The impact of protocol-based high-intensity pharmacological thromboprophylaxis on thrombotic events in critically ill COVID-19 patients.

The reported incidence rate of venous and arterial thrombotic events in critically ill patients with COVID-19 infections is high, ranging from 20% to 60%. We adopted a patient-tailored thromboprophylaxis protocol based on clinical and laboratory presentations for these patients in our institution. We hypothesised that patients who received high-intensity thromboprophylaxis treatment would experience fewer thrombotic events. The aims of our study were to explore the incidence of thrombotic events in this population; to assess independent factors associated with thrombotic events and to evaluate the incidence of haemorrhagic events. A retrospective review of all adult patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) between 1 March and 29 May 2020 was performed. The primary outcome was a composite of venous and arterial thrombotic events diagnosed during the ICU stay. Multivariable logistic regression was used to identify the independent factors associated with thrombotic events. A total of 188 patients met the inclusion criteria. All received some type of thromboprophylaxis treatment except for six patients who did not receive any prophylaxis. Of the 182 patients who received thromboprophylaxis, 75 (40%) received high-intensity thromboprophylaxis and 24 (12.8%) were treated with therapeutic anticoagulation. Twenty-one patients (11.2%) experienced 23 thrombotic events (incidence rate of 12.2% (95%CI 7.9-17.8)), including 12 deep venous thromboses, 9 pulmonary emboli and 2 peripheral arterial thromboses. The multivariable logistic regression analysis showed that only D-dimer (OR 2.80, p = 0.002) and high-intensity thromboprophylaxis regimen (OR 0.20, p = 0.01) were independently associated with thrombotic events. Thirty-one patients (16.5%) experienced haemorrhagic events; among them, 13 were classified as major bleeding according to the International Society on Thrombosis and Haemostasis criteria. Therapeutic anticoagulation, but not the high-intensity thromboprophylaxis regimen, was associated with major bleeding. A proactive approach to the management of thromboembolism in critically ill COVID-19 patients utilising a high-intensity thromboprophylaxis regimen in appropriately selected patients may result in lower thrombotic events without increasing the risk of bleeding.

Effect of the intra-abdominal pressure and the center of segmental body mass on the lumbar spine mechanics - a computational parametric study.

Determination of physiological loads in human lumbar spine is critical for understanding the mechanisms of lumbar diseases and for designing surgical treatments. Computational models have been used widely to estimate the physiological loads of the spine during simulated functional activities. However, various assumptions on physiological factors such as the intra-abdominal pressure (IAP), centers of mass (COMs) of the upper body and lumbar segments, and vertebral centers of rotation (CORs) have been made in modeling techniques. Systematic knowledge of how these assumptions will affect the predicted spinal biomechanics is important for improving the simulation accuracy. In this paper, we developed a 3D subject-specific numerical model of the lumbosacral spine including T12 and 90 muscles. The effects of the IAP magnitude and COMs locations on the COR of each motion segment and on the joint/muscle forces were investigated using a global convergence optimization procedure when the subject was in a weight bearing standing position. The data indicated that the line connecting the CORs showed a smaller curvature than the lordosis of the lumbar spine in standing posture when the IAP was 0 kPa and the COMs were 10 mm anterior to the geometric center of the T12 vertebra. Increasing the IAP from 0 kPa to 10 kPa shifted the location of CORs toward the posterior direction (from 1.4 ± 8.9 mm anterior to intervertebral disc (IVD) centers to 40.5 ± 3.1 mm posterior to the IVD centers) and reduced the average joint force (from 0.78 ± 0.11 Body weight (BW) to 0.31 ± 0.07 BW) and overall muscle force (from 349.3 ± 57.7 N to 221.5 ± 84.2 N). Anterior movement of the COMs from -30 mm to 70 mm relative to the geometric center of T12 vertebra caused an anterior shift of the CORs (from 25.1 ± 8.3 mm posterior to IVD centers to 7.8 ± 6.2 mm anterior to IVD centers) and increases of average joint forces (from 0.78 ± 0.1 BW to 0.93 ± 0.1 BW) and muscle force (from 348.9 ± 47.7 N to 452.9 ± 58.6 N). Therefore, it is important to consider the IAP and correct COMs in order to accurately simulate human spine biomechanics. The method and results of this study could be useful for designing prevention strategies of spinal injuries and recurrences, and for enhancing rehabilitation efficiency.

