Despite mounting evidence for a causal role in an increasing number of lymphoma subtypes, very few studies have systematically tested the entire spectrum of Hodgkin and non-Hodgkin lymphomas for the presence of Epstein-Barr virus (EBV). Here, we describe the prevalence of EBV in a large, unselected series of patients diagnosed with any type of lymphoma during 2020, in the pathology department of a single University Hospital in France. A total of 756 lymphoma cases (89% new diagnoses and 11% relapses), were registered in the department between Jan 1 and Sept 30, 2020 and 616 were successfully tested for EBV presence in tumour cells by EBV-encoding RNA in-situ hybridisation, using double-blinded assessment and a scoring system designed in accordance with the current state of knowledge in the literature A strong association with EBV was described in 27/87 (31%) classic Hodgkin lymphomas, 12/223 (5%) diffuse large B-cell lymphomas, and 18/71 (25%) NK and T-cell lymphomas: 4 extranodal NK/T-cell lymphomas, nasal type, 14 angioimmunoblastic T-cell lymphomas (48%). In Hodgkin and NK and T-cell lymphomas, there was a statistically significant association between EBER positivity and relapse (p < 0·01). Among other subtypes, a potential association with EBV (≥10% stained cells) was found in 2/97 (2%) follicular lymphomas, both of grades 1–2, 1/19 (5%) chronic lymphocytic leukaemia (CLL), 1/9 lymphoplasmacytic lymphomas (11%), and 2/47 (4%) marginal zone lymphomas. When applied to the distribution of lymphomas in France as described in the Lymphopath database, our data suggested that at least 8% of all combined Hodgkin and non-Hodgkin lymphomas are associated with EBV. International Agency for Research on Cancer (IARC/WHO).

It is well known that thyroid dysfunction increases with age. This study is aimed to determine reference intervals, in males and females, suitable for thyroid disease exploration during adult life using routinely collected serum thyrotropin (TSH) data in a tertiary center from 2007 to 2018. Over 11 years, 295,775 TSH levels were measured in a single lab. Among the 156,025 TSH results available for analysis, 90,538 values were from female subjects, 82,019 were from patients aged >60 years and 26,825 were from patients aged >80 years. By using an indirect approach, we determined reference values of TSH adapted to age and sex, and we then evaluated the proportion of patients who would have been reclassified with these reference values. The median TSH ranged from 1.2–1.4 mUI/L during the study period. The upper limit of reference range of TSH increased with age; in females the median to 97.5th percentile values increased continuously from the age of 30 years to the oldest age group. Using new calculated reference values in patients with TSH above the conventional upper-limit reference value (4 mUI/L), the proportion of results reclassified as within the reference interval among patients aged >60 years ranged, according to age group, from 50.5% to 65.1% of females and from 33.0% to 37.7% of males. The use of TSH age-specific and sex-specific upper-limit reference values led to the reclassification of a great number of samples, notably among women. This suggests that age-specific TSH upper-limit reference intervals in daily practice should be used in order to avoid misclassification.

PURPOSE: Alkylating agents (ALKY) are the main chemotherapies used for advanced neuroendocrine tumors (NETs). O ⁶ -Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may predict the response to ALKY. PATIENTS AND METHODS: MGMT-NET (ClinicalTrials.gov identifier: NCT03217097 ) was a phase II trial randomly assigning 1:1 for pMGMT or 2:1 for dMGMT-NETs to either ALKY or oxaliplatin (Ox). Inclusion criteria were a confirmed advanced pancreatic, thoracic, or unknown primary NETs with an indication for chemotherapy and tissue available. The primary aim was to detect a difference of 35% between the 3-month objective response rate (ORR) in pMGMT-NETs versus in dMGMT-NETs when treated with ALKY. A biomarker-stratified design was performed to compare ALKY and Ox in the dMGMT and pMGMT strata for the secondary end points. dMGMT was defined using pyrosequencing (PSQ; methylated MGMT ≥9%) and using immunochemistry ( H -score of MGMT <50) when PSQ was not interpretable. RESULTS: From October 2018 to October 2021, 105 patients (55 pancreas, 38 thorax, 12 unknown) started either ALKY (n = 62) or Ox (n = 43). The median age was 63 years (range, 30-84), and 59% were males. NETs were G1 (19%), G2 (69%), or G3 (10%). Among patients with interpretable MGMT status, 56.9% (58 of 102) had a dMGMT-NET. The primary end point was not reached; the 3-month ORR was 10 (29.4%) versus 2 (8%), and the odds ratio was 3.5 (0.58-21.16), P = .172. However, best ORR (18 [52.9%] v 3 [11.5%]) and median progression-free survival (14.6 [95% CI, 7.2 to 22.1] v 11.3 [9.4 to 13.2] months) were higher for dMGMT-NETs versus pMGMT-NETs. MGMT status does not seem to affect the Ox efficacy. CONCLUSION: Despite the fact that the primary end point was not reached, ALKY has clinical activity in patients with dMGMT-NETs.

