Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

BACKGROUND AND OBJECTIVES: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. METHODS: Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. RESULTS: A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. DISCUSSION: Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Circulating CD4+ T cells in people with HIV and history of pulmonary tuberculosis have more intact HIV DNA.

Background: The primary barrier to curing HIV infection is the pool of intact HIV proviruses integrated into host cell DNA throughout the bodies of people living with HIV (PLHIV), called the HIV reservoir. Reservoir size is impacted by the duration of HIV infection, delay in starting antiretroviral therapy (ART), and breakthrough viremia during ART. The leading infectious cause of death worldwide for PLHIV is TB, but we don't know how TB impacts the HIV reservoir. Methods: We designed a case-control study to compare HIV provirus-containing CD4 in PLHIV with vs. without a history of active TB disease. Study participants in the pilot and confirmatory cohort were enrolled at GHESKIO Centers in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of PBMC-derived CD4 cells. For a subset, Th1 and Th2 cytokines were assayed in plasma. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring. Results: In the pilot cohort, we found that PLHIV with history of active pulmonary TB (n=20) had higher intact provirus than PLHIV without history of active TB (n=47) (794 vs 117 copies per million CD4, respectively; p<0.0001). In the confirmatory cohort, the quantity of intact provirus was higher in the TB group (n=13) compared with the non-TB group (n=18) (median 102 vs. 0 intact provirus per million CD4, respectively p=0.03). Additionally, we found that the frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of IL1B (p= 0.0025) and IL2 (p=0.0002). Conclusions: This is the first assessment of HIV provirus using IPDA in a clinical cohort from a resource limited setting, and the finding of larger reservoir in PLHIV with history of TB has significant implications for our understanding of TB-HIV coinfection and HIV cure efforts in TB-endemic settings.

[First-line management of infertile couple. Guidelines for clinical practice of the French College of Obstetricians and Gynecologists 2022]. / Prise en charge de première intention du couple infertile : mise à jour des RPC 2010 du CNGOF.

OBJECTIVE: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples. MATERIALS AND METHODS: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts. RESULTS: The fertility work-up is recommended to be prescribed according to the woman's age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple's initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery. CONCLUSION: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

STAACS3: Simulation Tool for AAC with Single-Switch Scanning.

Communication for people with motor impairments is a difficult, yet necessary, task in daily activities. To do so, soft keyboards, digital counterpart of physical keyboards, are used. Depending on their features, several designs can be considered, however their thoughtful evaluation in real-life is not feasible. Therefore, it becomes necessary to filter the possible configurations wisely, taking advantage of simulation tools. This paper presents STAACS3, a Simulation Tool for AAC with Single-Switch scanning, that allows to model and simulate the performance of any type of scanning keyboard regardless of its keys configuration, scanning strategy or prediction systems.

Anti-AGO1 Antibodies Identify a Subset of Autoimmune Sensory Neuronopathy.

BACKGROUND AND OBJECTIVES: Autoantibodies (Abs) improve diagnosis and treatment decisions of idiopathic neurologic disorders. Recently, we identified Abs against Argonaute (AGO) proteins as potential autoimmunity biomarkers in neurologic disorders. In this study, we aim to reveal (1) the frequency of AGO1 Abs in sensory neuronopathy (SNN), (2) titers and IgG subclasses, and (3) their clinical pattern including response to treatment. METHODS: This retrospective multicentric case/control study screened 132 patients with SNN, 301 with non-SNN neuropathies, 274 with autoimmune diseases (AIDs), and 116 healthy controls (HCs) for AGO1 Abs through ELISA. Seropositive cases were also tested for IgG subclasses, titers, and conformation specificity. RESULTS: AGO1 Abs occurred in 44 patients, comprising significantly more of those with SNN (17/132 [12.9%]) than those with non-SNN neuropathies (11/301 [3.7%]; p = 0.001), those with AIDs (16/274 [5.8%]; p = 0.02), or HCs (0/116; p < 0.0001). Ab titers ranged from 1:100 to 1:100,000. IgG subclass was mainly IgG1, and 11/17 AGO1 Ab-positive SNN (65%) had a conformational epitope. AGO1 Ab-positive SNN was more severe than AGO1 Ab-negative SNN (e.g., SNN score: 12.2 vs 11.0, p = 0.004), and they more frequently and more efficiently responded to immunomodulatory treatments than AGO1 Ab-negative SNN (7/13 [54%] vs 6/37 [16%], p = 0.02). Regarding the type of treatments more precisely, this significant difference was confirmed for the use of IV immunoglobulins (IVIg) but not for steroids or second-line treatments. Multivariate logistic regression adjusted for potential confounders showed that AGO1 Ab positivity was the only predictor of response to treatment (OR 4.93, 1.10-22.24 95% CI, p = 0.03). DISCUSSION: Although AGO Abs are not specific for SNN, based on our retrospective data, they may identify a subset of cases with SNN with more severe features and a possibly better response to IVIg. The significance of AGO1 Abs in clinical practice needs to be explored on a larger series.

