Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.

Morphological and molecular data on the bat flies, Basilia silvae (Brèthes, 1913) and Trichobius parasiticus Gervais, 1844 parasitizing Chilean bats.

Among mammals, bats harbour the greatest taxonomic diversity of ectoparasitic arthropods. This is mainly due to their high mobility, wide distribution range and gregarious social behaviour. In Chile, 17 species of bats have been reported; however, their ectoparasitic arthropofauna has been little studied. There are currently 12 taxa recorded, belonging to two classes and associated with only four species of bats. This study aimed to investigate the diversity of parasitic flies associated with bats in three ecoregions: Atacama Desert, Chilean Matorral and Valdivian temperate forest. During 2021, using mist nets, bats were captured in Anzota caves (Atacama Desert ecoregion), Huelquén and Alto Jahuel (Chilean Matorral ecoregion), Cherquenco and San Patricio (Valdivian temperate forest). Each bat was carefully checked during a 15-min interval for the collection of ectoparasites. The arthropods were deposited in vials with 96% ethanol. A total of 26 bats corresponding to three species (Vespertilionidae: Histiotus magellanicus Philippi, 1866, Myotis arescens (Osgood, 1943); Phyllostomidae: Desmodus rotundus (Geoffroy, 1810)) were captured from which a total of 142 ectoparasitic arthropods were collected. Bat flies were separated/identified under a stereomicroscope. Additionally, from the fieldwork, we report the presence of other ectoparasites associated with Chilean bats. In our study, we report new host-parasite associations between Trichobius parasiticus Gervais, 1844 (Diptera: Streblidae) on D. rotundus, and Basilia silvae (Brèthes, 1913) (Diptera: Nycteribiidae) in M. arescens in Chile. Our study extended the latitudinal range of distribution for B. silvae to Araucanía region, and we report for first time T. parasiticus in the country. Additionally, partial sequences of the cytochrome c oxidase I gene were obtained from these specimens. Although there is slight morphological variation in the specimens of T. parasiticus, phylogenetic analyses suggest that they correspond to the same species. The sequences generated for B. silvae represent the first for the species. Authors recommend the use of an integrative approach in the identification of ectoparasites in poorly studied ecoregions and hosts. The integration of different markers is necessary to determine more precisely the phylogenetic relationships between South American populations and species of the genera Basilia and Trichobius.

Hidden species diversity and mito-nuclear discordance within the Mediterranean cone snail, Lautoconus ventricosus.

The Mediterranean cone snail, Lautoconus ventricosus, is currently considered a single species inhabiting the whole Mediterranean basin and the adjacent Atlantic coasts. Yet, no population genetic study has assessed its taxonomic status. Here, we collected 245 individuals from 75 localities throughout the Mediterranean Sea and used cox1 barcodes, complete mitochondrial genomes, and genome skims to test whether L. ventricosus represents a complex of cryptic species. The maximum likelihood phylogeny based on complete mitochondrial genomes recovered six main clades (hereby named blue, brown, green, orange, red, and violet) with sufficient sequence divergence to be considered putative species. On the other hand, phylogenomic analyses based on 437 nuclear genes only recovered four out of the six clades: blue and orange clades were thoroughly mixed and the brown one was not recovered. This mito-nuclear discordance revealed instances of incomplete lineage sorting and introgression, and may have caused important differences in the dating of main cladogenetic events. Species delimitation tests proposed the existence of at least three species: green, violet, and red + blue + orange (i.e., cyan). Green plus cyan (with sympatric distributions) and violet, had West and East Mediterranean distributions, respectively, mostly separated by the Siculo-Tunisian biogeographical barrier. Morphometric analyses of the shell using species hypotheses as factor and shell length as covariate showed that the discrimination power of the studied parameters was only 70.2%, reinforcing the cryptic nature of the uncovered species, and the importance of integrative taxonomic approaches considering morphology, ecology, biogeography, and mitochondrial and nuclear population genetic variation.

A Phylogenomic Backbone for Gastropod Molluscs.

