Neurofilament light chain in spinal fluid and plasma in multiple system atrophy: a prospective, longitudinal biomarker study.

PURPOSE: There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to cerebrospinal fluid (NfL-c) as a diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression. METHODS: Well-characterized patients with early MSA (n = 32), Parkinson's disease (PD; n = 21), and matched controls (CON; n = 15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high-sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression. RESULTS: Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson, r = 0.99), while correlation between NfL-c and -p was only moderate (r = 0.66). NfL was significantly higher in MSA compared with CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL nor baseline NfL were significantly associated with changes in clinical markers of disease severity. CONCLUSIONS: These findings confirm NfL-c as a faithful diagnostic marker of MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time and was not predictive of clinical disease progression.

Neurofilament Light Chain in Spinal Fluid and Plasma in Multiple System Atrophy - A Prospective, Longitudinal Biomarker Study.

Purpose There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to CSF (NfL-c) as diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression. Methods Well-characterized patients with early MSA (n=32), Parkinson's disease (PD, n=21), and matched controls (CON, n=15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression. Results Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson,r=0.99), while correlation between NfL-c and -p was only moderate (r=0.66). NfL was significantly higher in MSA compared to CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL nor baseline NfL were significantly associated with changes in clinical markers of disease severity. Conclusions These findings confirm NfL-c as faithful diagnostic marker of MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time and was not predictive of clinical disease progression.

Epidemiology of Invasive Infections Caused by Streptococcus agalactiae in Argentina.

In recent years, an increase in the number of cases of invasive infections due to Streptococcus agalactiae (group B Streptococcus [GBS]) in adults has been reported. During 2014 and 2015, a multicentric, observational, and prospective study, including 40 health centers, was developed to describe the phenotypic and genotypic characteristics of GBS isolates circulating in Argentina and to analyze the clinical and demographic characteristics of patients with invasive infections. We recovered 162 invasive (GBSi) isolates from adult patients (n = 130, 80.2%), neonates (n = 24, 15%), and children below 18 years of age (n = 8, 4.8%), and colonizing (GBSc) isolates were recovered in prenatal GBS screening. GBS infection in adults was associated with underlying diseases, mainly diabetes mellitus. All isolates were penicillin susceptible. Resistance rates to erythromycin (25%) and clindamycin (26%) among the GBSc isolates were significantly higher than those from GBSi strains (17.3% and 16.1%, respectively); by contrast, levofloxacin resistance was significantly higher in GBSi isolates (14.8% vs. 7%). Serotype Ia was the most frequent in neonates and Ib was most frequent in adults. Serotypes Ia and III were prevalent in GBSc isolates. The increase of levofloxacin resistance was associated with the presence of a serotype Ib clone. This work emphasizes the need for GBS infection surveillance studies to implement correct treatments and adequate prevention strategies.

Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0-10) was 7 (interquartile range, 6-7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722-1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Natural History of Afferent Baroreflex Failure in Adults.

OBJECTIVE: To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester. METHODS: We performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests). RESULTS: A total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group (p < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period. CONCLUSIONS: ABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.

Alpha-Synuclein Oligomers and Neurofilament Light Chain Predict Phenoconversion of Pure Autonomic Failure.

OBJECTIVE: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NfL) in cerebrospinal fluid (CSF) of patients with pure autonomic failure (PAF) as markers of future phenoconversion to multiple system atrophy (MSA). METHODS: Well-characterized patients with PAF (n = 32) were enrolled between June 2016 and February 2019 at Mayo Clinic Rochester and followed prospectively with annual visits to determine future phenoconversion to MSA, Parkinson's disease (PD), or dementia with Lewy bodies (DLB). ELISA was utilized to measure NfL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF collected at baseline. RESULTS: Patients were followed for a median of 3.9 years. Five patients converted to MSA, 2 to PD, and 2 to DLB. NfL at baseline was elevated only in patients who later developed MSA, perfectly separating those from future PD and DLB converters as well as non-converters. ASyn-PMCA was positive in all but two cases (94%). The PMCA reaction was markedly different in five samples with maximum fluorescence and reaction kinetics previously described in MSA patients; all of these patients later developed MSA. INTERPRETATION: αSyn-PMCA is almost invariably positive in the CSF of patients with PAF establishing this condition as α-synucleinopathy. Both NfL and the magnitude and reaction kinetics of αSyn PMCA faithfully predict which PAF patients will eventually phenoconvert to MSA. This finding has important implications not only for prognostication, but also for future trials of disease modifying therapies, allowing for differentiation of MSA from Lewy body synucleinopathies before motor symptoms develop. ANN NEUROL 2021;89:1212-1220.

