD patients were recruited from the German frontotemporal lobar degeneration (FTLD) consortium study. After defining two groups ("fast progressors" vs. "slow progressors"), we investigated the predictive value of MR brain volumes for disease progression rates performing exhaustive screenings with multivariate classification models., Results: We identified areas that predict disease progression rate within 1 year. Prediction measures revealed an overall accuracy of 80% across our 50 top classification models. Especially the pallidum, middle temporal gyrus, inferior frontal gyrus, cingulate gyrus, middle orbitofrontal gyrus, and insula occurred in these models., Discussion: Based on the revealed marker combinations an individual prognosis seems to be feasible. This might be used in clinical studies on an individualized progression model., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate which combine trastuzumab (T), a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), and a cytotoxic molecule derived from maytansine (DM1)., Case Report: We report the first case of T-DM1-associated pleural and pericardial effusions three weeks after the second course of T-DM1 in a patient with breast cancer. Drug-induced pleural and pericardial effusions was implicated in the absence of other etiologies. The Naranjo Scale indicated a probable drug-induced adverse reaction. Management & outcome: The patient fully recovered after thoracentesis and discontinuation of T-DM1. The patient has reported no side effect after the sixth course of trastuzumab., Discussion: To our knowledge, this is the first case in the literature of bilateral pleural and pericardial effusions in a patient treated with T-DM1. The successful initiation of treatment with trastuzumab following withdrawal of T-DM1 suggests that emtansine played a role in the development of bilateral pleural and pericardial effusions. We hypothesize that the patient's condition was a result of a local inflammatory reaction to emtansine by direct toxicity.

Study Design: Retrospective cohort database study., Objective: The aim of this study was to investigate trends in utilization and demographics in Spinal Deformity Surgery., Summary of Background Data: The aging population in the United States will likely result in increased incidence of adult degenerative scoliosis. With a national focus on resource utilization and value-based care, it is essential for surgeons, researchers, and health care policy makers to know utilization and demographic trends of spinal surgery with long fusion construct., Methods: The National Inpatient Sample (NIS) database was queried for patients who underwent fusion or refusion of nine or more vertebrae (ICD-9-CM 81.64) between 2004 and 2015 across 44 states. Demographic and economic data include annual number of surgeries, incidence, patient age, sex, region, insurance type, charge, routine discharge, length of stay, and data. The NIS database represents a 20% sample of discharges from US hospitals, excluding rehabilitation and long-term acute care hospitals, which is weighted to provide national estimates., Result: In 2014, there were 14,615 fusions involving nine or more vertebrae across the United States. The number of fusions involving nine or more levels has increased 141% from 6072 in 2004. Long fusion constructs increased 460% from 2004 to 2014 among patients 65 to 84 years' old. The mean hospital cost associated with long fusion spine surgery was $69,546 per case in 2015. Between 2004 and 2014, the payer breakdown for individuals receiving spinal deformity surgery is as follows: 54.2% private insurance, 18% Medicare, and 21.2% Medicaid., Conclusion: The massive increase (141%) in utilization of long construct spine fusion was primarily driven by 460% rise in incidence of the surgery among those aged 65 to 84. Although the cause is unknown, it is possible that this rise was, at least in part, driven by the implementation of the affordable care act, improved surgical safety, and better knowledge of spinopelvic parameters.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The term primary progressive aphasia (PPA) sums up the non-fluent (nfv), the semantic (sv), and the logopenic (lv) variant. Up to now, there is only limited data available concerning magnetic resonance imaging volumetry to monitor disease progression., Methods: Structural brain imaging and an extensive assessment were applied at baseline and up to 4-year(s) follow-up in 269 participants. With automated atlas-based volumetry 56 brain regions were assessed. Atrophy progression served to calculate sample sizes for therapeutic trials., Results: At baseline highest atrophy appeared in parts of the left frontal lobe for nfvPPA (-17%) and of the left temporal lobe for svPPA (-34%) and lvPPA (-24%). Severest progression within 1-year follow-up occurred in the basal ganglia in nfvPPA (-7%), in the hippocampus/amygdala in svPPA (-9%), and in (medial) temporal regions in lvPPA (-6%)., Conclusion: PPA presents as a left-dominant, mostly gray matter sensitive disease with considerable atrophy at baseline that proceeds variant-specific., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: Motor speech disorders (MSDs) are characteristic for nonfluent primary progressive aphasia (nfvPPA). In primary progressive aphasia (PPA) of the semantic (svPPA) and of the logopenic type (lvPPA), speech motor function is considered typically intact. However, knowledge on the prevalence of MSDs in svPPA and lvPPA is mainly based on studies with a priori knowledge of PPA syndrome diagnosis. This fully blinded retrospective study aims to provide data on the prevalence of all types of MSDs in a large sample of German-speaking patients with different subtypes of PPA., Method: Two raters, blinded for PPA subtype, independently evaluated connected speech samples for MSD syndrome and severity from 161 patients diagnosed with nfvPPA, svPPA or lvPPA in the database of the German Consortium of Frontotemporal Lobar Degeneration (FTLDc). In case of disagreement, a third experienced rater re-evaluated the speech samples, followed by a consensus procedure. Consensus was reached for 160 patients (74 nfvPPA, 49 svPPA, 37 lvPPA)., Main Results: Across all PPA syndromes, 43.8% of the patients showed MSDs. Patients with nfvPPA demonstrated the highest proportion of MSDs (62.2%), but MSDs were also identified in svPPA (26.5%) and lvPPA (29.7%), respectively. Overall, dysarthria was the most common class of MSDs, followed by apraxia of speech. In addition, we identified speech abnormalities presenting as "syllabic speech", "dysfluent speech", and "adynamic speech"., Discussion: Our study confirmed MSDs as frequently occurring in PPA. The study also confirmed MSDs to be most common in patients with nfvPPA. However, MSDs were also found in substantial proportions of patients with svPPA and lvPPA. Furthermore, our study identified speech motor deficits that have not received attention in previous studies on PPA. The results are discussed against the background of the existing literature on MSDs in PPA, including theoretical considerations of the neuroanatomical conditions described for each of the different subtypes of PPA., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Daratumumab is the first anti-CD38 monoclonal antibody of the class approved for recurrent and refractory multiple myeloma. Grade 3 and 4 Infusion-Related Reactions (IRRs) are frequent during the first and second infusions. Due to the risks associated with severe IRRs, daratumumab is systematically administered over a period of 3.5 hours.The main objective of this study was to evaluate the safety of a 90-minute daratumumab infusion from the third infusion., Patients and Methods: All patients who had received two or more doses of daratumumab in monotherapy or in combination with standard infusion rates were included. We excluded patients enrolled in clinical trials. For the rapid infusion protocol, 20% of the dose was administered over 30 minutes and the remaining 80% over 60 minutes., Results: From April 1 to May 31, 2019, 25 patients received 53 90-minute infusions of daratumumab. Premedication included corticosteroids, antipyretics, antihistamines, and if necessary a leukotriene receptor antagonist. No grade 3 or grade 4 IRRs were observed., Conclusion: From the third infusion, we found that a rapid administration of daratumumab (90 vs 210 minutes) was well tolerated and safe. It would be interesting to test this regimen from the second infusion.

