An observational study on the safety of COVID-19 vaccination in patients with myasthenia gravis.

OBJECTIVE: There is concern that the coronavirus disease (COVID-19) vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of COVID-19 vaccination on symptom severity in patients with myasthenia gravis (MG). METHODS: A total of 106 enrolled patients with MG who were vaccinated against COVID-19 were followed up, and a questionnaire was used to document in detail the exacerbation of muscle weakness after vaccination and all other uncomfortable reactions after vaccination. Demographic, clinical characteristics, medication, and vaccination data were collected by follow-up interview. The main observation outcome was whether the MG symptoms of patients were exacerbated. The definition of exacerbation is according to the subjective feeling of the patient or a 2-point increase in daily life myasthenia gravis activity score relative to before vaccination, within 30 days after vaccination. RESULTS: Of 106 enrolled patients [median age (SD) 41.0 years, 38 (35.8%) men, 53 (50.0%) with generalized MG, 74 (69.8%) positive for acetylcholine receptor antibody, and 21 (19.8%) with accompanying thymoma], muscle weakness symptoms were stable in 102 (96.2%) patients before vaccine inoculation. Muscle weakness worsened in 10 (9.4%) people after vaccination, of which 8 patients reported slight symptom worsening that resolved quickly (within a few days). Two (1.9%) of patients showed serious symptom aggravation that required hospitalization. CONCLUSION: Our results suggest that inactivated virus vaccines against COVID-19 may be safe for patients with MG whose condition is stable. Patients with generalized MG may be more likely to develop increased muscle weakness after vaccination.

[Characteristics of electromyography in 111 patients with generalized myasthenia gravis: a retrospective study].

Objective: To retrospectively analyze the characteristics of the electromyography (EMG) study in generalized myasthenia gravis (gMG) patients. Methods: A total of 111 gMG patients were enrolled. Patients were divided into two groups: 36 severe patients discontinuing pyridostigmine bromide (PB) for 8 hours were included in 8 h group, and 75 g MG patients discontinuing PB for at least 18 hours were included in>18 h group. The clinical information and EMG study data were collected and analyzed. Results: There were statistically significant differences in the initial location of the myasthenia muscle (P=0.027), the affected muscle detected by the EMG (P=0.015) and quantitative myasthenia gravis (QMG) score (P<0.01) between the two groups. Comparisons in each group revealed that the highest positive rate of low-frequency repetitive nerve stimulation (RNS) of facial in 8 h group and>18 h group was 94.4% and 60.0%, respectively. Comparisons between the two groups showed that the positive rate of low-frequency RNS in 8 h group was significantly higher than that in>18 h group (94.4% vs 70.7%, χ(2)=8.115, P=0.004). In particular, the positive rate of RNS in facial nerves and the extent of the amplitude decrease under different electrical stimulations (1 Hz, 3 Hz, and 5 Hz) were dramatically higher in the 8 h group (P<0.01). Conclusions: For gMG patients, the facial and accessory nerve detection can improve the positive rate of RNS. Different muscles had various sensitivity to PB, and orbicularis oculi muscle seemed the least sensitive muscle to PB. For suspect MG patients in severe condition, only discontinuing PB medication for 8 h before low-frequency RNS testing can avoid the deterioration and also obtain similar positive rate.

[Correlation factors of 127 times pre-crisis state in patients with myasthenia gravis].

Objective: To investigate the clinical features of the Pre-Crisis State and analyze the correlated risk factors of Pre-Crisis State of myasthenia crisis. Methods: We included 93 patients with myasthenia gravis (MG) who experienced 127 times Pre-Crisis State between October 2007 and July 2016. Those patients were hospitalized in the MG specialize center, Department of Neurological Science, first Affiliated Hospital of Sun Yat-sen University. The information of the general situation, the clinical manifestations and the blood gas analysis in those patients were collected using our innovated clinical research form. Statistic methods were applied including descriptive analysis, univariate logistic analysis, multivariate correlation logistic analysis, etc. Results: (1)The typical features of MG Pre-Crisis State included: dyspnea (127 times, 100% not requiring intubation or non-invasive ventilation), bulbar-muscle weakness (121 times, 95.28%), the increased blood partial pressure of carbon dioxide (PCO(2)) (94 times, 85.45%), expectoration weakness (99 times, 77.95%), sleep disorders (107 times, 84.25%) and the infection (99 times, 77.95%). The occurrence of dyspnea in combination with bulbar-muscle weakness (P=0.002) or the increased blood PCO(2) (P=0.042) often indicated the tendency of crisis. (2) The MG symptoms which were proportion to the occurrence of crisis includes: bulbar-muscle weakness (P=0.028), fever (P=0.028), malnutrition (P=0.066), complications (P=0.071), excess oropharyngeal secretions (P=0.005) and the increased blood PCO(2) (P=0.007). The perioperative period of thymectomy would not increase the risk of crisis. Conclusions: Dyspnea indicates the occurrence of the Pre-Crisis State of MG. In order to significantly reduce the morbidity of myasthenia crisis, the bulbar-muscle weakness, the increased blood PCO(2), expectoration weakness, sleep disorders, infection & fever and excess oropharyngeal secretions should be treated timely.

Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice.

Successful embryo implantation requires functional luminal epithelia to establish uterine receptivity and blastocyst-uterine adhesion. During the configuration of uterine receptivity from prereceptive phase, the luminal epithelium undergoes dynamic membrane reorganization and depolarization. This timely regulated epithelial membrane maturation and precisely maintained epithelial integrity are critical for embryo implantation in both humans and mice. However, it remained largely unexplored with respect to potential signaling cascades governing this functional epithelial transformation prior to implantation. Using multiple genetic and cellular approaches combined with uterine conditional Rac1 deletion mouse model, we demonstrated herein that Rac1, a small GTPase, is spatiotemporally expressed in the periimplantation uterus, and uterine depletion of Rac1 induces premature decrease of epithelial apical-basal polarity and defective junction remodeling, leading to disrupted uterine receptivity and implantation failure. Further investigations identified Pak1-ERM as a downstream signaling cascade upon Rac1 activation in the luminal epithelium necessary for uterine receptivity. In addition, we also demonstrated that Rac1 via P38 MAPK signaling ensures timely epithelial apoptotic death at postimplantation. Besides uncovering a potentially important molecule machinery governing uterine luminal integrity for embryo implantation, our finding has high clinical relevance, because Rac1 is essential for normal endometrial functions in women.

A single fas gene mutation changes lupus onset, severity, location, and molecular abnormalities in mice.

Although genetic predisposition plays a major role in the progression of systemic lupus erythematosus (SLE) and its variation in symptoms, the precise relationships between genetic changes and disease status are not well understood. Here, to demonstrate the effect of a single gene mutation on disease etiology, we examined two mouse models of SLE with the same genetic background but different Fas genes. Mice with the Fas(lpr) gene developed severe SLE with renal dysfunction and inflammatory responses in the lung and kidney. By contrast, mice with the Fas(+) gene showed disease-related abnormalities in the liver and joints. Patterns of inflammatory disease markers differed across organs between the two lines of mice. Fas(lpr) mice showed greater MMP signals in the kidney and IL-11 signals in the lung than Fas(+) mice. Fas(+) mice had higher IL-11 signal intensity in the knee region and higher CXCR4 signal intensity in the liver than Fas(lpr) mice. Our results exemplify the complexity of disease and suggest the need for individualized target-specific treatment regimens. Strengths and Limitations of this Study: Fas gene is a well characterized gene in this disease. The molecular components in human disease need more clinical data.

Differential effects of esomeprazole on the antiplatelet activity of clopidogrel in healthy individuals and patients after coronary stent implantation.

Clopidogrel plus aspirin is a standard antiplatelet aggregation regimen in cardiovascular diseases, especially after implantation of a coronary stent. Interaction between clopidogrel and proton pump inhibitors theoretically reduces clopidogrel's antiaggregation effect, but the evidence is controversial. A total of 30 healthy subjects and 74 patients with a coronary stent were given a 300 mg loading dose of aspirin and 300 mg clopidogrel and then 100 mg aspirin/75 mg clopidogrel daily for 14 days. Subgroups were concomitantly treated or not treated with esomeprazole (20 mg/day). Clopidogrel significantly reduced adenosine diphosphate-induced platelet aggregation in healthy and stent-implanted subjects on days 7 and 14. Healthy subjects receiving esomeprazole showed a significantly higher platelet aggregation rate than those not receiving esomeprazole, but esomeprazole had no effect in patients with a stent. Aspirin plus clopidogrel did not result in significant gastrointestinal complications. These differential effects of esomeprazole on the antiplatelet activity of clopidogrel in healthy individuals and patients after coronary stent implantation merit further investigation.

