Effects of renin-angiotensin system inhibitor and beta-blocker use on mortality in older patients with heart failure with reduced ejection fraction in Japan.

Introduction: Guideline-directed medical therapy with renin-angiotensin system (RAS) inhibitors and beta-blockers has improved the survival of patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, it is unclear whether RAS inhibitors and beta-blockers can be administered to older patients with HF. Therefore, this study aimed to investigate the effects of beta-blockers and RAS inhibitors on the prognosis of older patients with HFrEF. Methods: Demographic, clinical, and pharmacological data from 1,061 patients with acute decompensated HF, enrolled in the Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI study), were analyzed to assess their impact on mortality. Additionally, a machine learning approach was applied to complement the conventional statistical model for analysis. Patients with HFrEF (n = 314) were divided into the all-cause mortality within 2 years group (n = 80) and the survivor group (n = 234). Results: Overall, 41.1% (129/314) of the patients were aged ≥80, and 25.5% (80/314) experienced all-cause mortality within 2 years. Furthermore, 57.6% (181/314) and 79.0% (248/314) were prescribed RAS inhibitors and beta-blockers, respectively. Our analysis showed that RAS inhibitor use was associated with reduced all-cause mortality and cardiac death in patients with HFrEF of all ages (P < 0.001), and beta-blocker use had an interaction with age. Machine learning revealed that the use of beta-blockers altered the risk of mortality, with a threshold of approximately 80 years of age. Beta-blocker use was associated with lower all-cause mortality and cardiac death in patients with HFrEF aged <80 years (P < 0.001) but not in those aged ≥80 years (P = 0.319 and P = 0.246, respectively). These results suggest that beta blockers may differ in their all-cause mortality benefits according to age. Conclusions: RAS inhibitors prevented all-cause mortality and cardiac death at all ages, whereas beta-blockers had different effects depending on the patient's age. This study suggested that the choice of beta-blockers and RAS inhibitors is more important in older patients with HFrEF than in younger patients with the same condition.

Atractylodes lancea (Thunb.) DC. [Asteraceae] rhizome-derived exosome-like nanoparticles suppress lipopolysaccharide-induced inflammation in murine microglial cells.

Background: Exosome-like nanoparticles (ELNs) mediate interspecies intercellular communications and modulate gene expression. Hypothesis/Purpose: In this study, we isolated and purified ELNs from the dried rhizome of Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR-ELNs), a traditional natural medicine, and investigated their potential as neuroinflammatory therapeutic agents. Methods: ALR-ELN samples were isolated and purified using differential centrifugation, and their physical features and microRNA contents were analyzed through transmission electron microscopy and RNA sequencing, respectively. BV-2 microglial murine cells and primary mouse microglial cells were cultured in vitro, and their ability to uptake ALR-ELNs was explored using fluorescence microscopy. The capacity of ALR-ELNs to modulate the anti-inflammatory responses of these cells to lipopolysaccharide (LPS) exposure was assessed through mRNA and protein expression analyses. Results: Overall, BV-2 cells were found to internalize ALR-ELNs, which comprised three microRNAs (ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p) that could have anti-inflammatory activity. Pretreatment of BV-2 cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide, interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Notably, the mRNA levels of Il1b, Il6, iNos, ccl2, and cxcl10 in BV-2 cells, which increased upon LPS exposure, were significantly reduced following ALR-ELN treatment. Moreover, the mRNA levels of heme oxygenase 1, Irf7, ccl12, and Irg1 also increased significantly following ALR-ELN treatment. In addition, pretreatment of primary mouse microglial cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide. Conclusion: Our findings indicate that ALR-ELNs exhibit anti-inflammatory effects on murine microglial cells. Further validation may prove ALR-ELNs as a promising neuroinflammatory therapeutic agent.

Blood perfusion with polymyxin B immobilized columns in patients with COVID-19 requiring oxygen therapy.