Autonomic dysfunction following COVID-19 infection: an early experience.

PURPOSE: Post-COVID-19 syndrome is a poorly understood aspect of the current pandemic, with clinical features that overlap with symptoms of autonomic/small fiber dysfunction. An early systematic analysis of autonomic dysfunction following COVID-19 is lacking and may provide initial insights into the spectrum of this condition. METHODS: We conducted a retrospective review of all patients with confirmed history of COVID-19 infection referred for autonomic testing for symptoms concerning for para-/postinfectious autonomic dysfunction at Mayo Clinic Rochester or Jacksonville between March 2020 and January 2021. RESULTS: We identified 27 patients fulfilling the search criteria. Symptoms developed between 0 and 122 days following the acute infection and included lightheadedness (93%), orthostatic headache (22%), syncope (11%), hyperhidrosis (11%), and burning pain (11%). Sudomotor function was abnormal in 36%, cardiovagal function in 27%, and cardiovascular adrenergic function in 7%. The most common clinical scenario was orthostatic symptoms without tachycardia or hypotension (41%); 22% of patients fulfilled the criteria for postural tachycardia syndrome (POTS), and 11% had borderline findings to support orthostatic intolerance. One patient each was diagnosed with autoimmune autonomic ganglionopathy, inappropriate sinus tachycardia, vasodepressor syncope, cough/vasovagal syncope, exacerbation of preexisting orthostatic hypotension, exacerbation of sensory and autonomic neuropathy, and exacerbation of small fiber neuropathy. CONCLUSION: Abnormalities on autonomic testing were seen in the majority of patients but were mild in most cases. The most common finding was orthostatic intolerance, often without objective hemodynamic abnormalities on testing. Unmasking/exacerbation of preexisting conditions was seen. The temporal association between infection and autonomic symptoms implies a causal relationship, which however cannot be proven by this study.

Identification of a non-classical three-dimensional nuclear localization signal in the intestinal fatty acid binding protein.

The intestinal fatty acid binding protein (FABP) is a small protein expressed along the small intestine that bind long-chain fatty acids and other hydrophobic ligands. Several lines of evidence suggest that, once in the nucleus, it interacts with nuclear receptors, activating them and thus transferring the bound ligand into the nucleus. Previous work by our group suggests that FABP2 would participate in the cytoplasm-nucleus translocation of fatty acids. Because the consensus NLS is absent in the sequence of FABP2, we propose that a 3D signal could be responsible for its nuclear translocation. The results obtained by transfection assays of recombinant wild type and mutated forms of Danio rerio Fabp2 in Caco-2 cell cultures, showed that lysine 17, arginine 29 and lysine 30 residues, which are located in the helix-turn-helix region, would constitute a functional non-classical three-dimensional NLS.

Alpha-Synuclein Oligomers and Neurofilament Light Chain in Spinal Fluid Differentiate Multiple System Atrophy from Lewy Body Synucleinopathies.