Application of finite element analysis in pre-operative planning for deformity correction of abnormal hip joints--a case series.

In experimental and clinical research, it is difficult to directly measure responses in the human body, such as contact pressure and stress in a joint, but finite element analysis (FEA) enables the examination of in vivo responses by contact analysis. Hence, FEA is useful for pre-operative planning prior to orthopaedic surgeries, in order to gain insight into which surgical options will result in the best outcome. The present study develops a numerical simulation technique based on FEA to predict the surgical outcomes of osteotomy methods for the treatment of slipped capital femoral epiphyses. The correlation of biomechanical parameters including contact pressure and stress, for moderate and severe cases, is investigated. For severe slips, a base-of-neck osteotomy is thought to be the most reliable and effective surgical treatment, while any osteotomy may produce dramatic improvement for moderate slips. This technology of pre-operative planning using FEA can provide information regarding biomechanical parameters that might facilitate the selection of optimal osteotomy methods and corresponding surgical options.

Cloning and sequencing of a cDNA encoding the coat protein of a Korean isolate of cymbidium mosaic virus.

The 3'-terminal nucleotide (nt) sequence of the coat protein (CP)-encoding gene of the Korean isolate of cymbidium mosaic potexvirus (CyMV-K) has been determined. The sequence contained a full-length ORF coding for the viral CP. It comprises 663 nt and a polypeptide chain of 220 amino acids with a M(r) of 23,718. The stop codon (TGA) is followed by a 3'-untranslated region (3'-UTR) of 79 nt and a poly(A) tract. The putative polyadenylation signal, AATAAA motif, is found in the terminus of the 3'-UTR.

Electrode-derived myocardial pH measurements reflect intracellular myocardial metabolism assessed by phosphorus 31-nuclear magnetic resonance spectroscopy during normothermic ischemia.

To determine the ability of extracellular myocardial tissue pH measured with an intramural electrode to reflect myocardial intracellular metabolic status during normothermic ischemia, we studied 14 open-chest dogs with in vivo phosphorus 31-nuclear magnetic resonance spectroscopy during left anterior descending coronary artery occlusion (experimental group, group I, n = 7) or after a sham operation (control group, nonischemic, group II, n = 7). Phosphorus nuclear magnetic resonance spectra were acquired every 5 minutes at 4.7 tesla (256 averages, TR = 1000 msec, pulse width = 30 microseconds) with a 2 cm two-turn radiofrequency surface coil. Intracellular myocardial adenosine triphosphate peak area was normalized to an external phosphate standard. The change in adenosine triphosphate peak area was expressed as percent of baseline value. During 3 hours of normothermic ischemia the observed extracellular myocardial pH correlated with nuclear magnetic resonance-calculated myocardial pH in the ischemic dogs with an average r value of 0.94 (p less than 0.0001). During this same interval, the fall in extracellular myocardial pH correlated with the loss of adenosine triphosphate peak in each ischemic dog, with an average r value of 0.91 (p less than 0.0001). Thus extracellular myocardial pH, measured with an intramural electrode, correlated with nuclear magnetic resonance-derived myocardial pH and loss of myocyte adenosine triphosphate peak content and reflected the metabolic status of the myocyte during ischemia. These data validate the use of extracellular myocardial pH to assess the adequacy of myocardial preservation during aortic crossclamping for cardiac operations.

Rapid detection and identification of odontoglossum ringspot virus by polymerase chain reaction amplification.

The odontoglossum ringspot Tobamovirus (ORSV) movement and coat proteins genes were selected for the design of oligonucleotide primers for amplification of a 1,085 bp fragment. A combined assay of reverse transcription and the polymerase chain reaction (RT-PCR) was performed with 20-mer ORSV-specific primers and crude nucleic acid extracts from virus-infected orchids for rapid detection of the virus. The lowest concentration of template viral RNA required for detection was 10 fg. The RT-PCR is a 10(3) times more sensitive, reproducible and time-saving method than the enzyme-linked immunosorbent assay. No PCR product was observed when cymbidium mosaic potexvirus or a crude extract of healthy Cymbidium sp. were used as a template in RT-PCR with the same primers. The specificity of the primers was verified using other tobamoviruses RNAs.

Sequence analysis of the coat protein and 3'-noncoding region for Korean and other strains of sweet potato feathery mottle virus.