Gastropods have survived several mass extinctions during their evolutionary history resulting in extraordinary diversity in morphology, ecology, and developmental modes, which complicate the reconstruction of a robust phylogeny. Currently, gastropods are divided into six subclasses: Caenogastropoda, Heterobranchia, Neomphaliones, Neritimorpha, Patellogastropoda, and Vetigastropoda. Phylogenetic relationships among these taxa historically lack consensus, despite numerous efforts using morphological and molecular information. We generated sequence data for transcriptomes derived from 12 taxa belonging to clades with little or no prior representation in previous studies in order to infer the deeper cladogenetic events within Gastropoda and, for the first time, infer the position of the deep-sea Neomphaliones using a phylogenomic approach. We explored the impact of missing data, homoplasy, and compositional heterogeneity on the inferred phylogenetic hypotheses. We recovered a highly supported backbone for gastropod relationships that is congruent with morphological and mitogenomic evidence, in which Patellogastropoda, true limpets, are the sister lineage to all other gastropods (Orthogastropoda) which are divided into two main clades 1) Vetigastropoda $s.l.$ (including Pleurotomariida $+$ Neomphaliones) and 2) Neritimorpha $+$ (Caenogastropoda $+$ Heterobranchia). As such, our results support the recognition of five subclasses (or infraclasses) in Gastropoda: Patellogastropoda, Vetigastropoda, Neritimorpha, Caenogastropoda, and Heterobranchia. [Compositional heterogeneity; fast-evolving; long-branch attraction; missing data; Mollusca; phylogenetics; systematic error.].

Bilateral sacroiliac joint fusion in long constructs using self-harvesting porous S2-alar iliac screws with an integrated tulip: technical considerations and early clinical and radiographic experience.

OBJECTIVE: The incidence of sacroiliac joint (SIJ) dysfunction after lumbosacral fusion is high. Upfront bilateral SIJ fusion using novel fenestrated self-harvesting porous S2-alar iliac (S2AI) screws could reduce the incidence of SIJ dysfunction and need for subsequent SIJ fusion. In this study, the authors report their early clinical and radiographic results of SIJ fusion using this novel screw. METHODS: The authors began using self-harvesting porous screws in July 2022. This is a retrospective review of consecutive patients at a single institution who underwent long thoracolumbar surgery with extension to the pelvis using this porous screw. Radiographic parameters of regional and global alignment were collected preoperatively and at the time of last follow-up. The incidence of intraoperative complications and need for revision were collected. The incidences of mechanical complications, including screw breakage, implant loosening/pullout, and screw cap dislocation at the time of last follow-up were also collected. RESULTS: Ten patients with a mean age of 67 years were included, 6 of whom were male. Seven patients had a thoracolumbar construct with extension to the pelvis. Three patients had upper instrumented vertebrae at the proximal lumbar spine. Intraoperative breach was not encountered in any of the patients (0%). Postoperatively, 1 patient (10%) had screw breakage at the neck of the tulip of the modified iliac screw discovered at routine follow-up without clinical sequalae. CONCLUSIONS: Use of self-harvesting porous S2AI screws incorporated into long thoracolumbar constructs was safe and feasible, demanding unique technical considerations. Long-term clinical and radiographic follow-up with a large patient cohort is necessary to determine their durability and efficacy to achieve SIJ arthrodesis and prevent SIJ dysfunction.

Pseudarthrosis after four-level anterior cervical discectomy and fusion without posterior fixation.

