Second-order optimization strategies for neural network quantum states.

The Variational Monte Carlo (VMC) method has recently seen important advances through the use of neural network quantum states. While more and more sophisticated ansatze have been designed to tackle a wide variety of quantum many-body problems, modest progress has been made on the associated optimization algorithms. In this work, we revisit the Kronecker-Factored Approximate Curvature (KFAC), an optimizer that has been used extensively in a variety of simulations. We suggest improvements in the scaling and the direction of this optimizer and find that they substantially increase its performance at a negligible additional cost. We also reformulate the VMC approach in a game theory framework, to propose a novel optimizer based on decision geometry. We find that on a practical test case for continuous systems, this new optimizer consistently outperforms any of the KFAC improvements in terms of stability, accuracy and speed of convergence. Beyond VMC, the versatility of this approach suggests that decision geometry could provide a solid foundation for accelerating a broad class of machine learning algorithms. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.

Evaluating compliance with the best practice guidelines for wrong-level surgery prevention in high-risk pediatric spine surgery.

PURPOSE: In 2018, Best Practice Guidelines (BPGs) were published for preventing wrong-level surgery in pediatric spinal deformity, but successful implementation has not been established. The purpose of this study was to evaluate BPG compliance 5 years after publication. We hypothesized higher compliance among BPG authors and among surgeons with more experience, higher caseload, and awareness of the BPGs. METHODS: We queried North American and European surgeons, authors and nonauthors, and members of pediatric spinal study groups on adherence to BPGs using an anonymous survey consisting of 18 Likert scale questions. Respondents provided years in practice, yearly caseload, and guideline awareness. Mean compliance scores (MCS) were developed by correlating Likert responses with MCS scores ("None of the time" = no compliance = MCS 0, "Sometimes" = weak to moderate = MCS 1, "Most of the time" = high = MCS 2, and "All the time" = perfect = MCS 3). RESULTS: Of the 134 respondents, 81.5% reported high or perfect compliance. Average MCS for all guidelines was 2.4 ± 0.4. North American and European surgeons showed no compliance differences (2.4 vs. 2.3, p = 0.07). Authors and nonauthors showed significantly different compliance scores (2.8 vs 2.4, p < 0.001), as did surgeons with and without knowledge of the BPGs (2.5 vs 2.2, p < 0.001). BPG awareness and compliance showed a moderate positive correlation (r = 0.48, p < 0.001), with non-significant associations between compliance and both years in practice (r = 0.41, p = 0.64) and yearly caseload (r = 0.02, p = 0.87). CONCLUSION: Surgeons reported high or perfect compliance 81.5% of the time with BPGs for preventing wrong-level surgery. Authorship and BPG awareness showed increased compliance. Location, study group membership, years in practice, and yearly caseload did not affect compliance. LEVEL OF EVIDENCE: Level V-expert opinion.

Fusion mass to pelvis internal distraction technique using multiple-hook fixation for scoliosis correction: illustrative case.

BACKGROUND: Internal distraction rods have been described as an alternative to halo gravity traction for the treatment of severe scoliosis. Distraction rods can be challenging to use in patients with existing fusion masses. The authors report an internal distraction, construct-to-construct rod technique using multiple-hook fixation in a patient with a sharply angulated cervicothoracic scoliosis fusion mass. OBSERVATIONS: A 12-year-old female with previously diagnosed congenital scoliosis who had undergone cervical fusion in situ at age 2 presented to the clinic with shortness of breath exacerbated by increased levels of activity. Standing anteroposterior and lateral scoliosis radiographs revealed a left >150° cervicothoracic curve, right 140° thoracolumbar curve, and left 28° lumbosacral fractional curve with pelvic obliquity. The authors indicated this patient for a 3-stage all-posterior approach for spinal fusion and deformity correction. In the final fusion surgery, the authors set up a construct-to-construct internal distraction configuration connecting the left hemipelvis to the cervicothoracic fusion mass to aid in deformity correction. LESSONS: A construct-to-construct internal distraction rod technique connecting a fusion mass to the pelvis can assist with curve correction in severe scoliosis.