The 3'-terminal regions of the genomic RNAs of two Korean isolates of sweet potato feathery mottle potyvirus (SPFMV) were cloned and their nucleotide sequences of full-length coat protein (CP) gene and 3' noncoding region (NCR) were determined. The CP of the two Korean isolates contained 315 amino acid residues. The CP cistron sequences of the Korean isolates exhibit 72.7% to 98.7% nucleotide sequence identity and 79.9% to 99.0% amino acid identity when compared with those of 8 other known SPFMV strains. Pairwise comparison revealed sequence similarities of 47.4% to 62.1% at the nucleotide level, and 48.6% to 70.2% at the amino acid level between SPFMV and 21 other potyviruses. SPFMV CP has extensive amino acid sequence similarity to the other members of the genus Potyvirus throughout its central and C-terminal regions. The 3' NCR of the SPFMV showed 42.5% to 99.1% nucleotide sequence identities among the strains. The 3' NCR of SPFMV revealed 19.9% to 63.6% sequence similarities to those of 21 other potyviruses. These results support the assignment of SPFMV as a distinct member of the genus Potyvirus of the family Potyviridae.

Nucleotide sequence analysis of the 3'-terminal region of two Korean isolates of lily symptomless Carlavirus and expression of the coat protein in E. coli.

The 3'-terminal regions of the genomic RNAs of two Korean isolates of the lily symptomless Carlavirus (LSV), LSV-Ko and LSV-KII, were cloned and their nucleotide sequences were determined. The nucleotide sequence analysis and protein analysis by the Western blot revealed that E. coli expressed a 32-kDa protein that is the viral coat protein (CP) for the LSV. The two Korean strains share 98.4% and 98.3% sequence identities at the nucleotide and amino acid levels, respectively. The CP gene of LSV-Ko showed 99.1% and 87.0% nucleotide sequence identities, and 99.0% and 96.6% amino acid sequence identities with those of the Netherlands and the Japanese LSV strains, respectively. A pairwise amino acid sequence comparison revealed a sequence similarity of 29.6% to 69.8% between LSV-Ko and other species of the carlavirus. The 16 kDa protein of LSV-Ko shares 17.6% to 42.7% amino acid similarity with those of 8 other the carlaviruses, and they are variable in the N-terminal region. The Cys repeated zinc finger nucleic acid binding domain was found in the 16 kDa protein for all of the LSV strains. Sequence comparisons of the 7 kDa protein of LSV in the strain level showed significant identities from 100.0% to 98.4%. LSV-Ko shares 21.9% to 42.2% amino acid similarity with those of 8 other carlaviruses, 4 members of the potexviruses, and a closterovirus. LSV is closely related to blueberry scorch virus (BISV) based upon the phylogenetic tree analyses of the three proteins, indicating LSV to be a quite distinct member of the genus Carlavirus.

Gene silencing-mediated resistance in transgenic tobacco plants carrying potato virus Y coat protein gene.

Unlike other pathogens, plant viruses are hardly controlled by chemical agents. Potato virus Y (PVY) is distributed around the world, and causes a great loss economically. In an attempt to minimize the damage by viruses, the PVY coat protein (CP) gene was introduced into tobacco by Agrobacterium-mediated transformation. A significant proportion of the transgenic plants displayed resistance to PVY and showed substantially decreased CP transgene expression at both protein and steady-state mRNA levels compared to susceptible transgenic or nontransgenic plants. A resistant plant was selected and self-fertilized for several generations until T4 progenitor lines were obtained. Most of these T4 plants accumulated extremely low levels of CP protein and steady-state mRNA, and exhibited almost complete resistance to PVY. DNA gel blot analysis revealed that the transgenic plants typically had two or three copies of the transgene. These results are characteristic of pathogen-derived resistance, in which the resistance against virus is the consequence of post-transcriptional gene silencing directed by homologous transgenes. To uncover factors that may play roles in gene silencing, sequences in the 3' part of the transcribed region of the CP gene were transcribed in vitro and the RNA fragments were incubated with cell extracts from transgenic plants. A ribonuclease activity was detected that appeared to be specific for this transcript in the PVY-resistant transgenic plants.

Systolic arterial pressure recovery after ventricular fibrillation in pigs.

Ventricular fibrillation (VF) is induced during implantable cardioverter defibrillator insertion and can result in cardiovascular collapse. The relation between repeated VF trials of varying duration and systolic blood pressure (SBP) recovery rate was studied in 6 pigs. Two implantable cardioverter defibrillator patches were placed on the heart, and VF was varied in a cyclic pattern until cardiovascular collapse occurred. A negative logarithmic relation between SBP recovery rate and duration of VF was found in 4 of the pigs with correlation coefficients of 0.62 to 0.97 (p < 0.05). The overall correlation coefficient was 0.51 for all 116 data points (p < 0.001). Although there was a significant (p < 0.05) decrease in average (+/- standard error of the mean) baseline SBP in the second half of each experiment (83 +/- 5 mm Hg versus 77 +/- 6 mm Hg), no significant difference in SBP was observed during VF (17 +/- 1 mm Hg versus 16 +/- 1 mm Hg) or after 15 seconds of SBP recovery (51 +/- 4 mm Hg versus 46 +/- 3 mm Hg) between the two halves of the experiments. Cardiovascular collapse occurred without warning; epinephrine was effective in reversing it. In conclusion, SBP recovery rate and duration of VF have a negative logarithmic relation consistent with a negative effect on left ventricular contractility with prolongation of VF. The onset of cardiovascular collapse during implantable cardioverter defibrillator testing cannot be predicted on the basis of monitored blood pressure alone.

Successful repair of myocardial free wall rupture after thrombolytic therapy for acute infarction.

BACKGROUND: Controversy exists regarding the timing of thrombolytic administration and rupture rate. METHODS: Hospital records at St. Luke's-Roosevelt Hospital of the 4 study patients were reviewed and compared with those of 41 patients from a group of 537 patients concurrently admitted with a diagnosis of myocardial infarction (MI). RESULTS: Four patients experienced ventricular free wall rupture after having a MI between November 17, 1993, and July 28, 1995. All received tissue plasminogen activator. In 1 patient, pericardial effusion associated with a pseudoaneurysm was discovered in the operating room. The 3 others developed clinical pericardial tamponade before surgery. All 4 patients survived and left the hospital on postoperative days 10, 11, 11, and 82, respectively. During this same time period, 537 patients were admitted with MI, 41 of whom died; the study's 4 patients were compared with these 41. CONCLUSIONS: These data demonstrate that rupture of the ventricular free wall can occur early after thrombolytic therapy and may have a subacute course. Prompt diagnosis and surgery offer excellent chances of surviving this fatal condition.

RT-PCR detection and identification of three species of cucumoviruses with a genus-specific single pair of primers.

Reverse transcription and polymerase chain reaction (RT-PCR) was used for detection and identification of three cucumoviruses (cucumber mosaic virus, CMV; peanut stunt virus, PSV; tomato aspermy virus, TAV) in various plants sources with a single pair of primers, designed as CPTALL-3 and CPTALL-5. The pair of cucumovirus genus-specific primers that flank the coat protein gene were designed and used to amplify a DNA fragment of approximately ranging from 938 to 966 bp. The RT-PCR with the set of primers specifically amplified the target size of DNA fragment in all the tested cucumoviruses (CMV S-IA, S-IB and S-II, PSV and TAV). No DNA product of any length was produced when brome mosaic virus or tobacco mosaic virus RNA was used as templates. The cucumoviruses examined were differentiated by PCR-restriction fragment length polymorphism with different enzymes. This indicates that the designed primers are only specific for the cucumoviruses and useful for reliable information of identification of members of the Cucumovirus genus.

Diaphyseal osteosarcoma.

Fifteen cases of diaphyseal osteosarcomas were found in a review of 157 cases of long bone osteosarcoma (9.5%) and two further examples were added. The clinical and histological features of the diaphyseal osteosarcomas were indistinguishable from those of the commoner juxta metaphyseal osteosarcomas. The radiological features, however, fell into four distinct patterns: Group I had the classical appearance of a conventional osteosarcoma; Group II showed dense cortical sclerosis with bony expansion but no soft tissue swelling or break of the cortex at presentation; Group III presented with a pathological fracture through a purely osteolytic lesion; Group IV usually had the classical appearances of an osteosarcoma in the diaphysis but had, in addition, dense separate sclerotic lesions which were proximal to the tumour in the humerus and distal to it in the femur. The importance of these four groups lies in the quite distinct differential diagnosis which each presents.

Fracture of the cervical spine in ankylosing spondylitis.