OBJECTIVE: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NFL) in cerebrospinal fluid (CSF) as markers of early multiple system atrophy (MSA) and to contrast findings with Lewy body synucleinopathies. METHODS: In a discovery cohort of well-characterized early MSA patients (n = 24) and matched healthy controls (CON, n = 14), we utilized enzyme-linked immunosorbent assay to measure NFL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF. We confirmed findings in a separate prospectively enrolled cohort of patients with early MSA (n = 38), Parkinson disease (PD, n = 16), and dementia with Lewy bodies (DLB, n = 13), and CON subjects (n = 15). RESULTS: In the discovery cohort, NFL was markedly elevated in MSA patients, with perfect separation from CON. αSyn-PMCA was nonreactive in all CON, whereas all MSA samples were positive. In the confirmatory cohort, NFL again perfectly separated MSA from CON, and was significantly lower in PD and DLB compared to MSA. PMCA was again nonreactive in all CON, and positive in all but 2 MSA cases. All PD and all but 2 DLB samples were also positive for αSyn aggregates but with markedly different reaction kinetics from MSA; aggregation occurred later, but maximum fluorescence was higher, allowing for perfect separation of reactive samples between MSA and Lewy body synucleinopathies. INTERPRETATION: NFL and αSyn oligomers in CSF faithfully differentiate early MSA not only from CON but also from Lewy body synucleinopathies. The findings support the role of these markers as diagnostic biomarkers, and have important implications for understanding pathophysiologic mechanisms underlying the synucleinopathies. ANN NEUROL 2020;88:503-512.

Estrategias de Afrontamiento Familiar y la Prevalencia del Consumo de Alcohol en Adolescentes de Secundaria / Strategies of Family Coping and the Prevalence of Alcohol Consumption among Secondary School Adolescents / Estratégias de Enfrentamento Familiar e Prevalência do Consumo de Álcool em Adolescentes Secundários / Stratégies d'Adaptation Familiales et Prévalence de la Consommation d'Alcool chez des Adolescents de Niveau Secondaire

Resumen Objetivo Determinar las Estrategias de Afrontamiento Familiar y la Prevalencia de Consumo de Alcohol en Adolescentes de Secundaria. Materiales y Métodos El presente estudio fue descriptivo correlacional, con un muestreo probabilístico estratificado con asignación proporcional al tamaño de cada estrato y con selección aleatoria simple (n=171 estudiantes). Se utilizó el Cuestionario de Afrontamiento Familiar que analiza las estrategias de afrontamiento de la familiar, y entre estos recursos, estudia el apoyo social de la comunidad, los amigos y vecinos, las estrategias en la resolución de los problemas, la evaluación que la familiar del estresor, el apoyo espiritual y la inclinación a pedir ayuda. Resultados La prevalencia de consumo de alcohol teniendo la prevalencia global con un 59,6%, IC 95% [0,52-0,67]; la prevalencia lápsica con el 43,3% IC 95% [0,36-0,51]; la prevalencia actual con el 33,9% IC 95% [0,27-0,41] y con el 17% IC 95% [0,11-0,23] la prevalencia instantánea. En lo que respecta a la relación que existe entre las estrategias de afrontamiento familiar y la prevalencia de consumo de alcohol, se encontró una relación negativa y significativa (rs=-.290, p=.003). Conclusión A menor estrategias de afrontamiento familiares externas (apoyo amigo/familiares, apoyo espiritual, apoyo formal y apoyo vecinos) que perciben los adolescentes menor será la edad de inicio de consumo de alcohol de los estudiantes de secundaria.

Abstract Objective To determine the Family Coping Strategies and the Prevalence of Alcohol Consumption among Secondary school Adolescents. Materials and methods The present research was a descriptive correlational study, with a stratified probabilistic sampling with allocation proportional to the size of each stratum and with simple random selection (n = 171 students). The Family Coping Questionnaire that analyzes family coping strategies was used, and among these resources, study the social support of the community, friends and neighbors, strategies in solving problems, assessment that the family stressor, spiritual support and inclination to ask for help. Results The prevalence of alcohol consumption having the overall prevalence with 59.6%, 95% CI [0.52-0.67]; the lipsic prevalence with 43.3% 95% CI [0.36-0.51]; the current prevalence with 33.9% 95% CI [0.27-0.41] and with 17% 95% CI [0.11-0.23] instantaneous prevalence. Regarding the relationship between family coping strategies and the prevalence of alcohol consumption, a negative and significant relationship was found (rs =-.290, p =.003). Conclusion A lower external family coping strategy (friend / family support, spiritual support, formal support and neighbor's support) perceived by adolescents, a lower the age of alcohol consumption of secondary school students.