Evaluating compliance with the 2013 best practice guidelines for preventing surgical site infection in high-risk pediatric spine surgery.

PURPOSE: Best Practice Guidelines (BPGs) were published one decade ago to decrease surgical site infection (SSI) in pediatric spinal deformity. Successful implementation has not been established. This study evaluated surgeon compliance with items on the BPG. We hypothesized that BPG authors and surgeons with more experience, higher caseload, and awareness of the BPG would have higher compliance. METHODS: We queried North American and European surgeons, authors and non-authors, and members of various spine study groups on adherence to BPGs using an anonymous survey. Mean compliance scores (MCSs) were developed by correlating Likert responses with MCSs ("None of the time" = no compliance = MCS 0, "Sometimes" = weak to moderate = MCS 1, "Most of the time" = high = MCS 2, "All the time" = perfect = MCS 3). RESULTS: Of the 142 respondents, 73.7% reported high or perfect compliance. Average compliance scores for all guidelines was 2.2 ± 0.4. There were significantly different compliance scores between North American and European surgeons (2.3 vs 1.8, p < 0.001), authors and non-authors (2.5 vs. 2.2, p = 0.023), and surgeons with and without knowledge of the BPGs (2.3 vs. 1.8, p < 0.001). There was a weak correlation between BPG awareness and compliance (r = 0.34, p < 0.001) and no correlation between years in practice (r = 0.0, p = 0.37) or yearly caseload (r = 0.2, p = 0.78) with compliance. CONCLUSIONS: Compliance among our cohort of surgeons surveyed was high. North American surgeons, authors of the BPGs and those aware of the guidelines had increased compliance. Participation in a spine study group, years in practice, and yearly caseload were not associated with compliance. LEVEL OF EVIDENCE: Level V-expert opinion.

Comparison of the clinical characteristics of SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) infected patients from a single hospitalist service.

BACKGROUND: While existing evidence suggests less severe clinical manifestations and lower mortality are associated with the Omicron variant as compared to the Delta variant. However, these studies fail to control for differences in health systems facilities and providers. By comparing patients hospitalized on a single medical service during the Delta and Omicron surges we were able to conduct a more accurate comparison of the two varaints' clinical manifestations and outcomes. METHODS: We conducted a prospective study of 364 Omicron (BA.1) infected patients on a single hospitalist service and compared these findings to a retrospective analysis of 241 Delta variant infected patients managed on the same service. We examined differences in symptoms, laboratory measures, and clinical severity between the two variants and assessed potential risk drivers for case mortality. FINDINGS: Patients infected with Omicron were older and had more underlying medical conditions increasing their risk of death. Although they were less severely ill and required less supplemental oxygen and dexamethasone, in-hospital mortality was similar to Delta cases, 7.14% vs. 4.98% for Delta (q-value = 0.38). Patients older than 60 years or with immunocompromised conditions had much higher risk of death during hospitalization, with estimated odds ratios of 17.46 (95% CI: 5.05, 110.51) and 2.80 (1.03, 7.08) respectively. Neither vaccine history nor variant type played a significant role in case fatality. The Rothman score, NEWS-2 score, level of neutrophils, level of care, age, and creatinine level at admission were highly predictive of in-hospital death. INTERPRETATION: In hospitalized patients, the Omicron variant is less virulent than the Delta variant but is associated with a comparable mortality. Clinical and laboratory features at admission are informative about the risk of death.

Immunohistochemical Analysis of Knee Chondral Defect Repair after Autologous Particulated Cartilage and Platelet-Rich Plasma Treatment in Sheep.

This study performs an analysis that will enable the evaluation of the quality, durability, and structure of repaired cartilaginous extracellular matrix tissue using an autologous-based particulated autograft cartilage and platelet-rich plasma treatment (PACI + PRP). A single-blind controlled experiment was conducted on 28 sheep to evaluate the efficacy of the PACI + PRP treatment for cartilage defects. Full-thickness 8 mm diameter defects were created in the weight-bearing area of both knees. The right knees received PACI + PRP. The left knees were treated with Ringer's lactate solution (RLS) or hyaluronic acid (HA) injections. Sheep were euthanized at 9- or 18-months post-surgery. An extensive immunohistochemical analysis was performed to assess collagen types (I, II, III, V, VI, IX, X, XI) and aggrecan positivity. A semiquantitative scoring system provided a detailed evaluation of immunostaining. Collagens and aggrecan scores in the PACI + PRP groups were similar to healthy cartilage. Significant differences were found in collagens associated with matrix maturity (II and V), degradation (IX), structure and mechanics (VI), and hypertrophy (X) between healthy cartilage and RLS- or HA-repaired cartilage. The PACI + PRP treatment advanced the repair cartilage process in chondral defects with mature hyaline cartilage and enhanced the structural and mechanical qualities with better consistent cartilage, less susceptible to degradation and without hypertrophic formation over time.

Thoracic pediculectomy for acute spinal cord decompression in high-risk spinal deformity correction: illustrative case.

BACKGROUND: Neurological complications are higher in patients with severe spinal deformities (Cobb angle >100°). The authors highlight a known technique for thoracic concave apical pedicle resection that is useful for spinal cord decompression in patients with high-risk spinal deformities in the setting of intraoperative neuromonitoring (IONM) changes. OBSERVATIONS: A 14-year-old female with progressive idiopathic scoliosis presented for evaluation of her clinical deformity. Scoliosis radiographs showed a double major curve pattern comprising a 107° right main thoracic curve and a compensatory 88° left thoracolumbar curve. She underwent 2 weeks of halo-gravity traction that reduced her major thoracic curve to 72°. During thoracic posterior column osteotomies, the authors were alerted to decreases in IONM signals that were not responsive to increases in mean arterial pressure, traction weight reduction, and convex compression maneuvers. The dural surface was tightly draped over the two thoracic apical pedicles of T7 and T8, so emergent pediculectomies were performed at both levels for spinal cord decompression. IONM signals gradually improved and eventually became even better than baseline. The patient woke up without any neurological deficits. LESSONS: Pediculectomy of the concave apical pedicle(s) should be considered for spinal cord decompression if there are IONM changes during high-risk spinal deformity surgery.

S-Nitrosylation in endothelial cells contributes to tumor cell adhesion and extravasation during breast cancer metastasis.

BACKGROUND: Nitric oxide is produced by different nitric oxide synthases isoforms. NO activates two signaling pathways, one dependent on soluble guanylate cyclase and protein kinase G, and other where NO post-translationally modifies proteins through S-nitrosylation, which is the modification induced by NO in free-thiol cysteines in proteins to form S-nitrosothiols. High levels of NO have been detected in blood of breast cancer patients and increased NOS activity has been detected in invasive breast tumors compared to benign or normal breast tissue, suggesting a positive correlation between NO biosynthesis, degree of malignancy and metastasis. During metastasis, the endothelium plays a key role allowing the adhesion of tumor cells, which is the first step in the extravasation process leading to metastasis. This step shares similarities with leukocyte adhesion to the endothelium, and it is plausible that it may also share some regulatory elements. The vascular cell adhesion molecule-1 (VCAM-1) expressed on the endothelial cell surface promotes interactions between the endothelium and tumor cells, as well as leukocytes. Data show that breast tumor cells adhere to areas in the vasculature where NO production is increased, however, the mechanisms involved are unknown. RESULTS: We report that the stimulation of endothelial cells with interleukin-8, and conditioned medium from breast tumor cells activates the S-nitrosylation pathway in the endothelium to induce leukocyte adhesion and tumor cell extravasation by a mechanism that involves an increased VCAM-1 cell surface expression in endothelial cells. We identified VCAM-1 as an S-nitrosylation target during this process. The inhibition of NO signaling and S-nitrosylation blocked the transmigration of tumor cells through endothelial monolayers. Using an in vivo model, the number of lung metastases was inhibited in the presence of the S-nitrosylation inhibitor N-acetylcysteine (NAC), which was correlated with lower levels of S-nitrosylated VCAM-1 in the metastases. CONCLUSIONS: S-Nitrosylation in the endothelium activates pathways that enhance VCAM-1 surface localization to promote binding of leukocytes and extravasation of tumor cells leading to metastasis. NAC is positioned as an important tool that might be tested as a co-therapy against breast cancer metastasis.