The radiological features, clinical findings and mortality rates of patients with ankylosing spondylitis complicated by cervical trauma have been reviewed. All patients had long-standing disease and half had sustained their fractures as a result of trivial accidents. There were 19 cervical fractures in 18 patients, which were chalkstick in type and occurred predominantly at the 6th and 7th cervical levels. Ten fractures passed through the upper part of the vertebral body, one through the mid-vertebral body and the final eight were through the disc space. The site of the fracture line was related to neurological outcome. Those patients whose fracture line ran through the disc space had significantly less neurological injury and a much better prognosis. Distraction at the fracture site had some relation to prognosis but horizontal displacement and angulation were not found to be of importance. This study confirms that cervical fracture with neurological complications may follow minor trauma in ankylosing spondylitis. The site of the fracture in relation to the vertebral bodies and discs appears to be of some prognostic relevance and careful radiological assessment of all patients with ankylosing spondylitis and cervical injury should be undertaken.

Fissuring of the posterior annulus fibrosus in the lumbar spine.

Severe back-ache in young adults may present a difficult clinical problem when the absence of neurological signs results in delayed diagnosis. Fourteen patients, with discographic evidence of posterior annular fissuring are reported. The discrepancy between painful disability and negative radiographic examination including radiculography is stressed. Discography has proved to be the investigation of choice in these patients. This will demonstrate the morphology of the lesion and reproduce the symptomatology in the majority of cases. The clinical implications are discussed.

Osteonecrosis in Hodgkin's disease.

Four patients suffering from Hodgkin's disease developed osteonecrosis following therapy and both femoral heads were involved in each case. Retrospective review of abdominal radiographs taken for follow-up lymphography demonstrated that the earliest radiological changes in bone were evident between five and 18 months after treatment was started and between six and 21 months before the onset of symptoms. The clinical implications are discussed.

Gallium 67 scanning in rheumatoid arthritis.

Gallium 67 scans were performed on both knees of 38 patients with rheumatoid arthritis. There was a significantly higher level of 67Ga accumulation in those knees with clinically active synovitis (p less than 0.001). Synovial white cell concentration was also elevated in the group with active synovitis. The white cell concentration correlated with the 67Ga knee/femoral ratio at the p less than 0.001 level. 67Ga activity in the synovial fluid was predominantly in the supinate and activity was also present in the synovium. The findings indicate that 67Ga uptake occurs in rheumatoid joints and reflects the degree of synovial inflammation.

The detection of spinal pseudarthrosis in ankylosing spondylitis.

Spinal pseudarthrosis in ankylosing spondylitis can be difficult to detect radiologically. This paper assesses the value of bone radioscintigraphy in relation to radiological examination. The patterns of tracer uptake in the spine were recorded in 16 patients in whom established ankylosing spondylitis was complicated by pseudarthrosis. Twenty such lesions were identified in 16 patients, mostly occurring at one level in a junctional region of the spine. Four patients had two lesions. Standard radiography failed to demonstrate this abnormality in seven patients and in these, tomography was required to confirm the scintigraphic findings. On the other hand, bone scanning was much less accurate in detecting the minor forms of marginal vertebral end plate destruction (spondylo-discitis) than conventional radiology. This study suggests that 99TcmMDP scanning is a useful primary investigation for the detection of spinal pseudarthrosis in patients with chronic ankylosing spondylitis who suffer late onset back pain.

Experimentally induced hypermobility in the lumbar spine. A pathologic and radiologic study of the posterior ligament and annulus fibrosus.

Experimental destructive lesions were produced at autopsy in the lumbar discs of nine spines including 29 radiologically normal adult lumbar intervertebral discs. Limited transverse surgical division of the posterior longitudinal ligament and adjacent annular fibers were performed followed by, in addition, the removal of the intervertebral nucleus pulposus. Without interfering with any other major structure, radiologic evidence of hypermobility was recorded in 20 of 29 normal intervertebral segments. The patterns of movement were measured by standardized radiologic criteria. The available evidence suggests that localized damage to the region of the posterior longitudinal ligament and adjacent annulus fibrosus can produce radiologic patterns of hypermobility.

Induced pain referral from posterior lumbar elements in normal subjects.

Patterns of pain referral, induced from the posterior elements, have been studied in normal volunteer subjects. A series of intracapsular and pericapsular injections were performed at the L1-2 and L4-5 levels. The areas of pain referral indicate overlap between the upper and lower lumbar spine. It is also shown that the pericapsular and intrafacetal pain referral areas are similar and that the upper lumbar spine is more sensitive than the lower.