OBJECTIVE: Fusion rates and long-term outcomes are well established for anterior cervical discectomy and fusion (ACDF) of 3 levels or fewer, but there is a paucity of similar data on 4-level fusions. The authors evaluated long-term fusion rates and clinical outcomes after 4-level ACDF without supplemental posterior instrumentation. METHODS: The authors retrospectively reviewed patients who underwent 4-level ACDF at a single institution with at least 1-year of radiological follow-up. Fusion was determined by measuring change in interspinous distance at each segment on dynamic radiographs or by the presence of bridging bone on CT scans at minimum 1-year follow-up. Clinical outcomes were assessed using Neck Disability Index and Short Form-36. RESULTS: A total of 63 patients (252 levels) met the inclusion criteria for the study, with a mean follow-up of 2.6 years. Complete radiographic fusion at all 4 levels was observed in 26 patients (41.3%). Of the 37 patients (58.7%) with radiographic pseudarthrosis, there was a mean of 1.35 nonfused levels. The fusion rate per level, however, was 80.2% (202/252 levels). The most common level demonstrating nonunion was the distal segment (C6-7), showing pseudarthrosis in 29 patients (46.8%), followed by the most proximal segment (C3-4) demonstrating nonunion in 9 patients (14.5%). The mean improvement in Neck Disability Index and Short Form-36 was 15.7 (p < 0.01) and 5.8 (p = 0.14), respectively, with improvement in both scores surpassing the minimum clinically important difference. One patient (1.6%) required revision surgery for symptomatic pseudarthrosis, and 5 patients (7.9%) underwent revision for symptomatic adjacent-segment disease. Patient-reported outcomes results are limited by the low rate of 1-year follow-up (50.8%), whereas reoperation data were available for all 63 patients. CONCLUSIONS: More than half of patients undergoing 4-level ACDF without posterior fixation demonstrated pseudarthrosis of at least 1 level-most commonly the distal C6-7 level. One patient required revision for symptomatic pseudarthrosis. Patient-reported outcomes showed significant improvements at 1-year follow-up, but clinical follow-up was limited. This is the largest series to date to evaluate fusion outcomes in 4-level ACDF.

Extra-corporeal membrane oxygenation and emergency C-section for a pregnant COVID-19 positive patient.

INTRODUCTION: Data on extra-corporeal membrane oxygenation (ECMO) therapy for pregnant patients with Coronavirus 2019 (COVID-19) infection are limited. Here we report a case of an emergency cesarean section performed while the COVID-19 positive mother was on ECMO support. CASE REPORT: A 36-year-old COVID-19 positive patient at 26 weeks gestational age presented with respiratory failure requiring extra-corporeal membrane oxygenation therapy. Nine days later fetal distress demanded an emergency C-section. After 5 weeks on ECMO, the patient was weaned off. Both mother and child were discharged. DISCUSSION: The decision to perform an urgent C-section is one that requires meticulous thought from the attending team. Pulmonary maturation is key as pregnancy may need to be terminated at any time during ECMO. CONCLUSION: Data on ECMO support for pregnant patients with COVID-19 infection are scarce. Best results can be achieved ensuring adequate anticoagulation, meticulous choice of cannulas, continued fetal monitoring, early lung maturation, and precision timing of delivery.

Establishing a Standardized Clinical Consensus for Reporting Complications Following Lateral Lumbar Interbody Fusion.

Background and Objectives: Mitigating post-operative complications is a key metric of success following interbody fusion. LLIF is associated with a unique complication profile when compared to other approaches, and while numerous studies have attempted to report the incidence of post-operative complications, there is currently no consensus regarding their definitions or reporting structure. The aim of this study was to standardize the classification of complications specific to lateral lumbar interbody fusion (LLIF). Materials and Methods: A search algorithm was employed to identify all the articles that described complications following LLIF. A modified Delphi technique was then used to perform three rounds of consensus among twenty-six anonymized experts across seven countries. Published complications were classified as major, minor, or non-complications using a 60% agreement threshold for consensus. Results: A total of 23 articles were extracted, describing 52 individual complications associated with LLIF. In Round 1, forty-one of the fifty-two events were identified as a complication, while seven were considered to be approach-related occurrences. In Round 2, 36 of the 41 events with complication consensus were classified as major or minor. In Round 3, forty-nine of the fifty-two events were ultimately classified into major or minor complications with consensus, while three events remained without agreement. Vascular injuries, long-term neurologic deficits, and return to the operating room for various etiologies were identified as important consensus complications following LLIF. Non-union did not reach significance and was not classified as a complication. Conclusions: These data provide the first, systematic classification scheme of complications following LLIF. These findings may improve the consistency in the future reporting and analysis of surgical outcomes following LLIF.

Mitogenomics and hidden-trait models reveal the role of phoresy and host shifts in the diversification of parasitoid blister beetles (Coleoptera: Meloidae).

