Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain: the ProHEpiC-19 study.

BACKGROUND: Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. METHODS: We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. FINDINGS: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. INTERPRETATION: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. FUNDING: Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478).

The Link between Abdominal Obesity Indices and the Progression of Liver Fibrosis: Insights from a Population-Based Study.

There is currently no available information on the correlation between abdominal obesity indices and the risk of liver fibrosis progression. We aimed to investigate the relationship between the body mass index (BMI), waist circumference (WC), and the visceral adiposity index (VAI) with the progression of liver fibrosis. The study also evaluated the association between these indices and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. A total of 1403 subjects participated in the cross-sectional and longitudinal population-based study. Liver stiffness was assessed via transient elastography, at baseline and follow-up (median: 4.2 years). The subgroup with dysglycemia was also analyzed. In the cross-sectional study, the highest quartile of VAI, BMI ≥ 30 kg/m2, and abdominal obesity showed significant associations with the prevalence of MASLD and liver fibrosis, as well as with fibrosis progression. However, VAI showed no association with MASLD incidence. Among the dysglycemic subjects, there was no observed association between VAI and the incidence of MASLD or the progression of fibrosis. In conclusion, the BMI, WC, and the VAI are associated with an increased risk of progression to moderate-to-advanced liver fibrosis in the general population. However, the VAI does not perform better than the BMI and WC measurement.

Multimodal neuroimaging in Long-COVID and its correlates with cognition 1.8 years after SARS-CoV-2 infection: a cross-sectional study of the Aliança ProHEpiC-19 Cognitiu.

Introduction: There is a growing interest in the effect of Long-COVID (LC) on cognition, and neuroimaging allows us to gain insight into the structural and functional changes underlying cognitive impairment in LC. We used multimodal neuroimaging data in combination with neuropsychological evaluations to study cognitive complaints in a cohort of LC patients with mild to moderate severity symptoms. Methods: We conducted a 3T brain magnetic resonance imaging (MRI) study with diffusion tensor imaging (DTI) and functional MRI (fMRI) sequences on 53 LC patients 1.8 years after acute COVID-19 onset. We administered neuropsychological tests to evaluate cognitive domains and examined correlations with Tract-Based Spatial Statistics (TBSS) and resting state. Results: We included 53 participants with LC (mean age, 48.23 years; 88.7% females). According to the Frascati criteria, more than half of the participants had deficits in the executive (59%) and attentional (55%) domains, while 40% had impairments in the memory domain. Only one participant (1.89%) showed problems in the visuospatial and visuoconstructive domain. We observed that increased radial diffusivity in different white matter tracts was negatively correlated with the memory domain. Our results showed that higher resting state activity in the fronto-parietal network was associated with lower memory performance. Moreover, we detected increased functional connectivity among the bilateral hippocampus, the right hippocampus and the left amygdala, and the right hippocampus and the left middle temporal gyrus. These connectivity patterns were inversely related to memory and did not survive false discovery rate (FDR) correction. Discussion: People with LC exhibit cognitive impairments linked to long-lasting changes in brain structure and function, which justify the cognitive alterations detected.

Reduced Cortical Thickness Correlates of Cognitive Dysfunction in Post-COVID-19 Condition: Insights from a Long-Term Follow-up.

BACKGROUND AND PURPOSE: There is a paucity of data on long-term neuroimaging findings from individuals who have developed the post-coronavirus 2019 (COVID-19) condition. Only 2 studies have investigated the correlations between cognitive assessment results and structural MR imaging in this population. This study aimed to elucidate the long-term cognitive outcomes of participants with the post-COVID-19 condition and to correlate these cognitive findings with structural MR imaging data in the post-COVID-19 condition. MATERIALS AND METHODS: A cohort of 53 participants with the post-COVID-19 condition underwent 3T brain MR imaging with T1 and FLAIR sequences obtained a median of 1.8 years after Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. A comprehensive neuropsychological battery was used to assess several cognitive domains in the same individuals. Correlations between cognitive domains and whole-brain voxel-based morphometry were performed. Different ROIs from FreeSurfer were used to perform the same correlations with other neuroimaging features. RESULTS: According to the Frascati criteria, more than one-half of the participants had deficits in the attentional (55%, n = 29) and executive (59%, n = 31) domains, while 40% (n = 21) had impairment in the memory domain. Only 1 participant (1.89%) showed problems in the visuospatial and visuoconstructive domains. We observed that reduced cortical thickness in the left parahippocampal region (t(48) = 2.28, P = .03) and the right caudal-middle-frontal region (t(48) = 2.20, P = .03) was positively correlated with the memory domain. CONCLUSIONS: Our findings suggest that cognitive impairment in individuals with the post-COVID-19 condition is associated with long-term alterations in the structure of the brain. These macrostructural changes may provide insight into the nature of cognitive symptoms.

