Search

Abstract Background Alpha blockers (ABs) are frequently prescribed to patients with chronic kidney disease (CKD), which is often complicated by refractory hypertension (HT). Although there have been several reports on the association between AB use and the risk of fractures, their conclusions have not yet been drawn. Therefore, this study aimed to investigate the association between AB use and the risk of fractures in patients with CKD. Method This population-based cohort study used patient data obtained between April 2008 and August 2021 from a large-scale Japanese medical claims database. Consecutive patients with CKD who were newly prescribed ABs or non-AB antihypertensive drugs were included; males and females were analysed separately. The AB group was then divided into AB for HT and voiding dysfunction (VD) groups according to the drug approval in Japan. The primary outcome was the first hospitalisation due to fracture, and the variables were evaluated with weighted Cox proportional hazard model using overlap weights. Results A total of 65,012, 4,723, and 10,958 males constituted the non-AB, AB for HT (doxazosin), and AB for VD (naftopidil, silodosin, tamsulosin, or urapidil) groups, respectively. A total of 31,887, 2,409, and 965 females constituted the non-AB, AB for HT (doxazosin or guanabenz), and AB for VD (urapidil) groups, respectively. In males, hazard ratio (HR) for primary outcome was not increased in the non-AB and AB for VD groups compared with the AB for HT group (HR, 0.70; 95% confidence interval [CI], 0.38–1.28 and HR, 1.33; 95% CI, 0.67–2.66, in the non-AB and AB for VD groups, respectively). Whereas, in females, although HR for the primary outcome was not increased in the non-AB group (HR, 1.06; 95% CI, 0.56–1.99), it was significantly increased in the AB for VD group (HR, 2.28; 95% CI, 1.01–5.16) compared with the AB for HT group. Conclusion AB use in patients with CKD did not increase the risk of fractures when used for the treatment of HT; however, it increased the risk of fractures when used for the treatment of VD in females. These results suggest that ABs should be used with caution in these patients.

Abstract Background The treatment of membranous nephropathy involves a combination of conservative approaches, steroids, and immunosuppressive agents. Infection is an adverse effect of these treatments and its incidence is a critical issue for patients with membranous nephropathy, as many of them are older adults. However, the incidence of infections remains unclear; hence, this study investigated this issue using data from a large Japanese clinical claims database. Methods From a database of patients with chronic kidney disease (n = 924,238), those diagnosed with membranous nephropathy from April 2008 to August 2021 with a history of one or more prescriptions and undergoing medical care were included. Patients who had undergone kidney replacement therapy were excluded. Patients were divided into three groups based on their prescriptions after diagnosis: prednisolone(PSL), who received steroids; PSL + IS, who were prescribed steroids and immunosuppressive agents; and C, who were treated without steroid or immunosuppressive agent use. The primary outcome was death or the initiation of kidney replacement therapy. The secondary outcome was death or hospitalization due to infection. Infectious diseases such as sepsis, pneumonia, urinary tract infections, cellulitis, cytomegalovirus infection, colitis, or hepatitis were defined as infections. Hazard ratios were expressed using group C as a reference. Results Of 1,642 patients, the incidence of the primary outcome occurred in 62/460 individuals in the PSL group, 81/635 individuals in the PSL + IS group, and 47/547 individuals in the C group. The Kaplan–Meier survival curve showed no significant differences (P = 0.088). The incidence of secondary outcomes occurred in 80/460 individuals, 102/635 individuals, and 37/547 individuals in the PSL, PSL + IS, and C groups, respectively. The incidence of secondary outcomes was significantly higher in the PSL group (hazard ratio [HR] 2.43 [95% confidence interval [CI] 1.64–3.62, P