Resumo Objetivo Determinar as estratégias de enfrentamento familiar e a prevalência do consumo de álcool em adolescentes do ensino médio. Materiais e métodos Presente estudo foi correlacional descritivo, com amostragem probabilística estratificada, com alocação proporcional ao tamanho de cada estrato e com seleção aleatória simples (n = 171 alunos). Utilizou-se o Questionário de Coping Familiar, que analisa as estratégias de coping familiar e, dentre esses recursos, estuda o apoio social da comunidade, amigos e vizinhos, as estratégias de solução de problemas, a avaliação que a família estressor, apoio espiritual e vontade de pedir ajuda. Resultados A prevalência de consumo de álcool com prevalência geral de 59,6%, IC95% [0,52-0,67]; a prevalência labial com 43,3% IC95% [0,36-0,51]; a prevalência atual com 33,9% IC95% [0,27-0,41] e com 17% IC95% [0,11-0,23] prevalência instantânea. Em relação à relação entre estratégias de enfrentamento familiar e prevalência de consumo de álcool, foi encontrada uma relação negativa e significativa (rs = -. 290, p = 0,003). Conclusão Quanto menos estratégias externas de enfrentamento familiar (apoio a amigos / família, apoio espiritual, apoio formal e apoio ao vizinho) percebidas pelos adolescentes, menor a idade do consumo de álcool dos alunos do ensino médio.

Résumé Objectif Déterminer les stratégies d'adaptation familiale et la prévalence de la consommation d'alcool chez les adolescents de niveau secondaire. Matériels et méthodes L'étude réalisée est descriptive corrélationnelle; l'échantillon est aléatoire stratifié avec allocation proportionnelle á la taille de chaque strate et sélection aléatoire simple (n=171 élèves). Le Questionnaire d'Adaptation Familiale a été utilisé pour analyser les stratégies d'adaptation de la famille, en particulier le soutien social de la communauté, les amis et les voisins, les stratégies de résolution de problèmes, l'évaluation familiale des facteurs de stress, le soutien spirituel et la disposition á solliciter de l'aide. Résultats La prévalence globale de la consommation d'alcool a été de 59,6 % (IC á 95% = [0,52-0,67]); la prévalence au cours de l'année précédente de 43,3 % (IC á 95 % = [0,36-0,51]) ; la prévalence actuelle de 33,9 % (IC á 95 % [0,27-0,41]) et la prévalence instantanée de 17 % (IC á 95 % [0,11-0,23]). En ce qui concerne la relation entre les stratégies d'adaptation familiales et la prévalence de la consommation d'alcool, une relation négative et significative a été observée (rs=-.290, p=.003). Conclusion Plus les stratégies d'adaptation externes de la famille (soutien des amis /de la famille, soutien spirituel, soutien formel et soutien de la part des voisins) perçues par les adolescents sont faibles, plus les élèves de niveau secondaire commencent á consommer de l'alcool á un jeune âge.

Autonomic dysfunction and phenoconversion in idiopathic REM sleep behavior disorder.

BACKGROUND: REM sleep behavior disorder (RBD) is a common finding among patients with synucleinopathies. We aimed to determine the degree of autonomic dysfunction in patients presenting with idiopathic RBD (iRBD), and the predictive value of autonomic dysfunction for phenoconversion to a defined neurodegenerative disease. METHODS: We searched our electronic medical record for patients diagnosed with iRBD who also underwent standardized autonomic function testing within 6 months of iRBD diagnosis, and who had clinical follow-up of at least 3 years following iRBD diagnosis. The composite autonomic severity score (CASS) was derived and compared between phenoconverters and non-converters using chi-square and Wilcoxon rank-sum tests. RESULTS: We identified 18 patients who fulfilled inclusion and exclusion criteria. Average age at autonomic testing was 67 ± 6.6 years. Twelve (67%) patients phenoconverted during the follow-up period; six developed Parkinson's disease (PD), and the other six, dementia with Lewy bodies (DLB). Fifteen (83%) patients had at least mild autonomic dysfunction. There were no significant differences between overall converters and non-converters in total CASS or CASS subscores. However, iRBD patients who developed DLB had significantly higher total and cardiovagal CASS scores compared with those who developed PD (p < 0.05), and a trend for higher adrenergic CASS scores compared to those who developed PD and those who did not phenoconvert. DISCUSSION: Autonomic dysfunction was seen in 83% of iRBD patients, and more severe baseline cardiovagal autonomic dysfunction in iRBD was associated with phenoconversion to DLB but not PD. Prospective studies are needed to confirm the value of autonomic testing for predicting phenoconversion and disease phenotype in iRBD.

