Validating the usefulness of Sudoscan in ATTRv: a single centre experience.

BACKGROUND: Variant transthyretin amyloidosis (ATTRv) can cause sensorimotor and autonomic neuropathy. Objective quantification of sudomotor function may be essential for early diagnosis and early initiation of treatment. The aim of this study is to evaluate the diagnostic value of the Sudoscan® in ATTRv. METHODS: Electrochemical skin conductance (ESC) was measured in V30M ATTRv patients, asymtomatic V30M carriers and healthy controls. Comparisons between the three groups were made using the Kruskal-Wallis test, and ROC curves were used to estimate the discriminatory power of ESC values between groups. RESULTS: ESC was measured in 52 ATTRv patients, 107 asymptomatic carriers and 40 healthy controls. ESC was significantly lower in ATTRv patients compared to asymptomatic carriers and healthy controls in both feet and hands; median values are as follows: 40 µS, 78 µS and 81 µS, respectively (p < 0.001), and 53 µS, 69 µS and 74 µS, respectively (p < 0.001). ESC in feet < 70.5 µS had a sensitivity of 89.7% and specificity of 84.6% to discriminate asymptomatic carriers from patients with ATTRv. CONCLUSION: The determination of ESC by Sudoscan® is a rapid, noninvasive and easily reproducible technique capable of discriminating patients with ATTRv from asymptomatic carriers and healthy controls with adequate sensitivity and specificity.

Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island.

The hyperinflammatory response caused by SARS-CoV-2 infection contributes to its severity, and many critically ill patients show features of cytokine storm (CS) syndrome. We investigated, by next-generation sequencing, 24 causative genes of primary immunodeficiencies whose defect predisposes to CS. We studied two cohorts with extreme phenotypes of SARS-CoV-2 infection: critical/severe hyperinflammatory patients (H-P) and asymptomatic patients (AM-risk-P) with a high risk (older age) to severe COVID-19. To explore inborn errors of the immunity, we investigated the presence of pathogenic or rare variants, and to identify COVID-19 severity-associated markers, we compared the allele frequencies of common genetic polymorphisms between our two cohorts. We found: 1 H-P carries the likely pathogenic variant c.887-2 A>C in the IRF7 gene and 5 H-P carries variants in the MEFV gene, whose role in the pathogenicity of the familial Mediterranean fever (FMF) disease is controversial. The common polymorphism analysis showed three potential risk biomarkers for developing the hyperinflammatory response: the homozygous haplotype rs1231123A/A-rs1231122A/A in MEFV gene, the IFNAR2 p.Phe8Ser variant, and the CARMIL2 p.Val181Met variant. The combined analysis showed an increased risk of developing severe COVID-19 in patients that had at least one of our genetic risk markers (odds ratio (OR) = 6.2 (95% CI) (2.430-16.20)).

A multicentric study of the disease risks and first manifestations in hereditary transthyretin amyloidosis (ATTRv): insights for an earlier diagnosis.

BACKGROUND: In hereditary transthyretin amyloidosis (ATTRv), early manifestation and age at onset (AO) may vary strikingly. We assessed the disease'risk (penetrance), AO and initial features in ATTRv families to gain insights on the early disease presentation. METHODS: Genealogical information, AO and first disease manifestations were collected in ATTRv families, from Sweden, Italy (Sicily), Spain (Mallorca), France, Turkey, Brazil. Penetrance was computed using a non-parametric survival method. RESULTS: We analysed 258 TTRV30M kindreds and 84 carrying six other variants (TTRT49A, F64L, S77Y, S77F, E89Q, I107V). In ATTRV30M families, the earliest disease risk was found at age 20 years in the Portuguese and Mallorcan families and at age 30-35 years, in the French and Swedish groups. The risks were higher in men and in carriers of maternal descent. In families carrying TTR-nonV30M variants, the earliest disease risk ranged from 30 y-o in TTRT49A to 55 y-o in TTRI107V families. Peripheral neuropathy symptoms were the most frequent initial manifestations. Among patients carrying TTRnonV30M variants, about 25% had an initial cardiac phenotype, one third a mixed phenotype. CONCLUSION: Our work provided solid data on the risks and early features of ATTRv in a spectrum of families to enhance an early diagnosis and treatment.

Evolution, Clinical and Microbiological Characteristics of Invasive Pneumococcal Disease since the Introduction of the Pneumococcal Conjugate Vaccine 13-Valent in Adults over 18 Years Old.

