Second allogeneic transplantation using umbilical cord blood for a patient with relapsed ALK+ anaplastic large cell lymphoma after allogeneic bone marrow transplantation in the era of ALK inhibitors: A case report

Rationale:Anaplastic lymphoma kinase (ALK) + anaplastic large cell lymphoma (ALCL) is considered as a good prognosis lymphoma. However, in an extremely rare subset of patients, ALK+ ALCL with leukemic presentations is known to be chemotherapy-resistant. Although several novel therapies have been tested, the standard therapy for relapsed/refractory ALK+ ALCL has not been established yet.Patient concerns:An 18-year-old female patient who had conventional chemotherapy- and Brentuximab Vedotin (BV)-resistant ALK+ ALCL with leukemic presentation. She was successfully treated with an ALK inhibitor, crizotinib. Crizotinib induced complete remission (CR) and bridged to allogeneic bone marrow transplantation (BMT).Diagnosis:However, her ALCL relapsed on day 60 after BMT and she developed high grade fever and lymphadenopathy.Intervention:Although crizotinib was given to the patient immediately after relapse, she developed grade 3 nausea and could not continue to take it. Then, we gave alectinib to the patient, which promptly induced sustained CR without any further chemotherapy. The patient received second stem cell transplantation using umbilical cord blood with myeloablative regimen in 2^nd CR.Outcomes:The patient has been in CR under maintenance therapy of alectinib for more than 16 months.Lessons:Both ALK inhibitors demonstrated drastic efficacy for our patient who had chemotherapy- and BV-resistant ALK+ ALCL with leukemic presentation. Alectinib showed less gastro-intestinal toxicity than crizotinib and the patient was able to take it even at the relatively early phase of stem cell transplantation.     

Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report

Rationale:Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD.Patient concerns:We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient''s serum and cerebrospinal fluid.Diagnosis:A diagnosis of MOGAD complicated with MPA was made.Interventions:The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy.Outcomes:Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period.Conclusion:To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.     

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.     

Quantitative analysis of K-ras gene mutation in pancreatic tissue obtained by endoscopic ultrasonography-guided fine needle aspiration: clinical utility for diagnosis of pancreatic tumor

OBJECTIVES: Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has become established in the diagnosis of pancreatic cancer. The combination of pathological diagnosis and analysis for mutant K-ras gene was investigated to improve the accuracy of diagnosis. METHODS: EUS-FNA was performed in 34 patients with pancreatic masses (26 adenocarcinomas and eight chronic pancreatitis). Mutant ras gene was analyzed semiquantitatively in the specimens obtained by EUS-FNA as well as in pancreatic juice obtained by ERCP. RESULTS: Mutant gene was detected at high amounts (more than 2% of total ras genes) in 20 of 26 (77%) specimens of EUS-FNA and in 12 of 19 (63%) of pancreatic juice in cases with pancreatic carcinoma. Cytological diagnosis of malignancy by EUS-FNA was found in 16 of 26 (62%) patients with pancreatic cancer. Accurate diagnosis of the carcinoma was 21 of 26 (81%) by combined cytology and molecular method of EUS-FNA, and increased to 23 of 26 (88%) by adding molecular analysis of pancreatic juice. In contrast, mutant gene was absent or low level despite suspicious cytology in patients with benign pancreatic lesion. CONCLUSION: Quantitative analysis of mutant ras gene supplemented conventional cytology of EUS-FNA and ERCP. Detection of mutation at high amounts may represent pancreatic cancer, whereas its absence increased the possibility of benign lesion.     

Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases

OBJECTIVE: The Fas-Fas ligand (FasL) pathway is one of the important apoptosis-signalling molecule systems. We previously determined that this pathway may be involved in the pathogenesis of fibrosing lung diseases. In the present study, we evaluated the clinical significance of the levels of soluble forms of Fas (sFas) and FasL (sFasL) in serum from patients with fibrosing lung diseases. METHODOLOGY: We measured sFas, sFasL, KL-6 (a measure of alveolar type II cell damage), surfactant protein D (SP-D), and surfactant protein A (SP-A) levels in serum from 35 patients with idiopathic pulmonary fibrosis (IPF), 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and 13 normal healthy controls using enzyme-linked immunosorbent assays (ELISA). RESULTS: The serum levels of sFasL were significantly increased in patients with active IPF and CVD-IP, compared with those with inactive disease and controls. There was no significant difference in sFasL levels between patients with inactive disease and controls. Serum sFasL levels were significantly correlated with lactate dehydrogenase and KL-6 levels in IPF. The decrease in sFasL levels following corticosteroid therapy was not correlated with the clinical course of IPF. There was no significant difference in serum sFas levels between IPF or CVD-IP patients and controls. CONCLUSIONS: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.     

