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Purpose: To evaluate radiographic and clinical outcomes following revision surgery after HRC fusions. Methods: Single-institution, retrospective study of patients revised following HRC with minimum 2-year follow-up post-revision. Demographics, perioperative information, radiographic parameters, complications, and Oswestry disability index (ODI) scores were collected. Radiographic parameters included global alignment, coronal and sagittal measurements pre and postoperatively, as well as final follow-up time points. Results: 26 patients were included with a mean follow-up of 3.3 ± 1.1 years. Mean age was 55.5 ± 7.8 years, BMI 25.2 ± 5.8, and 22 (85%) were females. Instrumented levels increased from 9.7 ± 2.8 to 16.0 ± 2.2. Five (19.2%) patients underwent lumbar pedicle subtraction osteotomies, and 23 (88.4%) had interbody fusions. Patients significantly improved in all radiographic parameters at immediate and final follow-up (p< 0.005), except for thoracic kyphosis and pelvic incidence (p> 0.05). Correction was maintained from immediate postop to final follow-up (p> 0.05). 20 (76.9%) of patients experienced a complication at some point within the follow-up period with the most common being a lumbar nerve root deficit (n= 7). However, only one patient had a nerve root deficit at final follow-up, that being a 4/5 unilateral anterior tibialis function. 5 (19.2%) patients required further revision within a mean of 1.8 ± 1.1 years. On average, patients had an improvement in ODI score by final follow-up (35.6 ± 16.8 vs 25.4 ± 19.8, p= 0.035). Conclusion: Patients revised for HRCs significantly improve, both clinically and radiographically by final follow-up. This group did have a propensity for distal lumbar root neurological issues, which were common but all patients except for one, recovered to full strength by two-year follow-up.

Purpose: To determine whether maintaining good sagittal balance with significant knee flexion (KF) constitutes a suboptimal outcome after adult spinal deformity (ASD) correction. Methods: This single-center, single-surgeon retrospective study, assessed ASD patients who underwent posterior spinal fusion between 2014 and 2020. Inclusion criteria included meeting at least one of the following: PI–LL ≥ 25°, T1PA ≥ 20°, or CrSVA-H ≥ 2 cm. Those with lower-extremity contractures were excluded. Patients were classified into four groups based on their 6-week postoperative cranio-hip balance and KF angle, and followed for at least 2 years: Malaligned with Knee Flexion (MKF+) (CrSVA-H > 20 mm + KFA > 10), Malaligned without Knee Flexion (MKF−) (CrSVA-H > 20 mm + KFA < 10), Aligned without Knee Flexion (AKF−) (CrSVA-H < 20 mm + KFA < 10), and Aligned with Knee Flexion (AKF+) (CrSVA-H < 20 mm + KFA > 10). The primary outcomes of this study included one and two year reoperation rates. Secondy outcomes included clinical and patient reported outcomes. Results: 263 patients (mean age 60.0 ± 0.9 years, 74.5% female, and mean Edmonton Frailty Score 3.3 ± 0.2) were included. 60.8% (160/263 patients) exhibited good sagittal alignment at 6-week postop without KF. Significant differences were observed in 1-year (p= 0.0482) and 2-year reoperation rates (p= 0.0374) across sub-cohorts, with the lowest and highest rates in the AKF− cohort (5%, n= 8) and MKF + cohort (16.7%, n= 4), respectively. Multivariable Cox regression demonstrated the AKF− cohort exhibited significantly better reoperation outcomes compared to other groups: AKF + (HR: 5.24, p= 0.025), MKF + (HR: 31.7, p< 0.0001), and MKF− (HR: 11.8, p< 0.0001). Conclusion: Our findings demonstrate that patients relying on knee flexion compensation in the early postoperative period have inferior outcomes compared to those achieving sagittal balance without knee flexion. When compared to malaligned patients, those with CrSVA-H < 20 mm and KFA > 10 degrees experience fewer early reoperations but similar delayed reoperation rates. This insight emphasizes the importance of considering knee compensation perioperatively when managing sagittal imbalance in clinical practice.