Three-stage correction of severe idiopathic scoliosis with limited skeletal traction during a humanitarian surgical mission: illustrative case.

BACKGROUND: Underprivileged and underserved patients from developing countries often present late with advanced, untreated spinal deformities. We report a three-stage all-posterior approach using limited skeletal traction with Gardner-Wells tongs (GWTs) for the management of severe idiopathic scoliosis during a humanitarian surgical mission trip. OBSERVATIONS: A 17-year-old high-school female was previously diagnosed with juvenile idiopathic scoliosis (diagnosed at age 8) and progressed to a severe 135° kyphoscoliosis. Procedural stage 1 involved spinal instrumentation and posterior releases via posterior column osteotomies from T3 to L4. She then underwent 7 days of skeletal traction with GWTs in the intensive care unit as stage 2. In stage 3, rod engagement, posterior spinal fusion, and partial T10 vertebral column resection were performed. There were no changes in intraoperative neuromonitoring during either surgery and she woke up neurologically intact after both stages of the surgical procedure. LESSONS: Skeletal traction with GWTs is a viable alternative to traditional halo-gravity traction in settings with limited resources. Three-stage spinal deformity correction using limited skeletal traction is a feasible and effective approach for managing severe scoliosis during humanitarian surgical mission trips.

Construct-to-construct biplanar cantilever technique for spinal deformity correction: illustrative case.

BACKGROUND: There is a continued trend toward posterior-only approaches for achieving spinal deformity correction of idiopathic scoliosis. We present a posteriorly based correction technique and en bloc translation reduction maneuver that can be useful in the management of kyphoscoliosis. OBSERVATIONS: A 50-year-old female with a past medical history of untreated adolescent idiopathic scoliosis since she was 12 years old presented to the clinic for evaluation of progressive thoracolumbar spinal deformity and worsening mid-to-low back pain. Standing scoliosis radiographs shows an 85° left lumbar curve with an apex at the L1-2 disk. There was a compensatory 58° right thoracic curve with an apex at T9, a -1.4 cm central vertical axis, and a focal kyphotic deformity of 86° from T11-L3 with a corresponding apex at the L1-2 disk. She was diagnosed with adult idiopathic scoliosis and indicated for a T9-L4 posterior spinal fusion with T11-L4 Smith-Peterson osteotomies. A simple en bloc reduction maneuver was used to translate the apex of the coronal deformity toward the midline and simultaneously correct the patient's focal kyphosis. LESSONS: A construct-to-construct biplanar cantilever technique is ideal for the treatment of kyphoscoliosis and can provide effective deformity correction in both the sagittal and coronal planes.

Step-by-step guide to robotic-guided minimally invasive transforaminal lumbar interbody fusion (MI-TLIF).