Changes in life history traits are often considered speciation triggers and can have dramatic effects on the evolutionary history of a lineage. Here, we examine the consequences of changes in two life history traits, host-type and phoresy, in the hypermetamorphic blister beetles, Meloidae. Subfamilies Nemognathinae and Meloinae exhibit a complex life cycle involving multiple metamorphoses and parasitoidism. Most genera and tribes are bee-parasitoids, and include phoretic or nonphoretic species, while two tribes feed on grasshopper eggs. These different life strategies are coupled with striking differences in species richness among clades. We generated a mitogenomic phylogeny for Nemognathinae and Meloinae, confirming the monophyly of these two clades, and used the dated phylogeny to explore the association between diversification rates and changes in host specificity and phoresy, using state-dependent speciation and extinction (SSE) models that include the effect of hidden traits. To account for the low taxon sampling, we implemented a phylogenetic-taxonomic approach based on birth-death simulations, and used a Bayesian framework to integrate parameter and phylogenetic uncertainty. Results show that the ancestral hypermetamorphic Meloidae was a nonphoretic bee-parasitoid, and that transitions towards a phoretic bee-parasitoid and grasshopper parasitoidism occurred multiple times. Nonphoretic bee-parasitoid lineages exhibit significantly higher relative extinction and lower diversification rates than phoretic bee-and grasshopper-parasitoids, but no significant differences were found between the latter two strategies. This suggests that Orthopteran host shifts and phoresy contributed jointly to the evolutionary success of the parasitoid meloidae. We also demonstrate that SSE models can be used to identify hidden traits coevolving with the focal trait in driving a lineage's diversification dynamics.

Anatomical positional changes in the lateral lumbar interbody fusion.

INTRODUCTION: ALIFs and LLIFs are now becoming more utilized for adult spinal disease. As technologies advance, so do surgical techniques, with surgeons now modifying traditional supine-ALIF and lateral-LLIF to lateral-ALIF and prone-LLIF approaches to allow for more efficient surgeries. The objective of this study is to characterize the anatomical changes in the surgical corridor that occur with changes in patient positioning. METHODS: MRIs of ten healthy volunteers were evaluated in five positions: supine, prone with hips flexed, prone with hips extended, lateral with hips flexed, and lateral with hips extended. All lateral scans were in the left lateral decubitus position. The anatomical changes of the psoas muscles, inferior vena cava, aorta, iliac vessels were assessed with relation to fixed landmarks on the disc spaces from L1 to S1. RESULTS: The most anteriorly elongated ipsilateral to approach psoas when compared to supine was seen in lateral-flexed position (- 5.82 mm, p < 0.001), followed by lateral-extended (- 2.23 mm, p < 0.001), then prone-flexed (- 1.40 mm, p = 0.014), and finally supine and prone-extended (- 0.21 mm, p = 0.643). The most laterally extending or "thickest" psoas was seen in prone-flexed (- 1.40 mm, p = 0.004) and prone-extended (- 1.17 mm, p = 0.002). The psoas was "thinnest" in lateral-extended (2.03 mm, p < 0.001) followed by lateral-flexed (1.11 mm, p = 0.239). The contralateral psoas did not move as anteriorly as the ipsilateral. 3D volumetric analysis showed that the greatest changes in the psoas occur at its proximal and distal poles near T12-L1 and L4-S1. In lateral-flexed compared to prone-extended, the IVC moves medially to the left (p < 0.001). The aorta moves laterally to the left (p = 0.005). The venous structures appeared more full and open in the lateral positions and flattened in the supine and prone positions. The arteries remain in full calibre. CONCLUSION: The MRI anatomical evaluation shows that the psoas, and therefore lumbar plexus, and vasculature move significantly with changes in positioning. This is important for preoperative planning for proper intraoperative execution from preoperative supine MRI. Understanding that the psoas and vessels move the most anteriorly in the lateral-flexed position and to a least degree in the prone-extended is essential for safe and efficient utilization of techniques such as the traditional LLIF, traditional ALIF, prone-LLIF.

Setting for single position surgery: survey from expert spinal surgeons.

