Herniographic examinations were performed on more than 4,000 patients. The method was found to be of great value in patients with obscure symptoms in the groin or pelvis. Herniography shows not only hernial sacs but also the general condition and tissue strength of the inguinal part of the abdominal wall. The different types of hernias have different signs that, as a rule, allow an exact diagnosis. The pelvic floor and the pouch of Douglas can always be evaluated. Young athletes with severe symptoms in the groin, in most instances, were found to have some type of hernial rupture and often osteochondritis in the pubic symphysis as well. In women, the clinical diagnosis of hernia is often difficult. Herniography was of great value in these patients.
La herniographie a été effectuée chez plus de 4,000 patients. La méthode a été d'une grande aide chez des patients présentant des symptômes peu clairs de la région inguinale ou pelvienne: La herniographie non seulement montre le sac herniaire mais indique aussi l'état local et la solidité tissulaire de la composante inguinale de la paroi abdominale. Les différents types de hernie présentent des signes différents qui en règle générale permettent le diagnostic exact. Le plancher pelvien et le culde-sac de Douglas sont toujours visibles. C'est ainsi que le jeune sportif présentant des symptômes sévères de l'aine avait le plus souvent une hernie fréquemment associée à une ostéochondrite pubienne. Chez la femme, le diagnostic clinique de hernie est souvent difficile. La herniographie est un grand secours dans ces cas.
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A hernia operation is one of the most common surgical procedures performed worldwide, with over 100,000 of these surgeries carried out every year in the UK alone. Although the procedure is generally safe, there is a small risk of complications occurring after surgery.
After inguinal hernia surgery, for example, males may experience painful swelling in the scrotum or the presence of gangrene may lead to perforation of the bowel. Other serious problems that may occur after a hernia operation include infection, numbness at the surgery site, and recurrence of the hernia.
Another complication that can occur post-operation is rejection of the mesh used to repair the hernia, in which case the mesh will need to be removed. This can usually be detected through symptoms such as swelling and pain in the area where the mesh was placed. Once the mesh is removed, discharge from the surgical wound is likely to persist for a period.
Dr Kelly emphasises that repairs with mesh have reduced the incidence of recurrence. This is not corroborated by David Urbach who, last year, analysed 235,109 hernia repairs in Ontario, Canada in a 14-year study with an additional two-year follow-up. This study was carried out to compare the Shouldice repair with the meshes used throughout the province. The patients treated with mesh showed on average, a four- to five-times increase in the incidence of recurrences than observed at the Shouldice Hospital.10 Our hospital was never involved directly in the study, which was based on the data of our state-run health system!
Whether mesh is used in vaginal surgery, pelvic organ prolapse or hernias, the pathology is the same. Women are exposed to earlier complications because of the nature of the thin vaginal wall allowing earlier erosions, breakthrough, recurrent infections, bleeding and pain.
The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.
In a final attempt to reduce the viral load, a third course of remdesivir (day 93) and a third dose of convalescent plasma (day 95) were administered. We observed the re-emergence of the spike(D796H, ΔH69/ΔV70) viral population (Figs. 2, 3). The inferred linkage of spike(D796H) and spike(ΔH69/ΔV70) was maintained as evidenced by the highly similar frequencies of the two variants, suggesting that the third unit of convalescent plasma led to the re-emergence of this population under renewed positive selection. In further support of our proposed idea of competition, frequencies of these two variants appeared to mirror changes in the NSP2(I513T) variant (Fig. 2), suggesting that these variants are markers of opposing clades in the viral population. Ct values remained low throughout this period with hyperinflammation, which eventually led to multi-organ failure and death on day 102. The repeated increase in the frequency of the viral population with convalescent plasma therapy strongly supports the hypothesis that the combination of the deletion and mutation in the spike protein conferred a selective advantage.
For long-read sequencing, genomes were assembled with reference-based assembly and a curated bioinformatics pipeline with 20 minimum coverage across the whole genome27. For short-read sequencing, FASTQ files were downloaded, poor-quality reads were identified and removed, and both Illumina and PHiX adapters were removed using TrimGalore v.0.6.628. Trimmed paired-end reads were mapped to the National Center for Biotechnology Information SARS-CoV-2 reference sequence MN908947.3 using MiniMap2-2.17 with arguments -ax and sr29. BAM files were then sorted and indexed with Samtools v.1.11 and PCR optical duplicates were removed using Picard ( ). Consensus sequences of nucleic acids with a minimum whole-genome coverage of at least 20 were generated with BCFtools using a 0% majority threshold.
All available full-genome SARS-CoV-2 sequences were downloaded from the GISAID database ( )33 on 16 December 2020. Duplicate and low-quality sequences (>5% nucleocapsid regions) were removed, leaving a dataset of 212,297 sequences with a length of more than 29,000 bp. All sequences were sorted by name and only sequences sequenced with United Kingdom/England identifiers were retained. From this dataset, sequences were deduplicated and, in figures in which background sequences were required, randomly subsampled using seqtk ( ). All sequences were aligned to the SARS-CoV-2 reference strain MN908947.3, using MAFFT v.7.475 with automatic flavour selection34. Major SARS-CoV-2 clade memberships were assigned to all sequences using both the Nextclade server v.0.9 ( ) and Phylogenetic Assignment Of Named Global Outbreak Lineages (PANGOLIN)35. 2ff7e9595c
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