Robotics in spinal surgery offers a promising potential to refine and improve the minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) technique. Suitable surgeons for this technique include those who are already familiar with robotic-guided lumbar pedicle screw placement and want to advance their skillset by incorporating posterior-based interbody fusion. We provide a step-by-step guide for robotic-guided MI-TLIF. The procedure is divided into 7 practical and detailed techniques. The steps in sequential order include: (I) planning trajectories for pedicle screws and the tubular retractor; (II) robotic-guided pedicle screw placement; (III) placement of tubular retractor; (IV) unilateral facetectomy using the surgical microscope; (V) discectomy & disc preparation; (VI) interbody implant insertion; and (VII) percutaneous rod placement. We standardize surgeon training in robotic MI-TLIF by teaching our spine surgery fellows these 7 key technical steps highlighted in this guide. Current-generation robotics offers integrated navigation capability, K-wireless placement of pedicle screws through a rigid robotic arm, compatibility with tubular retractor systems to perform facetectomy, and allows for placement of interbody devices. We have found robotic-guided MI-TLIF to be a safe procedure that allows for accurate and reliable pedicle screw placement, less collateral damage to the soft tissues of the low back, and decreased radiation exposure.

Female Sex and Supine Proximal Lumbar Lordosis Are Associated With the Size of the LLIF "Safe Zone" at L4-L5.

STUDY DESIGN: Retrospective chart review. OBJECTIVE: Identify demographic and sagittal alignment parameters that are independently associated with femoral nerve position at the L4-L5 disk space. SUMMARY OF BACKGROUND DATA: Iatrogenic femoral nerve or lumbar plexus injury during lateral lumbar interbody fusion (LLIF) can result in neurological complications. The LLIF "safe zone" is the anterior half to two third of the disk space. However, femoral nerve position varies and is inconsistently identifiable on magnetic resonance imaging. The safe zone is also narrowest at L4-L5. METHODS: An analysis of patients with symptomatic lumbar spine pathology and magnetic resonance imaging with a visibly identifiable femoral nerve evaluated at a single large academic spine center from January 1, 2017, to January 8, 2020, was performed. Exclusion criteria were transitional anatomy, severe hip osteoarthritis, coronal deformity with cobb >10 degrees, > grade 1 spondylolisthesis at L4-L5 and anterior migration of the psoas.Standing and supine lumbar lordosis (LL) and its proximal (L1-L4) and distal (L4-S1) components were measured. Femoral nerve position on sagittal imaging was then measured as a percentage of the L4 inferior endplate. A stepwise multivariate linear regression of sagittal alignment and LL parameters was then performed. Data are written as estimate, 95% CI. RESULTS: Mean patient age was 58.2±14.7 years, 25 (34.2%) were female and 26 (35.6%) had a grade 1 spondylolisthesis. Mean femoral nerve position was 26.6±10.3% from the posterior border of L4. Female sex (-6.6, -11.1 to -2.1) and supine proximal lumbar lordosis (0.4, 0.1-0.7) were independently associated with femoral nerve position. CONCLUSIONS: Patient sex and proximal LL can serve as early indicators of the size of the femoral nerve safe zone during a transpsoas LLIF approach at L4-L5.

Particulate cartilage and platelet-rich plasma treatment for knee chondral defects in sheep.

PURPOSE: Articular cartilage is vulnerable to multiple types of damage and it has limited reparative and regenerative capacities due to its absence of vascularity. Although a large number of therapeutic strategies exist to treat chondral defects, they have some limitations, such as fibrocartilage formation. Therefore, the goal of the present study was to evaluate the chondrogenic regenerative properties of an autologous-made matrix of particulated cartilage and platelet-rich plasma (PACI + PRP) implantation for the treatment of full-thickness chondral defects in sheep. METHODS: A full-thickness 8 mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in both knees of 16 sheep. The right knees of all animals were treated with particulated autograft cartilage implantation and platelet-rich plasma, while the left knees were injected with Ringer's lactate solution or hyaluronic acid. The sheep were killed 9 or 18 months after surgery. Macroscopic evaluations were performed using three different scoring systems, and histopathological evaluations were performed using a modified scoring system based on different scoring systems. RESULTS: The PACI + PRP groups showed statistically significant differences in the percentage of defect repair and chondrocytes in the newly formed cartilage tissue at 18 months compared to 9 months. CONCLUSIONS: The results suggest that macroscopic appearance, histological structure and chondrocyte repair were improved when using PACI + PRP treatment for chondral defects, producing an outcome similar to the surrounding healthy cartilage. PACI + PRP is a totally autologous, easy, and unexpensive treatment that can be performed in one-step procedure and is useful as a therapeutic option for knee chondral defects.