Regression of atypical lymphoid hyperplasia after eradication ofHelicobacter pylori

A rare case of endescopic and histological regression of a gastric lymphoid mucosal lesion after eradication ofHelicobacter pylori is reported. A 72-year-old man was suspected of having a low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma by endoscopic and histological findings. Histology of biopsy specimens showed massive infiltration of atypical lymphocytes and lymphoepithelial lesions. Immunohistochemical staining revealed kappa light chain expression in the infiltrated atypical lymphocytes to be twofold that of lambda light chain. The above diagnosis was thus highly suspected but not confirmed. Antibiotic therapy was given on the basis of evidence ofH. pylori infection. Successful eradication ofH. pylori resulted in remarkable improvement of endoscopic and histological findings. Follow-up studies were carried out 8 months after eradication, with no evidence of relapse. The eradication ofH. pylori appears to be an effective alternative therapy for B-cell lymphoproliferative disease, although longer follow-up and further studies are needed before this treatment can be establisted.     

Relation between white blood cell counts and myocardial reperfusion in patients with recanalized anterior acute myocardial infarction.

BACKGROUND: The clinical significance of the white blood cell (WBC) count on admission in relation to the duration of ischemia in acute myocardial infarction (AMI) remains unclear. METHODS AND RESULTS: The relationship of the WBC count on admission to myocardial reperfusion was examined in 135 patients with recanalization of an anterior AMI within 6 h of symptom onset. Patients were classified according to the WBC count on admission: Group L (n=75), WBC count <12,000 cells/mm(3) and group H (n=60), WBC count >or=12,000 cells/mm(3). Peak creatine kinase (CK) was higher and impaired myocardial reperfusion, defined as a myocardial blush grade of 0/1, was more frequent in group H than in group L. Among the patients in group H, those with early (3 h) recanalization; however, peak CK and the incidence of impaired myocardial reperfusion were similar in these subgroups of patients. Multivariate analysis showed that WBC count >or=12,000 cells/mm(3) on admission was an independent predictor of impaired myocardial reperfusion in patients with early recanalization (odds ratio 7.9, p=0.04), but not in those with late recanalization. CONCLUSIONS: A higher WBC count may be associated with progression of myocardial damage after recanalization in patients with early recanalization of an anterior AMI.     

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2016–17 season: Comparison with the 2010–11 to 2015–16 seasons

To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) in the viruses epidemic in the 2016–17 Japanese influenza season, we measured the 50% inhibitory concentration (IC₅₀) of these NAIs for influenza virus isolates from patients and compared them with the results from the 2010–11 to 2015–16 seasons.Viral isolation was done with specimens obtained prior to treatment, and the type and subtype was determined by RT-PCR using type- and subtype-specific primers. The IC₅₀ was determined by a neuraminidase inhibition assay using a fluorescent substrate.A total of 276 virus isolates, 6 A (H1N1)pdm09 (2.2%), 249 A (H3N2) (90.2%), and 21 B (7.6%), had the IC₅₀ measured for the four NAIs. B isolates included 11 (52.4%), 9 (42.9%), and one (4.8%) of the Victoria, Yamagata, and undetermined strains, respectively.No A (H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2016–17 season. No isolate with highly reduced sensitivity to the four NAIs have been found for A (H3N2) or B from the 2010–11 to 2016–17 seasons. No significant trend of increase or decrease was found in the geometric mean IC₅₀s of the four NAIs during the seven studied seasons.These results indicate that the sensitivity to the four commonly used NAIs has been maintained and that any change in the effectiveness of these NAIs would be minute. Common usage of NAIs for patient treatment has not been a driving force in the selection of NAI resistant viruses.     

Potential Effect of Prolonged Sevoflurane Anesthesia on the Kinetics of [<Superscript>11</Superscript>C]Raclopride in Non-human Primates

Purpose

Positron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BP_ND) of [¹¹C]raclopride in NHP.

Procedures

Three cynomolgus monkeys underwent two to three PET measurements with [¹¹C]raclopride under continuous sevoflurane anesthesia on the same day. The concentration of sevoflurane was adjusted according to the general conditions and safety parameters of the NHP. Time to peak (TTP) radioactivity in the striatum was estimated from time-activity curves (TACs). The BP_ND in the striatum was calculated by the simplified reference tissue model using the cerebellum as reference region.

Results

In each NHP, the TTP became shorter in the later PET measurements than in the first one. Across all measurements (n = 8), concentration of sevoflurane correlated with TTP (Spearman’s ρ = ? 0.79, p = 0.03), but not with BP_ND (ρ = ? 0.25, p = 0.55).

Conclusions

These data suggest that sevoflurane affects the shape of TACs but has no evident effect on BP_ND in consecutive PET measurements.