Extracorporeal blood purification with polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP), is reported to be effective in treating COVID-19 pneumonitis with oxygen demand. This multicenter prospective study evaluated the efficacy and safety of PMX-DHP in oxygen-requiring patients with COVID-19 admitted between September 28, 2020, and March 31, 2022. The primary endpoint was the percentage of clinical improvement 15 days after treatment. The secondary endpoint was the percentage of worsened disease status. Data from the COVID-19 patient registry were used for the synthetic control group. The improvement rate on Day 15 did not differ between PMX-treated patients and controls; however, the deterioration rate was 0.38 times lower in the PMX-treated group, and the death rates on Day 29 were 0 and 11.1% in the PMX-treated and control groups, respectively. The PMX group showed a 0.73 times higher likelihood for reduced intensive care demand, as 16.7% of PMX-treated patients and 22.8% of controls worsened. After treatment blood oxygenation improved, urinary ß2-microglobulin and liver-type fatty acid-binding protein showed significant decreases, and IL-6 decreased once during treatment but did not persist. In this study, PMX treatment effectively prevented the worsening of COVID-19 pathology, accompanied by improved oxygenation. PMX treatment to remove activated cells may effectively improve patient outcomes.

Correlation between the thyroid computed tomography value and thyroid function in hyperthyroidism: a retrospective study.

OBJECTIVE: Radioiodine (I-131) therapy for hyperthyroidism is a well-established and safe treatment option. This study aimed to investigate the relationship between the computed tomography (CT) value and the function and volume of the thyroid gland by identifying the factors that induce changes in the CT value of patients with hyperthyroidism. METHODS: This retrospective study evaluated 38 patients with Graves' disease and 10 patients with Plummer disease. To obtain the mean CT value and volume of the thyroid gland, the entire thyroid gland was set as the region of interest. A test dose of 3.7 MBq I-131 was administered before initiating I-131 therapy, and the radioiodine uptake (RIU) rate was assessed after 3, 24, 96, and 168 h. An approximate curve was plotted based on the RIU values obtained, and the effective half-life (EHL) was calculated. The correlation between the mean CT value and the volume of the thyroid gland, 24-h RIU, EHL, and the free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and TSH receptor antibody (TRAb) levels was evaluated. RESULTS: The CT value exhibited a significant positive correlation with EHL in patients with Graves' disease (r = 0.62, p < 0.0001) as well as patients with Plummer disease (r = 0.74, p < 0.05). However, it did not display any correlation with the remaining parameters. CONCLUSION: The CT value is significantly correlated with EHL, suggesting that it reflects thyroid function and is mainly related to the factors associated with iodine discharge.

Prognostic significance of antifibrotic agents in idiopathic pulmonary fibrosis after initiation of long-term oxygen therapy.

BACKGROUND AND AIM: Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with varying degrees of hypoxemia. Long-term oxygen therapy (LTOT) is frequently used to treat hypoxemia, however the prognostic factors for better survival in IPF patients after initiation of LTOT remain unknown. METHODS: We retrospectively investigated favorable factors of survival in consecutive 55 IPF patients with chronic respiratory failure who were introduced LTOT. RESULTS: The 6-, 12-, 18-, and 24-month survival rates in IPF patients after introduction of LTOT were 70.9%, 49.0%, 45.2%, and 32.3%, respectively. Univariate analysis demonstrated that low Glasgow Prognostic Score (GPS) (hazard ratio [HR] 0.482, p=0.043) and treatment with antifibrotic agents (HR 0.401, p=0.013) were associated with favorable survival, while multivariate analysis revealed that treatment with antifibrotic agents was the independent predictor (HR 0.449, p=0.032). Moreover, IPF patients treated with antifibrotic agents with LTOT had significantly longer survival than those without antifibrotic agents (p = 0.0106). CONCLUSION: In IPF patients who were introduced LTOT, treatment with antifibrotic agents was the independent factor for favorable survival. Treatment with antifibrotic agents may improve prognosis of IPF even after initiation of LTOT.

Effective treatment of steroid-resistant immune checkpoint inhibitor pneumonitis with mycophenolate mofetil.

Insufficient evidence is available for treating steroid-resistant immune checkpoint inhibitor pneumonitis (CIP). Although guidelines recommend the use of immunosuppressants, the efficacy of mycophenolate mofetil (MMF) has not been sufficiently verified. We report two cases of steroid-resistant CIP treated with MMF. Both patients responded to initial treatment with prednisolone (PSL), but the CIP flared up repeatedly as the steroids were gradually tapered off. Upon receiving MMF in addition to PSL, their subjective symptoms improved, and the shadows gradually disappeared, allowing for a reduction in the steroid dose. Ultimately, no CIP recurrence was observed despite discontinuing PSL and MMF. Both cases were completely resolved by treatment with MMF. This indicates that MMF may be effective in treating steroid-resistant CIP. In the future, the effects and safety of MMF should be investigated in large-scale clinical trials targeting patients with steroid-resistant CIP.

A simple method to shorten the apparent dead time in the dosimetry of Lu-177 for targeted radionuclide therapy using a gamma camera.

BACKGROUND: The dead-time loss reportedly degrades the accuracy of dosimetry using a gamma camera for targeted radionuclide therapy with Lu-177; therefore, the dead-time loss needs to be corrected. However, the correction is challenging. In this study, we propose a novel and simple method to shorten the apparent dead time rather than correcting it through experiments and Monte Carlo simulations. METHODS: An energy window of 208 keV ± 10 % is generally used for the imaging of Lu-177. Lower-energy gamma photons and X-rays of Lu-177 do not contribute to image formation but lead to dead-time losses. In our proposed method, a thin lead sheet was used to shield gamma photons and X-rays with energies lower than 208 keV, while detecting 208 keV gamma photons that penetrated the thin sheet. We measured and simulated the energy spectra and count rate characteristics of a clinical gamma camera system using a cylindrical phantom filled with a Lu-177 solution. Lead sheets of 1.0- and 0.5-mm thicknesses were used as thin shields, and the dead-time losses in tumour imaging with consumed Lu-177 were simulated. RESULTS: The apparent dead times with lead sheets of 1.0- and 0.5-mm thicknesses and without a lead sheet were 1.7, 1.9, and 5.8 µs for an energy window of 208 keV ± 10 %, respectively. The dead-time losses could be reduced from 10 % to 1.3 % using the 1.0-mm thick lead sheet in the simulated imaging of tumour. CONCLUSION: Our method is promising in clinical situations and studies on Lu-177 dosimetry for tumours.

Posterior Papillary Muscle Suspension for Treating Systolic Anterior Motion in Hypertrophic Obstructive Cardiomyopathy.

Systolic anterior motion of the anterior mitral leaflet can persist after ventricular septal myectomy for obstructive hypertrophic cardiomyopathy, resulting in residual pressure gradients and mitral regurgitation. However, additional procedures for systolic anterior motion involving mitral valve leaflet suturing and resection may lead to future valve disease. Therefore, we adopted posterior papillary muscle suspension, a subvalvular procedure for functional mitral regurgitation, to treat systolic anterior motion without directly intervening in the mitral valve leaflets. Papillary muscle suspension toward the posterior mitral annulus moved the papillary muscles away from the interventricular septum and successfully eliminated the systolic anterior motion and midventricular pressure gradient. In terms of avoiding direct mitral interventions, this procedure is a viable option for systolic anterior motion, especially in cases of very mild mitral regurgitation.

Antipodoplanin antibody enhances the antitumor effects of CTLA-4 blockade against malignant mesothelioma by natural killer cells.

Combination immunotherapy with multiple immune checkpoint inhibitors (ICIs) has been approved for various types of malignancies, including malignant pleural mesothelioma (MPM). Podoplanin (PDPN), a transmembrane sialomucin-like glycoprotein, has been investigated as a diagnostic marker and therapeutic target for MPM. We previously generated and developed a PDPN-targeting Ab reagent with high Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the effects of anti-PDPN Abs on various tumor-infiltrating immune cells and their synergistic effects with ICIs have remained unclear. In the present study, we established a novel rat-mouse chimeric anti-mouse PDPN IgG2a mAb (PMab-1-mG2a ) and its core-fucose-deficient Ab (PMab-1-mG2a -f) to address these limitations. We identified the ADCC and CDC activity of PMab-1-mG2a -f against the PDPN-expressing mesothelioma cell line AB1-HA. The antitumor effect of monotherapy with PMab-1-mG2a -f was not sufficient to overcome tumor progression in AB1-HA-bearing immunocompetent mice. However, PMab-1-mG2a -f enhanced the antitumor effects of CTLA-4 blockade. Combination therapy with anti-PDPN Ab and anti-CTLA-4 Ab increased tumor-infiltrating natural killer (NK) cells. The depletion of NK cells inhibited the synergistic effects of PMab-1-mG2a -f and CTLA-4 blockade in vivo. These findings indicated the essential role of NK cells in novel combination immunotherapy targeting PDPN and shed light on the therapeutic strategy in advanced MPM.