PURPOSE: To describe a comprehensive setting of the different alternatives for performing a single position fusion surgery based on the opinion of leading surgeons in the field. METHODS: Between April and May of 2021, a specifically designed two round survey was distributed by mail to a group of leaders in the field of Single Position Surgery (SPS). The questionnaire included a variety of domains which were focused on highlighting tips and recommendations regarding improving the efficiency of the performance of SPS. This includes operation room setting, positioning, use of technology, approach, retractors specific details, intraoperative neuromonitoring and tips for inserting percutaneous pedicle screws in the lateral position. It asked questions focused on Lateral Single Position Surgery (LSPS), Lateral ALIF (LA) and Prone Lateral Surgery (PLS). Strong agreement was defined as an agreement of more than 80% of surgeons for each specific question. The number of surgeries performed in SPS by each surgeon was used as an indirect element to aid in exhibiting the expertise of the surgeons being surveyed. RESULTS: Twenty-four surgeons completed both rounds of the questionnaire. Moderate or strong agreement was found for more than 50% of the items. A definition for Single Position Surgery and a step-by-step recommendation workflow was built to create a better understanding of surgeons who are starting the learning curve in this technique. CONCLUSION: A recommendation of the setting for performing single position fusion surgery procedure (LSPS, LA and PLS) was developed based on a survey of leaders in the field.

Kickstand rods and correction of coronal malalignment in patients with adult spinal deformity.

PURPOSE: Coronal malalignment (CM) is a challenging spinal deformity to treat. The kickstand rod (KR) technique is powerful for correcting truncal shift. This study tested the hypothesis that the KR technique provides superior coronal alignment correction in adult deformity compared with traditional rod techniques. METHODS: A retrospective evaluation of a prospectively collected multicenter database was performed. A 2:1 matched cohort of non-KR accessory rod and KR patients was planned based on preoperative coronal balance distance (CBD) and a vector of global shift. Patients were subgrouped according to CM classification with a 30-mm CBD threshold defining CM, and comparisons of surgical and clinical outcomes among groups was performed. RESULTS: Twenty-one patients with preoperative CM treated with a KR were matched to 36 controls. KR-treated patients had improved CBD compared with controls (18 vs. 35 mm, P < 0.01). The postoperative CBD did not result in clinical differences between groups in patient-reported outcomes (P ≥ 0.09). Eight (38%) of 21 KR patients and 12 (33%) of 36 control patients with preoperative CM had persistent postoperative CM (P = 0.72). CM class did not significantly affect the likelihood of treatment failure (postoperative CBD > 30 mm) in the KR cohort (P = 0.70), the control cohort (P = 0.35), or the overall population (P = 0.31). CONCLUSIONS: Application of the KR technique to coronal spinal deformity in adults allows for successful treatment of CM. Compared to traditional rod techniques, the use of KRs did not improve clinical outcome measures 1 year after spinal deformity surgery but was associated with better postoperative coronal alignment.

COVID-19 convalescent plasma composition and immunological effects in severe patients.

Convalescent plasma (CP) has emerged as a treatment for COVID-19. However, the composition and mechanism of action are not fully known. Therefore, we undertook a two-phase controlled study in which, first the immunological and metabolomic status of recovered and severe patients were evaluated. Secondly, the 28-day effect of CP on the immune response in severe patients was assessed. Nineteen recovered COVID-19 patients, 18 hospitalized patients with severe disease, and 16 pre-pandemic controls were included. Patients with severe disease were treated with CP transfusion and standard therapy (i.e., plasma recipients, n = 9) or standard therapy alone (n = 9). Clinical and biological assessments were done on day 0 and during follow-up on days 4, 7, 14, and 28. Clinical parameters, viral load, total immunoglobulin (Ig) G and IgA anti-S1-SARS-CoV-2 antibodies, neutralizing antibodies (NAbs), autoantibodies, cytokines, T and B cells, and metabolomic and lipidomic profiles were examined. Total IgG and IgA anti-S1-SARS-CoV-2 antibodies were key factors for CP selection and correlated with NAbs. In severe COVID-19 patients, mostly interleukin (IL)-6 (P = <0.0001), IL-10 (P = <0.0001), IP-10 (P = <0.0001), fatty acyls and glycerophospholipids were higher than in recovered patients. Latent autoimmunity and anti-IFN-α antibodies were observed in both recovered and severe patients. COVID-19 CP induced an early but transient cytokine profile modification and increases IgG anti-S1-SARS-CoV-2 antibodies. At day 28 post-transfusion, a decrease in activated, effector and effector memory CD4+ (P < 0.05) and activated and effector CD8+ (P < 0.01) T cells and naïve B cells (P = 0.001), and an increase in non-classical memory B cells (P=<0.0001) and central memory CD4+ T cells (P = 0.0252) were observed. Moreover, IL-6/IFN-γ (P = 0.0089) and IL-6/IL-10 (P = 0.0180) ratios decreased in plasma recipients compared to those who received standard therapy alone. These results may have therapeutic implications and justify further post-COVID-19 studies.

Mortality and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with covid-19 in critically ill patients: an observational multicenter study (MISCO study).

BACKGROUND: The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is widespread and presents a very low mortality rate in high-income countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries and the factors associated with the rate of mortality and patients with critical outcomes. METHODS: An observational cohort study was conducted in 14 pediatric intensive care units (PICUs) in Colombia between April 01, 2020, and January 31, 2021. Patient age ranged between one month and 18 years, and each patient met the requirements set forth by the World Health Organization (WHO) for MIS-C. RESULTS: There were seventy-eight children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old, and 56 % were male. 35 % of patients (29/78) were obese or overweight. The PICU stay per individual was six days (IQR 4-7), and 100 % had a fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87 % (68/78) had shock or systolic myocardial dysfunction (78 %). Coronary aneurysms were found in 35 % (27/78) of cases, and pericardial effusion was found in 36 %. When compared to existing data in high-income countries, there was a higher mortality rate observed (9 % vs. 1.8 %; p=0.001). When assessing the group of patients that did not survive, a higher frequency of ferritin levels was found, above 500 ngr/mL (100 % vs. 45 %; p=0.012), as well as more cardiovascular complications (100 % vs. 54 %; p = 0.019) when compared to the group that survived. The main treatments received were immunoglobulin (91 %), vasoactive support (76 %), steroids (70.5 %) and antiplatelets (44 %). CONCLUSIONS: Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. The observed inflammatory response and cardiovascular involvement were conditions that, added to the later presentation, may explain the higher mortality seen in these children.

A mitogenomic phylogeny of chitons (Mollusca: Polyplacophora).

BACKGROUND: Polyplacophora, or chitons, have long fascinated malacologists for their distinct and rather conserved morphology and lifestyle compared to other mollusk classes. However, key aspects of their phylogeny and evolution remain unclear due to the few morphological, molecular, or combined phylogenetic analyses, particularly those addressing the relationships among the major chiton lineages. RESULTS: Here, we present a mitogenomic phylogeny of chitons based on 13 newly sequenced mitochondrial genomes along with eight available ones and RNAseq-derived mitochondrial sequences from four additional species. Reconstructed phylogenies largely agreed with the latest advances in chiton systematics and integrative taxonomy but we identified some conflicts that call for taxonomic revisions. Despite an overall conserved gene order in chiton mitogenomes, we described three new rearrangements that might have taxonomic utility and reconstructed the most likely scenario of gene order change in this group. Our phylogeny was time-calibrated using various fossils and relaxed molecular clocks, and the robustness of these analyses was assessed with several sensitivity analyses. The inferred ages largely agreed with previous molecular clock estimates and the fossil record, but we also noted that the ambiguities inherent to the chiton fossil record might confound molecular clock analyses. CONCLUSIONS: In light of the reconstructed time-calibrated framework, we discuss the evolution of key morphological features and call for a continued effort towards clarifying the phylogeny and evolution of chitons.

