Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories.

As the coronavirus disease 2019 (COVID-19) pandemic second wave is emerging, it is of the upmost importance to screen the population immunity in order to keep track of infected individuals. Consequently, immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and positive predictive values are needed to obtain an accurate epidemiological picture. As more data accumulate about the immune responses and the kinetics of neutralizing-antibody (nAb) production in SARS-CoV-2-infected individuals, new applications are forecast for serological assays such as nAb activity prediction in convalescent-phase plasma from recovered patients. This multicenter study, involving six hospital centers, determined the baseline clinical performances, reproducibility, and nAb level correlations of 10 commercially available immunoassays. In addition, three lateral-flow chromatography assays were evaluated, as these devices can be used in logistically challenged areas. All assays were evaluated using the same patient panels in duplicate, thus enabling accurate comparison of the tests. Seven immunoassays examined in this study were shown to have excellent specificity (98 to 100%) and good to excellent positive predictive values (82 to 100%) when used in a low (5%)-seroprevalence setting. We observed sensitivities as low as 74% and as high as 95% at ≥15 days after symptom onset. The determination of optimized cutoff values through receiver operating characteristic (ROC) curve analyses had a significant impact on the diagnostic resolution of several enzyme immunoassays by increasing the sensitivity significantly without a large trade-off in specificity. We found that spike-based immunoassays seem to be better correlates of nAb activity. Finally, the results reported here will add to the general knowledge of the interlaboratory reproducibility of clinical performance parameters of immunoassays and provide new evidence about nAb activity prediction.

Reversal of Hartmann's procedure in patients following failed colorectal or coloanal anastomosis: an analysis of 45 consecutive cases.

AIM: This study aimed to assess outcomes of Hartmann's reversal (HR) after failure of previous colorectal anastomosis (CRA) or coloanal anastomosis (CAA). METHODS: All patients planned for HR from 1997 to 2018 following the failure of previous CRA or CAA were included. RESULTS: From 1997 to 2018, 45 HRs were planned following failed CRA or CAA performed for rectal cancer (n = 19, 42%), diverticulitis (n = 16, 36%), colon cancer (n = 4, 9%), inflammatory bowel disease (n = 2, 4%) or other aetiologies (n = 4, 9%). In two (4%) patients, HR could not be performed. HR was performed in 43/45 (96%) patients with stapled CRA (n = 24, 53%), delayed handsewn CAA with colonic pull-through (n = 11, 24%), standard handsewn CAA (n = 6, 14%) or stapled ileal pouch-anal anastomosis (n = 2, 4%). One (2%) patient died postoperatively. Overall postoperative morbidity rate was 44%, including 27% of patients with severe postoperative complication (Clavien-Dindo ≥ 3). After a mean follow-up of 38 ± 30 months (range 1-109), 35/45 (78%) patients presented without stoma. Multivariate analysis identified a remnant rectal stump < 7.5 cm in length as the only independent risk factor for long-term persistent stoma. Among stoma-free patients, low anterior resection syndrome (LARS) score was ≤ 20 (normal) in 43%, between 21 and 29 (minor LARS) in 33% and ≥ 30 (major LARS) in 24% of the patients. CONCLUSION: HR can be recommended in patients following a failed CRA or CAA. It permits 78% of patients to be free of stoma. A short length of the remnant rectal stump is the only predictive factor of persistent stoma in these patients.

Local excision after neoadjuvant chemoradiotherapy versus total mesorectal excision: a case-matched study in 110 selected high-risk patients with rectal cancer.

AIM: The aim of this comparative study was to report a 10-year experience of an organ preservation strategy by local excision (LE) in selected high-risk patients (aged patients and/or patients with severe comorbidity and/or indication for abdominoperineal excision) versus total mesorectal excision (TME) after neoadjuvant radiochemotherapy (RCT) for patients with locally advanced (T3-T4 and/or N+) low and mid rectal cancer with suspicion of complete tumour response (CTR) or near-CTR. METHOD: Thirty-nine patients with rectal cancer who underwent LE after RCT for suspicion of CTR were matched to 71 patients who underwent TME according to body mass index, gender, tumour location and ypTNM stage. Operative, oncological and functional results were compared between groups. RESULTS: In the LE group, ypT0, ypTis or ypT1N0R0 were noted in 28/39 (72%). Overall morbidity was observed in 10/39 (26%) in LE vs 46/71 in the TME group (65%) (P = 0.001). Severe morbidity (Clavien-Dindo ≥ 3) was noted in 1/39 patients from the LE group (3%) vs 3/71 (4%) from the TME group (P = 1.000). After a mean follow-up of 63 ± 4 months (range 56-70 months), local recurrence was noted in 2/39 (5%) from the LE group vs 2/71 (3%) from the TME group (P = 0.601). Definitive stoma was noted in 2/39 (6%) from the LE group vs 8/71 (12%) from the TME group (P = 0.489). Major low anterior resection syndrome was noted in 5/23 (22%) from LE group vs 11/33 (33%) from the TME group (P = 0.042). CONCLUSION: The accuracy of response prediction after RCT was 72% after LE. In high-risk patients, LE represents a safe alternative to TME with better functional results and the same long-term oncological outcome.

