Non-severe Serovar Type E Capnocytophaga canimorsus Infection in a Post-splenectomy Male: A Case Report.

Capnocytophaga canimorsus (CP) causes severe infections in immunocompromised individuals. Three serovars (A, B, and C) are known to be responsible for more than 90% of infections associated with dog bites, although these three constitute only 8% of the serovars carried by dogs. We experienced a post-splenectomy non-severe case of CP withserovar type E, which has never been isolated in Japan. The prognosis of type E CP infections may be better than that of types A, B, and C infections because of the disproportion of serovars between clinical human isolates and dog oral isolates.

Effect of Past Chlamydophila pneumoniae Infection on the Short-Time Mortality of COVID-19: A Retrospective Cohort Study.

BACKGROUND: Although Chlamydophila pneumoniae (CP)is known to play a role in atherosclerosis and endothelial injury, its past infection on the mortality of coronavirus disease 2019 (COVID-19), which was also reported to be a vascular disease, remains unknown. METHODS: In this retrospective cohort study, we examined 78 COVID-19 patients and 32 bacterial pneumonia patients who visited a tertiary emergency center in Japan between April 1, 2021, and April 30, 2022. CP antibody levels, including IgM, IgG, and IgA, were measured. RESULTS: Among all patients, the CP IgA-positive rate was significantly associated with age (P = 0.002). Between the COVID-19 and non-COVID-19 groups, no difference in the positive rate for both CP IgG and IgA was observed (P = 1.00 and 0.51, respectively). The mean age and proportion of males were significantly higher in the IgA-positive group than in the IgA-negative group (60.7 vs. 75.5, P = 0.001; 61.5% vs. 85.0%, P = 0.019, respectively). Smoking and dead outcomes were significantly higher both in the IgA-positive group and IgG-positive group (smoking: 26.7% vs. 62.2, P = 0.003; 34.7% vs. 73.1%, P = 0.002, dead outcome: 6.5% vs. 29.8%, P = 0.020; 13.5% vs. 34.6%, P = 0.039, respectively). Although the log-rank test revealed higher 30-day mortality in the IgG-positive group compared to the IgG-negative group (P = 0.032), Cox regression analysis demonstrated no significant difference between the IgG-positive and negative groups (hazard ratio (HR) = 4.10, 95%CI = 0.94-18.0, P = 0.061). CONCLUSION: The effect of past CP infection on 30-day mortality in COVID-19 patients was not obvious.

A case of hemorrhagic shock in a patient with neurofibromatosis type 1.

Complications of neurofibromatosis type 1 include fatal bleeding events due to vascular fragility. In this case of hemorrhagic shock due to a neurofibroma, the bleeding was controlled using an occlusion balloon and endovascular treatment which stabilized the patient. Systemic vascular investigation for bleeding sites is important to prevent fatal outcomes.

Utility of dual-energy computed tomography in the association of COVID-19 pneumonia severity.

Aim: Coronavirus disease 2019 pneumonia differs from ordinary pneumonia in that it is associated with lesions that reduce pulmonary perfusion. Dual-energy computed tomography is well suited to elucidate the etiology of coronavirus disease 2019 pneumonia, because it highlights changes in organ blood flow. In this study, we investigated whether dual-energy computed tomography could be used to determine the severity of coronavirus disease 2019 pneumonia. Methods: Patients who were diagnosed with coronavirus disease 2019 pneumonia, admitted to our hospital, and underwent dual-energy computed tomography were included in this study. Dual-energy computed tomography findings, plane computed tomography findings, disease severity, laboratory data, and clinical features were compared between two groups: a critical group (18 patients) and a non-critical group (30 patients). Results: The dual-energy computed tomography results indicated that the percentage of flow loss was significantly higher in the critical group compared with the non-critical group (P < 0.001). Additionally, our data demonstrated that thrombotic risk was associated with differences in clinical characteristics (P = 0.018). Receiver operating characteristic analysis revealed that the percentage of flow loss, evaluated using dual-energy computed tomography, could predict severity in the critical group with 100% sensitivity and 77% specificity. However, there were no significant differences in the receiver operating characteristic values for dual-energy computed tomography and plane computed tomography. Conclusion: Dual-energy computed tomography can be used to associate the severity of coronavirus disease 2019 pneumonia with high accuracy. Further studies are needed to draw definitive conclusions.

Acute pancreatitis caused by duodenal bezoar and treated with endoscopic procedures.

Background: Acute pancreatitis triggered by causative agents, including alcohol consumption, gallstones, dyslipidemia, drugs, and infection, is frequently addressed. However, reports of acute pancreatitis caused by duodenal bezoars are limited. Case Presentation: A 75-year-old man experiencing abdominal pain and frequent vomiting was transferred to our hospital. His medical records presented history of diabetes, hypertension, dyslipidemia, and gastric cancer surgery. Computed tomography of the abdomen indicated duodenal dilatation, enlarged pancreas, and fluid retention, with no bile duct stones present. Minor bleeding and duodenal bezoar were endoscopically detected with esophagogastroduodenoscopy (EGD). He was diagnosed with severe acute pancreatitis caused by a bezoar and admitted to the intensive care unit. The duodenal bezoar was dissected and removed with three repetitions of EGD, and the patient was discharged without any complications. Conclusion: Herein, we report a case showing that endoscopic procedures could be effective treatment options in severe pancreatitis caused by duodenal bezoars.

Lemierre's Syndrome as a Sexually Transmitted Disease Due to Porphyromonas asaccharolytica Suspected to Be Caused by Pharyngitis Due to Mycoplasma pneumoniae and Epstein-Barr Virus.

Porphyromonas asaccharolytica rarely causes Lemierre's syndrome (LS), which is characterised by sepsis and thrombophlebitis of the internal jugular vein. An 18-year-old man presented with fever and a sore throat after sexual contact containing oral sex, and his blood sample was positive for atypical lymphocytes. Infectious mononucleosis was suspected initially. However, laboratory data showed elevated D-dimer and procalcitonin levels, and a computed tomography scan showed a thrombus in the internal jugular vein leading to the diagnosis of LS. The Mycoplasma pneumoniae (MP) IgM titre was 1:640 (normal, ≦1:40), and the Epstein-Barr nuclear antigen titre (taken 59 days after admission) was 1:10 (normal, <1:10). It was assumed that LS developed after infection with Epstein-Barr virus (EBV) and MP. LS should be suspected in young patients with fever and sore throat with a history of recent sexual contact. As pharyngitis was considered the cause of LS, evaluation of the preceding infection such as MP or EBV leading to pharyngitis should also be considered.

Methylprednisolone pulse therapy for critically ill patients with coronavirus disease 2019: A single-center retrospective observational study.

Aim: This study compared the clinical outcomes of critically ill patients with coronavirus disease (COVID-19) pneumonia treated with high-dose methylprednisolone and other steroids. Methods: This retrospective observational study included critically ill COVID-19 pneumonia adult patients with tracheal intubation treated between April 1, 2020, and September 15, 2021. Of the 46 patients who met the inclusion criteria, 36 received steroid pulse therapy (Group P) and 10 received steroids without pulse therapy (Group NP). Subgroup analyses in Group P by methylprednisolone dose of 1000 or 500 mg for 3 days during intensive care unit stay were carried out. The primary and secondary outcomes were 28-day mortality and steroid-associated complications, respectively. Results: In the Kaplan-Meier curve analysis, there was no difference in the 28-day survival between P and NP groups (log-rank P = 0.046). Univariate Cox proportional hazard model also showed that Group P had a decreased 28-day mortality (hazard ratio 0.30; [95% confidence interval, 0.20-0.44]; P < 0.01). After adjusting for covariates (age, sex, remdesivir, baricitinib, and favipiravir), using the multivariate Cox proportional hazards model, Group P had improved 28-day mortality (0.50 [0.30-0.85], P = 0.01). Conclusion: Steroid pulse therapy might improve the 28-day and in-hospital mortality in critically ill patients with COVID-19 pneumonia.

Early-Onset Drug Hypersensitivity Syndrome in a Man With Pneumonia Due to Pre-sensitization to Olanzapine.

Drug hypersensitivity syndrome (DHS) generally starts two weeks to two months after administration of certain drugs. Olanzapine has been reported to cause drug reaction with eosinophilia and systemic symptoms (DRESS), but rarely causes drug-induced hypersensitivity syndrome (DIHS). A 49-year-old schizophrenic man was hospitalized for pneumonia and developed DIHS/DRESS 10 days after starting olanzapine. Although reactivation of human herpesvirus 6, which is one of the diagnostic criteria for DIHS, was not confirmed, the diagnostic criteria for DRESS were met. The patient may have developed early-onset DIHS/DRESS because he was sensitized to olanzapine prior to hospitalization.

Chronic Pulmonary Aspergillosis During Convalescence From Severe COVID-19 Treated With Oral Itraconazole: A Report of Two Cases.

Invasive pulmonary aspergillosis (IPA) has been reported to occur secondary to coronavirus disease 2019 (COVID-19), and the condition has been termed COVID-19-associated pulmonary aspergillosis (CAPA). We diagnosed two severe COVID-19 cases with multiple cavitary lung lesions and chronic pulmonary aspergillosis (CPA) on days 58 and 48 of admission, respectively, with gradual improvement in the respiratory status. Both patients were positive for Aspergillus-precipitating antibodies (APAb). We chose oral itraconazole (ITCZ) for both patients because of its convenience in terms of long-term treatment. Cavitary lesions diminished after ITCZ administration. The risk factors for pulmonary aspergillosis in both patients were determined to be steroid pulse therapy, use of baricitinib, diabetes mellitus (DM), ICU admission, long hospital stay, and the use of broad-spectrum antibiotics. Pulmonary aspergillosis must be suspected in patients with severe COVID-19, even if they are asymptomatic, because not only IPA but also CPA can occur following COVID-19. Therefore, oral ITCZ may be a treatment option for CPA following COVID-19.

Awake intubation with videolaryngoscopy and fiberoptic bronchoscope.

By combining video laryngoscopy and fiberoptic bronchoscopy, awake intubation can be performed more safely.

Mechanism of jet injector-induced plasmid DNA uptake: Contribution of shear stress and endocytosis.

The administration of plasmid DNA (pDNA) using a pyro-drive jet injector allows gene expression in cells of the treated tissue; however, the detailed plasmid uptake process remains to be determined. A recent theory suggests that shear stress enhances the endocytosis pathway and pDNA internalization. Here, we investigated the process of pDNA uptake in the context of a pyro-drive jet injector-based administration as a way to optimize gene transfer efficiency via the increase in DNA uptake. The gene expression was significantly improved when the shear stress caused by the jet was generated where the pDNA was retained. Contrarily, heparin, an inhibitor of the spontaneous uptake of injected DNA, inhibited the gene expression in jet injection. In addition, treatment with typical endocytosis inhibitors (chlorpromazine, methyl-ß-cyclodextrin, dimethyl amiloride, rottlerin, and NSC23766) also reduced plasmid expression efficiency in the context of jet injection; conversely, endosome escape in the context of chloroquine treatment increased the expression efficiency. Altogether, our results not only clarify the mechanism of pDNA uptake in the context of jet injection but also highlight the key role of endosomes on the intracellular trafficking of pDNA. Importantly, such findings may impact other studies on gene transfer and endocytosis and boost further efforts to improve the efficiency and safety of jet injection in the context of both basic and translational applications.

Two cases of post-traumatic inferior vena cava thrombosis.

BACKGROUND: Inferior vena cava thrombosis is a rare blunt abdominal trauma complication often associated with severe liver injury. We present two cases of inferior vena cava thrombosis due to mild liver injuries. CASE PRESENTATION: Case 1 was a 25-year-old woman taking oral contraceptives for dysmenorrhea who was injured in a motorcycle accident. Contrast-enhanced computed tomography revealed hepatic contusion of the sixth segment. At 1 week after the accident, inferior vena cava thrombosis was detected. Case 2 was a 58-year-old man injured in a motorcycle accident. Contrast-enhanced computed tomography showed traumatic subarachnoid hemorrhage, right hemothorax, and liver injury with hepatic contusion of the sixth segment. At 1 week after the accident, inferior vena cava thrombosis was observed. CONCLUSION: Inferior vena cava thrombosis can occur following liver injury, regardless of damage severity. When there are thrombogenic factors and damage near the inferior vena cava, follow-up examinations should be carried out.

DUAL-energy computed tomography findings in a case of COVID-19.

BACKGROUND: COVID-19 pneumonia has lesions with a decreased blood flow. Dual-energy computed tomography is suitable to elucidate the pathogenesis of COVID-19 pneumonia because it highlights the blood flow changes in organs. We report the dual-energy computed tomography findings of a successfully treated case of COVID-19 pneumonia. CASE PRESENTATION: An obese 49-year-old man with COVID-19 pneumonia was transferred from another hospital on day 11 after onset of illness. Although he was hypoxemic (PaO2/FiO2 = 100), tracheal intubation was not performed after anticipating difficulty in weaning from mechanical ventilation. Prone position therapy and nasal high flow therapy were administered, and the patient was discharged after his condition improved. Dual-energy computed tomography was performed three times during hospitalization, and it revealed improvement in the blood flow defect, unlike plain computed tomography that did not show much improvement. CONCLUSION: Dual-energy computed tomography can assess perfusion in COVID-19 pneumonia in real time and may be able to predict its severity.

Title: Gene transfer by pyro-drive jet injector is a novel therapeutic approach for muscle diseases.

The angiogenic gene therapy is an attractive approach for the treatment of ischemic muscle diseases, including peripheral arterial disease and ischemic heart diseases. Although a variety of gene transfer methods have been developed, the efficiency of gene transfer is still limited. We have been developing the needleless high-energy bioinjector device, Pyro-drive Jet Injector (PJI), based on pyrotechnics using a combination of ignition powder and gunpowder, however, the utility of PJI in gene transfer into muscle tissues remains unclear. pcDNA3.1 plasmid containing Flag was injected to the thigh muscles of C57BL/6J mice using PJI or needle, as a control. Histological analysis demonstrated that the protein expression of Flag was observed in a wider range in PJI group than in needle group. To assess the validity of PJI for gene therapy, pcDNA3.1-human fibroblast growth factor 2 (FGF2), which has angiogenic activity and tissue protective properties, was injected into the ischemic thigh muscles with PJI or needle. ELISA assay revealed that the protein expression of FGF2 was increased in the thigh muscle tissues by PJI-mediated gene delivery. Significantly, histological analyses revealed that muscle fiber cross-sectional area and the number of endothelial marker CD31 (+) cells was increased in ischemic hind-limb tissues of the PJI-FGF2 group but not in those of needle-FGF2 group. To expand the applicability of the PJI-mediated gene transfer, pcDNA3.1-venus plasmid was injected into murine hearts with PJI or needle. PJI method was successful in gene transfer into murine hearts, especially into cardiomyocytes, with high efficiency when compared to needle method. Collectively, the non-needle, non-liposomal and non-viral gene transfer by PJI could be a novel therapeutic approach for muscle diseases.

Patchwork metasurface quantum well photodetectors with broadened photoresponse.

Complex lightwave manipulation such as broadband absorption has been realized with metasurfaces based on laterally arranged metal-dielectric-metal cavities with different geometries. However, application of these metasurfaces for optoelectronic devices by incorporating functional dielectrics remains challenging. Here, we integrate a quantum well infrared photodetector (QWIP) with a metasurface made of a patchwork of square cavities with different dimensions arranged in a subwavelength unit cell. Our detector realizes wideband photoresponse approaching the entire responsivity spectrum of the QWIP-single-sized square cavities can utilize only 60% of the possible bandwidth-and external quantum efficiencies of up to 78% at 6.8 µm. Our highly flexible design scheme enables integration of photodetectors and metasurfaces with arbitrary arrangements of cavities selectively responding to incidence with a specific wavefront.

Potent Intradermal Gene Expression of Naked Plasmid DNA in Pig Skin Following Pyro-drive Jet Injection.

Intradermal administration of naked DNA with a conventional needle syringe is a simple and inexpensive method to expose an encoded antigen to the dermal immune system. We aimed to enhance intradermal gene expression with a pyro-drive jet injector using pig skin, which is similar in structure and biomechanical properties to human skin. When Cy3-labeled plasmid (pCy3) was applied to pig skin with the jet injector, pCy3 was distributed preferentially in the intradermal tissue. Precise localization analysis revealed that pCy3 was also detected in the intracellular nucleus, and the frequency was substantially higher with the jet injector than with a needle syringe. When a luciferase expression plasmid (pLuc) was injected transdermally, the luciferase activity was 380-fold higher with the jet injector than with a needle syringe. Furthermore, immunohistochemistry analysis showed that the epidermis was positive for luciferase protein expression. These data indicate that the jet injector facilitates stable intradermal administration, resulting in more efficient gene expression compared to that with conventional syringe methods. Thus, intradermal administration of an antigen-expression plasmid with the pyro-drive jet injector may provide a clinically viable method for future gene therapy.

