Magnetic resonance imaging evaluation of age and level dependence of multifidus fatty infiltration in normal Indian healthy volunteers

Background: Multifidus is one of the main stabilizers of lumbar spine. Fatty infiltration of multifidus varies with the age, sex, side and level of spine studied. The present study aims at the evaluation and comparison of the trends of multifidus fatty infiltration in normal population at various levels in both genders, side and different decade groups in healthy individual volunteers.Methods: Twenty-five normal healthy volunteers equally distributed across different age groups (3rd-7th decades) formed the healthy study group. In step 1, normal population magnetic resonance (MR) images are collected and evaluated individually. In step 2, fatty infiltration of all people ascending in age was calculated at each lumbar level and on either side. In step 3, normal population were divided into decades and fatty infiltration at each decade and segment wise comparison was done. In step 4, statistical analysis of significance was done between the groups. All the T2 MR images were measured using Image j 1.50i software. Exclusion criteria included no proper visualization of paraspinal musculature in the T2 MR images. Associated conditions affecting the degeneration (other lytic lesions/vertebral fractures-healed or unhealed). Other etiology included disc prolapse, listhesis, infections, tumors, and trauma. For each MRI scan, at least 3 cuts for each segment were obtained in which the central cut will be selected for measurement.Results: In study population, at all age groups the multifidus fatty infiltration (MFI) at all given levels upper lumbar levels (L1-2, L2-3) showed less fatty infiltration than lower levels. With increasing age there is increase in MFI in all levels. On either side, as the age increases fat % increases and in individual people as the segment going caudal the fat % increases. At each segment left side has more fat % than right side and overall fat % increase from L1 to S1 levels. As decades increases fat % increases in each individual segment, and also fat % increases from cephalad to caudal. There is a rapid increase in fat % transition from 4th to 5th decade. Overall fat % increase is seen from L1 to S1 in each decade. Females L1-2 to L3-4 does not show significant fat % increase. There are more fat % in females than males in lower lumbar levels, but the body mass index (BMI), daily activities may be a confounding factor.Conclusions: Lumbar paravertebral muscle fat content increases with aging, in healthy volunteers 3nd to 7th decade of age. Women, low lumbar levels, left side the multifidus muscle are most affected

C-Arm-Free Minimally Invasive Cervical Pedicle Screw Fixation (MICEPS): A Technical Note

A minimally invasive posterolateral approach designed to avoid the lateral misplacement of midcervical pedicle screws was reported, but there is no technical report that describes this technique without C-arm fluoroscopy. We report the results of a 2.5 years follow-up of a 62-year-old female patient with C4 metastatic breast cancer. The patient suffered from severe neck pain and impending quadriplegia for 2 months after radiation therapy. We performed C-arm-free minimally invasive cervical pedicle screw fixation (MICEPS). The patient was suc-cessfully treated with surgery, and her neck pain was well controlled. She had neither neurological deficits nor neck pain at the final (2.5-year) follow-up. C-arm-free MICEPS is a useful technique; in addition, the sur-geons and staff have no risk of radiation exposure, there is a reduced need for postoperative imaging, and a decreased revision rate can be expected with C-arm-free MICEPS

A prospective study of functional evaluation of distal radius fracture by external fixator using the principle of ligamentotaxis

Background: Preservation of the articular congruity is the principal prerequisite for successful recovery following distal radius fractures. The best method of obtaining and maintaining an accurate restoration of articular anatomy however, remains a topic of considerable controversy. External fixation as a method of treatment for distal end of radius fracture has more than 60 years of documented clinical experience. The main aim of the study is to evaluate the results obtained by treatment of distal end radius fractures by external fixation using the principle of ligamentotaxis. Methods: In a prospective controlled study, 30 cases of distal end radius fractures with intra articular extension were treated with uniplanar bridging type of external fixation using the principle of ligamentotaxis. Mean age of the patients was 40.2 years, external fixator was applied for a mean duration of 6 weeks. Results: In this study there were 8 patients with excellent results comprising 27%, 14 patients with good results comprising 47%, 7 patients with fair results comprising 23%, 1 patient with poor results comprising 3%. Conclusions: In a prospective investigation, static external fixators were applied to 30 intra-articular fractures of the distal end of the radius. Fixator was kept up for a total of six weeks. The results were 8 excellent, 14 good, 7 fair, and 1 poor. Only one complication, pin loosening (10%), occurred. This series concludes that ligamentotaxis by external fixation consistently produces a good result in the management of intra-articular distal end of radius fractures in younger age groups (50 years)

A comparison of outcomes in ultrasonography guided versus landmark guided corticosteroid injection for the treatment of adhesive capsulitis

Background: Adhesive capsulitis is a debilitating disease in an otherwise healthy individual. Intra-articular corticosteroid injections offer a cost-effective, non-operative treatment option. However, it is currently unclear whether an ultrasound-guided injection relieves the symptoms of shoulder pain more effectively than if the injection was delivered landmark-guided. Methods: Eighty patients with adhesive capsulitis were randomized to two intervention groups - landmark guided and ultrasound (USG) guided. The functional status of the patients was documented prior to the intervention. Following allocation, the intra-articular steroid was administered either under USG guidance or following identification of the site of injection using landmarks. Follow-up was done on day 5, 3 weeks, 6 weeks, and 12 weeks post procedure to document the functional status. Results: The difference in visual analogue score (VAS) between the two arms was found to be statistically significant in favour of the ultrasound guided technique only on day 5 and day 21. On the other hand, the difference in disability of arm, shoulder, and hand (DASH) score between the 2 arms was found to be statistically significant in favour of the ultrasound guided technique on day 5, 21, 42 and 84. Finally, in our study, both shoulder flexion and abduction on day 84 achieved a statistically significant improvement, favouring the ultrasound guided arm. Conclusions: Ultrasound guided corticosteroid injections may offer modestly better short-term functional outcome and symptom relief when compared with landmark guided corticosteroids

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Comparative evaluation of screw accuracy and complications of new C-arm free O-arm navigated minimally invasive cervical pedicle screw fixation (MICEPS) with conventional cervical screw fixation

Study design: Retrospective comparative study. Objective: Comparative study of C-arm free O-arm navigated minimally invasive cervical pedicle screw (MICEPS) fixation with conventional cervical pedicle screw fixation. Methods: Twenty-five patients with different cervical spine pathologies were operated with MICEPS with O-arm navigation (group M; 18 patients) and conventional pedicle screw (group C; 7 patients) from June 2017 to January 2020. Operative time, blood loss were recorded. Preoperative and postoperative radiograms, CT scans and MRI were evaluated. Postoperatively screw position accuracy and angulation was determined on CT. Breach rate was evaluated on CT scan and classified according to Neo grading. Complications if any were noted. Results: The average blood loss in group M and group C was 129 ml and 329 ml, respectively. The average operative time in group M and group C was 77.4 min and 82.3 min, respectively. A total of 148 screws were inserted. In group M, no patient showed grade 2 and 3 breach while in group C, grade 0 and 1 breach was found in 85.7% screws and grade 2 in 14.3% screws. Mean screw medial angulation was 45.2 degrees in group M and 33.4 degrees in group C. There was one dural tear and two C5 palsies in each group. Conclusion: With C -arm free O-arm navigated MICEPS fixation operative time and blood loss are less though not statistically significant. It has less pedicle breach rate, less incidence of neurovascular complications than conventional technique. There is no radiation exposure to operating surgeon and staff

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)