IMPORTANCE: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population. OBJECTIVE: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents. DESIGN, SETTING, AND PARTICIPANTS: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021. INTERVENTIONS: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up). MAIN OUTCOMES AND MEASURES: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points). RESULTS: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate. CONCLUSIONS AND RELEVANCE: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up)

Study Design Systematic review and meta-analysis. OBJECTIVESSurgical decompression alone for patients with neurogenic leg pain in the setting of degenerative lumbar scoliosis (DLS) and stenosis is commonly performed, however, there is no summary of evidence for outcomes.Methods A systematic search of English language medical literature databases was performed for studies describing outcomes of decompression alone in DLS, defined as Cobb angle >10˚, and 2-year minimum follow-up. Three outcomes were examined: 1) Cobb angle progression, 2) reoperation rate, and 3) ODI and overall satisfaction. Data were pooled and weighted averages were calculated to summarize available evidence.Results Across 15 studies included in the final analysis, 586 patients were examined. Average preoperative and postoperative Cobb angles were 17.6˚ (Range: 12.7 - 25˚) and 18.0 (range 14.1 - 25˚), respectively. Average change in Cobb angle was an increase of 1.8˚. Overall rate of reoperation ranged from 3 to 33% with an average of 9.7%. Average ODI before surgery, after surgery, and change in scores were 56.4%, 27.2%, and an improvement of 29% respectively. Average from 8 studies that reported patient satisfaction was 71.2%.Conclusions Current literature on decompression alone in the setting of DLS is sparse and is not high quality, limited to patients with small magnitude of lumbar coronal Cobb angle, and heterogenous in the type of procedure performed. Based on available evidence, select patients with DLS who undergo decompression alone had minimal progression of Cobb angle, relatively low reoperation rate, and favorable patient-reported outcomes.

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1–3during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6–14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

Study Design Systematic review and meta-analysis.Objectives Patients with lateral cervical disc and foraminal pathology can be treated with anterior and posterior approaches including anterior cervical discectomy and fusion(ACDF), cervical total disc arthroplasty(TDA), and minimally invasive posterior cervical foraminotomy(MIS-PCF). Although MIS-PCF may have some advantages over the anterior approaches, few comparative studies and meta-analyses have been done to assess superiority.Methods This study includes a systematic review of the literature and meta-analysis of studies directly comparing minimally invasive posterior cervical foraminotomy to either anterior cervical discectomy and fusion or cervical total disc arthroplasty.Results In comparing patients undergoing ACDF and MIS-PCF, operative time ranged from 68 to 97.8 minutes in the ACDF group compared to 28 to 93.9 minutes in the MIS-PCF group. Mean postoperative length of stay ranged from 33.84 to 112.8 hours in the ACDF group compared to 13.68 to 83.6 hours in the MIS-PCF group. The total complication rates were 3.72% in the ACDF group and 3.73% in the MIS-PCF group. A random-effects model meta-analysis was carried out which failed to show a statistically significant difference in the complication rate between the two procedures(OR .91; 95% CI 0.13, 6.43; P = .92, I2= 59%). The total reoperation rate was 3.5% in the ACDF group and 5.4% in the MIS-PCF group. A random-effects model meta-analysis was carried out which failed to show a statistically significant difference in the reoperation rate between the two procedures(OR .66; 95% CI 0.33, 1.33; P = .25, I2= 0). In comparing patients undergoing TDA and MIS-PCF, operative time ranged from 90.3 to 106.7 minutes in the TDA group compared to 77.4 to 93.9 minutes in the MIS-PCF group. Mean postoperative length of stay ranged from 103.2 to 165.6 hours in the TDA group and 93.6 to 98.4 hours in the MIS-PCF group. The complication rate ranged from 23.5 to 28.6% in the TDA group and 0 to 14.3% in the MIS-PCF group. The overall reoperation rates were 2.6% in the TDA group and 10.2% in the MIS-PCF group.Conclusions There is no clear superiority between MIS-PCF and ACDF/TDA in terms of operative time, postoperative length of stay, or rate of complications/reoperations. Further studies with increased follow-up intervals >48 months, and higher sample sizes are necessary to determine the true superiority of MIS-PCF and anterior neck approaches in treatment of lateral disc and foraminal pathology.

