Background The mortality rate of Coronavirus disease 2019 (COVID-19) is extremely high in hemodialysis patients (HDP). These patients also develop lower antibody titers after vaccination. Therefore, factors associated with antibody titers and vaccine efficacy in HDP with breakthrough infection need to be investigated. Methods We measured anti-S1 antibody titers in HDP (n = 104) and controls (n = 35), evaluating the influence of background on HDP by multivariable regression analysis. We classified 26 HDP patients admitted with COVID-19 into the unvaccinated (n = 15) and breakthrough infection group (n = 11), performing between-group comparisons of laboratory findings and prognosis. Vaccinated COVID-19 patients were classified into HDP and non-HDP controls, and compared the relationship between antibody titer and severity, and the prognosis of breakthrough infection. ResultsThe antibody titer was significantly lower in the HDP group than in the control group. Among HDP, age and smoking history were significantly independent factors associated with antibody titer. The breakthrough infection group had significantly better laboratory findings (KL-6 and LDH), severity, and hospitalization period than the unvaccinated group even if antibody titers were lower than the known threshold for neutralization (p < 0.05). There was no significant difference in prognosis between the HDP and non-HDP with breakthrough infection. Severity of COVID-19 tended to be higher with lower antibody titer in non-HDP, but not in HDP. Conclusion Vaccines improved the severity of COVID-19 and hospitalization period of breakthrough infection in HDP, although HDP, especially in elderly smokers had lower antibody titers than control. There was no significant association between antibody titer and severity in HDP.

Background Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers. Methods Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers. Results Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination (p < 0.0001), 2 weeks after second vaccination (p = 0.0002), and 3 months after the second vaccination (p = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control (p = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group (p = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group (p = 0.039 and p = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p = 0.0383, Control: p = 0.0096). Conclusion HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers.

Recent studies have reported an association between myopia development and local ocular inflammation. Lactoferrin (LF) is an iron-binding protein present in saliva, tears, and mother’s milk. Furthermore, sequestering iron by LF can cause its antibacterial property. Moreover, LF has an anti-inflammatory effect. We aimed to determine the suppressive effect of LF against the development and progress of myopia using a murine lens-induced myopia (LIM) model. We divided male C57BL/6J mice (3 weeks old) into two groups. While the experimental group was orally administered LF (1600 mg/kg/day, from 3-weeks-old to 7-weeks-old), a similar volume of Ringer’s solution was administered to the control group. We subjected the 4-week-old mice to −30 diopter lenses and no lenses on the right and left eyes, respectively. We measured the refraction and the axial length at baseline and 3 weeks after using a refractometer and a spectral domain optical coherence tomography (SD-OCT) system in both eyes. Furthermore, we determined the matrix metalloproteinase-2 (MMP-2) activity, and the amount of interleukin-6 (IL-6), MMP-2, and collagen 1A1 in the choroid or sclera. The eyes with a minus lens showed a refractive error shift and an axial length elongation in the control group, thus indicating the successful induction of myopia. However, there were no significant differences in the aforementioned parameters in the LF group. While LIM increased IL-6 expression and MMP-2 activity, it decreased collagen 1A1 content. However, orally administered LF reversed these effects. Thus, oral administration of LF suppressed lens-induced myopia development by modifying the extracellular matrix remodeling through the IL-6–MMP-2 axis in mice.

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Background Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. Methods From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. Results Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0–1 L/min within 3 weeks post-administration. Conclusion TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.

Regenerative medicine and anti-tumoral therapy have been developed through understanding tissue stem cells and cancer stem cells (CSCs). The concept of tissue stem cells has been applied to the pituitary gland (PG). Recently, PG stem cells (PGSCs) were successfully differentiated from human embryonic stem cells and induced pluripotent stem cells, showing an in vivo therapeutic effect in a hypopituitary model. Pituitary adenomas (PAs) are common intracranial neoplasms that are generally benign, but treatment resistance remains a major concern. The concept of CSCs applies to PA stem cells (PASCs). Genetic alterations in human PGSCs result in PASC development, leading to treatment-resistant PAs. To determine an efficient treatment against refractory PAs, it is of paramount importance to understand the relationship between PGSCs, PASCs and PAs. The goal of this review is to discuss several new findings about PGSCs and the roles of PASCs in PA tumorigenesis.

Background We experienced that some hemodialysis (HD) patients with coronavirus disease 2019 (COVID-19) exacerbated hypoxemia during HD. Though HD-induced hypoxemia has been reported, there have been no reports of HD-induced hypoxemia in patients with COVID-19 and its effect on prognosis of COVID-19. Methods Eleven HD patients admitted with COVID-19 from August 2020 to April 2021 were classified into the patients whose oxygen demand increased by more than 3 L/min with mask during HD (worsened group, n = 5) and others (not-worsened group, n = 6). The background, laboratory findings, severity of COVID-19 and prognosis were compared between the two groups. In addition, blood gases were measured before and after dialysis among HD patients admitted with COVID-19 on April 2021 (n = 3). Results There were no significant differences in backgrounds, except for a higher proportion of diabetes mellitus in worsened group (p = 0.04). Although laboratory findings were not significantly different on admission day, albumin and LDH levels 7 days after admission were significantly lower and higher in worsened group, respectively (p = 0.03 and < 0.01). The severity of COVID-19 and survival rate were significantly worse in worsened group (p = 0.01 and 0.03). The alveolar-arterial oxygen pressure difference (Aa-DO2) opened during HD in a patient with HD-induced hypoxemia, but did not open in patients without HD-induced hypoxemia. Conclusions There is a close relationship among HD-induced hypoxemia and poor prognosis of COVID-19. The HD-induced hypoxemia of patients with COVID-19 may be caused by ventilation/perfusion mismatching.

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