DNA sequencing reveals AMELX, ODAM and MMP20 variations in dental fluorosis.

OBJECTIVE: Dental fluorosis (DF) is a dental development disorder caused by chronic fluoride overconsumption. There are differences in the susceptibility to and severity of DF in studied populations. The objective of the present study was to determine if single-nucleotide variations (SNVs) in the genes Amelogenin (AMELX), Odontogenic Ameloblast Associated (ODAM) and Matrix Metalloproteinase 20 (MMP20) are associated with DF by evaluating the relationship between variations in these genes and the degree of DF severity. SUBJECTS AND METHODS: Schoolchildren from two regions of Durango State and Mexico City, Mexico, were studied. The DF phenotype was determined using the Thylstrup and Fejerskov (TF) index. DNA was obtained from the buccal mucosa of each participant, and the presence of the variations rs946252 in AMELX, rs1514392 in ODAM and rs1784418 in MMP20 was determined by bidirectional DNA sequencing. RESULTS: A total of 180 DNA samples from 30 schoolchildren from 2 areas of Durango State were sequenced and analyzed. Differences in the severity of DF were found between the study areas (p = 0.006). SNVs in theMMP20 gene were present in 76.9 % of the participants in the high fluoride concentration and lower DF severity area. CONCLUSION: AMELX and ODAM variations was not different between the two populations with respect to DF severity; however, the presence of rs1784418 differed between phenotypes with regard to susceptibility to DF. Therefore, MMP20 might be related to the various phenotypes of DF and may serve as a protective marker.

Intrathecal administration of autologous mesenchymal stem cells in multiple system atrophy.

OBJECTIVE: This phase I/II study sought to explore intrathecal administration of mesenchymal stem cells (MSCs) as therapeutic approach to multiple system atrophy (MSA). METHODS: Utilizing a dose-escalation design, we delivered between 10 and 200 million adipose-derived autologous MSCs intrathecally to patients with early MSA. Patients were closely followed with clinical, laboratory, and imaging surveillance. Primary endpoints were frequency and type of adverse events; key secondary endpoint was the rate of disease progression assessed by the Unified MSA Rating Scale (UMSARS). RESULTS: Twenty-four patients received treatment. There were no attributable serious adverse events, and injections were generally well-tolerated. At the highest dose tier, 3 of 4 patients developed low back/posterior leg pain, associated with thickening/enhancement of lumbar nerve roots. Although there were no associated neurologic deficits, we decided that dose-limiting toxicity was reached. A total of 6 of 12 patients in the medium dose tier developed similar, but milder and transient discomfort. Rate of progression (UMSARS total) was markedly lower compared to a matched historical control group (0.40 ± 0.59 vs 1.44 ± 1.42 points/month, p = 0.004) with an apparent dose-dependent effect. CONCLUSIONS: Intrathecal MSC administration in MSA is safe and well-tolerated but can be associated with a painful implantation response at high doses. Compelling dose-dependent efficacy signals are the basis for a planned placebo-controlled trial. CLASSIFICATION OF EVIDENCE: This phase I/II study provides Class IV evidence that for patients with early MSA, intrathecal MSC administration is safe, may result in a painful implantation response at high doses, and is associated with dose-dependent efficacy signals.

Sex and gender influence symptom manifestation and survival in multiple system atrophy.