Meta-analysis: the effect and adverse events of Lactobacilli versus placebo in maintenance therapy for Crohn disease.

BACKGROUND: Lactobacilli are used in an attempt to maintain remission for Crohn disease. The aim of this study was to evaluate the efficacy and adverse events of Lactobacilli compared with placebo in maintenance therapy for Crohn disease. METHODS: We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, OVID and BIOSIS. All randomized trials comparing Lactobacilli with placebo in maintenance therapy for Crohn disease were included. RESULTS: Six randomized controlled trials with a total of 359 participants met the inclusion criteria. From the meta-analyses, the relative risk (RR) of clinical relapse rate was 1.15 (95% confidence interval (CI) 0.90-1.48) comparing Lactobacilli with placebo and RR of endoscopic relapse rate was 1.31 (95%CI 0.57-3.00). Subgroup analyses showed RR for clinical relapse rates of Lactobacilli versus placebo was 0.99 (95%CI 0.76-1.29) in adults, 1.85 (95%CI 1.00-3.41) in children, 1.68 (95%CI 1.07-2.64) in Lactobacillus rhamnosus strain GG and 0.91 (95%CI 0.68-1.23) in Lactobacillus johnsonii respectively. The pooled RR of adverse events was 0.83 (95%CI 0.61-1.12). CONCLUSION: Our meta-analysis suggests that compared with placebo, administration of L. rhamnosus strain GG as maintenance therapy may increase the relapse rates of Crohn disease. L. johnsonii is inefficacious in reducing the incidence of relapse.

Treatment of xenografted ovarian carcinoma using paclitaxel-loaded ultrasound microbubbles.

RATIONALE AND OBJECTIVES: The aim of this study was to explore the antitumor effects on mice xenografted ovarian carcinoma using the technique of ultrasound-mediated drug release from paclitaxel-loaded lipid microbubbles (PLMs). MATERIALS AND METHODS: Twenty-five ovarian cancer-bearing nude mice were randomly divided into five groups of five mice each. Each group received a unique kind of treatment once a day. These treatments were PLMs combined with ultrasound, intravenous paclitaxel administration, non-drug-loaded microbubbles combined with ultrasound, intravenous PLM administration, and normal saline administration (the control group). After 7 days of consecutive treatment, all mice were sacrificed, and their tumors were harvested to measure volumes and weights. The tumor inhibition rate was calculated by weight. Expressions of vascular endothelial growth factor (VEGF) and p53 in tumor tissues were detected by immunohistochemical staining. RESULTS: Mean tumor volume and weight were the lowest in the first group (PLMs combined with ultrasound), so this group's tumor inhibition rate was the highest (P < .05). On immunohistology, VEGF and p53 expression levels were lowest (P < .05) in the first group. CONCLUSION: Ultrasound irradiation mediates PLM destruction so that the drug is released from the vehicles at the same time. It helps achieve targeted chemotherapy in tumor tissues. This technique has potential to be adopted as a novel tool for ovarian cancer chemotherapy.

Vulval intraepithelial neoplasia and periungual Bowen's disease concordant for mucosal (HPV-34) and epidermodysplasia verruciformis (HPV-21) human papillomavirus types.

Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple alpha and beta papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited.

Fatal sporotrichosis.

Disseminated sporotrichosis is a serious fungal infection caused by the soil inhabitant Sporothrix schenckii. It is seen in immunocompromised patients, with a substantial number of recent cases involving patients with acquired immunodeficiency syndrome (AIDS). However, individuals with other conditions that affect the immune system also are at increased risk. We report a case of fatal disseminated sporotrichosis in a patient with liver disease and a diagnosis of a granulomatous condition presumed to be sarcoidosis; the patient was receiving systemic corticosteroid therapy. The various presentations of S schenckii infection, the risk of disseminated disease in immunocompromised hosts, and the importance of making accurate histologic diagnoses are reviewed.

Traumatic keratoacanthoma arising in a 15-year-old boy following a motor vehicle accident.

