Risk of cardiovascular events leading to hospitalisation after Streptococcus pneumoniae infection: a retrospective cohort LIFE Study.

OBJECTIVES: To elucidate the risk of cardiovascular event occurrence following Streptococcus pneumoniae infection. DESIGN: Retrospective cohort study using a LIFE Study database. SETTING: Three municipalities in Japan. PARTICIPANTS: Municipality residents who were enrolled in either National Health Insurance or the Latter-Stage Elderly Healthcare System from April 2014 to March 2020. EXPOSURE: Occurrence of S. pneumoniae infection. PRIMARY OUTCOME MEASURES: Occurrence of one of the following cardiovascular events that led to hospitalisation after S. pneumoniae infection: (1) coronary heart disease (CHD), (2) heart failure (HF), (3) stroke or (4) atrial fibrillation (AF). RESULTS: S. pneumoniae-infected patients were matched with non-infected patients for each cardiovascular event. We matched 209 infected patients and 43 499 non-infected patients for CHD, 179 infected patients and 44 148 non-infected patients for HF, 221 infected patients and 44 768 non-infected patients for stroke, and 241 infected patients and 39 568 non-infected patients for AF. During follow-up, the incidence rates for the matched infected and non-infected patients were, respectively, 38.6 (95% CI 19.9 to 67.3) and 30.4 (29.1 to 31.8) per 1000 person-years for CHD; 69.6 (41.9 to 108.8) and 50.5 (48.9 to 52.2) per 1000 person-years for HF; 75.4 (48.3 to 112.2) and 35.5 (34.1 to 36.9) per 1000 person-years for stroke; and 34.7 (17.9 to 60.6) and 11.2 (10.4 to 12.0) per 1000 person-years for AF. Infected patients were significantly more likely to develop stroke (adjusted HR: 2.05, 95% CI 1.22 to 3.47; adjusted subdistribution HR: 1.94, 95% CI 1.15 to 3.26) and AF (3.29, 1.49 to 7.26; 2.74, 1.24 to 6.05) than their non-infected counterparts. CONCLUSIONS: S. pneumoniae infections elevate the risk of subsequent stroke and AF occurrence. These findings indicate that pneumococcal infections have short-term effects on patients' health and increase their midterm to long-term susceptibility to serious cardiovascular events.

Successful treatment with daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome: a case report.

BACKGROUND: Transplant-eligible patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome are treated with induction therapy and autologous stem cell transplantation. Conventional induction therapies may exacerbate neuropathy and a high rate of disease progression within 5 years. Furthermore, only 50% of patients are able to walk independently after the therapies. Daratumumab, lenalidomide, and dexamethasone therapy has been reported as a less neurotoxic, highly effective therapy for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome who are ineligible for transplant or whose syndrome is relapsed/refractory, but no reports have provided data from untreated transplant-eligible patients. CASE PRESENTATION: A 34-year-old Japanese woman displayed weakness, pain and edema in the lower limbs, decreased grip strength, amenorrhea, and abdominal distention. She was unable to walk independently. The patient was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and performed four courses of daratumumab, lenalidomide, and dexamethasone therapy, which enabled her to walk independently and did not exacerbate the neuropathy. Hematopoietic stem cells were collected using plerixafor and filgrastim in combination. Autologous stem cell transplantation was performed with high-dose melphalan. At 3-month post-transplantation follow-up, most of her clinical symptoms had disappeared. CONCLUSIONS: Daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation may be more effective than conventional therapy for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome. Although there was concerns that daratumumab, lenalidomide, and dexamethasone therapy might lead to poor mobilization of hematopoietic stem cells, this was overcome with the combination of plerixafor and filgrastim. The benefit of daratumumab, lenalidomide, and dexamethasone as induction therapy prior to autologous stem cell transplantation should be confirmed in future clinical trials.

Risk factors for pneumococcal disease in persons with chronic medical conditions: Results from the LIFE Study.

OBJECTIVES: This study aimed to identify the risk factors for pneumococcal disease. METHODS: The study was performed using insurance claims data from the residents of 12 Japanese municipalities. Based on recorded diagnoses, we identified chronic medical conditions in each patient between April 2015 and March 2016 and examined the subsequent occurrence of a pneumococcal disease from April 2016 onward. Cox proportional hazards models were used to estimate the hazard ratio of each chronic medical condition for a pneumococcal disease occurrence. RESULTS: The study was conducted on 732,235 patients, of whom, 61,306 (8.4%) were aged 0-18 years, 184,367 (25.2%) were aged 19-49 years, 126,078 (17.2%) were aged 50-64 years, and 360,484 (49.2%) were aged ≥65 years. A higher number of conditions was associated with a higher incidence of pneumococcal disease. Significant risk factors for pneumococcal disease in all patients included chronic heart disease, chronic lung disease, diabetes mellitus, cancer, and chronic renal disease. Furthermore, chronic lung disease, diabetes mellitus, aspiration pneumonia, and immunosuppressant use were risk factors among patients aged 50-64 years. CONCLUSIONS: Persons aged 50-64 years with multiple chronic medical conditions or with specific conditions are at a higher risk of developing pneumococcal disease, indicating a need to consider their inclusion in routine vaccination programs.

Addition of plerixafor for mobilization of stem cells with bortezomib is feasible in dialysis-dependent multiple myeloma.

Plerixafor and bortezomib have recently been used in autologous stem cell collection to increase the amount of stem cells collected. However, no reports have described the combined use of plerixafor and bortezomib in cases of dialysis-dependent multiple myeloma. The dialysis-dependent multiple myeloma patient in the present study had a small amount of CD34-positive cells with plerixafor and filgrastim, and also with bortezomib and cyclophosphamide. However, by adding plerixafor to bortezomib and cyclophosphamide, collected CD34-positive cells were increased six-fold compared to the previous day. These findings suggest that the combination of plerixafor and bortezomib may be effective in those patients.

Purification and biochemical characterization of a novel ecto-apyrase, MP67, from Mimosa pudica.

We have previously reported the presence of an apyrase in Mimosa pudica. However, only limited information is available for this enzyme. Thus, in this study, the apyrase was purified to homogeneity. The purified enzyme had a molecular mass of around 67 kD and was able to hydrolyze both nucleotide triphosphate and nucleotide diphosphate as substrates. The ratio of ATP to ADP hydrolysis velocity of the purified protein was 0.01 in the presence of calcium ion, showing extremely high substrate specificity toward ADP. Thus, we designated this novel apyrase as MP67. A cDNA clone of MP67 was obtained using primers designed from the amino acid sequence of trypsin-digested fragments of the protein. In addition, rapid amplification of cDNA ends-polymerase chain reaction was performed to clone a conventional apyrase (MpAPY2). Comparison of the deduced amino acid sequences showed that MP67 is similar to ecto-apyrases; however, it was distinct from conventional apyrase based on phylogenetic classification. MP67 and MpAPY2 were expressed in Escherichia coli, and the recombinant proteins were purified. The recombinant MP67 showed high substrate specificity toward ADP rather than ATP. A polyclonal antibody raised against the recombinant MP67 was used to examine the tissue distribution and localization of native MP67 in the plant. The results showed that MP67 was ubiquitously distributed in various tissues, most abundantly in leaves, and was localized to plasma membranes. Thus, MP67 is a novel ecto-apyrase with extremely high substrate specificity for ADP.