Abstract Background Combinatorial gene regulation by multiple microRNAs (miRNAs) is widespread and closely spaced target sites often act cooperatively to achieve stronger repression (“neighborhood” miRNA cotargeting). While miRNA cotarget sites are suggested to be more conserved and implicated in developmental control, the pathological significance of miRNA cotargeting remains elusive. Results Here, we report the pathogenic impacts of combinatorial miRNA regulation on inflammation in systemic lupus erythematosus (SLE). In the SLE mouse model, we identified the downregulation of two miRNAs, miR-128 and miR-148a, by TLR7 stimulation in plasmacytoid dendritic cells. Functional analyses using human cell lines demonstrated that miR-128 and miR-148a additively target KLF4 via extensively overlapping target sites (“seed overlap” miRNA cotargeting) and suppress the inflammatory responses. At the transcriptome level, “seed overlap” miRNA cotargeting increases susceptibility to downregulation by two miRNAs, consistent with additive but not cooperative recruitment of two miRNAs. Systematic characterization further revealed that extensive “seed overlap” is a prevalent feature among broadly conserved miRNAs. Highly conserved target sites of broadly conserved miRNAs are largely divided into two classes—those conserved among eutherian mammals and from human to Coelacanth, and the latter, including KLF4-cotargeting sites, has a stronger association with both “seed overlap” and “neighborhood” miRNA cotargeting. Furthermore, a deeply conserved miRNA target class has a higher probability of haplo-insufficient genes. Conclusions Our study collectively suggests the complexity of distinct modes of miRNA cotargeting and the importance of their perturbations in human diseases.

Abstract Background Femoral neck stress fractures are rare and often recognized as overuse injuries that occur in young athletes or military personnel. A case following osteonecrosis of the femoral head is quite rare; even more uncommon is its occurrence in the bilateral hips. Magnetic resonance imaging has been established as the preferred tool for diagnosing nondisplaced femoral neck stress fracture due to overuse injury. Magnetic resonance imaging was also useful to detect the initial lesion even in this case, although the etiology was different between overuse injury and insufficiency fracture. Case presentation A 41-year-old Japanese woman diagnosed with bilateral early stage idiopathic osteonecrosis of the femoral head was observed non-weight-bearing as much as possible using a stick. However, her pain and difficulty in walking progressed. Bilateral femoral neck stress fractures were subsequently detected by magnetic resonance imaging. The fracture initially appeared as a spot of bone marrow edema at the medial site of the femoral neck, and then developed into a fracture line. The patient underwent internal fixation of both hips with sliding hip screws to stabilize the stress fractures. In addition, the preparatory reaming served as core decompression of the femoral heads, as well as being treatment for osteonecrosis. Her bone mineral density and 25-hydroxy vitamin D values were low for her age. We administered eldecalcitol and teriparatide acetate. Her symptoms mostly improved, and the fracture lines and necrotic lesions on magnetic resonance imaging reduced at 5 months after the surgery. Conclusions Bilateral femoral neck stress fractures are a very rare condition and are often missed. It is important to listen to the patient’s complaints and perform an appropriate examination. We encountered a case of bilateral femoral neck stress fracture that occurred in a patient with early stage osteonecrosis of the femoral head, and were able to observe progression of stress fracture since before fracture occurred. This is considered to be the first report to capture imaging changes before and after the onset.

Abstract Background Sepsis is a systemic inflammatory response syndrome caused by infectious disease. Severe sepsis and septic shock are extremely serious conditions with poor prognoses. It is reported that cytokines are deeply involved in the disease mechanism. Continuous hemodiafiltration (CHDF) using a poly(methyl methacrylate) (PMMA) membrane is reported to adsorb various cytokines and improve the status of patients with sepsis. Recently, another cytokine-adsorbing hemofilter, acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane, has become available for CHDF in patients with sepsis. However, the clinical efficacy of this membrane remains unclear. Therefore, in this study, we compared the efficacy of AN69ST and PMMA membranes. Methods This retrospective study included patients with severe sepsis or septic shock who underwent CHDF for at least 24 h in the intensive care unit from January 2013 to August 2016. Results This study included 49 patients who underwent CHDF, 32 using an AN69ST membrane and 17 using a PMMA membrane. In the AN69ST and PMMA groups, average age was 71.1 ± 11.4 years and 74.7 ± 9.4 years, respectively, and percentage of men was 71.9 and 88.2%, respectively. Severity of sepsis and vital signs were not significantly different between groups at the start of CHDF. In addition, 28-day mortality was not significantly different between groups (43.8 vs. 35.3%, P = 0.1625). However, heart rate in the AN69ST group decreased significantly early in the course of CHDF (6, 12, and 24 h, P