Cryptotanshinone is a candidate therapeutic agent for interstitial lung disease associated with a BRICHOS-domain mutation of SFTPC.

Interstitial lung disease (ILD) represents a large group of diseases characterized by chronic inflammation and fibrosis of the lungs, for which therapeutic options are limited. Among several causative genes of familial ILD with autosomal dominant inheritance, the mutations in the BRICHOS domain of SFTPC cause protein accumulation and endoplasmic reticulum stress by misfolding its proprotein. Through a screening system using these two phenotypes in HEK293 cells and evaluation using alveolar epithelial type 2 (AT2) cells differentiated from patient-derived induced pluripotent stem cells (iPSCs), we identified Cryptotanshinone (CPT) as a potential therapeutic agent for ILD. CPT decreased cell death induced by mutant SFTPC overexpression in A549 and HEK293 cells and ameliorated the bleomycin-induced contraction of the matrix in fibroblast-dependent alveolar organoids derived from iPSCs with SFTPC mutation. CPT and this screening strategy can apply to abnormal protein-folding-associated ILD and other protein-misfolding diseases.

Fenofibrate attenuates the cytotoxic effect of cisplatin on lung cancer cells by enhancing the antioxidant defense system in vitro.

Fenofibrate (FF) is a peroxisome proliferator- activated receptor (PPAR)-α agonist that is widely used for the treatment of hyperlipidemia. It has been shown to have pleiotropic actions beyond its hypolipidemic effect. FF has been shown to exert a cytotoxic effect on some cancer cells when used at higher than clinically relevant concentrations; on the other hand, its cytoprotective effect on normal cells has also been reported. The present study assessed the effect of FF on cisplatin (CDDP) cytotoxicity to lung cancer cells in vitro. The results demonstrated that the effect of FF on lung cancer cells depends on its concentration. FF at ≤50 µM, which is a clinically achievable blood concentration, attenuated CDDP cytotoxicity to lung cancer cells, whereas FF at ≥100 µM, albeit clinically unachievable, had an anticancer effect. The mechanism of FF attenuation of CDDP cytotoxicity involved PPAR-α-dependent aryl hydrocarbon receptor (AhR) expression, which in turn stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production, resulting in lung cancer cell protection from CDDP-evoked oxidative damage. In conclusion, the present study revealed that FF, at clinically relevant concentrations, attenuated CDDP cytotoxicity to lung cancer cells by enhancing the antioxidant defense system through activation of a pathway that involves the PPAR-α-PPAR response element-AhR xenobiotic response element-Nrf2-antioxidant response element. These findings suggested that concomitant use of FF with CDDP may compromise the efficacy of chemotherapy. Although the anticancer property of FF has recently attracted much attention, concentrations that exceed clinically relevant concentrations are required.

Comparative examination of the pons and corpus callosum as reference regions for quantitative evaluation in positron emission tomography imaging for Alzheimer's disease using 11C-Pittsburgh Compound-B.

OBJECTIVES: Standardised uptake value ratio (SUVR) is usually obtained by dividing the SUV of the region of interest (ROI) by that of the cerebellar cortex. Cerebellar cortex is not a valid reference in cases where amyloid ß deposition or lesions are present. Only few studies have evaluated the use of other regions as references. We compared the validity of the pons and corpus callosum as reference regions for the quantitative evaluation of brain positron emission tomography (PET) using 11C-PiB compared to the cerebellar cortex. METHODS: We retrospectively evaluated data from 86 subjects with or without Alzheimer's disease (AD). All subjects underwent magnetic resonance imaging, PET imaging, and cognitive function testing. For the quantitative analysis, three-dimensional ROIs were automatically placed, and SUV and SUVR were obtained. We compared these values between AD and healthy control (HC) groups. RESULTS: SUVR data obtained using the pons and corpus callosum as reference regions strongly correlated with that using the cerebellar cortex. The sensitivity and specificity were high when either the pons or corpus callosum was used as the reference region. However, the SUV values of the corpus callosum were different between AD and HC (p < 0.01). CONCLUSIONS: Our data suggest that the pons and corpus callosum might be valid reference regions.