A case of colonoscopy-induced Wunderlich's syndrome in a hemodialysis patient: coincidence or association? / Um caso de síndrome de Wunderlich induzida por colonoscopia em um paciente em hemodiálise: coincidência ou associação?

Abstract Wunderlich syndrome, or spontaneous renal hemorrhage (SRH), is a rare condition encountered in patients undergoing chronic hemodialysis (HD) usually attributed to acquired cystic kidney disease (ACKD) among other causes. In the literature, colonoscopy is associated with splenic injuries, and renal hemorrhage has not been previously described. Management can range from conservative treatment to angiographic embolization or exploration and nephrectomy. Here we report an unusual case of a 54-year-old woman HD patient who presented with SRH within a few days of colonoscopy. The reason of SRH was rupture of an ACKD cyst. We assumed that colonoscopy was a provoking factor and elaborated hypotheses for its etiopathogenesis. The patient underwent successful left nephrectomy. The importance of this case lies in the fact that colonoscopy is not always an innocent procedure in HD patients, and could be complicated by renal cyst hemorrhage.

Resumo A síndrome de Wunderlich, ou hematoma perirrenal espontâneo (HPE), é uma condição rara encontrada em pacientes submetidos à hemodiálise crônica (HD) geralmente atribuída à doença renal cística adquirida (DRCA), entre outras causas. Na literatura, a colonoscopia está associada a lesões esplênicas, e o hematoma renal não foi descrito anteriormente. O manejo pode variar de tratamento conservador a embolização angiográfica ou exploração e nefrectomia. Aqui relatamos um caso incomum de uma paciente em HD de 54 anos de idade que se apresentou com HPE dentro de poucos dias após a colonoscopia. O motivo do HPE foi a ruptura de um cisto de DRCA. Consideramos que a colonoscopia foi um fator provocador e elaboramos hipóteses para sua etiopatogenia. A paciente foi submetida a uma nefrectomia esquerda bem-sucedida. A importância deste caso reside no fato de que a colonoscopia nem sempre é um procedimento inocente em pacientes em HD, e pode ser complicada por hemorragia do cisto renal.

A case of colonoscopy-induced Wunderlich's syndrome in a hemodialysis patient: coincidence or association?

Wunderlich syndrome, or spontaneous renal hemorrhage (SRH), is a rare condition encountered in patients undergoing chronic hemodialysis (HD) usually attributed to acquired cystic kidney disease (ACKD) among other causes. In the literature, colonoscopy is associated with splenic injuries, and renal hemorrhage has not been previously described. Management can range from conservative treatment to angiographic embolization or exploration and nephrectomy. Here we report an unusual case of a 54-year-old woman HD patient who presented with SRH within a few days of colonoscopy. The reason of SRH was rupture of an ACKD cyst. We assumed that colonoscopy was a provoking factor and elaborated hypotheses for its etiopathogenesis. The patient underwent successful left nephrectomy. The importance of this case lies in the fact that colonoscopy is not always an innocent procedure in HD patients, and could be complicated by renal cyst hemorrhage.

Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies.

