Partial Versus Total Thyroidectomy: What Influences Most Surgeons' Decision? Analysis of a Nationwide Cohort of 375,810 Patients Over 10 Years

International audienceNational and international guidelines about thyroid surgery seem to be moving more and more towards less radical surgical procedures but everyday practice does not seem to always align with them. We describe for the first time the role of non-surgical parameters in the surgeon's choice for thyroid surgery.Objective: The ain of this study was to describe thyroid surgery and to identify the factors leading to either a total or a partial thyroidectomy regardless of the severity of the thyroid disease.Summary Background Data: National and international guidelines about thyroid surgery seem to be moving more and more toward less radical surgical procedures but everyday practice does not seem to always align with them.Methods: We based this nationwide retrospective cohort study on a national database that compiles discharge abstracts for every admission for thyroidectomy to French acute healthcare facilities (PMSI database 2010 to 2019).Results: In this study, 375,810 patients (male: 23%; age = 53 ± 15 years) had a thyroidectomy (partial: 28%) for cancer (17%), hyperthyroidism (16%), nonfunctioning goiter (64%), or other (3%). We noticed a global trend toward more partial thyroidectomy (P < 0.001) with a significant increase in the proportion of lobectomy in the post-ATA recommendations’ period (P < 0.001) as well as in the “French Levothyrox crisis” period, in which we saw an unexpected rise of adverse events notifications associated with the marketing of a new formula of Levothyrox (P < 0.001) amid widespread media coverage. In a multivariate analysis, we also identified that complete resection was more frequently performed in centers with a caseload >40/year [P < 0.001, odds ratio (OR) = 1.48], for obese patients (body mass index >30 kg/m2; P < 0.001, OR = 1.42), and according to the indication of surgery (OR benign = 1, OR cancer = 2.25, OR hyperthyroidism = 4.13).Conclusion: We describe for the first time the role of non-surgical parameters in the surgeon's choice for thyroid surgery

Risk Factors of Redo Surgery After Unilateral Focused Parathyroidectomy: Conclusions From a Comprehensive Nationwide Database of 13,247 Interventions Over 6 Years.

International audienceBackground: Surgical removal of hyperfunctional parathyroid gland is the definitive treatment for primary hyperparathyroidism (pHPT). Postoperative follow-up shows variability in persistent/recurrent disease rate throughout different centers.Objective: To evaluate the incidence of redo surgery after targeted parathyroidectomy for pHPT.Methods: We performed a nationwide retrospective cohort study on the “Programme de Medicalisation des Systemes d’Information,” the French administrative database that collects information on all healthcare facilities’ discharges. We extracted data from 2009 to 2018 for all patients who underwent parathyroidectomy for pHPT between January 2011 to December 2016. The primary outcome was the reoperation rate within 2 years since first surgery. Patients who had a first attempt of surgery within the previous 24 months, familial hyperparathyroidism, multiglandular disease, and renal failure were excluded. Results were adjusted according to sex and the Elixhauser Comorbidity Index. Operative volume thresholds to define high-volume centers were achieved by the Chi-Squared Automatic Interaction Detector method.Results: In the study period, 13,247 patients (median age 63, F/M=3.6) had a focused parathyroidectomy by open (88.7%) or endoscopic approach. Need of remedial surgery was 2.8% at 2 years. In multivariate analysis, factors predicting redo surgery were: cardiac history (P=0.008), obesity (P=0.048), endoscopic approach (P=0.005), and low-volume center (P<0.001). We evaluated that an annual caseload of 31 parathyroidectomies was the best threshold to discriminate high-volume centers and carries the lowest morbidity/failure rate.Conclusion: Although focused parathyroidectomy represents a standardized operation, cure rate is strongly associated with annual hospital caseload, type of procedure (endoscopic), and patients’ features (obesity, cardiac history). Patients with risk factors for redo surgery should be considered for an open surgery in a high-volume center

Survival and Prognostic Factors after Adrenalectomy for Secondary Malignancy: A Combined Analysis of a French University Center Registry (Eurocrine ®) of 307 Patients and a French Nationwide Study of 2,515 Patients.

International audienceObjective: To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases.Background: Adrenal glands are a common site of metastases in many malignancies. Diagnosis of adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management.Methods: We conducted a population-based study between January 2012 and December 2022 using the French National Health Data System (SNDS) and the Eurocrine registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers.Results: From the SNDS, we extracted 2515 patients who underwent adrenalectomy for secondary malignancy and 307 from the Eurocrine database. The most common primary malignancies were lung cancer (n=1203, 47.8%) and renal cancer (n=555, 22.1%). One-year survival was 84.3% (n=2120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n=32) and 29.9% (n=753, including planned intensive care unit - stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates (P=0.039). In the Eurocrine database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were the presence of extra-adrenal metastases (hazard ratio =0.64; P=0.031) and incomplete resection (≥R1; hazard ratio=0.41; P=0.015).Conclusions: The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis

International audienceBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis.MethodsTo better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels.FindingsThe most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling.ConclusionsThese results provide potential for a better understanding of disease pathophysiology

DOCK11 deficiency in patients with X-linked actinopathy and autoimmunity

International audienceDedicator of cytokinesis (DOCK) proteins play a central role in actin cytoskeleton regulation. This is highlighted by the DOCK2 and DOCK8 deficiencies leading to actinopathies and immune deficiencies. DOCK8 and DOCK11 activate CDC42, a RHO-GTPase involved in actin cytoskeleton dynamics, among many cellular functions. The role of DOCK11 in human immune disease has been long suspected but has never been described so far. We studied eight male patients, from seven unrelated families, with hemizygous DOCK11 missense variants leading to reduced DOCK11 expression. The patients were presenting with early-onset autoimmunity, including cytopenia, systemic lupus erythematosus, skin, and digestive manifestations. Patients’ platelets exhibited abnormal ultrastructural morphology and spreading as well as impaired CDC42 activity. In vitro activated T cells and B lymphoblastoid cell lines (B-LCL) of patients exhibited aberrant protrusions and abnormal migration speed in confined channels concomitant with altered actin polymerization during migration. A DOCK11 knock-down recapitulated these abnormal cellular phenotypes in monocytes-derived dendritic cells (MDDC) and primary activated T cells from healthy controls. Lastly, in line with the patients’ autoimmune manifestations, we also observed abnormal regulatory T cells (Tregs) phenotype with profoundly reduced FOXP3 and IKZF2 expression. Moreover, we found a reduced T cell proliferation and an impaired STAT5B phosphorylation upon IL2 stimulation of the patients’ lymphocytes. In conclusion, DOCK11 deficiency is a new X-linked immune-related actinopathy leading to impaired CDC42 activity and STAT5 activation, and associated with abnormal actin cytoskeleton remodeling as well as Tregs phenotype culminating in immune dysregulation and severe early-onset autoimmunity