Automated volume measurement of abdominal adipose tissue from entire abdominal cavity in Dixon MR images using deep learning.

The purpose of this study was to realize an automated volume measurement of abdominal adipose tissue from the entire abdominal cavity in Dixon magnetic resonance (MR) images using deep learning. Our algorithm involves a combination of extraction of the abdominal cavity and body trunk regions using deep learning and extraction of a fat region based on automatic thresholding. To evaluate the proposed method, we calculated the Dice coefficient (DC) between the extracted regions using deep learning and labeled images. We also compared the visceral adipose tissue (VAT) and subcutaneous adipose tissue volumes calculated by employing the proposed method with those calculated from computed tomography (CT) images scanned on the same day using the automatic calculation method previously developed by our group. We implemented our method as a plug-in in a web-based medical image processing platform. The DCs of the abdominal cavity and body trunk regions were 0.952 ± 0.014 and 0.995 ± 0.002, respectively. The VAT volume measured from MR images using the proposed method was almost equivalent to that measured from CT images. The time required for our plug-in to process the test set was 118.9 ± 28.0 s. Using our proposed method, the VAT volume measured from MR images can be an alternative to that measured from CT images.

Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study.

BACKGROUND: Polymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of systemic inflammatory response syndrome caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. The SARS-CoV-2 virus causes COVID-19, which emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity, and prolonged prothrombin time were significant factors in nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes, and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible. OBJECTIVE: This study aims to access treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leukocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia. METHODS: We will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 6 on day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia. RESULTS: The study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023. CONCLUSIONS: From a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37426.

Development of a high-resolution two-dimensional detector-based dose verification system for tumor-tracking irradiation in the CyberKnife system.

We aim to evaluate the basic characteristics of SRS MapCHECK (SRSMC) for CyberKnife (CK) and establish a dose verification system using SRSMC for the tumor-tracking irradiation for CK. The field size and angular dependence of SRSMC were evaluated for basic characterization. The output factors (OPFs) and absolute doses measured by SRSMC were compared with those measured using microDiamond and microchamber detectors and those calculated by the treatment planning system (TPS). The angular dependence was evaluated by comparing the SRSMC with a microchamber. The tumor-tracking dose verification system consists of SRSMC and a moving platform. The doses measured using SRSMC were compared with the doses measured using a microchamber and radiochromic film. The OPFs and absolute doses of SRSMC were within ±3.0% error for almost all field sizes, and the angular dependence was within ±2.0% for all incidence angles. The absolute dose errors between SRSMC and TPS tended to increase when the field size was smaller than 10 mm. The absolute doses of the tumor-tracking irradiation measured using SRSMC and those measured using a microchamber agreed within 1.0%, and the gamma pass rates of SRSMC in comparison with those of the radiochromic film were greater than 95%. The basic characteristics of SRSMC for CK presented acceptable results for clinical use. The results of the tumor-tracking dose verification system realized using SRSMC were equivalent to those of conventional methods, and this system is expected to contribute toward improving the efficiency of quality control in many facilities.

Verification of morphological and physical properties for the development of a lung substitute phantom using microspheres.

This paper proposes a new concept of phantom development, along with the utilization of new materials that can reproduce lung morphology and density. A lung substitute phantom using microspheres was fabricated; then, its dosimetric utility in radiotherapy was investigated, during which the density was adjusted to closely resemble the morphology of the actual human lung. Microspheres were used to reproduce alveoli, which are the main components of the lung. By changing the ratio of urethane, which is commonly used in soft tissue phantoms, to microspheres, we reproduced the density change of the lungs due to respiration. Here, we fabricated two slab-like lung substitutes to emulate commercially used phantoms. Although there is room for improvement in terms of practicality, the substitutes were easy to fabricate. Microscopic observation of the cut surface of the phantoms showed that the morphology of the phantoms mimicked the alveoli more faithfully than commercial phantoms. Furthermore, to compensate for the energy-independent mass attenuation and mass collision inhibition ability required by the tissue substitute phantom, we examined the physical properties of the phantom and confirmed that there was negligible energy dependence.