Carotid endarterectomy (CEA) has a 1-5% risk of periprocedural stroke. The ability to emerge patients from anesthesia quickly to detect neurological abnormalities immediately after surgery is vital in this patient population. The objective of this pilot study was to assess if any of three general anesthetic techniques for CEA are associated with a shorter time to a reliable postoperative neurological exam. Secondary objectives were to assess postoperative cognitive dysfunction (POCD), postoperative delirium (POD), and hemodynamic stability. Twenty-one patients undergoing CEA were enrolled and randomized to different combinations of inhalational and intravenous anesthesia: Group A: propofol, remifentanil, and desflurane; Group B: dexmedetomidine, remifentanil, and desflurane; Group C: remifentanil and desflurane. Anesthetic depth was titrated using a bispectral index (BIS) monitor to a goal of 50-60. Time was recorded from surgery end to first meaningful neurological exam. Neurocognitive testing was completed preoperatively and up to 1 week postoperatively to assess POD (3D-CAM) and POCD (Short Blessed Test). Time to first reliable neurological exam was 2 minutes longer in group A (9 min ± 4 min) compared to group B and group C (7 min ± 3 min; 7 min ± 4 min), although this was not statistically significant. In addition, extubation time was significantly longer in group A (11 min) compared to group B and group C (5 min; 6 min) (P = 0.03). 3D -CAM and Short Blessed Test data along with hemodynamics did not differ significantly between the groups. Time to first useful neurologic exam and hemodynamics did not differ between the groups. However, extubation time was significantly prolonged in patients who received propofol, but not dexmedetomidine, as part of their anesthetic for CEA. These findings are best verified in an adequately powered prospective randomized study., Competing Interests: Rhea Temmermand, MSN, CRNA, has declared no financial relationships with any commercial entity related to the content of this article. Ludmil Mitrev, MD, has declared no financial relationships with any commercial entity related to the content of this article. Noud van Helmond, MD, has declared no financial relationships with any commercial entity related to the content of this article. Dean Roberts, MSN, CRNA, has declared no financial relationships with any commercial entity related to the content of this article. Joseph Lombardi, MD, has declared no financial relationships with any commercial entity related to the content of this article. Dejan Vuckovic, MD, has declared no financial relationships with any commercial entity related to the content of this article. The authors did not discuss off-label use within the article. Disclosure statements are available for viewing upon request., (Copyright © by the American Association of Nurse Anesthetists.)

Background: In 2014, inpatient spinal fusion surgery had the highest aggregate cost of any inpatient surgery performed in the United States, costing 12 billion dollars. As the national health care system seeks to improve value-based care, there is increased motivation to perform surgery on an outpatient basis. To ensure improved patient outcomes with this transition, patient selection has become increasingly important to identify who would most benefit from outpatient spine fusion, for example. This demands an improved understanding of the demographics of patients who have been receiving outpatient spine fusion on which the spine surgery community can build to improve cost-effective care delivered., Methods: The Healthcare Cost and Utilization Project, State Ambulatory Surgery Databases, and Agency for Healthcare Research and Quality databases were queried for demographic data regarding all-cause outpatient spine surgery between 2012 and 2014. Outpatient surgery volume was compared with inpatient surgery volume-which was provided by the State Inpatient Databases., Results: A total of 1,164,040 spine fusion procedures were identified between 2012 and 2014, of which 132,900 procedures were performed as outpatient surgery (11.4%). Of all fusion procedures amongst 18- to 44-year-old patients, 18.4% were outpatient. A larger proportion of white patients, rather than black or Hispanic patients, underwent ambulatory procedures (12.14% vs 9.53% vs 7.46%, respectively); 16.54% of spinal fusion procedures for patients with private insurance was performed on an outpatient basis. Based on patient income, 76% of all outpatient fusions were performed on patients who live in "not low" income ZIP codes., Conclusions: There has been a gradual trend toward performing more outpatient spinal fusion procedures over the studied period. This study has also revealed unique trends in the demographics of patients who have received outpatient spine fusion during this time., Level of Evidence: 3., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2021 ISASS.)