Background: New CFTR Modulator triple therapy Elexacaftor‐Ivacaftor‐Tezacaftor (ETI) prove efficacy in pulmonary outcomes. However, its impact on nasal sinus symptoms in children has not been specifically studied. The aim of this study is to evaluate the impact of this therapy on nasal sinus symptomatology in children aged 6–12 years. Methods: A prospective, single‐center cohort study was conducted over a 12‐month follow‐up period in children aged 6–12 years at the initiation of ETI therapy. The primary outcome was evolution of the SN‐5 score, a validated pediatric questionnaire measuring quality of life related to nasal sinus symptoms. A decrease of 0.5 points is considered clinically significant. Secondary outcomes included changes in clinical examination findings (obstructive turbinate hypertrophy, polyps, presence of pus in the middle meatus, and externalized mucocele), quality of life measured by the Visual Analog Scale (VAS), and number of antibiotic courses during the study period. Results: Twenty‐six patients were included between March and September 2023, with no lost to follow‐up. The initial mean SN‐5 score was 2.88 (95% CI {1.91; 3.85}). After 1 year, the mean SN‐5 score was significantly lower (1.41, 95% CI {1.00; 1.88}, Delta = 1.47, p < 0.001). The VAS related to symptoms also improved (Delta = 1.7, p < 0.001), and the number of antibiotic courses decreased (25 vs. 69, p < 0.001). A trend toward improvement in clinical examination parameters was observed. Conclusion: ETI therapy appears to significantly improve nasal sinus symptoms in children aged 6–12 years, as evidenced by improved quality‐of‐life scales and reduced antibiotic use.

A decrement on repetitive nerve stimulation (RNS) is essential for the diagnosis of myasthenia gravis (MG). The decrement pattern is typically "U-shaped" in MG caused by acetylcholine receptor antibodies (AChR-MG) but is less well described in MG caused by muscle-specific kinase antibodies (MuSK-MG). The aim of this study was to investigate RNS abnormalities in MuSK-MG, and to describe the differences in the decrement pattern as compared to AChR-MG. This retrospective case-control study included patients diagnosed with generalized MuSK-MG, compared to a control group of generalized AChR-MG. The five most frequently explored nerve-muscle pairs in RNS were analyzed: radial-anconeus, fibular nerve-tibialis anterior (TA), XI-trapezius, XII/V-submental complex (SMC), and VII-orbicularis oculi (OO). Decreased amplitude between the 1st and 4th responses (early decrement) and the late/early ratio were calculated (late/early ratio <100 %=U-shaped pattern, and ≥100 %=progressive pattern). For MuSK-MG, 25 patients were included and compared to 35 AChR-MG patients. An early decrement was present in 38/83 (54.2 %) muscles in MuSK-MG compared to 88/130 (67.7 %) muscles in AChR-MG; and in MuSK-MG was less frequently found in anconeus (4/22 [18.2 %] vs 27/31 [87.1 %], p < 0.001) and in TA (0/12 [0.0 %] vs 9/30 [30 %], p = 0.04). A progressive pattern was more frequent in MuSK-MG (19/38 [50.0 %] of muscles vs 15/88 [17.0 %], p < 0.001). The late/early ratio was greater in MuSK-MG (median value was 98.4 % [IQR, 86.8-106.8] vs 89.7 % [IQR, 79.5-96.5]). The first response with minimal amplitude during the RNS (Amin) was significantly different between the two groups (p < 0.001). Compared to AChR-MG, RNS in MuSK-MG showed fewer affected muscles, with less frequent involvement of anconeus and TA in particular; and a more progressive decrement pattern.

(1) Background: to investigate the correlation between structural (retinal ganglion cells and retinal nerve fibers) and functional alterations analyzed point-by-point in the central 10 degrees of the visual field of patients with advanced glaucoma using Humphrey 10-2 visual field tests. (2) Methods: Single-center prospective cohort study carried on from October 2018 to February 2019 at the Croix-Rousse hospital, Lyon, France. The primary outcome measure was the point-by-point correlation between retinal sensitivity (Humphrey 10-2) and retinal ganglion cell complex (GCC) thickness. (3) Results: 29 eyes of 27 patients were examined. Of these, 15 eyes had a mean deviation (MD) less than −20 dB. There were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the lower part of the visual field, with lower retinal sensitivity being associated with thicker GCC layers. There were no strong linear relationships or statistically significant correlations in the other regions of the visual field. For the patients with MD < −20 dB, there were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the superior nasal region. Retinal sensitivity was not correlated with retinal nerve fibre layer thickness. (4) Conclusions: In this study of patients with advanced glaucoma, GCC thickness was linearly associated with 10-2 visual field sensitivity in certain regions, negatively for patients with less-severe glaucoma. The initial thickening raises questions about the apoptosis mechanism, while the thinning observed in the most severe cases is consistent with the ganglion cell death identified on visual field tests.