Mass Spectrometry-Based Solid Phase Peptide Reaction Assay for Detecting Allergenicity Using an Immobilized Peptide-Conjugating Photo-Cleavable Linker.

The biological process of skin sensitization depends on the ability of a sensitizer to modify endogenous proteins. A direct peptide reactivity assay (DPRA), based on the biological process of skin sensitization, was developed as an alternative to controversial animal experiments. Although DPRA has been endorsed by industries and is internationally accepted as promising, it has several drawbacks, such as incompatibility with hydrophobic chemicals, inability to perform detailed reaction analysis, and ability to evaluate only single components. Here, we demonstrated that sensitizers and peptide adducts can be easily identified using a mass spectrometry-based solid-phase peptide reaction assay (M-SPRA). We synthesized peptides with a photo-cleavable linker immobilized on resins. We showed the potential of M-SPRA in predicting skin sensitization by measuring the peptide adducts that were selectively eluted from the resin after cleaving the linker post-reaction. M-SPRA provides more detailed information regarding chemical reactivity and accurate assessment of test samples, including mixtures. M-SPRA may be helpful for understanding the binding mechanism of sensitizers (toxicology), which may assist in further refining reactivity assays and aiding in the interpretation of reactivity data.

Development of a chromophore-solid phase peptide reaction assay (C-SPRA) for assessing skin sensitization in vitro.

We developed an in vitro chromophore-solid phase peptide reaction assay (C-SPRA) using microbead-immobilized peptides and chromophores. Peptide-resins (microbeads) reacted with 14 representative chemicals to demonstrate the test's capacity to predict skin sensitization. C-SPRA enables accurate and high-throughput assessments of various chemicals, including poorly water-soluble sensitizers that are regarded as weakly potent by other methods.

Synchronously wired infrared antennas for resonant single-quantum-well photodetection up to room temperature.

Optical patch antennas sandwiching dielectrics between metal layers have been used as deep subwavelength building blocks of metasurfaces for perfect absorbers and thermal emitters. However, for applications of these metasurfaces for optoelectronic devices, wiring to each electrically isolated antenna is indispensable for biasing and current flow. Here we show that geometrically engineered metallic wires interconnecting the antennas can function to synchronize the optical phases for promoting coherent resonance, not only as electrical conductors. Antennas connected with optimally folded wires are applied to intersubband infrared photodetectors with a single 4-nm-thick quantum well, and a polarization-independent external quantum efficiency as high as 61% (responsivity 3.3 A W-1, peak wavelength 6.7 µm) at 78 K, even extending to room temperature, is demonstrated. Applications of synchronously wired antennas are not limited to photodetectors, but are expected to serve as a fundamental architecture of arrayed subwavelength resonators for optoelectronic devices such as emitters and modulators.

Stable Immune Response Induced by Intradermal DNA Vaccination by a Novel Needleless Pyro-Drive Jet Injector.

DNA vaccination can be applied to the treatment of various infectious diseases and cancers; however, technical difficulties have hindered the development of an effective delivery method. The efficacy of a DNA vaccine depends on optimal antigen expression by the injected plasmid DNA. The pyro-drive jet injector (PJI) is a novel system that allows for adjustment of injection depth and may, thus, provide a targeted delivery approach for various therapeutic or preventative compounds. Herein, we investigated its potential for use in delivering DNA vaccines. This study evaluated the optimal ignition powder dosage, as well as its delivery effectiveness in both rat and mouse models, while comparing the results of the PJI with that of a needle syringe delivery system. We found that the PJI effectively delivered plasmid DNA to intradermal regions in both rats and mice. Further, it efficiently transfected plasmid DNA directly into the nuclei, resulting in higher protein expression than that achieved via needle syringe injection. Moreover, results from animal ovalbumin (OVA) antigen induction models revealed that animals receiving OVA expression plasmids (pOVA) via PJI exhibited dose-dependent (10 µg, 60 µg, and 120 µg) production of anti-OVA antibodies; while only low titers (< 1/100) of OVA antibodies were detected when 120 µg of pOVA was injected via needle syringe. Thus, PJI is an effective, novel method for delivery of plasmid DNA into epidermal and dermal cells suggesting its promise as a tool for DNA vaccination.