Correlation of Isotope Count With Sentinel Node Positivity in Vulvar Cancer

Objective: Sentinel node biopsy (SNB) has become standard of care in early stage vulvar cancer. As the correlation of isotope count with the presence of metastases remains unclear, often several active nodes are excised per groin. This can result in increased morbidity in node-negative disease despite of SNB. In the current analysis, we assess whether resection of the hottest node could be sufficient to detect sentinel lymph node (SLN) metastasis. Methods: Patients with primary vulvar cancer receiving an SNB with radioactive tracer at the University Medical Center Hamburg-Eppendorf between 2008 and 2015 were evaluated. Results: A total of 145 patients with SNB were analyzed;thereof, 144 underwent bilateral SNB, resulting in 289 analyzed groins. A median of 2 SLNs (range, 1-7) per groin were removed. From 94 (32.5%) of 289 groins, more than 2 SLNs were excised. Median overall SLN isotope count was 1400 cps. In 50 groins, a positive SLN was detected (unilateral in 38 patients, bilateral in 6). The median number of positive SLN per groin was 1 (range, 1-4). The SLN with the highest isotope count carried metastases in 36 (78.3%) of 46 groins (in 4 cases, the highest count was unknown). In 10 (21.7%) of 46 positive groins, the SLN with the highest count was not the metastatic SLN (9/10 second highest count). Median count of these 10 SLN was 60% of the highest count with a range from 11.0% to 74.0%. Conclusions: The highest isotope count does not reliably detect the positive SLN in vulvar cancer. To prevent mostly fatal groin recurrences, surgeons should continue to remove all SLN accumulating relevant radioactive tracer over background activity

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Rho-kinase inhibition prevents proteinuria in immune-complex-mediated antipodocyte nephritis

Podocyte foot process retraction is a hallmark of proteinuric glomerulonephritis. Cytoskeletal rearrangement causes a redistribution of slit membrane proteins from the glomerular filtration barrier towards the cell body. However, the underlying signaling mechanisms are presently unknown. Recently, we have developed a new experimental model of immune-mediated podocyte injury in mice, the antipodocyte nephritis (APN). Podocytes were targeted with a polyclonal antipodocyte antibody causing massive proteinuria around day 10. Rho-kinases play a central role in the organization of the actin cytoskeleton of podocytes. We therefore investigated whether inhibition of Rho-kinases would prevent podocyte disruption. C57/BL6 mice received antipodocyte serum with or without daily treatment with the specific Rho-kinase inhibitor HA-1077 (5 mg/kg). Immunoblot analysis demonstrated activation of Rho-kinase in glomeruli of antipodocyte serum-treated mice, which was prevented by HA-1077. Increased Rho-kinase activity was localized to podocytes in APN mice by immunostainings against the phosphorylated forms of Rho-kinase substrates. Rho-kinase inhibition significantly reduced podocyte loss from the glomerular tuft. Periodic acid staining demonstrated less podocyte hypertrophy in Rho-kinase-inhibited APN mice, despite similar amounts of immune complex deposition. Electron microscopy revealed reduced foot process effacement compared with untreated APN mice. Internalization of the podocyte slit membrane proteins nephrin and synaptopodin was prevented by Rho-kinase inhibition. Functionally, Rho-kinase inhibition significantly reduced proteinuria without influencing blood pressure. In rats with passive Heymann nephritis and human kidney biopsies from patients with membranous nephropathy, Rho-kinase was activated in podocytes. Together, these data suggest that increased Rho-kinase activity in the podocyte may be a mechanism for in vivo podocyte foot process retraction

The radiologically isolated syndrome: revised diagnostic criteria

International audienceThe radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the central nervous system within individuals lacking symptoms typical of multiple sclerosis. The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfill 3-4 of 4 criteria for 2005 dissemination in space [DIS] and subjects fulfilling only 1 or 2 lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. 747 subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled 1 or 2 2017 DIS criteria (designated as Group 1 and Group 2, respectively), and 496 (66.4%) fulfilled 3 or 4 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS Group and were more likely to develop new T2 lesions over time (p < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to multiple sclerosis. At five years, the cumulative probability for a clinical event was 29.0% for Groups 1-2 compared to 38.7% for 2009-RIS (p = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at five years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (p < 0.001). The 2009-RIS subjects or Group 1-2 with at least 2 of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria