Risk factors of severe COVID-19 in people with multiple sclerosis : A systematic review and meta-analysis.

OBJECTIVES: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS). METHODS: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data. RESULTS: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs. CONCLUSION: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome.

Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the 'hygiene hypothesis'?

BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non-early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. METHODS: Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein-Barr virus and human herpesvirus-6, as well as T-cell and natural killer (NK)-cell immunophenotypes. RESULTS: Cytomegalovirus seroprevalence in early MS was lower than in non-early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01-1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T-cells (CD27-CD28-, CD57+, LILRB1+) and NKG2C+ NK-cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age-related decline in serum anti-EBNA-1 antibodies (P < 0.01), but no CMV-related differences in anti-human herpesvirus-6 humoral responses. CONCLUSIONS: Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T-cell and NK-cell subsets and/or modulation of Epstein-Barr virus-specific immune responses at early stages of the disease.

Haplo-Cord transplantation compared to haploidentical transplantation with post-transplant cyclophosphamide in patients with AML.

For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients. Cumulative incidence of neutrophil engraftment was 97% in the Haplo-Cord and 100% in the PTCY-haplo group, achieved in a median of 12 and 17 days, respectively (P=0.01). Grade II-IV acute GvHD rate was significantly higher in the PTCY-haplo group (9.8% vs 29%, P=0.02) as well as chronic GvHD rates (20% vs 38%, P=0.03). With a median follow-up of 61 months for the Haplo-Cord group and 26 months for the PTCY-haplo cohort, overall survival at 2 years was 55% and 59% (P=0.66), event-free survival was 45% vs 56% (P=0.46), relapse rate was 27% vs 21% (P=0.79), and non-relapse mortality was 17% vs 23% (P=0.54), respectively. In this multicenter experience, Haplo-Cord and PTCY-haplo HSCT offer valid alternatives for patients with AML. Neutrophil engraftment was faster in the Haplo-Cord cohort, with similar survival rates, with higher GvHD rates after haploidentical HSCT.

Busulfan-based reduced intensity conditioning regimens for haploidentical transplantation in relapsed/refractory Hodgkin lymphoma: Spanish multicenter experience.

Relapsed or refractory Hodgkin lymphoma (advanced HL) still remains a therapeutic challenge. Recently, unmanipulated haploidentical related donor transplant with reduced conditioning regimen (HAPLO-RIC) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has became a promising rescue strategy potentially available to almost every patient. This paper reports our multicenter experience using an IV busulfan-based HAPLO-RIC regimen and PT-Cy in the treatment of 43 patients with advanced HL. Engraftment occurred in 42 patients (97.5%), with a median time to neutrophil and platelet recovery of 18 and 26 days. Cumulative incidences of grades II-IV acute GvHD and chronic GvHD were 39% and 19%, respectively. With a median follow-up of 25.5 months for survivors, 27 patients are alive, with 22 of them disease free. Cumulative incidences of 1-year non-relapse mortality and relapse at 2 years were 21% and 24%, respectively. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 48% and 58%, respectively. CR prior to HAPLO-RIC correlated with better EFS (78.5% vs 33.5%; P=0.015) and OS (86% vs 46%; P=0.044). Our findings further confirm prior reports using HAPLO-RIC in advanced HL in a multicenter approach employing an IV busulfan-based conditioning regimen.

Both foliar and residual applications of herbicides that inhibit amino acid biosynthesis induce alternative respiration and aerobic fermentation in pea roots.

The objective of this work was to ascertain whether there is a general pattern of carbon allocation and utilisation in plants following herbicide supply, independent of the site of application: sprayed on leaves or supplied to nutrient solution. The herbicides studied were the amino acid biosynthesis-inhibiting herbicides (ABIH): glyphosate, an inhibitor of aromatic amino acid biosynthesis, and imazamox, an inhibitor of branched-chain amino acid biosynthesis. All treated plants showed impaired carbon metabolism; carbohydrate accumulation was detected in both leaves and roots of the treated plants. The accumulation in roots was due to lack of use of available sugars as growth was arrested, which elicited soluble carbohydrate accumulation in the leaves due to a decrease in sink strength. Under aerobic conditions, ethanol fermentative metabolism was enhanced in roots of the treated plants. This fermentative response was not related to a change in total respiration rates or cytochrome respiratory capacity, but an increase in alternative oxidase capacity was detected. Pyruvate accumulation was detected after most of the herbicide treatments. These results demonstrate that both ABIH induce the less-efficient, ATP-producing pathways, namely fermentation and alternative respiration, by increasing the key metabolite, pyruvate. The plant response was similar not only for the two ABIH but also after foliar or residual application.

