Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study

Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.     

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy

The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4^＋ and CD8^＋ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.     

Combining the Tumor Contact Length and Apparent Diffusion Coefficient Better Predicts Extraprostatic Extension of Prostate Cancer with Capsular Abutment: A 3 Tesla MR Imaging Study

Purpose: To assess the diagnostic performance of the tumor contact length (TCL) and apparent diffusion coefficient (ADC) for predicting extraprostatic extension (EPE) of prostate cancer with capsular abutment (CA).Methods: Ninety-three patients with biopsy-proven prostate cancer underwent 3-Tesla MRI, including diffusion-weighted imaging (b value = 0, 2000 s/mm²) and radical prostatectomy. Two experienced radiologists, blinded to the clinicopathological data, retrospectively assessed the presence of CA on T2-weighted imaging (T2WI). TCL on T2WI and ADC values were measured on detecting CA in prostate cancer. We used the receiver operating characteristic curves to assess the diagnostic performance of TCL and ADC values for predicting EPE.Results: CA was present in 58 prostate cancers among 93 patients. The cut-off value for TCL was 6.9 mm, which yielded an area under the curve (AUC) of 0.75. This corresponded to a sensitivity, specificity, and accuracy of 84.2%, 61.5%, and 69.0%, respectively. The cut-off value for ADC was 0.63 × 10^–3 mm²/s, which yielded an AUC of 0.76. This, in turn, corresponded to a sensitivity, specificity, and accuracy of 84.2%, 59.0%, and 67.2%, respectively. The combined cut-off value of TCL and ADC yielded an AUC of 0.82. The specificity (84.6%) and accuracy (81.0%) of the combined value were superior to their individual values (P < 0.05).Conclusion: A combination of TCL and ADC values provided high specificity and accuracy for detecting EPE of prostatic cancer with CA.     

Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice

Licochalcone A, 3-a,a-dimethylallyl-4,4'-dihydroxy-6-methoxychalcone, from the root of Glycyrrhiza inflata Beta (Leguminosae) (Xin-jiang liquorice) showed anti-inflammatory action towards mouse ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol 13-acetate (TPA) by topical application. Anti-tumour promoting action of licochalcone A was also observed in vivo for mouse skin papilloma initiated by dimethylbenz[a]anthracene (DMBA) and promoted by TPA. It inhibited in vitro 32Pi-incorporation to phospholipids in HeLa cells promoted by TPA. A competitive interaction of licochalcone A with the TPA-receptors in the cell membrane has been suggested.     

Precise immunological evaluation rationalizes the design of a self-adjuvanting vaccine composed of glycan antigen,TLR1/2 ligand,and T-helper cell epitope

Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam₃CSK₄), and T-helper (Th) cell epitope, and found that this three-component self-adjuvanting vaccine effectively resulted in the production of anti-triSTn IgG antibodies. We herein analyzed immune responses induced by this self-adjuvanting vaccine in detail. We newly synthesized two-component vaccines, i.e., Pam₃CSK₄- or Th epitope-conjugated triSTn, as references to evaluate the immune-stimulating functions of Pam₃CSK₄ and Th epitope. Immunological evaluation of the synthesized vaccine candidates revealed that Pam₃CSK₄ was essential for antibody production, indicating that the uptake of triSTn antigen by antigen-presenting cells (APCs) was promoted by the recognition of Pam₃CSK₄ by TLR1/2. The function of the Th epitope was also confirmed. Th cell activation was important for boosting antibody production and IgG subclass switching. Furthermore, flow cytometric analyses of immune cells, including T cells, B cells, dendritic cells, and other monocytes, were first employed in the evaluation of self-adjuvanting vaccines and revealed that the three-component vaccine was able to induce antigen-specific immune responses for efficient antibody production without excessive inflammatory responses. Importantly, the co-administration of Freund''s adjuvants was suggested to cause excessive myeloid cell accumulation and decreased plasma cell differentiation. These results demonstrate that vaccines can be designed to achieve the desired immune responses via the bottom-up construction of each immune element.

Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responses via bottom-up construction of the necessary immune elements.     

Chylous Ascites Due to Hyperthyroidism and Heart Failure

Chylous ascites (CA) is the accumulation of fluid with a high triglyceride content in the peritoneal cavity. Only two cases in the literature have reported CA with hyperthyroidism. A 28-year-old previously healthy woman presented with gradual-onset abdominal swelling, exertional dyspnea, and diarrhea. Hyperthyroidism and heart failure were diagnosed using laboratory investigation and echocardiography. Ultrasonography revealed a large amount of ascites. The ascitic fluid was milky with elevated triglyceride levels. Treatment with anti-thyroid therapy and diuretics improved all symptoms, and the free triiodothyronine (T3) level normalized after five days. Hyperthyroidism and heart failure should be considered as reversible causes of CA.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Safe Concurrent Use of Anti-tuberculosis Drugs and Pembrolizumab in a Patient with Non-small-cell Lung Cancer Who Was Infected with Mycobacterium tuberculosis

A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited.