Safety of mRNA COVID-19 vaccines in patients with well-controlled myasthenia gravis.

INTRODUCTION/AIMS: Data on safety and tolerability of the vaccines against severe acute respiratory virus coronavirus-2 (SARS-CoV-2, or coronavirus disease-2019 [COVID-19]) in patients with myasthenia gravis (MG) are currently limited. In this study we investigated the safety of mRNA-based two-dose vaccination in a cohort of patients with MG. METHODS: This investigation was a prospective observational study of messenger RNA (mRNA)-based vaccines administered to patients with MG with stable disease. Local and systemic reactogenicity after injection was monitored for each dose administered. The patients were categorized and clinically assessed following the recommendations of the Myasthenia Gravis Foundation of America. RESULTS: Thirty-six males and 55 females (mean age at first vaccine dose, 58.8 years; standard deviation, = 17.1 years) received vaccines. Seventy-two patients (79.1%) were taking one or more immunosuppressant(s). The most frequent adverse effects were injection-site pain, fatigue, myalgia, chills, fever, and headache. Local and systemic reactions were transient; 58.2% of the patients developed one or more reaction(s). There were no anaphylactic reactions. None of the patients had a myasthenic crisis, and two developed a mild deterioration compared with their Quantitative Myasthenia Gravis baseline score. The clinical outcome scores showed no exacerbation of MG symptoms. Patients over 65 years of age developed fewer adverse effects. COVID-19 vaccination did not induce clinical exacerbation in stable patients with MG, regardless of their age, sex, history of myasthenic crisis, or whether they were taking immunosuppressants. DISCUSSION: Our data are consistent with the mRNA COVID-19 vaccine being well tolerated in patients with well-controlled MG. The findings may contribute to decisions in vaccination campaigns in the future.

Patient Information and Informed Consent for Research in the Elderly: Lessons Learned from a Randomized Controlled Trial.

The informed consent (IC) of subjects participating in experimental studies is the mainstay to comply with the ethical principle of autonomy to ensure that the participation is voluntary. This experience was performed within the context of a single-center randomized clinical trial in elective prosthetic surgery. Obtaining IC in clinical trials is not without difficulties, and especially in the case of vulnerable populations it can be very challenging. This work aimed to identify the difficulties during the IC process for a clinical trial in subjects older than 65 years old and quantify and describe the use of IC in front of a witness. METHODS: This is a mixed methodology study with a qualitative part (focus group with 4 nurses involved in the inclusion of subjects) and a quantitative part describing the characteristics of patients who signed IC forms. RESULTS: The main difficulties identified are related to comprehension, sensory impairments, education level, and time. IC in front of witnesses was used in 20 patients out of 508. CONCLUSIONS: The participation of subjects older than 65 years old in clinical trials requires an adaptation of the process. The use of IC in front of a witness should always be considered in studies including elderly subjects.

Intravenous immunoglobulin to prevent myasthenic crisis after thymectomy and other procedures can be omitted in patients with well-controlled myasthenia gravis.

BACKGROUND: Myasthenic crisis (MC) is a potentially life-threatening complication of myasthenia gravis. Its precipitating factors include surgical procedures, particularly thymectomy. The role of preoperative intravenous immunoglobulin (IVIg) in preventing MC in patients scheduled for thymectomy and other surgery with general anaesthesia is unknown. Our objective was to test the hypothesis that preoperative IVIg is effective in preventing myasthenic crisis in patients with myasthenia gravis scheduled for surgery under general anaesthesia, including thymectomy. METHODS: A prospective, randomized, double-blind, single-centre study was conducted over a 4-year period. The treatment group received IVIg, 0.4 g/kg/day preoperatively for 5 consecutive days, and the placebo group received saline solution under the same conditions. The two groups were age-matched, with similar functional status, and Myasthenia Gravis Foundation of America class. All patients had well-controlled myasthenia gravis with minimal manifestations before surgery. The primary outcome measured was MC. Intubation times, time in the recovery room, number of postoperative complications, and days of hospitalization were the secondary outcomes measured. RESULTS: A total of 47 patients were randomized, 25 to the IVIg group and 22 to placebo. There were 19 men and 28 women, with a mean age of 58.6 years, mean body mass index of 27.8 kg/m2, and mean acetylcholine receptor antibodies of 12.9 nmol/l. The mean forced vital capacity was 84.4%. The mean quantitative myasthenia gravis sum score was 6.3. Ten patients (five in each arm) had a history of MC. Thymectomy was performed in 16 patients. Only one patient in the placebo group presented with MC requiring non-invasive ventilation (but no reintubation) for 6 days. Neither differences between groups in the univariate analysis nor risk factors for MC in the multivariate analysis were found. CONCLUSIONS: Preoperative IVIg to prevent MC does not appear to be justified in well-controlled myasthenia gravis patients. This study provides class I evidence that preparation with IVIg to prevent MC is not necessary in well-controlled myasthenia gravis patients scheduled for surgery with general anaesthesia.