Antifungal prophylaxis with anidulafungin to minimize drug interactions with an antiepileptic treatment in a hematopoietic stem cell transplant recipient.

WHAT IS KNOWN AND OBJECTIVE: Invasive fungal infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). This provides a clear rationale for antifungal prophylaxis in this population. A concern is the potential for drug interactions, given that most of antifungals are metabolized through the P450 cytochrome system. CASE SUMMARY: We present a case of a 33-year-old woman, with a past history of high-risk epilepsy, who underwent allogeneic HSCT for a myelodysplastic syndrome. Anidulafungin was successfully used as antifungal prophylaxis to minimize drug interactions with her antiepileptic treatment. WHAT IS NEW AND CONCLUSION: This is the first reported case of antifungal prophylaxis with this echinocandin in HSCT. Anidulafungin may be an option in transplant recipients with multiple risk factors for drug interactions.

[Surveillance report on Diseases of Compulsory Declaration (DCD) in Navarra. 2000]. / Situación de las Enfermedades de Declaración Obligatoria (EDO) en Navarra. 2000.

The Epidemiological Surveillance System of Navarra includes the notification of 34 transmissible infectious diseases, to which epidemic outbreaks of any aetiology and cause are added. In 2000, under the heading of diseases of respiratory transmission, 31,106 cases of flu were reported; 80% of total annual cases were reported in the first 6 weeks of the year, with a maximum in week 1 when 7,949 cases were reported. Twelve cases of meningococcal disease were reported to the system. Eight cases were confirmed microbiologically and appeared in a sporadic way. With respect to the causative serogroup, Neisseria meningitidis serogroup B was isolated on 5 occasions. On 2 occasions serogroup C was isolated, and serogroup Y was isolated on 1 occasion. By age groups, 5 cases were declared in infants of 2 years of age (Rate: 57.6 per 100,000), two cases in children between 2 and 4 years of age (14.7 per 100,000), one case in children between 5 and 9 years of age (3.5 per 100,000), two cases between 10 and 19 years of age (2.5 per 100,000) and the remaining 2 cases in persons aged 20 years or over (0.50 per 100,000). Twenty three cases of legionellosis were declared in 2000, all under the clinical form of pneumonia. These were isolated cases in persons of middle or advanced age. No indication was found of prior tourist trips to areas of high prevalence. In the majority of cases the origin was considered to be in the community, while one outbreak was identified as nosocomial. Similarly, there was a notable increase in the declaration of cases of hepatitis A, with 24 cases (EI: 2.00), pertussis, with 23 cases (EI: 1.64) and varicella, with 4,232 reported cases (EI: 1.86).

[Situation of Diseases of Compulsory Declaration (DCDs) in Navarra. 1998]. / Situación de las Enfermedades de Declaración Obligatoria (E.D.O.s) en Navarra. 1998.

The System of Epidemiological Vigilance of Navarra comprises the notification of 33 transmissible infectious diseases, to which are added epidemic outbreaks of any etiology or cause. Notification to the system is carried out on a weekly basis by any doctor who suspects or diagnoses any of the processes. In our Autonomous Community, the Diseases of Compulsory Declaration (DCDs) are reported to the Section of Vigilance and Epidemiological Control of the Institute of Public Health, on a weekly basis by the doctors of Primary and Specialised Care. Subsequently, the information is sent to the National Centre of Epidemiology, where data from the Autonomous Communities is centralised. In 1998, with respect to the heading of diseases of respiratory transmission, the only disease that showed an epidemic index higher than 1 was Flu, with 44,666 reported cases, (Estimated Incidence: 1.15), and which has a clear seasonal component ñin the first 8 weeks of the year 67% of the cases corresponding to the yearly total were reportedñ with a maximum in week 4 with 6,361 reported cases. Fifteen cases of meningococcal disease were diagnosed, (Rate 2.88 cases per 100,000 inhabitants), lower to that declared in 1997 and the second lowest in the last 25 years after the rate of 2.31 in 1994. All of the cases were confirmed microbiologically and appeared in a sporadic way. With respect to the causative serogroup, on 9 occasions serogroup C was isolated, with the latter responsible for the death of a girl and an elderly woman. On 6 occasions Neisseria meningitidis serogroup B was isolated. By age group, 4 cases were declared in children under 2 years of age (46.1 per 100,000), nine cases in children between 2 and 19 years of age (8.65 per 100,000) and the two remaining cases in persons of 20 years or above (0.49 per 100,000). The predominant clinical form was sepsis in 9 cases and meningitis in the 6 remaining cases. Six cases of Legionnaire's disease were declared in 1998, all under the clinical form of pneumonia; these were isolated cases of middle-aged persons resident, in five cases, in different localities in the south of Navarra without any antecedents of travelling.