Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Association of Cadaveric Factors with the Degree and Region of Discoloration on Pink Teeth: An Approach to Serial Cases

The pink teeth phenomenon has been observed in cases of hanging and drowning, but the relationship of this phenomenon with cause of death has not been positively affirmed. To date, teeth with a pinkish tone have been simply regarded as pink teeth. However, we speculated that classification and evaluation of the degree and region of discoloration with reference to how color is classified in prosthodontic dentistry may produce novel findings regarding the pink teeth phenomenon. Therefore, we classified the degree and region of discoloration on teeth into three grades and attempted to evaluate the relationship of grade with various cadaveric factors in 68 cases of pink teeth. The degree and region scores of discoloration did not show significant differences in terms of sex, age, cause of death, and place of discovery, but the degree of discoloration in terms of time after death showed a significant increase at 6 months (p < 0.01) and a significant decrease after 7 months (p < 0.05), while the region score also showed a significant decrease after 7 months. Furthermore, in 18 cases of drowning, the degree of discoloration significantly increased with time after death (p < 0.01). Thus, it was clarified that time after death was most strongly related to the pink teeth phenomenon, suggesting cadaveric decomposition may affect the occurrence of pink teeth. Further investigation in cases of early postmortem changes would be required to determine whether pink teeth in putrefactive cadavers have utility in medico–legal assessments

Association of Cadaveric Factors with the Degree and Region of Discoloration on Pink Teeth: An Approach to Serial Cases

The pink teeth phenomenon has been observed in cases of hanging and drowning, but the relationship of this phenomenon with cause of death has not been positively affirmed. To date, teeth with a pinkish tone have been simply regarded as pink teeth. However, we speculated that classification and evaluation of the degree and region of discoloration with reference to how color is classified in prosthodontic dentistry may produce novel findings regarding the pink teeth phenomenon. Therefore, we classified the degree and region of discoloration on teeth into three grades and attempted to evaluate the relationship of grade with various cadaveric factors in 68 cases of pink teeth. The degree and region scores of discoloration did not show significant differences in terms of sex, age, cause of death, and place of discovery, but the degree of discoloration in terms of time after death showed a significant increase at 6 months (p p p < 0.01). Thus, it was clarified that time after death was most strongly related to the pink teeth phenomenon, suggesting cadaveric decomposition may affect the occurrence of pink teeth. Further investigation in cases of early postmortem changes would be required to determine whether pink teeth in putrefactive cadavers have utility in medico–legal assessments

Suppression of MUC5AC expression in human bronchial epithelial cells by interferon-γ

Background: Excessive mucin secretion in the airway is an important feature of airway inflammatory diseases. MUC5AC expression is regulated by a variety of stimuli such as cytokines. Little is known about the role of interferon (IFN)-γ in MUC5AC expression in human bronchial epithelial cells. Methods: Human pulmonary mucoepidermoid carcinoma cell line (NCI-H292) and normal human bronchial epithelial (NHBE) cells were used to assess the effects of IFN-γ on MUC5AC transcription. Results: Transforming growth factor (TGF)-α and double-stranded RNA (polyI:C)-induced MUC5AC mRNA and protein expression was repressed by IFN-γ in a concentration-dependent manner. IFN-γ showed limited effects on TGF-α and polyI:C-induced activation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). A chromatin immunoprecipitation assay indicated that Sp1 bound to its cognate sequence located on the MUC5AC promoter. The Sp1 inhibitor mithramycin A inhibited MUC5AC mRNA expression, implying a critical role for Sp1 in MUC5AC induction. Importantly, IFN-γ impeded Sp1 binding to the MUC5AC promoter. Conclusions: These results suggest that IFN-γ represses MUC5AC expression, disturbing binding of Sp1 to its target sequences

Analysis of radiocarbon, stable isotopes and DNA in teeth to facilitate identification of unknown decedents.

International audienceThe characterization of unidentified bodies or suspected human remains is a frequent and important task for forensic investigators. However, any identification method requires clues to the person's identity to allow for comparisons with missing persons. If such clues are lacking, information about the year of birth, sex and geographic origin of the victim, is particularly helpful to aid in the identification casework and limit the search for possible matches. We present here results of stable isotope analysis of (13)C and (18)O, and bomb-pulse (14)C analyses that can help in the casework. The (14)C analysis of enamel provided information of the year of birth with an average absolute error of 1.8±1.3 years. We also found that analysis of enamel and root from the same tooth can be used to determine if the (14)C values match the rising or falling part of the bomb-curve. Enamel laydown times can be used to estimate the date of birth of individuals, but here we show that this detour is unnecessary when using a large set of crude (14)C data of tooth enamel as a reference. The levels of (13)C in tooth enamel were higher in North America than in teeth from Europe and Asia, and Mexican teeth showed even higher levels than those from USA. DNA analysis was performed on 28 teeth, and provided individual-specific profiles in most cases and sex determination in all cases. In conclusion, these analyses can dramatically limit the number of possible matches and hence facilitate person identification work

Useful DNA typing using AmpFlSTR® Identifiler® Kit for formaldehyde-fixed paraffin-embedded (FFPE) tissues in early gastric cancer patient with lymph node metastasis

After distal gastrectomy in a patient with early gastric cancer, 27 regional lymph nodes around the stomach were evaluated for the existence of metastasis. There was a 0IIa+IIc type tumor 2.0x1.5cm in size in the gastric angle of the lesser curvature according to the Japanese Classification of Gastric Carcinoma (JCGC). Histologically, the lesion extended no deeper than the muscularis mucosae. The cancer stage was so early that no metastasis was expected to occur but a lymph node with metastasis was found in one lymph node along the common anterior hepatic artery (station No.8a). This histological type was a little different from that of a primary tumor. The doctor began to suspect that the lymph node with metastasis might have been from another patient by mistake. Therefore, DNA typing using the AmpFlSTR® Identifiler® kit was performed in formaldehyde-fixed paraffin-embedded (FFPE) tissues: 2 parts of gastric mucosa without cancer, one part of gastric mucosa with cancer, 4 lymph nodes without metastasis, and the lymph node station No.8a with metastasis. STR typing was successful in 6~14 STR loci and amelogenin gene, and the detected STR type was the same in all samples. Compared with the STR type using DNA from the patient’s blood, the lymph node station No.8a was from the same patient. The lymph node with metastasis turned out to be not from another patient. Therefore, we suggest that DNA typing using the AmpFlSTR® Identifiler® Kit for FFPE samples is useful in such clinical cases

The principle for age estimation by analyzing ¹⁴C in dental enamel, exemplified by two teeth from cases 30 and 15, respectively.

<p>Horizontal lines represent their radiocarbon values crossing the ¹⁴C bomb curve, and corresponding date of enamel formation indicated by the vertical lines crossing the abscissa. By subtracting the average formation time (arrows) for each tooth, the DOB of the person can be calculated (dashed vertical lines). The true DOB was 0.3 and 0.4 years, respectively, from the estimated DOB of these persons.</p

¹⁴C levels in enamel and roots from the same teeth.

<p>¹⁴C levels in enamel and roots from the same teeth.</p