Invasive pneumococcal disease (IPD) presents high mortality in the population at risk. The aim of this work is to know the evolution, clinical and microbiological characteristics of IPD in the adult population of Majorca, since the introduction of a public funded program for pneumococcal conjugate vaccine (PCV-13) in the pediatric population in the Balearic Islands in 2016. For this purpose, a retrospective multicenter study was carried out in which all episodes of IPD in adult patients from the four hospitals of the public health system of Majorca were included, comparing the periods between 2012 and 2015 and between 2016 and 2019. Clinical variables, serotypes and antibiotic sensitivity were collected. There were 498 cases of IPD; 56.8% were male with a mean age of 67 (standard deviation: 16). Most infections were bacterial pneumonias (73.7%). Of the total cases, 264 (53%) presented complications. Of the 498 cases, 351 strains were obtained, of which 145 (41.3%) belong to vaccinal serotypes (included in the PCV-13 vaccine) and 206 (58.7%) to non-vaccinal serotypes (not included in the PCV-13 vaccine). The percentage of IPD caused by vaccinal serotypes was lower in the second period (47.8% vs. 34.5%; p = 0.012).

Anticipation on age at onset in kindreds with hereditary ATTRV30M amyloidosis from the Majorcan cluster.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRV30M) is a rare disease caused by amyloid deposition and characterized by a heterogeneous presentation. Anticipation (AC) is described as the decrease in age at onset (AO) within each generation. Our aim was to study AC in a large number of ATTRV30M kindred from Majorca (Spain), and gain further insight into parent-of-origin effects. METHODS: In a cohort of 262 subjects with ATTRV30M amyloidosis belonging to 51 families, we found 37 affected pairs. AO is defined as the age at the first symptom and AC (parent's age at disease onset minus that of the offspring) were calculated. Chi-square test, independent t-test and paired t-test were used for comparisons between groups. Association between AO of parents and offsprings were assessed by Pearson's correlation coefficient. RESULTS: Offspring mean AO was 16 years lower than that of the parents (p < .001) regardless of the sex of the parents and the offspring. AC occurred in 31 out of the 37 pairs, with no differences related to the sex of parents or offspring. There was a moderate correlation (r = 0.49; p < .001) between AO of the parents and that of the offsprings. CONCLUSION: AC was no uncommon in our cohort, and AO tended to decrease in successive generations.

Polyserositis: a diagnostic challenge.

BACKGROUND: Polyserositis (PS) is the inflammation, with effusion, of different serous membranes. It has been associated with different aetiologies, but the aetiology of PS remains unknown in a high percentage of patients. AIMS: The general objective of this retrospective study was to analyse the aetiology of PS cases seen at Son Llàtzer Hospital in an 11-year period. Other objectives were to determine the epidemiological, clinical and analytical characteristics of these patients. METHODS: An observational, descriptive and retrospective study to analyse the aetiology of PS cases seen at Son Llàtzer Hospital. The inflammation of two or more serous membranes confirmed by an imaging test was required and at least one of the serous fluid should be an exudate. RESULTS: A total of 92 patients was included in the study. The most common diagnosis was neoplasm (nearly one-third of cases) followed by infectious and autoimmune diseases. PS aetiology was unknown in more than one-third. Pleura and pericardium were the most common sites of serosal involvement (83%). Antinuclear antibodies' positivity in serum and increased levels of adenosine deaminase in pleural effusion were significantly associated with a final diagnosis of autoimmune disease. Increased pleural lactate dehydrogenase levels were significantly associated with a final diagnosis of neoplasm. In 9 of 14 patients with a previous cancer, PS represented a recurrence of their cancer. Cases of unknown aetiology presented most frequently as pleural and pericardial involvement, and the majority resolved. In very few patients, an infectious aetiology could be proven. CONCLUSION: PS is a frequent clinical entity that is associated with different diseases and its diagnosis could be challenging, with a high rate of unknown aetiologies.

Bisphosphonates in patients with autoimmune rheumatic diseases: Can they be used in women of childbearing age?

Autoimmune rheumatic diseases (ARD) are prevalent in women during their childbearing age. For their treatment, high doses of corticosteroid (CS) for long-term periods are often required, increasing the risk of bone loss. According to recent guidelines, bisphosphonates (BP) should be used as first line treatment to prevent CS induced osteoporosis. However, due to their long-term release from bone and their ability to cross the placenta, it has been suggested to avoid BP in women during their fertile years. BP seem to decrease foetus bone length in pregnant animals, but not in humans, at least, when they are administered at therapeutic dosage. BP are embryo toxic in animals when used at high dosage. In a systematic literature review, we found 58 women treated with BP close before or during pregnancy, showing no related congenital malformations. However, the Unit of Clinical and Epidemiological Genetics in University of Padova collected ten cases of women treated with BP during pregnancy, reporting 20% of congenital malformations. Thus, we suggest to avoid BP during pregnancy and caution with their use in fertile women. When they have to be given before pregnancy, specific affinities of the BP have to be considered to plan the washout period beforehand.

Bacteriemia por anaerobios estrictos: estudio de 68 pacientes / Anaerobic bloodstream infections: Study of 68 episodes

Introducción Existe controversia en la literatura médica sobre la bacteriemia por anaerobios: algunos autores detectaron en las últimas décadas un aumento de su incidencia, y otros, una franca disminución, e incluso se ha propuesto el no hacer de forma habitual hemocultivos para anaerobios. Presentamos un análisis prospectivo de los casos de bacteriemia por anaerobios diagnosticados en nuestro centro entre enero de 2003 y mayo de 2008.ResultadosSe identificaron 68 pacientes con bacteriemia verdadera por anaerobios estrictos. La edad media fue de 64±19 años. La mayoría (63,2%) tenía al menos una comorbilidad, en el 20,6% de los casos fue una neoplasia sólida frecuentemente relacionada con el tracto digestivo. El foco principal de la bacteriemia fue abdominal (42,6%). Los gérmenes más frecuentemente aislados fueron diversas especies del grupo Bacteroides fragilis (36,7%), Clostridium spp. (17,6%), Peptostreptococcus spp. (16,1%) y Prevotella spp. (16,1%). El tratamiento antibiótico empírico más utilizado fue un carbapenémico en el 35,3% de los casos y se utilizó biterapia en el 30,9%. En la mayoría de los casos el tratamiento antibiótico empírico fue adecuado. La mortalidad bruta fue del 23,5% y directamente relacionada con la bacteriemia (9,2%). La presencia de sepsis, shock séptico o un score de Pitt mayor de 4 fueron predictores de mortalidad. Conclusiones La incidencia de bacteriemia por anaerobios en nuestro centro se cifra en 0,89 casos/1.000 ingresos hospitalarios. Los pacientes de mayor riesgo son los ancianos con diferentes comorbilidades o con procesos oncológicos; la mortalidad fue elevada (AU)

Introduction There is some controversy regarding the current rates of anaerobic bacteremia. Some authors have described an increasing incidence in recent years, whereas others report declining rates. There is even debate over whether to routinely perform anaerobic blood cultures. We present a prospective analysis of anaerobic bloodstream infections diagnosed at our medical center from January 2003 to May 2008.ResultsSixty-eight patients had bloodstream infection caused exclusively by anaerobic bacteria. Median age was 64±19 years and 63.2% had at least one comorbid condition, including 20.6% with a solid neoplasm, often related to the gastrointestinal tract. The main focus of anaerobic bacteremia was the abdomen (42.6%). The most common isolates were several species from the Bacteroides fragilis group (36.7%), Clostridium spp. (17.6%), Peptostreptococcus spp. (16.1%), and Prevotella spp. (16.1%). Empirical antimicrobial treatment was adequate in 69.1%. Overall mortality was 23.5%, and bacteremia-related mortality was 9.2%. Sepsis, septic shock, and a Pitt score >4 were independent predictors of mortality. Conclusions The incidence of anaerobic bacteremia in our hospital was 0.89 cases per 1000 hospital admissions. Patients at high risk were elderly persons with associated underlying diseases including malignant disease. Mortality was high (AU)

[Anaerobic bloodstream infections: study of 68 episodes]. / Bacteriemia por anaerobios estrictos: estudio de 68 pacientes.

INTRODUCTION: There is some controversy regarding the current rates of anaerobic bacteremia. Some authors have described an increasing incidence in recent years, whereas others report declining rates. There is even debate over whether to routinely perform anaerobic blood cultures. We present a prospective analysis of anaerobic bloodstream infections diagnosed at our medical center from January 2003 to May 2008. RESULTS: Sixty-eight patients had bloodstream infection caused exclusively by anaerobic bacteria. Median age was 64+/-19 years and 63.2% had at least one comorbid condition, including 20.6% with a solid neoplasm, often related to the gastrointestinal tract. The main focus of anaerobic bacteremia was the abdomen (42.6%). The most common isolates were several species from the Bacteroides fragilis group (36.7%), Clostridium spp. (17.6%), Peptostreptococcus spp. (16.1%), and Prevotella spp. (16.1%). Empirical antimicrobial treatment was adequate in 69.1%. Overall mortality was 23.5%, and bacteremia-related mortality was 9.2%. Sepsis, septic shock, and a Pitt score >4 were independent predictors of mortality. CONCLUSIONS: The incidence of anaerobic bacteremia in our hospital was 0.89 cases per 1000 hospital admissions. Patients at high risk were elderly persons with associated underlying diseases including malignant disease. Mortality was high.