Long COVID: cognitive, balance, and retina manifestations.

Background: The neurological symptoms of Long COVID (LC) and the impact of neuropsychological manifestations on people's daily lives have been extensively described. Although a large body of literature describes symptoms, validating this with objective measures is important. This study aims to identify and describe the effects of Long COVID on cognition, balance, and the retinal fundus, and determine whether the duration of symptoms influences cognitive impairment. Methods: This cross-sectional study involved LC volunteers with cognitive complaint from public health centers in northern Barcelona who participated between January 2022 and March 2023. This study collected sociodemographic characteristics, information on substance use, comorbidities, and clinical data related to COVID-19. We measured five cognitive domains using a battery of neuropsychological tests. Balance was assessed through posturography and retinal vascular involvement by retinography. Results: A total of 166 people with LC and cognitive complaints participated, 80.72% were women and mean age was 49.28 ± 8.39 years. The most common self-reported symptoms were concentration and memory deficit (98.80%), brain fog (82.53%) and insomnia (71.17%). The 68.67% presented cognitive deficit in at least one domain, with executive functions being the most frequent (43.98%). The 51.52% of the participants exhibited a dysfunctional pattern in balance, and 9.2% showed some alteration in the retina. There were no statistically significant differences between cognitive impairment and symptom duration. Conclusion: Our findings contribute to a more comprehensive understanding of the pathology associated with Long COVID. They highlight the diversity of self-reported symptoms, the presence of abnormal balance patterns, and some cognitive impairment. These findings underscore the necessity of addressing the clinical management of this condition in primary care through follow-up and the pursuit of multidisciplinary and comprehensive treatment.

Clinical epidemiology of non-alcoholic fatty liver disease in children and adolescents. The LiverKids: Study protocol.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is rapidly increasing alongside overweight and obesity, not only in adults but also in children and adolescents. It is unknown what impact the development of NAFLD in childhood may have in later life. The importance of early detection and treatment lies in its potential for progression to cirrhosis, liver cancer and liver-related death, as well as its associated extrahepatic comorbidities. Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP) is an effective, non-invasive and safe diagnostic method to estimate the degree of fibrosis and steatosis in the liver, but little is known about its applicability in the paediatric population. AIMS: 1) To assess the prevalence of significant liver fibrosis (Liver Stiffness Measurement (LSM) ≥6.5 kPa) using VCTE, and that of non-alcoholic fatty liver disease (≥225 dB/m) using CAP in children and adolescents. 2) To determine the optimal cut-off points of the CAP to achieve maximum concordance with the Magnetic Resonance Imaging (MRI) findings in the diagnosis of mild, moderate and severe NAFLD in children and adolescents. METHODS: Cross-sectional population-based study which will include 2,866 subjects aged between 9 and 16 years. Participants will undergo: anamnesis, physical examination, blood extraction, VCTE, MRI and questionnaires on socio-demographic data, personal and family medical history and lifestyle assessment. APPLICABILITY AND RELEVANCE: The study aims to establish the foundations for the use of VCTE in children and adolescents in order to achieve early diagnosis of NAFLD. Moreover, it will serve to understand in further detail the disease and to identify the risk groups of children and adolescents who may be at risk of developing it. Ultimately, this will help determine to which subgroups of the population we need to target resources for prevention and early detection of this entity, as well as possible intervention for its treatment. TRIAL REGISTRATION: The LiverKids study is registered on Clinicaltrials.gov (NCT05526274).

Spirometry and Smoking Cessation in Primary Care: The ESPIROTAB STUDY, A Randomized Clinical Trial.

This study aims to evaluate the effect of regularly reporting spirometry results during smoking cessation counseling from a primary care physician on the quit rate in adult smokers. METHODS: A randomized, two-arm intervention study was conducted at six primary care centers. A total of 350 smokers, ≥18 years of age, who consulted their primary care physician, participated in the study. At the selection visit, smokers who gave their consent to participate underwent spirometry. Subsequently, an appointment (visit 0) was scheduled to complete a nicotine dependence test, a smoking cessation motivation questionnaire, and a sociodemographic questionnaire. Participants were also offered brief, structured advice on how to quit smoking, as well as detailed information on spirometry results. Patients were then randomized and scheduled for follow-up visits at 3, 6, 12, and 24 months. Both arms received brief, structured advice and detailed information on spirometry results at visit 0. At consecutive follow-up visits, the control group only received brief, structured smoking cessation advice, while the intervention group also received information on initial spirometry results at visits 3 and 6, and a spirometry retest at visit 12. Exhaled carbon monoxide testing was used to check smoking cessation. RESULTS: The study included 350 smokers; 179 were assigned to the control group and 171 to the intervention group. Smoking cessation at one year was 24.0% in the intervention group compared to 16.2% in the control group. At two years, it was 25.2% in the intervention group and 18.4% in the control group. Overall, the adjusted odds of quitting smoking in the intervention group were 42% higher than in the control group (p = 0.018). CONCLUSIONS: Regular and detailed feedback of spirometry results with smokers increases smoking cessation. Specifically, the likelihood of quitting smoking in the intervention group is 1.42 times higher than in the control group (p = 0.018).

Neurocognitive Profile of the Post-COVID Condition in Adults in Catalonia-A Mixed Method Prospective Cohort and Nested Case-Control Study: Study Protocol.

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case-control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition.

Defective Conduction of Anorectal Afferents Is a Very Prevalent Pathophysiological Factor Associated to Fecal Incontinence in Women.

BACKGROUND/AIMS: Fecal incontinence (FI) is a prevalent condition among women. While biomechanical motor components have been thoroughly researched, anorectal sensory aspects are less known. We studied the pathophysiology of FI in community-dwelling women, specifically, the conduction through efferent/afferent neural pathways. METHODS: A cross-sectional study was conducted on 175 women with FI and 19 healthy volunteers. The functional/structural study included anorectal manometry/endoanal ultrasound. Neurophysiological studies including pudendal nerve terminal motor latency (PNTML) and sensory-evoked-potentials to anal/rectal stimulation (ASEP/RSEP) were conducted on all healthy volunteers and on 2 subgroups of 42 and 38 patients, respectively. RESULTS: The main conditions associated with FI were childbirth (79.00%) and coloproctological surgery (37.10%). Cleveland score was 11.39 ± 4.09. Anorectal manometry showed external anal sphincter and internal anal sphincter insufficiency in 82.85% and 44.00%, respectively. Sensitivity to rectal distension was impaired in 27.42%. Endoanal ultrasound showed tears in external anal sphincter (60.57%) and internal anal sphincter disruptions (34.80%). Abnormal anorectal sensory conduction was evidenced through ASEP and RSEP in 63.16% and 50.00% of patients, respectively, alongside reduced activation of brain cortex to anorectal stimulation. In contrast, PNTML was delayed in only 33.30%. Stools were loose/very loose in 56.70% of patients. CONCLUSIONS: Pathophysiology of FI in women is mainly associated with mechanical sphincter dysfunctions related to either muscle damage or, to a lesser extent, impaired efferent conduction at pudendal nerves. Impaired conduction through afferent anorectal pathways is also very prevalent in women with FI and may play an important role as a pathophysiological factor and as a potential therapeutic target.

Trasplante renal grupo sanguíneo ABO incompatible. Experiencia colaborativa inédita España y Perú / Incompatible ABO blood group renal transplant. Unprecedented collaborative experience between Spain and Peru

La incompatibilidad de grupo sanguíneo ABO y la sensibilización al HLA constituyen grandes barreras a vencer en pro de la óptima utilización de riñones de donante vivo. Describimos en nuestro medio el primer trasplante renal exitoso ABO incompatible en un paciente de 24 años, retrasplantado renal, altamente sensibilizado (PRA: 89%) y sin opción alguna en disponer de donantes cadavéricos ni familiares. Sin embargo, su único donante vivo HLA compatible era de grupo sanguíneo A incompatible con el grupo O del receptor. El paciente requirió de un régimen precondicionante consistente en recambios plasmáticos, rituximab, imunoglobulina y terapia inmunosupresora cuádruple, a fin de reducir los títulos elevados de isoaglutininas anti A de 1:128 a niveles de seguridad de 1:8, para el éxito del trasplante. Este fue realizado en Coordinación con la Unidad de Trasplante Renal del Hospital Clínic de Barcelona España (HCB). La ausencia de rechazo mediado por isoaglutininas muestra el potencial beneficio del protocolo al remover los anticuerpos anti grupo sanguíneo. A los dos años del trasplante, la función renal se mantiene estable con niveles de creatinina 1,5 mg%. Concluimos que el trasplante renal ABO incompatible (ABOi) es opción viable para pacientes cuyo único donante sea grupo sanguíneo incompatible, y entre nosotros representa esperanzadora fuente de órganos.