Keratoacanthomas appear most commonly in sun-damaged skin in middle-aged and elderly people. We present a 15-year-old boy who developed a rapidly growing nodule within a hypertrophic scar that was the result of trauma suffered in a roll-over motor vehicle accident 8 months prior to presentation. Histologic analysis of a biopsy specimen of the nodule confirmed the presence of squamous cell carcinoma, keratoacanthoma type. The development of keratoacanthoma has been associated with sun exposure, chemical carcinogens, radiation therapy, genetic factors, and various forms of antecedent trauma, including surgery or grafting, thermal burns, laser resurfacing, and vaccination. This report describes the youngest patient with traumatically-induced keratoacanthoma, and is the first instance of this entity arising in a friction burn.

Reliable methods to evaluate the burden of actinic keratoses.

Dermatologists treat actinic keratoses to prevent non-melanoma skin cancer. Evaluation of actinic keratosis therapy depends on reliable measures of the lesions. The commonly used method of directly counting all visible lesions has been shown to be unreliable. We performed a prospective, single-blinded study to explore the reliability of body surface area involvement and direct counting of lesions measuring greater than 0.5 cm. Consecutively available subjects with >2% body surface area involvement of both upper extremities were recruited from the Albuquerque, NM Veterans Administration Dermatology Clinic upon their arrival. Blinded investigators evaluated 37 subjects during two visits, baseline and 2 weeks later, using both methods. Data were analyzed using the 26 pairs where evaluating physician was the same at both time points. Both methods correlated well when comparing the two time points. Our results did not change when we added the pairs where the evaluating physician differed in the two time points. Our study demonstrates that both methods are viable ways to evaluate actinic keratoses, even when the investigators differ at different time points, a practical matter in clinical trials. Our study provides a promising option to evaluate emerging new actinic keratoses therapies. However, given that the method was only tested on upper extremities of a veteran population, further testing must be performed in different anatomical locations and in non-veteran populations.

Case reports: successful treatment of Mycobacterium marinum infection with minocycline after complication of disease by delayed diagnosis and systemic steroids.

Mycobacterium marinum, an aerobic, non-tuberculous, environmental mycobacterium, is the etiologic agent responsible for "fish tank granuloma." Found in aquatic environments, particularly where water is relatively still or stagnant, M. marinum produces infection in fish, as well as humans. Infection follows exposure to contaminated water and direct inoculation of the organism via breaks in the skin. The resulting primary lesion is usually a red-to-violaceous plaque or nodule, which can have an overlying crust or verrucous surface that may ulcerate and, in some cases, may be accompanied by satellite lesions and lymphangitic spread. We present an aggressive case of M. marinum infection with prominent lymph node involvement in an otherwise healthy 34-year-old woman whose course was complicated by delayed diagnosis and treatment with systemic steroids.

A case of primary mucinous carcinoma of the scalp treated with mohs surgery.

BACKGROUND: Primary mucinous carcinoma of the skin is a rare sweat gland malignancy that is associated with locally aggressive behavior and a high rate of local recurrence following simple excision. OBJECTIVE: A patient with primary mucinous carcinoma of the scalp, which was treated with Mohs micrographic surgery (MMS), is described. METHODS: Case report and literature review. RESULTS: The patient underwent MMS to remove the tumor. Thirty months after the procedure, the patient remains tumor free. CONCLUSION: Simple excision of primary mucinous carcinoma of the skin is associated with a high recurrence rate. Given the low rate of metastasis and characteristic histologic tumor continuity associated with primary mucinous carcinoma of the skin, as well as the tendency for the tumor to involve cosmetically sensitive areas, such as the face and eyelids, MMS appears to represent a preferable treatment alternative for this particular sweat gland tumor. MMS appears to be associated with a very low risk of tumor recurrence.

Giant dermatofibroma with monster cells.

We report a case of a 64-year-old woman with a giant dermatofibroma on her back with the unusual histologic feature of monster cells. The firm, exophytic, 3-cm nodule had purple and yellow components with surface telangiectasia. Histologic examination demonstrated characteristic findings of a dermatofibroma, including rete ridge flattening and bridging; a stroma containing scattered, large, round, eosinophilic collagen bundles; and a polymorphous dermal infiltrate of spindle and xanthomatous cells with scattered siderophages. Some xanthomatous cells demonstrated features consistent with monster cells, including huge bizarre nuclei and one or more nucleoli. Immunohistochemical staining for factor XIIIa was positive. A diagnosis of giant dermatofibroma with monster cells (DFMC) was made. Giant dermatofibromas are rare, with monster cells being an uncommon finding in dermatofibroma. To our knowledge, this is the first report of DFMC.