Efficacy of the Spiration Valve System in Patients with Severe Heterogeneous Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Spiration Valve System (SVS) is an alternative for patients with severe heterogeneous emphysema; however, data about efficacy from randomized controlled trials (RCT) are unclear. OBJECTIVES: To explore both efficacy and safety of SVS in patients with severe emphysema and hyperinflation. METHODS: We included PubMed, EMBASE, Coch-rane database. All searches were performed until August 2019. Only RCTs were included for analysis. Risk of bias was assessed using Cochrane risk of bias tool. A meta-analysis evaluated change in forced expiratory volume in 1 s (FEV1), 6-min walking test (6MWT), residual volume, modified medical research council (mMRC) and Saint George respiratory questionnaire (SGRQ), all-cause mortality, risk of pneumothorax, and risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Quality of the evidence was rated using GRADE approach. RESULTS: Four RCTs including 629 subjects were included. SVS showed an overall change of 0.03 L (-0.07 to 0.13, I2 = 90%) in the in FEV1 (L) and a 2.03% (-2.50 to 6.57, I2 = 96%) in the predicted FEV1 (%) compared to baseline; however, studies without collateral ventilation (CV) showed an improvement of 0.12 L (95% CI 0.09-0.015, I2 = 0%), This subgroup also reported better results in SGRQ -12.27 points (95% CI -15.84 to -8.70, I2 = 0%) and mMRC -0.54 (95% CI -0.74 to -0.33, I2 = 0%). We found no benefit in 6MWT mean difference = 4.56 m (95% CI -21.88 to 31.00, I2 = 73%). Relative risk of mortality was 2.54 (95% CI 0.81-7.96, I2 = 0%), for pneumothorax 3.3 (95% CI 0.61-18.12, I2 = 0%) and AECOPD 1.68 (95% CI 1.04-2.70, I2 = 0%). CONCLUSION: In patients with severe heterogeneous emphysema and hyperinflation without CV, SVS is an alternative that showed an improvement in pulmonary function, quality of life, and dyspnea score with an acceptable risk profile.

Mini-open lateral retropleural/retroperitoneal approaches for thoracic and thoracolumbar junction anterior column pathologies.

OBJECTIVE: Advancements in less invasive lateral retropleural/retroperitoneal approaches aim to address the limitation of posterolateral approaches and avoid complications associated with anterior open thoracotomy or thoracoabdominal approaches. METHODS: Consecutive patients treated with a mini-open lateral approach for thoracic or thoracolumbar anterior column pathologies were analyzed in a retrospective case series including clinical and radiographic outcomes. Special attention is given to operative techniques and surgical nuances. RESULTS: Eleven patients underwent a mini-open lateral retropleural or combined retropleural/retroperitoneal approach for thoracic or thoracolumbar junction lesions. Surgical indications included chronic fracture/deformity (n = 5), acute fracture (n = 2), neoplasm (n = 2), and osteomyelitis (n = 2). The mean length of postoperative hospital stay was 7.2 days (range 2-19 days). All patients ultimately had successful decompression and reconstruction with a mean follow-up of 16.7 months (range 6-29 months). Axial back pain assessed by the visual analog scale improved from a mean score of 8.2 to 2.2. Complications included 1 patient with deep venous thrombosis and pulmonary embolism and 1 with pneumonia. One patient developed increased leg weakness, which subsequently improved. One patient undergoing corpectomy with only lateral plate fixation developed cage subsidence requiring posterior stabilization. CONCLUSIONS: Mini-open lateral retropleural and retroperitoneal corpectomies can safely achieve anterior column reconstruction and spinal deformity correction for various thoracic and thoracolumbar vertebral pathologies.

Single-position prone lateral approach: cadaveric feasibility study and early clinical experience.

OBJECTIVE: Lateral lumbar interbody fusion (LLIF) is a useful minimally invasive technique for achieving anterior interbody fusion and preserving or restoring lumbar lordosis. However, achieving circumferential fusion via posterior instrumentation after an LLIF can be challenging, requiring either repositioning the patient or placing pedicle screws in the lateral position. Here, the authors explore an alternative single-position approach: LLIF in the prone lateral (PL) position. METHODS: A cadaveric feasibility study was performed using 2 human cadaveric specimens. A retrospective 2-center early clinical series was performed for patients who had undergone a minimally invasive lateral procedure in the prone position between August 2019 and March 2020. Case duration, retractor time, electrophysiological thresholds, implant size, screw accuracy, and complications were recorded. Early postoperative radiographic outcomes were reported. RESULTS: A PL LLIF was successfully performed in 2 cadavers without causing injury to a vessel or the bowel. No intraoperative subsidence was observed. In the clinical series, 12 patients underwent attempted PL surgery, although 1 case was converted to standard lateral positioning. Thus, 11 patients successfully underwent PL LLIF (89%) across 14 levels: L2-3 (2 of 14 [14%]), L3-4 (6 of 14 [43%]), and L4-5 (6 of 14 [43%]). For the 11 PL patients, the mean (± SD) age was 61 ± 16 years, mean BMI was 25.8 ± 4.8, and mean retractor time per level was 15 ± 6 minutes with the longest retractor time at L2-3 and the shortest at L4-5. No intraoperative subsidence was noted on routine postoperative imaging. CONCLUSIONS: Performing single-position lateral transpsoas interbody fusion with the patient prone is anatomically feasible, and in an early clinical experience, it appeared safe and reproducible. Prone positioning for a lateral approach presents an exciting opportunity for streamlining surgical access to the lumbar spine and facilitating more efficient surgical solutions with potential clinical and economic advantages.

Intermediate-term clinical and radiographic outcomes with less invasive adult spinal deformity surgery: patients with a minimum follow-up of 4 years.

BACKGROUND: Little information exists regarding longer-term outcomes with minimally invasive spine surgery (MISS), particularly regarding long-segment and deformity procedures. We aimed to evaluate intermediate-term outcomes of MISS for adult spinal deformity (ASD). METHODS: This retrospective review of a prospectively collected multicenter database examined outcomes at 4 or more years following circumferential MIS (cMIS) or hybrid (HYB) surgery for ASD. A total of 53 patients at 8 academic centers satisfied the following inclusion criteria: age > 18 years and coronal Cobb > 20°, pelvic incidence-lumbar lordosis (PI-LL) > 10°, or sagittal vertical axis (SVA) > 5 cm. RESULTS: Radiographic outcomes demonstrated improvements of PI-LL from 16.8° preoperatively to 10.8° and coronal Cobb angle from 38° preoperatively to 18.2° at 4 years. The incidence of complications over the follow-up period was 56.6%. A total of 21 (39.6%) patients underwent reoperation in the thoracolumbar spine, most commonly for adjacent level disease or proximal junctional kyphosis, which occurred in 11 (20.8%) patients. Mean Oswestry Disability Index (ODI) at baseline and years 1 through 4 were 49.9, 33.1, 30.2, 32.7, and 35.0, respectively. The percentage of patients meeting minimal clinically important difference (MCID) (defined as 12% or more from baseline) decreased over time, with leg pain reduction more durable than back pain reduction. CONCLUSIONS: Intermediate-term clinical and radiographic improvement following MISS for ASD is sustained, but extent of improvement lessens over time. Outcome variability exists within a subset of patients not meeting MCID, which increases over time after year two. Loss of improvement over time was more notable in back than leg pain. However, average ODI improvement meets MCID at 4 years after MIS ASD surgery.

Characterization of the complete mitochondrial genome of Amblyomma ovale, comparative analyses and phylogenetic considerations.

In this study, we sequenced two complete mitochondrial genomes of Amblyomma ovale, a tick of public health importance. Sequencing two distinct individuals, the resulting mitochondrial genomes were 14,756 and 14,760 bp in length and maintained the same gene order previously reported in Amblyomma. These were combined with RNA-seq derived mitochondrial sequences from three additional species, Amblyomma aureolatum, Amblyomma maculatum, and Amblyomma moreliae, to carry out mitogenome comparative and evolutionary analyses against all previously published tick mitochondrial genomes. We described a derivative genome rearrangement that isolates Ixodes from the remaining Ixodidae and consists of both a reverse translocation as well as an event of Tandem Duplication Random Loss. Genetic distance analyses indicated that cox2, nd1, nd5, and 16S are good candidates for future population studies in A. ovale. The phylogenetic analyses corroborated the utility of complete mitochondrial genomes as phylogenetic markers within the group. This study further supplements the genome information available for Amblyomma and facilitates future evolutionary and population genetic studies within the genus.