Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti‐topoisomerase I‐positive systemic sclerosis‐associated interstitial lung disease

Systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is the most frequent cause of death for SSc but there is still no sufficient treatment available. Although cyclophosphamide (CYC) therapy is a common treatment which has shown statistical efficacy against SSc‐ILD to date, its effects are temporary and not enough. Rituximab (RTX), the anti‐CD20 monoclonal antibody, has recently shown efficacy in many autoimmune diseases. In SSc‐ILD, RTX is also considered to be one of the novel treatment candidates. However, studies of SSc‐ILD in Japanese treated with RTX have only a few case reports. Therefore, in this study, we retrospectively compared nine patients treated with RTX and 30 patients treated with CYC to investigate the efficacy of RTX treatment for Japanese anti‐topoisomerase I‐positive SSc‐ILD patients. At the 24‐month evaluation, the improvement rates of percent predicted of forced vital capacity and percent predicted of diffusing capacity of the lung carbon monoxide in the RTX‐treated group were significantly higher than those in the CYC‐treated group (20.6 ± 8.8% vs 1.1 ± 3.9%; P < 0.05 and 34.0 ± 6.0% vs ?1.5 ± 2.8%; P < 0.01, respectively). In addition, skin thickness scores also showed a marked improvement from 13.5 points before the start of treatment to 5.8 points after 24 months by RTX therapy (P < 0.05). These results suggest that RTX treatment is more effective for Japanese SSc‐ILD patients than CYC treatment. In the future, it is expected that large‐scale clinical trials will show the usefulness of RTX treatment for SSc‐ILD.     

Efficacy of local therapy for oligoprogressive disease after programmed cell death 1 blockade in advanced non‐small cell lung cancer

Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option.     

Copeptin concentration following cardiac surgery as a prognostic marker of postoperative acute kidney injury: a prospective cohort study

BackgroundCopeptin, the C-terminal portion of the arginine vasopressin precursor, is a novel candidate biomarker. This study investigated the prognostic value of copeptin levels following cardiac surgery for the occurrence of postoperative acute kidney injury.MethodsWe studied 23 patients who underwent cardiac surgery between January 2018 and December 2019. The primary endpoint was postoperative acute kidney injury onset. Copeptin levels were measured before, right after, and daily for 7 days. The patients were divided into two groups according to the copeptin levels: low (values <43.7 pmol/L) and high (values ≥43.7 pmol/L). Correlations between copeptin levels and variables, such as central venous pressure, were assessed by bivariate analysis.ResultsThe high copeptin group exhibited significantly higher levels of arginine vasopressin and cortisol following surgery, compared to those of the low copeptin group. The copeptin concentration following surgery was correlated to central venous pressure (P=0.03) and norepinephrine administered dose (P=0.008). Also, the copeptin levels right after surgery robustly predicted the onset of postoperative acute kidney injury (area under the receiver operating characteristic curve of 0.83, P=0.004).ConclusionsElevated copeptin levels in patients following cardiac surgery predicted postoperative acute kidney injury development. Therefore, the copeptin concentration after surgery could represent a promising clinical biomarker of the postoperative cardiac outcome.     

Coffin-Siris syndrome with bilateral macular dysplasia caused by a novel exonic deletion in ARID1B

Coffin-Siris syndrome (CSS) is a congenital anomaly syndrome characterized by developmental delay, coarse facial features, and hypoplasia of the fifth digit's nail or phalanges. Herein, we report a case of the 8-year-old female patient who showed developmental delay associated with dysplasia in the macular and large toe area. Comprehensive genomic analysis showed no possible candidate variants, but the subsequent genomic copy number analysis revealed a novel exonic deletion in the coding region of AT-rich interactive domain-containing protein 1B (ARID1B), a gene responsible for CSS. Genomic copy number analysis can aid in diagnosing CSS by confirming undiagnosed exonic deletions in ARID1B. Furthermore, this is the first report of CSS associated with bilateral macular dysplasia.     

Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.