Clinical Characterization of Patients With COVID-19 in Primary Care in Catalonia: Retrospective Observational Study.

BACKGROUND: The country of Spain has one of the highest incidences of COVID-19, with more than 1,000,000 cases as of the end of October 2020. Patients with a history of chronic conditions, obesity, and cancer are at greater risk from COVID-19; moreover, concerns surrounding the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin type II receptor blockers (ARBs) and its relationship to COVID-19 susceptibility have increased since the beginning of the pandemic. OBJECTIVE: The objectives of this study were to compare the characteristics of patients diagnosed with COVID-19 to those of patients without COVID-19 in primary care; to determine the risk factors associated with the outcome of mortality; and to determine the potential influence of certain medications, such as ACEIs and ARBs, on the mortality of patients with COVID-19. METHODS: An observational retrospective study of patients diagnosed with COVID-19 in the Catalan Central Region of Spain between March 1 and August 17, 2020, was conducted. The data were obtained from the Primary Care Services Information Technologies System of the Catalan Institute of Health in Barcelona, Spain. RESULTS: The study population included 348,596 patients (aged >15 years) registered in the Primary Care Services Information Technologies System of the Catalan Central Region. The mean age of the patients was 49.53 years (SD 19.42), and 31.17% of the patients were aged ≥60 years. 175,484/348,596 patients (50.34%) were women. A total of 23,844/348,596 patients (6.84%) in the population studied were diagnosed with COVID-19 during the study period, and the most common clinical conditions of these patients were hypertension (5267 patients, 22.1%) and obesity (5181 patients, 21.7%). Overall, 2680/348,596 patients in the study population (0.77%) died during the study period. The number of deaths among patients without COVID-19 was 1825/324,752 (0.56%; mean age 80.6 years, SD 13.3), while among patients diagnosed with COVID-19, the number of deaths was 855/23,844 (3.58%; mean age 83.0 years, SD 10.80) with an OR of 6.58 (95% CI 6.06-7.15). CONCLUSIONS: We observed that women were more likely to contract COVID-19 than men. In addition, our study did not show that hypertension, obesity, or being treated with ACEIs or ARBs was linked to an increase in mortality in patients with COVID-19. Age is the main factor associated with mortality in patients infected with SARS-CoV-2.

Review of the main surgical and angiographic-oriented classifications of the course of the internal carotid artery through a novel interactive 3D model.

The course of the internal carotid artery (ICA) and its segment classifications were reviewed by means of a new and freely available 3D interactive model of the artery and the skull base, based on human neuroimages, that can be freely downloaded at the Public Repository of the University of Barcelona (http://diposit.ub.edu/dspace/handle/2445/112442) and runs under Acrobat Reader in Mac and Windows computers and Windows 10 tablets. The 3D-PDF allows zoom, rotation, selective visualization of structures, and a predefined sequence view. Illustrative images of the different classifications were obtained. Fischer (Zentralbl Neurochir 3:300-313, 1938) described five segments in the opposite direction to the blood flow. Gibo-Rothon (J Neurosurg 55:560-574, 1981) follow the blood flow, incorporated the cervical and petrous portions, and divided the subarachnoid course-supraclinoid-in ophthalmic, communicating, and choroidal segments, enhancing transcranial microscopic approaches. Bouthillier (Neurosurgery 38:425-433, 1996) divided the petrous portion describing the lacerum segment (exposed in transfacial procedures and exploration of Meckel's cave) and added the clinoid segment between the proximal and distal dural rings, of interest in cavernous sinus surgery. The Kassam's group (2014), with an endoscopic endonasal perspective, introduces the "paraclival segment," including the "lacerum segment" and part of the intracavernous ICA, and details surgical landmarks to minimize the risk of injury. Other classifications are also analyzed. This review through an interactive 3D tool provides virtual views of the ICA and becomes an innovative perspective to the segment classifications and neuroanatomy of the ICA and surrounding structures.

A Novel and Freely Available Interactive 3d Model of the Internal Carotid Artery.

We describe a new and freely available 3D interactive model of the intracranial internal carotid artery (ICA) and the skull base that also allows to display and compare its main segment classifications. High-resolution 3D human angiography (isometric voxel's size 0.36 mm) and Computed Tomography angiography images were exported to Virtual Reality Modeling Language (VRML) format for processing in a 3D software platform and embedding in a 3D Portable Document Format (PDF) document that can be freely downloaded at http://diposit.ub.edu/dspace/handle/2445/112442 and runs under Acrobat Reader on Mac and Windows computers and Windows 10 tablets. The 3D-PDF allows for visualisation and interaction through JavaScript-based functions (including zoom, rotation, selective visualization and transparentation of structures or a predefined sequence view of the main segment classifications if desired). The ICA and its main branches and loops, the Gasserian ganglion, the petrolingual ligament and the proximal and distal dural rings within the skull base environment (anterior and posterior clinoid processes, silla turcica, ethmoid and sphenoid bones, orbital fossae) may be visualized from different perspectives. This interactive 3D-PDF provides virtual views of the ICA and becomes an innovative tool to improve the understanding of the neuroanatomy of the ICA and surrounding structures.

Electron Microscopy of Dural and Arachnoid Disruptions After Subarachnoid Block.

BACKGROUND: It has been customary to attribute postdural puncture headache (PDPH) incidence and severity to size and nature of the dural hole produced during major neuraxial blockade or diagnostic dural puncture. Needle orientation in relation to the direction of dural fibers was thought to be of importance because of the propensity for horizontal bevel placement to cause cutting rather than splitting of the dural fibers. METHODS: In vitro punctures of stringently quality-controlled human dural sac specimens were obtained with 27-gauge (27G) Whitacre needle (n = 33), with 29G Quincke used parallel to the spinal axis (n = 30), and with 29G Quincke in perpendicular approach (n = 40). The samples were studied with a scanning electron microscope, and the perimeter, appearance, and area (%) of the lesion were calculated. RESULTS: When using small 27G to 29G needles, neither needle tip characteristics nor needle orientation had a substantial bearing on the damage to dural fibers in the dural lesion. Of ultimate importance was the characteristic and size of the hole in the arachnoid. Arachnoid layer lesions produced by different types of spinal needles were not markedly different. CONCLUSIONS: Accepted theories of the etiology of PDPH need to be revised. This article marks the first time that arachnoid layer damage has been quantified. Dural fibers tend to have sufficient "memory" to close back the hole created by a spinal needle, whereas arachnoid has diminished capacity to do so. The pathogenesis of PDPH and its resolution algorithm are a far more complex process that involves many more "stages" of development than hitherto imagined.

Pythagoras and Cosines: The skin-dural sac distance and optimal angles in paramedian spinal anesthesia.

The classical recommendation for paramedian approaches is needle insertion 1-2 cm paramedian and an angle of 10°-15° medial-cephalad to the plane of the back, but contact with vertebrae is frequent. A mathematical approach to individualizing punctures is proposed on the basis of skin-dural sac distance (d): Optimal angle ∼ inverse cosine [d/ √(1+d^2) ] and the distance covered by the needle ∼ √(1+d^2) for 1 cm paramedian punctures. The inferred angles were compared to optimal angles leading to the central dorsal part of the dural sac from 1 to 2 cm paramedian, measured by Magnetic Resonance Imaging (MRI) in seven cases and in a short stature volunteer (1.58 m, Body Mass Index (BMI) 23.2), to study supine and fetal positions using both closed MR and ultrasound. The average (d) decreased rostrally [6.8 cm (L4-L5)-4.3 cm (T11-T12)] while the mean optimal incidence angles increased [8.3°-16.5° (L4-L5) to 12.7°-24.1° (T11-T12) at 1-2 cm paramedian, respectively] and coincided with the estimated angles with a correlation coefficient = 0.98. In the volunteer, the optimal lateromedial angles increased from 14.4° to 26.7° (L3-L4) to 17.1°-30.3° (T11-T12) for a (d) = 3.7 cm (L3-L4)-3.1 cm (T11-T12) and increased ≤3.7° and ≤5.1° at 1 and 2 cm paramedian, respectively, in fetal positions in MR. Ultrasound yielded comparable figures. The range of possible angles for dural punctures is wider at 1 cm paramedian in lower approaches in lateral decubitus [from 3.6° at T12L1 (12.2°-15.8°) to 9° at L3L4 (8.8°-18.7°)]. The classically recommended angles of 10°-15° differ from the optimal angles, particularly in small patients, suggesting the need for ultrasound guidance or for inferring angles prior to spinal anesthesia. Clin. Anat. 29:1046-1052, 2016. © 2016 Wiley Periodicals, Inc.

Human Lumbar Ligamentum Flavum Anatomy for Epidural Anesthesia: Reviewing a 3D MR-Based Interactive Model and Postmortem Samples.

The ligamentum flavum (LF) forms the anatomic basis for the loss-of-resistance technique essential to the performance of epidural anesthesia. However, the LF presents considerable interindividual variability, including the possibility of midline gaps, which may influence the performance of epidural anesthesia. We devise a method to reconstruct the anatomy of the digitally LF based on magnetic resonance images to clarify the exact limits and edges of LF and its different thickness, depending on the area examined, while avoiding destructive methods, as well as the dissection processes. Anatomic cadaveric cross sections enabled us to visually check the definition of the edges along the entire LF and compare them using 3D image reconstruction methods. Reconstruction was performed in images obtained from 7 patients. Images from 1 patient were used as a basis for the 3D spinal anatomy tool. In parallel, axial cuts, 2 to 3 cm thick, were performed in lumbar spines of 4 frozen cadavers. This technique allowed us to identify the entire ligament and its exact limits, while avoiding alterations resulting from cutting processes or from preparation methods. The LF extended between the laminas of adjacent vertebrae at all vertebral levels of the patients examined, but midline gaps are regularly encountered. These anatomical variants were reproduced in a 3D portable document format. The major anatomical features of the LF were reproduced in the 3D model. Details of its structure and variations of thickness in successive sagittal and axial slides could be visualized. Gaps within LF previously studied in cadavers have been identified in our interactive 3D model, which may help to understand their nature, as well as possible implications for epidural techniques.

Cryostat Slice Irregularities May Introduce Bias in Tissue Thickness Estimation: Relevance for Cell Counting Methods.

Stereological techniques using the optical disectors require estimation of final section thickness, but frozen tissue irregularities may interfere with this estimation. Cryostat slices from rodent nerve tissues (dorsal root ganglia, spinal cord, and brain), cut at 16, 40, and 50 µm, were digitized with a confocal microscope and visualized through 3D software. Geometric section thickness of tissue (T geom) was defined as tissue volume/area. Maximal section thicknesses (T max), from the top to the bottom of the section, were measured in a random sample of vertical ZX planes. Irregularities were mostly related to blood vessels traversing the tissue and neuronal somas protruding over the cut surfaces, with other neuron profiles showing a fragmented appearance. Irregularities contributed to increasing the distance between the tops and bottoms of slices sectioned in different laboratories. Significant differences were found between T max and T geom for all thickness studies and counting frames (p<0.01). The T geom/T max average rate was 68.4-85.7% in volumes around cell profiles (∼600-1,200 µm2) and 83.3-91.8% in subcellular samples (∼25-160 µm2). Confocal microscopy may help to assess tissue irregularities, which might lead to an overestimation of tissue volume if section thickness is estimated by focusing on the top and bottom of the sections.

Threshold selection criteria for quantification of lumbosacral cerebrospinal fluid and root volumes from MRI.

BACKGROUND AND PURPOSE: The high variability of CSF volumes partly explains the inconsistency of anesthetic effects, but may also be due to image analysis itself. In this study, criteria for threshold selection are anatomically defined. METHODS: T2 MR images (n = 7 cases) were analyzed using 3-dimentional software. Maximal-minimal thresholds were selected in standardized blocks of 50 slices of the dural sac ending caudally at the L5-S1 intervertebral space (caudal blocks) and middle L3 (rostral blocks). Maximal CSF thresholds: threshold value was increased until at least one voxel in a CSF area appeared unlabeled and decreased until that voxel was labeled again: this final threshold was selected. Minimal root thresholds: thresholds values that selected cauda equina root area but not adjacent gray voxels in the CSF-root interface were chosen. RESULTS: Significant differences were found between caudal and rostral thresholds. No significant differences were found between expert and nonexpert observers. Average max/min thresholds were around 1.30 but max/min CSF volumes were around 1.15. Great interindividual CSF volume variability was detected (max/min volumes 1.6-2.7). CONCLUSIONS: The estimation of a close range of CSF volumes which probably contains the real CSF volume value can be standardized and calculated prior to certain intrathecal procedures.

3D interactive model of lumbar spinal structures of anesthetic interest.

A 3D model of lumbar structures of anesthetic interest was reconstructed from human magnetic resonance (MR) images and embedded in a Portable Document Format (PDF) file, which can be opened by freely available software and used offline. The MR images were analyzed using a specific 3D software platform for biomedical data. Models generated from manually delimited volumes of interest and selected MR images were exported to Virtual Reality Modeling Language format and were presented in a PDF document containing JavaScript-based functions. The 3D file and the corresponding instructions and license files can be downloaded freely at http://diposit.ub.edu/dspace/handle/2445/44844?locale=en. The 3D PDF interactive file includes reconstructions of the L3-L5 vertebrae, intervertebral disks, ligaments, epidural and foraminal fat, dural sac and nerve root cuffs, sensory and motor nerve roots of the cauda equina, and anesthetic approaches (epidural medial, spinal paramedial, and selective nerve root paths); it also includes a predefined sequential educational presentation. Zoom, 360° rotation, selective visualization, and transparency graduation of each structure and clipping functions are available. Familiarization requires no specialized informatics knowledge. The ease with which the document can be used could make it valuable for anatomical and anesthetic teaching and demonstration of patient information.

Unintentional subdural placement of epidural catheters during attempted epidural anesthesia: an anatomic study of spinal subdural compartment.

BACKGROUND: Although infrequent, subdural block is a complication of epidural anesthesia with obvious implications. Knowledge of the spinal subdural compartment (dura-arachnoid interface) may help elucidate controversies arising from evidence that subdural catheter placement is feasible and may be difficult to identify clinically. METHODS: Samples of arachnoid lamina obtained during in vivo lumbosacral surgery (n = 4) and from cadavers (n = 6) were obtained and prepared for transmission electron microscopy and scanning electron microscopy. Subdural spaces were artificially produced in suitable samples, and an epidural catheter was inserted between the arachnoid and dura to compare the dimensions of meninges in relation to epidural catheters. RESULTS: Scanning electron microscopy of the dural sac showed areas of continuity between the arachnoid lamina and dura mater and other parts with both membranes separated by a subdural space. Transmission electron microscopy allowed the study of such border zones, where alternating cellular and collagen layers could be seen. A layer rich in collagen fibers and some fibroblasts separated arachnoid and neurothelial cells (dural border cells). Few specialized membrane junctions were found among cells adjacent to collagen fibers. Dura mater had an average thickness of 260 to 400 µm, with a dural lamina of approximately 4 to 6 µm. In areas where the arachnoid appeared separated from the dural lamina, its thickness measured 35 to 45 µm. Catheters with a diameter of 700 µm were successfully inserted inside the subdural space, between the dura mater and the arachnoid lamina. CONCLUSIONS: Dura mater and arachnoid layers act as a single unit but may be pulled apart by traction forces during cadaver processing of the dural sac or in vivo placement of catheters. This generates subdural spaces, either parallel or concentric, because of the minimal resistance offered by the tissue, which may be explained by its few specialized membrane junctions.

Estimations of topographically correct regeneration to nerve branches and skin after peripheral nerve injury and repair.

Peripheral nerve injury is typically associated with long-term disturbances in sensory localization, despite nerve repair and regeneration. Here, we investigate the extent of correct reinnervation by back-labeling neuronal soma with fluorescent tracers applied in the target area before and after sciatic nerve injury and repair in the rat. The subpopulations of sensory or motor neurons that had regenerated their axons to either the tibial branch or the skin of the third hindlimb digit were calculated from the number of cell bodies labeled by the first and/or second tracer. Compared to the normal control side, 81% of the sensory and 66% of the motor tibial nerve cells regenerated their axons back to this nerve, while 22% of the afferent cells from the third digit reinnervated this digit. Corresponding percentages based on quantification of the surviving population on the experimental side showed 91%, 87%, and 56%, respectively. The results show that nerve injury followed by nerve repair by epineurial suture results in a high but variable amount of topographically correct regeneration, and that proportionally more neurons regenerate into the correct proximal nerve branch than into the correct innervation territory in the skin.

On regenerative and collateral sprouting to hind limb digits after sciatic nerve injury in the rat.

PURPOSE: This study examines the proportions of regenerative and collateral sprouting to the skin after peripheral nerve injury. METHODS: In the first experimental paradigm, primary afferent neurones were pre-labelled with Diamidino Yellow (DY), injected in digit 3, followed by sciatic nerve section and repair. After three months of regeneration, digit 3 was re-injected with Fast Blue (FB) to label regenerating cells. Fluoro-Gold (FG) was applied to the femoral (FEM) and musculocutaneous (MC) nerves four days later to quantify their contribution to the innervation. In the second experimental paradigm, sciatic nerve was first sectioned and repaired. Three months later, the sciatic was resected, and digit 3 injected with FB. After four more days, FEM and MC were resected and FG injected in all digits. RESULTS: Neurones in dorsal root ganglion (DRG) L5 had a higher rate of correct reinnervation of digit 3 (44-72%) than neurones in DRG L4 (14-44%). Like in control cases, only occasional axons were traced from the FEM and MC. In the second experiment, only occasional labelled neurones appeared. CONCLUSIONS: The results indicate differences in the capacity for correct peripheral sensory reinnervation between segmental levels, and that in this model collateral sprouting was practically non-existent compared to regenerative sprouting.

Persistence of tracer in the application site--a potential confounding factor in nerve regeneration studies.

Selective reinnervation of peripheral targets after nerve injury might be assessed by injecting a first tracer in a target before nerve injury to label the original neuronal population, and applying a second tracer after the regeneration period to label the regenerated population. However, altered uptake of tracer, fading, and cell death may interfere with the results. Furthermore, if the first tracer injected remains in the target tissue, available for "re-uptake" by misdirected regenerating axons, which originally innervated another region, then the identification of the original population would be confused. With the aim of studying this problem, the sciatic nerve of adult rats was sectioned and sutured. After 3 days, to allow the distal axon to degenerate avoiding immediate retrograde transport, one of the dyes: Fast Blue (FB), Fluoro-Gold (FG) or Diamidino Yellow (DY), was injected into the tibial branch of the sciatic nerve, or in the skin of one of the denervated digits. Rats survived 2-3 months. The results showed labelled dorsal root ganglion (DRG) cells and motoneurones, indicating that late re-uptake of a first tracer occurs. This phenomenon must be considered when the model of sequential labelling is used for studying the accuracy of peripheral reinnervation.

On the use of fast blue, fluoro-gold and diamidino yellow for retrograde tracing after peripheral nerve injury: uptake, fading, dye interactions, and toxicity.

The usefulness of three retrograde fluorescent dyes for tracing injured peripheral axons was investigated. The rat sciatic was transected bilaterally and the proximal end briefly exposed to either Fast Blue (FB), Fluoro-Gold (FG) or to Diamidino Yellow (DY) on the right side, and to saline on the left side, respectively. The nerves were then resutured and allowed to regenerate. Electrophysiological tests 3 months later showed similar latencies and amplitudes of evoked muscle and nerve action potentials between tracer groups. The nerves were then cut distal to the original injury and exposed to a second (different) dye. Five days later, retrogradely labelled neurones were counted in the dorsal root ganglia (DRGs) and spinal cord ventral horn. The number of neurones labelled by the first tracer was similar for all three dyes in the DRG and ventral horn except for FG, which labelled fewer motoneurones. When used as second tracer, DY labelled fewer neurones than FG and FB in some experimental situations. The total number of neurones labelled by the first and/or second tracer was reduced by about 30% compared with controls. The contributions of cell death as well as different optional tracer combinations for studies of nerve regeneration are discussed.