Role of ICG-99mTc-nanocolloid for sentinel lymph node detection in cervical cancer: a pilot study.

PURPOSE: Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-99mTc-nanocolloid in SLN detection in patients with cervical cancer. METHODS: This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19-21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry. RESULTS: Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved. CONCLUSIONS: SLNB with ICG-99mTc-nanocolloid is feasible and safe in patients with early cervical cancer. This hybrid tracer provided bilateral SLN detection in all patients and a higher detection rate than blue dye, so it could become an alternative to the combined technique.

Influence of early neurological complications on clinical outcome following lung transplant.

BACKGROUND: Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. METHODS: We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. RESULTS: Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. CONCLUSIONS: The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

TLR-activated conventional DCs promote γ-secretase-mediated conditioning of plasmacytoid DCs.

Cooperative events between DC subsets involve cell contact and soluble factors. Upon viral challenge, murine pDCs induce cDC cooperation through CD40-CD40L interactions and IL-15 secretion, whereas in humans, the same effect is mediated by IFN-α. Conversely, during bacterial infections, pDC maturation may be induced by activated cDCs, although no mechanisms had been described so far. Here, we investigate how human pDCs are "conditioned" by cDCs. Blood-borne DC subsets (cDCs and pDCs) were sorted from healthy donors. IL-3-maintained pDCs were cocultured with LPS-activated, poly (I:C)-activated, or control cDCs [cDC(LPS), cDC(P(I:C)), cDC(CTRL)]. Coculture experiments showed that cDC(LPS)-conditioned pDCs up-regulated maturation markers, such as CD25 and CD86, whereas SNs contained higher amounts of IL-6 and CCL19 compared with control conditions. Gene-expression analyses on sorted cDC(LPS) or cDC(P(I:C)) conditioned pDCs confirmed the induction of several genes, including IL-6 and CCL19 and remarkably, several Notch target genes. Further studies using the γ-secretase/Notch inhibitor DAPT and soluble Notch ligands resulted in a significantly reduced expression of canonical Notch target genes in conditioned pDCs. DAPT treatment also hampered the secretion of CCL19 (but not of IL-6) by cDC(LPS) conditioned pDCs. These results reveal the involvement of γ-secretase-mediated mechanisms, including the Notch pathway, in the cell contact-dependent communication between human DC subsets. The resulting partial activation of pDCs after encountering with mature cDCs endows pDCs with an accessory function that may contribute to T cell recruitment and activation.

Cellular transplants in amyotrophic lateral sclerosis patients: an observational study.

BACKGROUND AIMS: Cytotherapy is a promising option for neurodegenerative disease treatment. Because of the fatal prognosis and imperative need for effective treatment, amyotrophic lateral sclerosis (ALS) patients request this therapy before its effectiveness has been verified. The increase in clinics offering cytotherapies but providing little scientific information has prompted considerable medical tourism. We present an observational study of Spanish ALS patients receiving cytotherapy, analyzing the experiences arising from the treatment (TX) and considering two progression markers, FVC and ALSFRS-R. METHODS: Twelve ALS patients with a mean age of 48.6 years (SD 12.8) received cytotherapy 26.9 months (SD 15.8) after clinical onset. ALSFRS-R and FVC at TX were 32.3 (SD 6.8) and 63.4% (SD 15.3), respectively. TX involved transplants of olfactory ensheathing cells in three patients, and autologous mesenchymal stromal cells in the remainder. RESULTS: One patient died 33 months post-TX after surviving for 49 months. Five required mechanical non-invasive home ventilation 7.4 months post-TX. Two required invasive ventilation 13 months post-TX. Five patients needed gastrostomy feeding 23.3 months post-TX. Survival between clinical onset and the study end date was 50 months (SD 17.2). No significant adverse events or changes in the decline of FVC and ALSFRS-R compared with the disease's natural history were observed. CONCLUSIONS: Our observations suggest that these therapies do not halt the course of the disease. Cytotherapy cannot yet be considered a curative treatment for ALS.