ABO blood group incompatibility and HLA sensitization are major barriers that need to be overcome in order to make optimum use of kidneys from living donors possible. We report the first successful ABO- incompatible kidney transplant in a 24-year old, highly sensitized (panel reactive antibodies (PRA) 89% kidney retransplantation patient, who lacked any option to get a cadaveric or family donor. However, the patient's sole HLA-compatible living donor had group A blood incompatible with the recipient's O blood group. The < patient required a pre-conditioning regime that consisted of plasma exchange, rituximab, immunoglobulin, and quadruple immunosuppressive therapy in order to reduce high titers of anti-A isoagglutinins from 1:128 to a safe level of 1:8, for successful transplant. This was performed in coordination with the Renal Transplant Unit of Hospital Clinic de Barcelona (HCB), Spain. Absence of rejection mediated by isoagglutinins shows the potential benefit of a protocol consisting in removing antibodies from the anti-blood group. Two yearsafter transplantation, the kidney function remains stable, with creatinine levels of 1.5 mg%. We conclude that an ABO-incompatible kidney transplant is a viable option for patients whose only donor has blood of an incompatible blood group and for us this represents a hope-inspiring source of organs .

Nefropatía asociada a poliomavirus BK en trasplante renal / BK polyomavirus-associated nephropathy in kidney transplant

El objetivo del presente reporte es dar a conocer los dos primeros casos de nefropatía del injerto asociada a poliomavirus BK (NPBK) ocurridos en el Hospital Edgardo Rebagliati Martins, EsSalud, Lima, Perú. El diagnóstico definitivo de la NPBK se corroboró mediante biopsia renal y estudio de microscopia electrónica. En el caso 1, el deterioro funcional renal no se controló a pesar de reducir la inmunosupresión y añadir drogas antivirales (leflunamide y ciprofloxacina), evolucionando a falla renal y su posterior acceso a retrasplante renal. En el caso 2, la alternativa terapéutica se basó en infusión de inmunoglobulina endovenosa asociada a reducción de la inmunosupresión, resultando en moderada mejora histológica y estabilización de la función renal. En ambos injertos renales hubo concomitantemente NPBK y lesiones histológicas compatibles con rechazo agudo celular pendientes de interpretar. En conclusión, la presencia del poliomavirus BK representa serio problema en el riñón trasplantado. La mejor conducta terapéutica se basa en el diagnóstico precoz y subsecuente reducción de la inmunosupresión. Es imprescindible disponer de metodología apropiada que posibilite un diagnóstico preciso. Se utiliza tamizaje de células señuelo o marcadoras (decoy cells) en orina, reacción de cadena polimerasa (PCR), biopsia renal o la microscopia electrónica como método valioso de ayuda en el diagnóstico etiológico viral. Se considera el retrasplante como opción ante la pérdida del injerto por NPBK (caso 1)...

Two documented cases of BK polyomavirus-associated nephropathy (BKVN) seen at Hospital Edgardo Rebagliati Martins, EsSalud, Lima, Peru are reported. Final BKVN diagnosis was confirmed by renal biopsy and electron microscopy study. Case 1: Renal functional deterioration was not controlled despite reduction of immunosuppression and addition of antiviral drugs (leflunomide and ciprofloxacin), evolving to renal failure and subsequent kidney retransplantation. Case 2: The therapeutical management consisted in intravenous immunoglobulin infusion linked to reduction of immunosuppression; this resulted in modest histological improvement and stabilization of renal function. Both renal grafts concomitantly presented BKVN and histological lesions consistent with acute rejection, pending interpretation. In conclusion presence of BK polyomavirus is a serious problem for transplanted kidneys. The best treatment is based on early diagnosis and subsequent reduction of immunosuppression. It is essential to have an appropriate methodology for precise diagnosis. Early electron microscopy is a valuable method for viral etiologic diagnosis. Retransplantation is considered a treatment option when faced with possible BKVN-related graft loss (Case 1)...