Study Design: Systematic review and meta-analysis.Objectives: Indications for surgical decompression of gunshot wounds to the lumbosacral spine are controversial and based on limited data.Methods: A systematic review of literature was conducted to identify studies that directly compare neurologic outcomes following operative and non-operative management of gunshot wounds to the lumbosacral spine. Studies were evaluated for degree of neurologic improvement, complications, and antibiotic usage. An odds ratio and 95% confidence interval were calculated for dichotomous outcomes which were then pooled by random-effects model meta-analysis.Results: Five studies were included that met inclusion criteria. The total rate of neurologic improvement was 72.3% following surgical intervention and 61.7% following non-operative intervention. A random-effects model meta-analysis was carried out which failed to show a statistically significant difference in the rate of neurologic improvement between surgical and non-operative intervention (OR 1.07; 95% CI 0.45, 2.53; P= 0.88). In civilian only studies, a random-effects model meta-analysis failed to show a statistically significant difference in the rate of neurologic improvement between surgical and non-operative intervention (OR 0.75; 95% CI 0.21, 2.72; P= 0.66). Meta-analysis further failed to show a statistically significant difference in the rate of neurologic improvement between patients with either complete (OR 4.13; 95% CI 0.55, 30.80; P= 0.17) or incomplete (OR 0.38; 95% CI 0.10, 1.52; P= 0.17) neurologic injuries who underwent surgical and non-operative intervention. There were no significant differences in the number of infections and other complications between patients who underwent surgical and non-operative intervention.Conclusions: There were no statistically significant differences in the rate of neurologic improvement between those who underwent surgical or non-operative intervention. Further research is necessary to determine if surgical intervention for gunshot wounds to the lumbosacral spine, including in the case of retained bullet within the spinal canal, is efficacious.

Ice nucleating particles (INPs) are a small subset of atmospheric particles that can initiate the formation of ice in clouds, including mixed-phase clouds. Here we report concentrations of INPs during October and November of 2018 at Alert, Nunavut, in the Canadian High Arctic. Our results show that average INP concentrations in October were higher than those in November. Based on an ammonium sulfate assay, mineral dust was an important component of the INP population at temperatures (T) ≤ −21 °C and T≤ −20 °C for October and November, respectively. Based on a heat assay, biological particles were an important component of the INP population at T≥ −21 °C and T≥ −16.5 °C for October and November, respectively. In addition, INP concentrations were correlated with aluminum concentrations (a tracer for mineral dust), possibly suggesting a significant fraction of the mineral dust and biological INPs came from the same source. Particle dispersion modelling and correlations between INP concentrations and aluminum suggest a significant fraction of the INPs came from ice-free and snow-free land at latitudes >50 °N. Since the coverage of ice-free and snow-free land in the Arctic is expected to increase as temperatures increase in the Arctic, these results have important implications for climate feedback mechanisms in the region.

Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR–positive eyes from four other patients were evaluated by in situhybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situhybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.

Autoimmune diseases such as rheumatoid arthritis (RA) pose an increasing, worldwide economic and health burden. Significantly, no cure exists for the majority of autoimmune diseases and consequently treatment is largely aimed at controlling disease symptoms. Therefore, there exists a critical need to develop new approaches that directly address the cause of disease, leading to disease remission and ultimately cure.

The use of vaccines has led to tremendous decreases in disease burdens across the world. Many challenges remain in expanding vaccine coverage to new pathogens, however, a struggle further hampered by a lack of understanding into many of the fundamental processes through which vaccines elicit robust immunity. In this review we cover recent advances in the field of innate immunity and vaccinology that offer new insights into the reasons some vaccines may succeed or fail. We begin with the secreted cytokines that can influence the nature of the adaptive immune response, and how these may be tuned with the use of particular adjuvants. From there we cover dendritic cells, perhaps the key cell at the interface between innate and adaptive immunity. We discuss mechanisms for targeting specific subsets of dendritic cells, and the effects of this targeting. We further discuss additional modifications of the vaccine formulation to enhance interactions with innate immunity, including phagocytocis and antigen presentation. Finally, we step back to review recent advances in systems biology, and the ability of these new tools to provide deeper understanding of innate immune functions. We hope that this review will provide researchers with access to a breadth and depth of recent work that will allow for the rational design of novel vaccines to combat the most serious infectious diseases of today and tomorrow.

We present optical, photoluminescent (PL), and photoconductive properties of functionalized anthradithiophene (ADT) derivatives and their composites. Solution-deposited ADT films exhibit charge carrier mobilities of over 1.5 cm2/(Vs), high PL quantum yields, and high photoconductivity. We show that molecular arrangement and intermolecular interactions significantly contribute to (opto)electronic properties of guest-host thin films of these pi-stacked materials. Specifically, the formation of aggregates plays an important role in establishing efficient conduction pathways in ADT derivatives dispersed in a host matrix. In addition, the extent and nature of aggregation and the resulting changes in PL and photoconductive behavior can be effectively manipulated through different film fabrications techniques. Furthermore, energy transfer and exciplex formation has been shown to occur between two different ADT derivatives, which also alters the photoconductive response of the systems. We explore the dependence of the photoconductive response of such guest-host systems on excitation wavelength.

The optical, fluorescent, and photoconductive properties of solution-processable functionalized pentacene and anthradithiophene (ADT) derivatives are presented. Considerable fluorescence quantum yields of ∼70−75% and ∼40−50% were observed in several ADT derivatives in toluene solutions and in thin films, respectively. No electric field-induced fluorescence quenching was observed in films at applied electric fields of up to at least 2 × 105V/cm. Strong temperature dependence of fluorescence quantum yields was observed in all ADT films but not solutions, which emphasizes importance of intermolecular interactions in these materials. All films exhibited fast charge carrier photogeneration upon 100 fs 400 nm excitation and power-law decay dynamics of the transient photocurrent over many orders of magnitude in time. In solution-deposited ADT thin films, effective charge carrier mobilities calculated from the space-charge-limited currents reached ∼0.1 cm2/V·s. In the same films, bulk photoconductive gains of up to 130 were observed at 532 nm continuous wave excitation with light intensity of 0.58 mW/cm2at the applied electric field of 4 × 104V/cm.

The preparation of complexes of EtO2POCH2POOEt2 L, with lanthanide nitrates is described. Stable complexes with composition LnL2NO33can be isolated for Ln La–Eu and fully characterised. For Ln Gd–Lu solid compounds could not be isolated. Conductivity and 31P NMR spectroscopy indicate structural changes in solution between the lighter and heavier lanthanides and, whilst electrospray mass spectrometry confirms a dramatic difference in behaviour with complexes of the heavier lanthanides readily decomposing vialoss of EtNO3, other experiments show that this does not occur under the conditions of complex formation. The single crystal X-ray structures for Ln La and Sm show the nitrates and OEt groups to be in close proximity. The changes in spectroscopic properties correlate well with the difficulties in isolating the complexes of heavier metals, and are possibly due to the formation of dimeric complexes rather than loss of ethyl nitrate.

Reactions of lanthanide chlorides LnCl3 with NaH2PO2 in aqueous solution afforded a series of complexes [Ln(H2PO2)3(H2O)n] (Ln 4;= 4;La–Tb, n 4;= 4;1; Ce–Nd, Dy–Lu; n 4;= 4;0) with members falling into at least four separate structural types. The crystal structures of members of two of these types, [Ce(H2PO2)3(H2O)] and [Dy(H2PO2)3], have been determined for the first time, along with that of [Pr(H2PO2)(HPO3)(H2O)]·H2O, one of a new series of complexes [Ln(H2PO2)(HPO3)(H2O)n]·nH2O (Ln 4;= 4;La–Gd, n 4;= 4;1; Tb–Lu; n 4;= 4;0) obtained by controlled oxidation of [Ln(H2PO2)3(H2O)n]. The hydrated members of this series are notable due to their incorporation of chiral channels inhabited by water molecules, and to their ability reversibly to dehydrate. Steric angle sum calculations have been used to rationalise the morphologies of the new complexes.

31P n.m.r. spectroscopy has led to the identification in solution of several ions in the series [PCl6-n(NCO)n]- and [PCl6-n(OCN)n]-, which were obtained by different preparative routes; isomeric configurations have been assigned by the method of pairwise interactions from the observed chemical shifts. The complexes are all unstable, and decompose readily at room temperature.

Several new pseudo-halogeno phosphorus species, including isomeric N- and O-bonded cyanato-derivatives of the PCl6- ion, cyano-derivatives of RPCl5- ions (R = Ph or Me), and organo-phosphorus (III) cyanide adducts RP(CN)2X- (R = Me, Et, Ph or C6F5; X = Cl, Br or I) have been prepared in solution, and identified by means of 31P n.m.r. spectroscopy. Isomeric configurations in the six-coordinate species have been assigned by the method of pairwise interactions.