To evaluate the influence of sex and gender on clinical characteristics and survival in multiple system atrophy (MSA), we reviewed MSA patients with autonomic testing 1998-2012. Of 685 patients, 52% were male. Median survival overall was 7.3 years for males, 7.6 years for females. Survival from diagnosis was 2.9 years in males, 3.8 years in females. Females were more likely to initially manifest motor symptoms. Males were more likely to have orthostatic intolerance and early catheterization. In conclusion, our data show longer survival from diagnosis in females and slight overall survival benefit which may be related to initial motor manifestations.

Fluoroquinolone-Resistant Streptococcus agalactiae Invasive Isolates Recovered in Argentina.

Background: Streptococcus agalactiae or group B Streptococcus (GBS) is an important pathogen in neonates and nonpregnant individuals. Epidemiological studies of GBS resistance to fluoroquinolones (FQs) in Latin America are scarce. This study aimed to determine the local prevalence of FQ resistance in the frame of a national, prospective multicenter study of invasive GBS infections and to investigate mechanisms of resistance, serotype distribution, and clonal relationships among resistant isolates. Methods: From July 2014 to July 2015, 162 invasive GBS isolates were collected from 86 health care centers in 32 Argentinean cities. All isolates were screened for FQ nonsusceptibility using a five-disc scheme: levofloxacin (LVX), ciprofloxacin, norfloxacin (NOR), ofloxacin, and pefloxacin (PF). LVX minimal inhibitory concentration (MIC) was determined by the agar dilution method. Sequencing of internal regions of gyrA and parC genes was performed. Capsular typing and genetic characterization of nonsusceptible isolates were assessed by latex agglutination, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. Results: Twenty-four of one hundred sixty-two GBS isolates exhibited no inhibition zones to all tested FQs with an MIC range of 16-32 mg/L for LVX, and one isolate with MIC = 1 mg/L showed no inhibition zones around NOR and PF discs. In all resistant isolates, point mutations were detected in both genes. Serotype Ib was prevalent (88%). One PFGE type accounted for 84% of the FQ-resistant isolates and belonged to serotype Ib, sequence type 10. Conclusions: The prevalence of FQ resistance was 14.8% likely to be associated with dissemination of an ST10/serotype Ib clone. The unexpected high rate of resistance emphasizes the relevance for continuous surveillance of GBS epidemiology and antibiotic susceptibility.

Argentinian multicenter study on urinary tract infections due to Streptococcus agalactiae in adult patients.

INTRODUCTION: Streptococcus agalactiae (group B streptococcus, GBS) is a recognized urinary pathogen both in males and pregnant or non-pregnant women. Data regarding GBS serotypes recovered from urinary tract infections (UTIs) are scarce. The aim of this study was to describe the clinical and microbiological characteristics of UTIs caused by GBS in adult patients in Argentina. METHODOLOGY: A prospective multicenter study involving 86 centers was conducted in Argentina between July 1st, 2014 and June 30th, 2015. Antimicrobial susceptibility and serotype distribution of GBS isolated from the urinary tract of adult patients were determined. Susceptibility tests were performed by the disk diffusion and/or agar dilution methods. Epidemiological and clinical characteristics of the patients were considered to identify associated comorbilities. RESULTS: Seven hundred and one GBS were sent to the reference laboratory in the above mentioned period, however, only 211 fulfilled our selection criteria (demographic data availability, underlying diseases reported, colony counts greater than 105 CFU/mL, single organism isolated from the urine sample). No penicillin-resistant GBS was found but fluoroquinolone resistance was high (12.8%), especially among GBS isolated from men and non-pregnant women. UTIs due to GBS were associated to underlying diseases in men and non-pregnant women, particularly diabetes mellitus. Most of the isolates showed serotypes Ia and III. CONCLUSIONS: GBS are still susceptible to penicillin but fluoroquinolone resistance is a growing concern, at least in Argentina. There are underlying conditions that could be associated to urinary infections caused by GBS.