Initial experience of CT-guided pulsed radiofrequency ablation of the pudendal nerve for chronic recalcitrant pelvic pain.

AIM: To evaluate initial experience with computed tomography (CT)-guided pulsed radiofrequency ablation (pRFA) of the pudendal nerve in cases of recalcitrant neuropathic pelvic pain. Endpoints include technical feasibility, safety, and efficacy of therapy. MATERIALS AND METHODS: Ten patients who underwent pRFA ablation for neuropathic pudendal nerve pain during the trial period were followed for response to treatment for 6 months. Each patient was treated with pRFA under CT-guidance with concurrent perineural injection of anaesthetic and/or corticosteroid. Pain scores were then measured using a numeric rating scale at fixed intervals up to 6 months. RESULTS: All procedures were considered technically successful with no immediate complications. pRFA demonstrated improved duration of pain improvement compared to the most recent perineural injection (p=0.0195), but not compared to the initial injection (p=0.64). Reported pain scores were lower with pRFA than with both the first and most recent injection but this did not reach statistical significance (p=0.1094 and p=0.7539, respectively). CONCLUSION: Overall, pRFA of the pudendal nerve using CT-guidance can be a safe and effective therapy. This technique provides direct visualisation of the nerve to maximise safety and efficacy while offering a novel form of therapy for patients with chronic, recalcitrant pelvic pain.

Centre-level variation in dental treatment and oral health and individual- and area-level predictors of oral health in 5-year-old children with non-syndromic unilateral cleft lip and palate: the Cleft Care UK study. Part 3.

OBJECTIVES: To explore centre-level variation in fluoride treatment and oral health outcomes and to examine the association of individual- and area-level risk factors with dental decay in Cleft Care UK (CCUK). SETTING: Two hundred and sixty-eight 5-year-old British children with non-syndromic unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: Data on caries and developmental defects of enamel (DDE) were collected. The child's history of fluoride ingestion and postcode was used to assess exposure to fluoridated water. Centre-level variation in fluoride exposure and caries was examined using hierarchical regression. Poisson regression was used to estimate the association between individual- and area-level fluoride exposures and outcome. RESULTS: Children had high levels of caries, rampant caries and DDE. There was no evidence of variation between centres in the number of children with caries or rampant decay. There was evidence of variation in prescription of fluoride tablets and varnish and the type of toothpaste used. Area level of deprivation was associated with a higher risk of dental caries-risk ratio (RR) in the lowest quartile versus the rest was 1.43 (95% CI 1.13 to 1.81). Use of fluoride tablets and varnish was associated with higher risk of caries-RR 1.73 (95% CI 1.29 to 2.32) and RR 1.33 (95% CI 1.04 to 1.70), respectively, adjusted for age, sex and deprivation. CONCLUSION: The association with use of fluoride tablets and varnish probably reflects reverse causality but indicates the need for early preventative interventions in children with UCLP.

Adult appendicitis: Clinical practice guidelines from the French Society of Digestive Surgery and the Society of Abdominal and Digestive Imaging.

INTRODUCTION: The French Society of Digestive Surgery (SFCD) and the Society of Abdominal and Digestive Imaging (SIAD) have collaborated to propose recommendations for clinical practice in the management of adult appendicitis. METHODS: An analysis of the literature was carried out according to the methodology of the French National Authority for Health (HAS). A selection was performed from collected references and then a manual review of the references listed in the selected articles was made in search of additional relevant articles. The research was limited to articles whose language of publication was English or French. Articles focusing on the pediatric population were excluded. Based on the literature review, the working group proposed recommendations whenever possible. These recommendations were reviewed and approved by a committee of experts. RESULTS: Recommendations about appendicitis in adult patients were proposed with regard to clinical, laboratory and radiological diagnostic modalities, treatment strategy for uncomplicated and complicated appendicitis, surgical technique, and specificities in the case of macroscopically healthy appendix, terminal ileitis and appendicitis in the elderly and in pregnant women. CONCLUSION: These recommendations for clinical practice may be useful to the surgeon in optimizing the management of acute appendicitis in adults.