Double-ring sign in granulocyte colony-stimulating factor-induced vasculitis.

The double-ring sign found in contrast-enhanced computed tomography, which reflects inflammatory changes in the adventitia and oedema of the intima, is thought to be characteristic of Takayasu arteritis; however, herein, it was also observed for granulocyte colony-stimulating factor-induced vasculitis.

Surfactant protein D: A useful biomarker for distinguishing COVID-19 pneumonia from COVID-19 pneumonia-like diseases.

Introduction: Computed tomography is useful for the diagnosis of coronavirus disease (COVID-19) pneumonia. However, many types of interstitial lung diseases and even bacterial pneumonia can show abnormal chest shadows that are indistinguishable from those observed in COVID-19 pneumonia. Thus, it is necessary to identify useful biomarkers that can efficiently distinguish COVID-19 pneumonia from COVID-19 pneumonia-like diseases. Herein, we investigated the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein D (SP-D) for identifying patients with COVID-19 pneumonia among patients with abnormal chest shadows consistent with COVID-19 pneumonia. Method: This was a retrospective cohort study of consecutive patients who underwent evaluation of serum KL-6 and SP-D at a single center from February 2019 to December 2020. A total of 54 patients with COVID-19 pneumonia and 65 patients with COVID-19 pneumonia-like diseases were enrolled in this study from the source population. Serum KL-6 and SP-D levels in both groups were analyzed. Result: The serum levels of KL-6 and SP-D in patients with COVID-19 pneumonia were significantly lower than those in patients with COVID-19 pneumonia-like disease (median [interquartile range]: 208.5 [157.5-368.5] U/ml vs. 430 [284.5-768.5] U/ml, p < 0.0001 and 24.7 [8.6-51.0] ng/ml vs. 141 [63.7-243.5] ng/ml, p < 0.0001, respectively). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curves (95% confidence intervals) of serum KL-6 and SP-D levels for distinguishing COVID-19 pneumonia from COVID-19 pneumonia-like diseases were 0.761 (0.675-0.847) and 0.874 (0.812-0.936), respectively. The area under the ROC curve of serum SP-D was significantly larger than that of serum KL-6 (p = 0.0213), suggesting that serum SP-D can more efficiently distinguish COVID-19 pneumonia from COVID-19 pneumonia-like diseases. Conclusion: Serum SP-D is a promising biomarker for distinguishing COVID-19 pneumonia from COVID-19 pneumonia-like diseases. Serum SP-D can be useful for the management of patients with abnormal chest shadow mimicking COVID-19 pneumonia.

Mouthpiece polymer-gel dosimeter for in vivo oral dosimetry during head and neck radiotherapy.

In this study, we developed a mouthpiece-type gel dosimeter to prevent the oral mucositis caused by the perturbation effect of dental alloys in the radiotherapy of the head and neck regions and to enable in vivo dosimetry. Understanding the dose distribution in the oral cavity during radiotherapy helps identify the possible site for oral mucositis during treatment. Here agarose, which has a higher melting point than gelatin, was added as a coagulant to stabilize the shape of the dosimeter. The strength and dose response of the dosimeter were investigated. The strength was measured at room temperature, 20°C-40 °C, which is higher than the intraoral temperature. The dose-response curves were obtained by magnetic resonance imaging with R2 ranging from 0 to 25 Gy. The strength and dose response of the mouthpiece-type gel dosimeter were approximately 4 and 2.1 times higher than those of polyacrylamide gel and tetrakis hydroxymethyl phosphonium chloride dosimeters commonly used in the prescribed doses per fraction of treatment. The dosimeter is composed of 4 wt% MgCl2 and 1.5 wt% agarose; thus, it can retain the water equivalence. Through in vivo oral dosimetry in three dimensions for head and neck radiotherapy with dental alloys using the mouthpiece-type gel dosimeter, we obtained three-dimensional dose distributions in the dosimeter. The properties of the dosimeter show that it can be used in the clinic, depending on the prescribed dose.