Infecciones urinarias por Streptococcus agalactiae y Staphylococcus saprophyticus y embarazo / Urinary tract infections due to Streptococcus agalactiae and Staphylococcus saprophyticus and pregnancy / Infecções urinárias por Streptococcus agalactiae y Staphylococcus saprophyticus e gravidez

Distintos autores difieren en la mayor o menor prevalencia de las infecciones urinarias (IU) por Streptococcus agalactiae y Staphylococcus saprophyticus en mujeres embarazadas (ME) y no embarazadas (NE). Se realizó un estudio retrospectivo, comparativo, de cohortes con el objetivo de evaluar la frecuencia de IU por S. agalactiae y S. saprophyticus en ME asintomáticas pertenecientes a centros de atención primaria de la salud del Municipio de La Plata (CAPS) entre 2008 y 2016 y se la comparó con la de NE sintomáticas en edad fértil, no internadas, que asistieron al Hospital "San Roque" (HSR) entre 2014 y 2017. Se procesaron 2.378 orinas de ME que concurrieron a las CAPS. De ese total, 201 fueron positivas (8,5%), el 10,4% de las mismas (n: 21) correspondieron a S. agalactiae y el 10,0% a S. saprophyticus (n: 20). En el 54% se aisló Escherichia coli. El total de urocultivos en la población de NE fue de 2.281 y 526 fueron positivos (23,1%): 7 correspondieron a S. agalactiae (1,3%), 18 a S. saprophyticus (3,4%) y el 78% a E. coli. En conclusión, la frecuencia de aislamiento de S. agalactiae y S. saprophyticus fue significativamente mayor en la población de ME pertenecientes a las CAPS respecto de las NE estudiadas en el HSR.

Several authors differ in the greater or lesser prevalence of urinary tract infections (UTI) due to Streptococcus agalactiae and Staphylococcus saprophyticus in pregnant women (PW) and non-pregnant women (NPW). A retrospective, comparative, cohort study was carried out with the objective of evaluating the frequency of UTI by S. agalactiae and S. saprophyticus in asymptomatic PW from primary care centers of the Municipality of La Plata (PCC) between 2008 and 2016 and comparing it with symptomatic NPW in a fertile age, not hospitalized women, who attended the "San Roque" Hospital (HSR) between 2014 and 2017. A total of 2,378 urine samples from PW assisted at the PCC were processed. Two hundred and one were positive (8.5%); 10.4% of them (n: 21) corresponded to S. agalactiae and 10.0% to S. saprophyticus (n: 20). Escherichia coli was isolated in 54%. The total of urine cultures in the population of NPW of the HSR was 2,281 and 526 were positive (23.1%): 7 corresponded to S. agalactiae (1.3%), 18 to S.saprophyticus (3.4%) and 78% to E. coli. In conclusion, the frequency of isolation of S. agalactiae and S. saprophyticus was significantly higher in the population of PW belonging to the PCC than in the NPW studied in the HSR.

Diferentes autores diferem na maior ou menor prevalência das infecções do trato urinário (ITU) devido a Streptococcus agalactiae e Staphylococcus saprophyticus em mulheres grávidas (MG) e mulheres não grávidas (NG). Realizou-se um estudo retrospectivo e comparativo de coortes com o objetivo de avaliar a frequência de ITU por S.agalactiae e S.saprophyticus em MGs assintomáticas pertencentes a salas de atendimento primário do município de La Plata (CAPS) entre 2008 e 2016 e compará-lo com NG sintomáticas em idade fértil, não hospitalizadas, que frequentaram o Hospital "San Roque" (HSR) entre 2014 e 2017. Foram processadas 2.378 amostras de urina de MG atendidas nas CAPS. Desse total, 201 foram positivos (8,5%), 10,4% das mesmas (n: 21) corresponderam a S. agalactiae e 10,0% a S. saprophyticus (n: 20). Escherichia coli foi isolada em 54%. As culturas de urina total na população de NG foram de 2.281 e 526 foram positivas (23.1%): 7 correspondem a S.agalactiae (1.3%), 18 a S.saprophyticus (3.4%) e 78% para E. coli. Em conclusão, a frequência de isolamento de S. agalactiae e S. saprophyticus foi significativamente maior na população de MG pertencente às CAPS do que as NG estudadas no HSR.

Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure.