A Reappraisal of Outcome of Elective Surgery After Successful Non-Operative Management of an Intra-Abdominal Abscess Complicating Ileocolonic Crohn's Disease: A Subgroup Analysis of a Nationwide Prospective Cohort.

BACKGROUND AND AIMS: Few prospective data exist on outcomes of surgery in Crohn's disease [CD] complicated by an intra-abdominal abscess after resolution of this abscess by antibiotics optionally combined with drainage. METHODS: From 2013 to 2015, all patients undergoing elective surgery for CD after successful non-operative management of an intra-abdominal abscess [Abscess-CD group] were selected from a nationwide multicentre prospective cohort. Resolution of the abscess had to be computed tomography/magnetic resonance-proven prior to surgery. Abscess-CD group patients were 1:1 matched to uncomplicated CD [Non-Penetrating-CD group] using a propensity score. Postoperative results and long-term outcomes were compared between the two groups. RESULTS: Among 592 patients included in the registry, 63 [11%] fulfilled the inclusion criteria. The abscess measured 37 ±â€…20 mm and was primarily managed with antibiotics combined with drainage in 14 patients and nutritional support in 45 patients. At surgery, a residual fluid collection was found in 16 patients [25%]. Systemic steroids within 3 months before surgery [p = 0.013] and the absence of preoperative enteral support [p = 0.001] were identified as the two significant risk factors for the persistence of a fluid collection. After propensity score matching, there was no significant difference between the Abscess-CD and Non-Penetrating-CD groups in the rates of primary anastomosis [84% vs 90% respectively, p = 0.283], overall [28% vs 15% respectively, p = 0.077] and severe postoperative morbidity [7% vs 7% respectively, p = 1.000]. One-year recurrence rates for endoscopic recurrence were 41% in the Abscess-CD and 51% in the Non-Penetrating-CD group [p = 0.159]. CONCLUSIONS: Surgery after successful non-operative management of intra-abdominal abscess complicating CD provides good early and long-term outcomes.

Antibiotics alone as an alternative to appendectomy for uncomplicated acute appendicitis in adults: Changes in treatment modalities related to the COVID-19 health crisis.

The massive inflow of patients with COVID-19 requiring urgent care has overloaded hospitals in France and impacts the management of other patients. Deferring hospitalization and non-urgent surgeries has become a priority for surgeons today in order to relieve the health care system. It is obviously not simple to reduce emergency surgery without altering the quality of care or leading to a loss of chance for the patient. Acute appendicitis is a very specific situation and the prevalence of this disease leads us to reconsider this particular disease in the context of the COVID-19 crisis. Indeed, while the currently recommended treatment for uncomplicated acute appendicitis is surgical appendectomy, the non-surgical alternative of medical management by antibiotic therapy alone has been widely evaluated by high-quality studies in the literature. Insofar as the main limitation of exclusively medical treatment of uncomplicated acute appendicitis is the risk of recurrent appendicitis, this treatment option represents an alternative of choice to reduce the intra-hospital overload in this context of health crisis. The aim of this work is therefore to provide physicians and surgeons with a practical guide based on a review of the literature on the medical treatment of uncomplicated acute appendicitis in adults, to offer this alternative treatment to the right patients and under good conditions, especially when access to the operating room is limited or impossible.

[Antibiotics alone as an alternative to appendectomy for uncomplicated acute appendicitis in adults: Changes in treatment modalities related to the COVID-19 health crisis]. / Crise sanitaire liée au COVID-19 : modalités du traitement de l'appendicite aiguë non compliquée de l'adulte par antibiothérapie seule comme alternative à l'appendicectomie.