Histological and biochemical evaluation of plasma rich in growth factors treatment for grade II muscle injuries in sheep.

The purpose of this study was to perform a histological and biochemical evaluation of the influence of plasma rich in growth factors (PRGF) on muscle regeneration process after a surgically induced grade II muscle laceration. A randomized, single blind, controlled experimental research was conducted including twenty-one adult healthy sheep, randomly divided in three groups (n = 7). A grade II surgical section was performed in the biceps femoris muscle of both hindlimbs. After two days (basal time), intralesional infiltration of autologous PRGF or Saline solution was randomly administered in both hindlimbs. Treatment was repeated once a week. Animal groups were euthanized at 1 (T1), 2 (T2) or 4 (T4) weeks. Histological assessment showed that PRGF intralesional injection induced a significant decrease of inflammatory cells density, significant higher centrally nucleated fibers percentage and significantly smaller fibrotic areas compared to Saline-treated muscles at T1, T2 and T4. Also, lower vascular density, with lower capillaries cross-sectional area, in PRGF group compared to Saline was observed. Biochemical analysis revealed a significant higher expression level of MYOD1, MYF5 and MYOG genes in PRGF groups at T1 compared to Saline treated muscles. At ultrastructural level, PRGF groups presented scarce edema and loss of connective tissue structure, as well as higher mitochondrial density adequately associated to the sarcomere unit in contrast to the Saline group. In conclusion, histological, biochemical, and ultrastructural results showed that PRGF treatment improved muscle regeneration process leading to more mature histological aspect in newly formed muscle tissue after a surgically induced grade II muscle injury.

Acute development of spinal lumbar synovial facet cyst within 1 week after lumbar decompression: illustrative case.

BACKGROUND: Synovial facet cysts can sometimes develop in patients with lumbar spinal stenosis after decompressive laminectomy. The etiology of spinal lumbar synovial cysts is still unclear, but their formation is associated with underlying spinal instability, facet joint arthropathy, and degenerative spondylolisthesis. OBSERVATIONS: A 61-year-old-male patient presented with neurogenic claudication due to lumbar spinal stenosis. Radiographic studies showed grade I spondylolisthesis and radiological predictors of delayed spinal instability. He underwent lumbar decompression and shortly thereafter developed spinal instability and recurrent symptoms, with formation of a new spinal lumbar synovial facet cyst. He required revisional decompression, cyst excision, and posterolateral spinal fusion for definitive treatment. LESSONS: The literature reports postoperative spinal instability in up to one-third of patients with lumbar spinal stenosis and stable degenerative spondylolisthesis who undergo decompressive laminectomy. Close radiographic monitoring and early advanced imaging may be prudent in this patient population if they develop new postoperative neurological symptoms and show radiographic predictors of instability on preoperative imaging. Posterolateral spinal fusion with instrumentation should be considered in addition to lumbar decompression in this select group of patients who demonstrate radiographic predictors of delayed spinal instability if they are medically capable of tolerating a spinal fusion procedure.

Anterior Cervical Foraminotomy for Radiculopathy After Cervical Artificial Disc Replacement: Technique Description and Case Report.