OBJECTIVE: To assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. PATIENTS AND METHODS: We searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab-seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. RESULTS: Of 289 patients who met inclusion criteria, 163 (56.4%) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92% specificity and 56% sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25%), a level of at least 0.20 nmol/L had 80% specificity and 59% sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1%). CONCLUSION: Ganglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25% or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.

Vaginosis bacteriana en embarazadas y su impacto en la prematurez y en el bajo peso al nacer / Bacterial vaginosis in pregnant women and its impact on prematurity and low birth weight / Vaginose bacteriana em mulheres grávidas e seu impacto na prematuridade e baixo peso ao nascer

La vaginosis bacteriana (VB) es un síndrome producido por el desbalance de la microbiota vaginal normal, frecuente en mujeres en edad fértil, incluyendo embarazadas (ME). Los objetivos de este trabajo fueron conocer la prevalencia de VB en el segundo trimestre de embarazo en la población estudiada y su impacto sobre la producción de partos prematuros (PP) y/o de bajo peso al nacer (BPN). Se realizó un estudio retrospectivo, comparativo, de casos y controles, de 315 ME con y sin vaginosis en el segundo trimestre de embarazo entre 2009 y 2016. Se consideraron “casos” a aquellas mujeres afectadas por VB (estadio IV) y “controles” a las que exhibían una microbiota habitual (estadio I). El 20% de las ME presentaron VB (estadio IV). Se registraron 16 BPN (11 entre los 62 casos y 5 entre los 120 controles) (p=0,025). En 16 oportunidades el parto fue prematuro (10 entre los casos y 6 entre los controles) (p=0,007) En total, las dificultades en el parto fueron significativamente más numerosas entre los casos que entre los controles (p=0,009). Al menos en la población estudiada la presencia de vaginosis en el segundo trimestre de las ME estuvo significativamente asociada con PP y/o BPN.

Bacterial vaginosis (BV) is a syndrome produced by the imbalance of the normal vaginal microbiota, common in women of childbearing age including pregnant women (PW). The objectives of this study were to know the prevalence of BV in the second trimester of pregnancy in the population studied and its impact on the production of premature births (PB) and/or low birth weight infants (LBWI). A retrospective, comparative study of cases and controls of 315 PW with and without vaginosis was carried out in the second trimester of pregnancy between 2009 and 2016. Those cases affected by BV (stage IV) were considered “cases”, and “controls” those that exhibited a habitual microbiota (stage I). Twenty percent of PW presented VB (stage IV) and 16 LBWI were recorded (11 among 62 cases and 5 among 120 controls) (p=0.025). On 16 occasions, labour was premature (10 among cases and 6 among controls) (p=0.007). In total, the difficulties in delivery were significantly more numerous among the cases than among the controls (p=0.009), at least in the population studied the presence of vaginosis in the second trimester of the ME was significantly associated with PB delivery and/or LBWI.

A vaginose bacteriana (VB) é uma síndrome produzida pelo desequilíbrio da microbiota vaginal normal, comum em mulheres em idade fértil, incluindo mulheres grávidas (MG). Os objetivos deste estudo foram conhecer a prevalência de VB no segundo trimestre da gravidez na população estudada e seu impacto na produção de nascimentos prematuros (NP) e/ou com baixo peso ao nascer (BPN). Um estudo retrospectivo e comparativo de casos e controles de 315 ME com e sem vaginose foi realizado no segundo trimestre de gravidez entre 2009 e 2016. Os casos afetados por VB (estágio IV) foram considerados “casos”, e “controles” aqueles que exibíam uma microbiota habitual (estagio I). Vinte por cento dos MG apresentaram VB (estagio IV), 16 BPN foram registrados (11 entre 62 casos e 5 entre 120 controles) (p=0,025). Em 16 ocasiões, o parto foi prematuro (10 entre os casos e 6 entre os controles) (p=0,007). No total, as dificuldades no parto foram significativamente mais numerosas entre os casos do que entre os controles (p=0,009). Pelo menos na população estudada a presença de vaginose no segundo trimestre das MG foi significativamente aos à PN e/ou BPN.