Autoantibodies (Abs) are biomarkers for many disease conditions and are increasingly used to facilitate diagnosis and treatment decisions. To guarantee high sensitivity and specificity, the choice of their detection method is crucial. Via cell-based assays, we recently found 21 patients with neurological diseases positive for antibodies against argonaute (AGO), 10 of which having a neuropathy (NP). Here, we established a simple and conformation-sensitive ELISA with the aim to distinguish between AGO1 Abs against conformational epitopes and non-conformational epitopes and to reveal further characteristics of AGO1 antibodies in NP and autoimmune disease (AID). In a retrospective multicenter case/control and observational study, we tested 434 patients with NP, 274 disease controls with AID, and 116 healthy controls (HC) for AGO1 Abs via conformation-stabilizing ELISA. Seropositive patients were also tested for conformation-specificity via comparative denaturing/stabilizing ELISA (CODES-ELISA), CBA positivity, AGO1 titers and IgG subclasses, and AGO2 reactivity. These parameters were statistically compared among different epitope-specific patient groups. We found Abs in 44 patients, including 28/434 (6.5%) NP, 16/274 (5.8%) AID, and 0/116 (0%) HC. Serum reactivity was consistently higher for AGO1 than AGO2. Globally among the 44 AGO1 Abs-positive patients, 42 were also tested in CBA for AGO1 Abs positivity and 15 (35.7%) were positive. Furthermore, 43 were tested for conformation-specificity and 32 (74.4%) bound a conformational epitope. Among the subgroups of highly positive patients (ELISA z-score >14) with sera binding conformational epitopes (n=23), 14 patient sera were also CBA positive and 9 bound a second conformational but CBA-inaccessible epitope. A third, non-conformational epitope was bound by 11/43 (15.6%). Among the epitope-specific patient subgroups, we found significant differences regarding the Abs titers, IgG subclass, and AGO2 reactivity. When comparing AGO1 Abs-positive NP versus AID patients, we found the conformation-specific and CBA inaccessible epitope significantly more frequently in AID patients. We conclude that 1) conformational ELISA was more sensitive than CBA in detecting AGO1 Abs, 2) serum reactivity is higher for AGO1 than for AGO2 at least for NP patients, 3) AGO1 Abs might be a marker-of-interest in 6.5% of NP patients, 4) distinguishing epitopes might help finding different patient subgroups.

Sensory neuronopathies, diagnostic criteria and causes.

PURPOSE OF REVIEW: To stress on the diagnostic strategy of sensory neuronopathies (SNN), including new genes and antibodies. RECENT FINDING: SNN involve paraneoplastic, dysimmune, toxic, viral and genetic mechanisms. About one-third remains idiopathic. Recently, new antibodies and genes have reduced this proportion. Anti-FGFR3 and anti-AGO antibodies are not specific of SNN, although SNN is predominant and may occur with systemic autoimmune diseases. These antibodies are the only marker of an underlying dysimmune context in two-thirds (anti-FGFR3 antibodies) and one-third of the cases (anti-AGO antibodies), respectively. Patients with anti-AGO antibodies may improve with treatment, which is less clear with anti-FGFR3 antibodies. A biallelic expansion in the RFC1 gene is responsible for the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) in which SNN is a predominant manifestation. Most of the patients have an adult onset and are sporadic. The RFC1 mutation may represent one-third of idiopathic sensory neuropathies. Finally, the criteria for the diagnosis of paraneoplastic SNN have recently been updated. SUMMARY: The diagnostic of SNN relies on criteria distinguishing SNN from other neuropathies. The strategy in search of their cause now needs to include these recent findings.

Usefulness and prognostic value of diagnostic tests in patients with possible chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION/AIMS: Recent guidelines define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and possible CIDP. The aims of our study were to evaluate the value of diagnostic tests to support the diagnosis of CIDP in patients with possible CIDP and to identify prognostic factors of therapeutic success. METHODS: We conducted an observational retrospective two-center study between 2014 and 2019. We selected patients with a clinical presentation suggesting CIDP, but whose electrodiagnostic (EDX) test results did not meet the EFNS/PNS 2021 criteria. We analyzed epidemiologic and clinical features, axonal loss on EDX, cerebrospinal fluid (CSF), somatosensory evoked potentials (SSEPs), plexus magnetic resonance imaging (MRI), nerve biopsy, and therapeutic response. RESULTS: We selected 75 patients, among whom 30 (40%) responded to treatment. The positivity rates of CSF analysis, MRI and SSEPs were not influenced by the clinical presentation or by the delay between symptom onset and medical assessment. A high protein level in CSF, female gender, and a relapsing-remitting course predicted the therapeutic response. DISCUSSION: It is important to properly diagnose suspected CIDP not meeting EFNS/PNS 2021 EDX criteria by using supportive criteria. Specific epidemiological factors and a raised CSF protein level predict a response to treatment. Further prospective studies are needed to improve diagnosis and the prognostic value of diagnostic tests in CIDP.

The Impact of Vitamin A Deficiency on Tuberculosis Progression.

BACKGROUND: Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression. METHODS: We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of dietary vitamin A deficiency. RESULTS: Among 773 participants, 96 developed incident TB during follow-up, 62.5% (60) of whom had stored serum samples obtained 90-365 days before TB diagnosis. In age- and sex- adjusted and multivariate analyses, respectively, incident TB cases were 3.99 times (95% confidence interval [CI], 2.41 to 6.60) and 3.59 times (95% CI, 2.05 to 6.29) more likely to have been vitamin A deficient than matched controls. Vitamin A-deficient guinea pigs manifested more extensive pulmonary pathology, atypical granuloma morphology, and increased bacterial growth after experimental TB infection. Reintroduction of dietary vitamin A to deficient guinea pigs after established TB disease successfully abrogated severe disease manifestations and altered cellular immune profiles. CONCLUSIONS: Human and animal studies support the role of baseline vitamin A deficiency as a determinant of future TB disease progression.

Prognostic Factors and Treatment Efficacy in Spinal Cord Sarcoidosis: An Observational Cohort With Long-term Follow-up.

BACKGROUND AND OBJECTIVES: Spinal cord sarcoidosis is a rare manifestation of sarcoidosis with a consequent risk of neurologic sequelae for the patient. We investigated prognostic factors and efficacy of immunosuppressive treatments in a longitudinal cohort. METHODS: We retrospectively studied patients with spinal cord sarcoidosis followed between 1995 and 2021 in 7 centers in France. Patients with definite, probable, or possible spinal cord sarcoidosis according to the Neurosarcoidosis Consortium Consensus Group criteria and with spinal cord involvement confirmed by MRI were included. We analyzed relapse or progression rate with a Poisson model, initial Rankin score with a linear model, and change in the Rankin score during follow-up with a logistic model. RESULTS: A total of 97 patients were followed for a median of 7.8 years. Overall mean relapse or progression rate was 0.17 per person-year and decreased over time. At last visit, 46 (47.4%) patients had a loss of autonomy (Rankin score ≥2). The main prognostic factors significantly associated with relapse or progression rate were gadolinium enhancement (relative rate [95% CI] 0.61 [0.4, 0.95]) or meningeal involvement (relative rate [95% CI] 2.05 [1.31, 3.19]) on spinal cord MRI and cell count (relative rate [95% CI] per 1 log increase 1.16 [1.01, 1.33]) on CSF analysis. Relapse or progression rate was not significantly associated with initial Rankin score or Expanded Disability Status Scale. Tumor necrosis factor-α (TNF-α) antagonists significantly decreased relapse or progression rate compared with corticosteroids alone (relative rate [95% CI] 0.33 [0.11, 0.98]). Azathioprine was significantly less effective than methotrexate on relapse or progression rate (relative rate [95% CI] 2.83 [1.04, 7.75]) and change in Rankin score (mean difference [95% CI] 0.65 [0.23, 1.08]). DISCUSSION: Regarding the relapse or progression rate, meningeal localization of sarcoidosis was associated with a worse prognosis, TNF-α antagonists resulted in a significant decrease compared to corticosteroids alone, and methotrexate was more effective than azathioprine. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in individuals with spinal cord neurosarcoidosis, TNF-α antagonists were associated with decreased relapse or progression rate compared to corticosteroids alone, but other therapies showed no significant benefit.

Secondary infertility with a history of vaginal childbirth: Ready to have another one?

INTRODUCTION: Up to 30% of couples may face secondary infertility. The impact of ectopic pregnancy, spontaneous abortion, pregnancy termination or live birth with caesarean section may impair further fertility in different ways. However, secondary infertility after physiological vaginal life childbirth has been little studied. The aim of this study was to describe the population and the fertility issues and analyze the predictive factors of success in in vitro fertilization in women presenting secondary infertility after a physiological vaginal childbirth. MATERIAL AND METHODS: This single-centre retrospective study included women aged 18-43 years consulting between 2013 and 2020 for secondary infertility in a couple having already had previous vaginal life childbirth. Couples' characteristics, management decision after the first consultation and IVF outcomes were analyzed. RESULTS: Secondary infertility was found in 286 couples, out of whom 138 had a history of vaginal life childbirth. Population was characterized by an advanced female age and overweight. After the first consultation, IVF was performed in only 40% of couples. No predictive factor of live birth was found. CONCLUSION: Our study shows that in couples with secondary infertility after prior physiological delivery cigarette smoking is frequent in male partners, and ovarian reserve markers are altered. However, no statistically significant predictive factor of live birth after IVF treatment has been identified. Further large prospective studies are necessary.

Anti-FGFR3 antibody epitopes are functional sites and correlate with the neuropathy pattern.

Antibodies against FGFR3 define a subgroup of sensory neuropathy (SN). The aim of this study was to identify the epitope(s) of anti-FGFR3 autoantibodies and potential epitope-dependent clinical subtypes. Using SPOT methodology, five specific candidate epitopes, three in the juxtamembrane domain (JMD) and two in the tyrosine kinase domain (TKD), were screened with 68 anti-FGFR3-positive patients and 35 healthy controls. The identified epitopes cover 6/15 functionally relevant sites of the protein. Four patients reacted with the JMD and 11 with the TKD, partly even in a phosphorylation-state dependent manner. The epitope could not be identified in the others. Patients with antibodies recognizing TKD exhibited a more severe clinical and electrophysiological impairment than others.

A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases.

BACKGROUND: Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus. RESULTS: Physicians reported 84 patients, including: 34 with myasthenia gravis, 27 with myopathy and 23 with neuropathy. COVID-19 had no effect on NMD for 48 (58%) patients and 48 (58%) patients developed low COVID-19 severity. COVID-19 caused the death of 9 (11%) NMD patients. Diabetic patients were at greater risk of dying. Patients with diabetes, hypertension or severe forms of NMD had a higher risk of developing a moderate or severe form of COVID-19. In our cohort, corticosteroids and other immunosuppressants were not significantly associated with higher COVID-19 severity for acquired NMD. CONCLUSION: During this period, a small percentage of French NMD patients was affected by COVID-19 compared to the general French population and COVID-19 had a limited short-term effect on them. Diabetes, hypertension and a severe degree of NMD were identified as risk factors of unfavorable outcome following COVID-19. Conversely, in our cohort of patients with acquired NMD, corticosteroids or other immunosuppressants did not appear to be risk factors for more severe COVID-19.

Mild COVID-19 infection does not alter the ovarian reserve in women treated with ART.

RESEARCH QUESTION: Does mild COVID-19 infection affect the ovarian reserve of women undergoing an assisted reproductive technology (ART) protocol? DESIGN: A prospective observational study was conducted between June and December 2020 at the ART unit of Tenon Hospital, Paris. Women managed at the unit for fertility issues by in-vitro fecundation, intracytoplasmic sperm injection (IVF/ICSI), fertility preservation, frozen embryo transfer or artificial insemination, and with an anti-Müllerian hormone (AMH) test carried out within 12 months preceding ART treatment, were included. All the women underwent a COVID rapid detection test (RDT) and AMH concentrations between those who tested positive (RDT positive) and those who tested negative (RDT negative). RESULTS: The study population consisted of 118 women, 11.9% (14/118) of whom were COVID RDT positive. None of the tested women presented with a history of severe COVID-19 infection. The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (-1.33 ng/ml [-0.35 to -1.61) versus -0.59 ng/ml [-0.15 to -1.11], P = 0.22). CONCLUSION: A history of mild COVID-19 infection does not seem to alter the ovarian reserve as evaluated by AMH concentrations. Although these results are reassuring, further studies are necessary to assess the effect of COVID-19 on pregnancy outcomes in women undergoing ART.

Long-term mortality after tuberculosis treatment among persons living with HIV in Haiti.

INTRODUCTION: Long-term mortality among TB survivors appears to be higher than control populations without TB in many settings. However, data are limited among persons with HIV (PWH). We assessed the association between cured TB and long-term mortality among persons with PWH in Haiti. METHODS: A prospective cohort of PWH from the CIPRA HT-001 trial was followed from study enrolment (August 2005 to July 2008) to study closure (December 2018) to compare mortality between participants with and without TB. The index date for the survival analysis was defined as 240 days after TB diagnosis or randomization date. Time to death was described using Kaplan-Meier curves, and log-rank tests were used to compare time to death between the TB and no-TB cohorts. The association between TB and long-term mortality was estimated with multivariable Cox models. RESULTS: Of the 816 participants in the CIPRA HT-001 trial, 77 were excluded for a history of TB prior to study enrolment and 31 were excluded due to death or attrition prior to the index date, leaving 574 in the no-TB and 134 in the TB cohort. Twenty-four (17.9%) participants in the TB and 48 (8.4%) in the no-TB cohort died during follow-up. Five and 10-year mortality rates were 14.2% and 17.9% respectively, in the TB cohort, and 6.1% and 8.4% in the no-TB cohort. In Kaplan-Meier analysis, participants in the TB cohort had a significantly shorter time to death (log-rank p < 0.001). In multivariable analysis, TB treatment was the only predictor of mortality (HR: 2.78; 95% CI: 1.61, 4.79). Sensitivity analyses, which included only baseline TB cases, an index date of two years after TB diagnosis, and study enrolment and case-control matching yielded results that were consistent with primary analyses. CONCLUSIONS: PWH who are successfully treated for TB have higher long-term mortality than those who are never diagnosed with TB, even after accounting for acute TB-related mortality. A better understanding of the underlying mechanisms associated with TB sequelae is critically needed to guide specific interventions. Until then, more aggressive measures for health promotion and disease prevention are essential to improve long-term survival for PWH after TB treatment.

Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases.

OBJECTIVE: To identify and characterize autoantibodies (Abs) as novel biomarkers for an autoimmune context in patients with central and peripheral neurologic diseases. METHODS: Two distinct approaches (immunoprecipitation/mass spectrometry-based proteomics and protein microarrays) and patients' sera and CSF were used. The specificity of the identified target was confirmed by cell-based assay (CBA) in 856 control samples. RESULTS: Using the 2 methods as well as sera and CSF of patients with central and peripheral neurologic involvement, we identified Abs against the family of Argonaute proteins (mainly AGO1 and AGO2), which were already reported in systemic autoimmunity. AGO-Abs were mostly of immunoglobulin G 1 subclass and conformation dependent. Using CBA, AGO-Abs were detected in 21 patients with a high suspicion of autoimmune neurologic diseases (71.4% were women; median age 57 years) and only in 4/856 (0.5%) controls analyzed by CBA (1 diagnosed with small-cell lung cancer and the other 3 with Sjögren syndrome). Among the 21 neurologic patients identified, the main clinical presentations were sensory neuronopathy (8/21, 38.1%) and limbic encephalitis (6/21, 28.6%). Fourteen patients (66.7%) had autoimmune comorbidities and/or co-occurring Abs, whereas AGO-Abs were the only autoimmune biomarker for the remaining 7/21 (33.3%). Thirteen (61.9%) patients were treated with immunotherapy; 8/13 (61.5%) improved, and 3/13 (23.1%) remained stable, suggesting an efficacy of these treatments. CONCLUSIONS: AGO-Abs might be potential biomarkers of autoimmunity in patients with central and peripheral nonparaneoplastic neurologic diseases. In 7 patients, AGO-Abs were the only biomarkers; thus, their identification may be useful to suspect the autoimmune character of the neurologic disorder. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that AGO-Abs are more frequent in patients with autoimmune neurologic diseases than controls.

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes.

OBJECTIVE: The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS. METHODS: A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project. RESULTS: The panel proposed to substitute "classical syndromes" with the term "high-risk phenotypes" for cancer and introduce the concept of "intermediate-risk phenotypes." The term "onconeural antibody" was replaced by "high risk" (>70% associated with cancer) and "intermediate risk" (30%-70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided. CONCLUSIONS: The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.

High-Dose Supplementation of Folic Acid in Infertile Men Improves IVF-ICSI Outcomes: A Randomized Controlled Trial (FOLFIV Trial).

Dietary supplementation is commonly used in men with male infertility but its exact role is poorly understood. The aim of this multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the impact of high-dose folic acid supplementation on IVF-ICSI outcomes. 162 couples with male infertility and an indication for IVF-ICSI were included for one IVF-ICSI cycle. Male partners of couples wishing to conceive, aged 18-60 years old, with at least one abnormal spermatic criterion were randomized in a 1:1 ratio to receive daily supplements containing 15 mg of folic acid or a placebo for 3 months from Day 0 until semen collection for IVF-ICSI. Sperm parameters and DNA fragmentation before and after the treatment and the biochemical and clinical pregnancy rates after the fresh embryo transfer were analyzed. We observed an increase in the biochemical pregnancy rate and a trend for a higher clinical pregnancy rate in the folic acid group compared to placebo (44.1% versus 22.4%, p = 0.01 and 35.6% versus 20.4%, p = 0.082, respectively). Even if no changes in sperm characteristics were observed, a decrease in DNA fragmentation in the folic acid group was noted (8.5 ± 4.5 vs. 6.4 ± 4.6, p < 0.0001). High-dose folic acid supplementation in men requiring IVF-ICSI for male infertility improves IVF-ICSI outcomes.