BACKGROUND: Patients may occasionally have persistent or recurrent radicular symptoms after cervical artificial disc replacement (ADR) for cervical spondylotic radiculopathy. We describe our approach using anterior cervical foraminotomy (ACF) to provide symptom relief in such patients without the need to convert to a fusion or remove the ADR implant. METHODS: Our operative technique for ACF after cervical ADR begins by starting at the lateral edge of the ADR at the superior end plate of the inferior vertebral body. The ipsilateral uncovertebral joint is drilled with a combination of a high-speed burr and diamond-coated burr to minimize the risk of injury to the vertebral artery. The neuroforamen is entered after drilling through the posterior aspect of the uncinate process. The exiting cervical nerve root should be directly visualized, and a Kerrison rongeur may be used to trace along the nerve root laterally to remove any remaining uncinate osteophyte or process. We queried our internal database for patients with recurrent or new radicular pain following cervical ADR who underwent ACF. Clinical characteristics and outcomes were reported. RESULTS: Five patients with recurrent radicular symptoms after ADR were reviewed. Two ACFs were performed at C5-6, and 2 were performed at C6-7. Four patients developed ipsilateral recurrent radicular symptoms, and only 1 patient developed contralateral new radicular symptoms. Three patients reported complete resolution of their new or recurrent radicular symptoms following ACF, and 2 patients reported only partial resolution. No patients required conversion to a fusion. CONCLUSIONS: In patients with recurrent symptoms of cervical spondylotic radiculopathy following ADR, ACF with uncovertebral joint resection can be used to provide direct foraminal decompression without the need for implant removal. This approach also preserves motion at the affected level, preserves cervical spinal stability, and prevents the need for spinal fusion. CLINICAL RELEVANCE: Patients with persistent or recurrent radicular symptoms after cervical ADR may achieve resolution of symptoms through a modified ACF technique.

Severe bradycardia in a teenager as the initial manifestation for Guillain Barré syndrome: a case report.

BACKGROUND: Guillain-Barré syndrome is the most common cause of flaccid paralysis, with multiple known clinical variants. Autonomic dysfunction, although frequently reported in the clinical course, is often overlooked in the pediatric population and is usually not the initial presenting symptom in this age group CASE PRESENTATION: We present the case of a previously healthy 17-year-old who arrived at the Emergency Department complaining of gastrointestinal symptoms associated with lipothymia. An initial electrocardiogram (ECG) showed sustained sinus bradycardia subsequently associated with arterial hypertension. Structural and inflammatory cardiac pathology were ruled out, as well as auriculoventricular conduction block and posterior reversible encephalopathy syndrome. On the ninth day after initial symptoms, the patient presented sensory and motor nerve disturbances with the cerebrospinal fluid analysis showing a clear albumin-cytologic dissociation, consistent with an atypical presentation of GBS with autonomic dysfunction. Immunoglobulin therapy was administered, developing subsequent aseptic meningitis, that required discontinuation of previous therapy and treatment with plasmapheresis. Clinical improvement was achieved with full motor function recovery. CONCLUSION: This case illustrates a Guillain-Barré syndrome variant in which autonomic dysfunction preceded neurologic deficit, a finding uncommon in children, emphasizing this as an important differential diagnosis for severe bradycardia in pediatric patients.

Effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir and combinations thereof in hospitalized patients with COVID-19: a pragmatic, open-label randomized trial.