The massive inflow of patients with COVID-19 requiring urgent care has overloaded hospitals in France and impacts the management of other patients. Deferring hospitalization and non-urgent surgeries has become a priority for surgeons today in order to relieve the health care system. It is obviously not simple to reduce emergency surgery without altering the quality of care or leading to a loss of chance for the patient. Acute appendicitis is a very specific situation and the prevalence of this disease leads us to reconsider this particular disease in the context of the COVID-19 crisis. Indeed, while the currently recommended treatment for uncomplicated acute appendicitis is surgical appendectomy, the non-surgical alternative of medical management by antibiotic therapy alone has been widely evaluated by high-quality studies in the literature. Insofar as the main limitation of exclusively medical treatment of uncomplicated acute appendicitis is the risk of recurrent appendicitis, this treatment option represents an alternative of choice to reduce the intra-hospital overload in this context of health crisis. The aim of this work is therefore to provide physicians and surgeons with a practical guide based on a review of the literature on the medical treatment of uncomplicated acute appendicitis in adults, to offer this alternative treatment to the right patients and under good conditions, especially when access to the operating room is limited or impossible.

The human genus.

A general problem in biology is how to incorporate information about evolutionary history and adaptation into taxonomy. The problem is exemplified in attempts to define our own genus, Homo. Here conventional criteria for allocating fossil species to Homo are reviewed and are found to be either inappropriate or inoperable. We present a revised definition, based on verifiable criteria, for Homo and conclude that two species, Homo habilis and Homo rudolfensis, do not belong in the genus. The earliest taxon to satisfy the criteria is Homo ergaster, or early African Homo erectus, which currently appears in the fossil record at about 1.9 million years ago.

Operating room hygiene: Clinical practice recommendations.

INTRODUCTION: The French Society of Gastro-Intestinal Surgery (SociétéFrançaisedeChirurgieDigestive) and the Association of hepato-bilio-pancreatic and transplantation surgery (AssociationdeChirurgieHépato-Bilio-PancréatiqueetTransplantation) requested that clinical practice recommendations be established with regard to operating room hygiene. METHODS: The literature was analyzed according to the High Authority of Health (HauteAutoritédesanté [HAS]) methodology and after consultation of the Cochrane and Medline databases. Pertinent references were selected, and supplementary references were hand-picked from the reference lists. Only English or French language papers were retained. The recommendations of learned societies and the World Health Organization were also considered. RESULTS: Recommendations were proposed with regard to pre-operative patient preparation, skin preparation, draping, wound edge protectors, surgeon hygiene, wound closure, and operating room environment. CONCLUSION: These clinical practice recommendations should guide and improve the daily practice of gastro-intestinal surgeons.

Translational control of germ cell-expressed mRNA imposed by alternative splicing: opioid peptide gene expression in rat testis.

The three genes encoding the opioid peptide precursors (prodynorphin, proenkephalin, and proopiomelanocortin) are expressed in the rat testis. The sizes of the three opioid mRNAs in the testis differ from the sizes of the corresponding mRNAs in other rat tissues in which these genes are expressed. The smaller testicular proopiomelanocortin mRNA has previously been demonstrated to arise from alternative transcriptional initiation. In the present study, we found that the smaller testicular prodynorphin mRNA, expressed in Sertoli cells, results from alternative mRNA processing. Exon 2, which makes up 5' untranslated sequence, is removed from the mature transcript. Polysome analysis of brain and testis RNA indicates that the alteration of the prodynorphin leader sequence in the testis-specific transcript does not affect the efficiency of translation of this mRNA. The larger testicular proenkephalin transcript, expressed in developing germ cells, also results from alternative mRNA processing. Alternative acceptor site usage in the splicing of intron A results in a germ cell-specific proenkephalin transcript with a 491-nucleotide 5' untranslated leader sequence preceding the preproenkephalin-coding sequence. Polysome analysis indicates that this germ cell-specific proenkephalin mRNA is not efficiently translated. Mechanisms by which alternative mRNA splicing may serve to confer translational regulation upon the testicular proenkephalin transcript are discussed.

A transferrinlike (hemiferrin) mRNA is expressed in the germ cells of rat testis.

In the testis, germ cells which are separated from the serum by the blood-testis barrier rely primarily on the Sertoli cell to obtain nutrients. For example, transferrin synthesized by the Sertoli cell is important in delivering iron from the serum to the developing germ cells. Because of its role in the testis, Sertoli cell transferrin protein and mRNA have been extensively studied. By using RNA blot analysis of rat testicular tissue, we detected a transcript of 2.6 kb which is attributed to transferrin. In addition, we detected a novel mRNA of 0.9 kb which had sequence similarity to the 3' end of transferrin. This 0.9-kb mRNA was present in germ cells, but not Sertoli cells, liver, or brain. The primary source of this mRNA in the testis was round spermatids. Sequence analysis of a cDNA clone showed that this mRNA encoded a protein with sequence similarity to the carboxy terminus of transferrin. Polysome analysis indicated that this transcript was translated and may therefore have importance in the iron metabolism of germ cells. The evolutionary implications between the transferrinlike mRNA germ cells and the gene duplication event which resulted in the diferric binding of transferrin are discussed.

Regulation of the human enkephalin promoter by two isoforms of the catalytic subunit of cyclic adenosine 3',5'-monophosphate-dependent protein kinase.

Cyclic AMP regulates a variety of cellular responses through activation of the catalytic subunit of cAMP-dependent protein kinase. The cDNAs for two protein isoforms of the catalytic subunit, C alpha and C beta, were placed into expression vectors, and their ability to stimulate cAMP-dependent transcription of the human enkephalin promoter was examined in transiently transfected CV-1 cells. Expression vectors for C alpha and C beta that were directed by the human cytomegalovirus promoter produced up to 350- and 200-fold increases in chloramphenicol acetyltransferase activity, respectively, when cotransfected with the ENKAT-12 reporter plasmid. Transcriptional activation was shown to be dependent upon functional kinase activity by point mutations in catalytic subunit vectors which eliminated activation. Transcriptional activation by C alpha and C beta was eliminated when the cAMP response elements (CREs) were deleted from the native enkephalin promoter, but activation was recovered when this region was replaced with an oligonucleotide containing two copies of the somatostatin CRE consensus TGACGTCA. C alpha expression vectors were found to produce 2-fold greater transcriptional activation than C beta expression vectors. These results were most likely due to the cellular kinase activity produced by the catalytic subunit expression vectors and did not appear to be dependent on CRE motif or substrate specificity. In vitro mutagenesis indicates that neither C alpha nor C beta requires N-terminal myristylation for transcriptional activation, but threonine-197 is critical to subunit function.

Sertoli cells are the primary site of prodynorphin gene expression in rat testis: regulation of mRNA and secreted peptide levels by cyclic adenosine 3' ,5'-monophosphate analogs in cultured cells.

Prodynorphin is one of three endogenous opioid peptide genes expressed in testis. Through the use of cell fractionation procedures and Northern blot analysis, Sertoli cells were found to be the primary site of prodynorphin mRNA synthesis in rat testis. In situ hybridization of a prodynorphin cRNA probe to fixed adult tissue confirmed this result. Treatment of primary cultures of rat Sertoli cells with a cAMP analog, 8-(4-chlorophenylthio)cAMP, resulted in a transient 5.6-fold increase in steady state prodynorphin mRNA levels relative to those in control cells. This increase was maximal at 48 h of treatment, after which mRNA levels gradually declined. Treatment of Sertoli cells with cAMP analogs resulted in concurrent 2.6-fold decreases in sulfated glycoprotein-2 mRNA levels. Culture medium from Sertoli cells showed a 3.1-fold increase in secreted dynorphin immunoreactivity after treatment with 8-(4-chlorophenylthio)cAMP. Chromatographic analysis indicates that the majority of the immunoreactive dynorphin peptide synthesized in Sertoli cells is present as high mol wt species, with some processing to bioactive peptides.

Modification of the retinoic acid signaling pathway by the catalytic subunit of protein kinase-A.

Retinoic acid receptors (RARs) are ligand-activated nuclear transcription factors that belong to the steroid-thyroid hormone receptor superfamily. We have used the transient transfection of a retinoic acid-responsive reporter plasmid (RARECAT) to investigate the potential interactions between the retinoic acid (RA) and cAMP signaling pathways. Cotransfections of expression plasmids for the catalytic (C) subunits of cAMP-dependent protein kinase with RARECAT showed ligand-independent activation in both CV-1 and HeLa cells and a further 2-fold increase in RARECAT activity in the presence of RA. In CV-1 cells, cotransfections of the expression plasmids for RAR and the C-subunits produced increases in RARECAT activity (12- and 8-fold in the absence of ligand and 21- and 15-fold in the presence of RA for the C alpha- and C beta-isoforms, respectively). Cotransfections of both the C beta-subunit and RAR expression plasmids in HeLa cells produced 22- and 114-fold increases in RARECAT activity in the absence and presence of RA, respectively. These results provide evidence to suggest that the RA and cAMP signaling pathways are coupled, and signaling cross-talk may occur through the direct phosphorylation of RARs by the C-subunit as indicated by in vitro phosphorylation of the receptor.