BACKGROUND: The use of rosuvastatin plus colchicine and emtricitabine/tenofovir in hospitalized patients with SARS-CoV-2 disease (COVID-19) has not been assessed. The objective of this study was to assess the effectiveness and safety of rosuvastatin plus colchicine, emtricitabine/tenofovir, and their combined use in these patients. METHODS: This was a randomized, controlled, open-label, multicentre, parallel, pragmatic study conducted in six referral hospitals in Bogotá, Colombia. The study enrolled hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 complicated with pneumonia, not on chronic treatment with the study medications, and with no contraindications for their use. Patients were assigned 1:1:1:1. 1) emtricitabine with tenofovir disoproxil fumarate (FTC/TDF, 200/300 mg given orally for 10 days); 2) colchicine plus rosuvastatin (COLCH+ROSU, 0.5 mg and 40 mg given orally for 14 days); 3) emtricitabine with tenofovir disoproxil plus colchicine and rosuvastatin at the same doses and for the same period of time (FTC/TDF+COLCH+ROSU); or 4) the Colombian consensus standard of care, including a corticosteroid (SOC). The primary endpoint was 28-day all-cause mortality. A modified intention-to-treat analysis was used together with a usefulness analysis to determine which could be the best treatment. The trial was registered at ClinicalTrials.gov: NCT04359095. FINDINGS: Out of 994 candidates considered between August 2020 and March 2021, 649 (65.3%) patients agreed to participate and were enrolled in this study; among them, 633 (97.5%) were included in the analysis. The mean age was 55.4 years (SD ± 12.8 years), and 428 (68%) were men; 28-day mortality was significantly lower in the FTC/TDF+COLCH+ROSUV group than in the SOC group, 10.7% (17/159) vs. 17.4% (28/161) (hazard ratio [HR] 0.53; 95% CI 0.29 to 0.96). Mortality in the FTC/TDF group was 13.8% (22/160, HR 0.68, 95% CI 0.39 to 1.20) and 14.4% in the COLCH+ROSU group (22/153) (HR 0.78, 95% CI 0.44 to 1.36). A lower need for invasive mechanical ventilation was observed in the FTC/TDF+COLCH+ROSUV group than in the SOC group (risk difference [RD] - 0.08, 95% CI 0.11 to 0.04). Three patients presented severe adverse events, one severe diarrhoea in the COLCH+ROSU and one in the FTC/TDF+COLCH+ROSU group and one general exanthema in the FTC/TDF group. INTERPRETATION: The combined use of FTC/TDF+COLCH+ROSU reduces the risk of 28-day mortality and the need for invasive mechanical ventilation in hospitalized patients with pulmonary compromise from COVID-19. More randomized controlled trials are needed to compare the effectiveness and cost of treatment with this combination versus other drugs that have been shown to reduce mortality from SARS-CoV-2 infection and its usefulness in patients with chronic statin use.

Preperitoneal ropivacaine infusion versus epidural ropivacaine-morphine for postoperative analgesia in dogs undergoing ovariohysterectomy: a randomized clinical trial.

OBJECTIVE: To assess the effect of continuous wound infusion (CWI) with preperitoneal ropivacaine on postoperative analgesia and compare it with the epidural administration of ropivacaine and morphine in bitches undergoing ovariohysterectomy. STUDY DESIGN: A parallel, randomized, clinical, prospective and nonblinded study. ANIMALS: A group of 38 Greyhound bitches. METHODS: In the catheter group (CathG), CWI with ropivacaine 1% (1 mg kg-1 + 0.8 mg kg-1 hour-1) was applied to the preperitoneal space over the surgical incision. In the epidural group (EpiG), ropivacaine 0.5% (1.3 mg kg-1) and morphine (0.1 mg kg-1) were epidurally administered. Occipital-coccygeal length was used to calculate the volume for the epidural. Pain was scored using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale-short form (CMPS-SF) before anaesthesia and at 2, 4, 6, 18, 21 and 24 hours after extubation. Incisional sensitivity using a dynamometer (MWTs-incision) was evaluated simultaneously. Plasma ropivacaine and cortisol concentrations, degree of sedation, motor blockade and response to interdigital clamping were measured or assessed. A two-way mixed analysis of variance and a Mann-Whitney U test were used to analyse data; p < 0.05. RESULTS: No differences were detected in the DIVAS (p = 0.301), CMPS-SF (p = 0.600) scores, MWTs-incision measurements (p = 0.257) and cortisol values (p = 0.878) between the groups. Rescue analgesia was required in two dogs, one in each group, at 2 hours. Sedation, motor blockade and negative response to interdigital clamping were detected in EpiG at 2, 4 and 6 hours. Mean plasma ropivacaine values were higher in CathG (0.475 ± 0.164 ng mL-1) than in EpiG (0.184 ± 0.213 ng mL-1; p = 0.001). CONCLUSION AND CLINICAL RELEVANCE: Compared with epidural ropivacaine and morphine, CWI with preperitoneal ropivacaine is an effective analgesic technique for postoperative pain management in bitches undergoing ovariohysterectomy without motor blockade.