Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry.

OBJECTIVES: Pretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). METHODS: Clients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. RESULTS: In total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80-0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14-0.63) were significantly associated with YFV. CONCLUSIONS: Preventive interventions other than YFV should be offered to older adults.

COVID-19-Triggered Acute Liver Failure and Rhabdomyolysis: A Case Report and Review of the Literature.

COVID-19 is primarily known for its respiratory tract involvement, often leading to severe pneumonia and exacerbation of underlying diseases. However, emerging evidence suggests that COVID-19 can result in multiorgan failure, affecting organs beyond the respiratory system. We present the case of a 62-year-old male with COVID-19 who developed acute liver failure (ALF) and rhabdomyolysis in the absence of respiratory failure. Initially, the patient presented with significantly elevated aspartate transaminase (5398 U/L) and alanine transaminase (2197 U/L) levels. Furthermore, a prolonged prothrombin time international normalized ratio (INR) of 2.33 indicated the diagnosis of ALF without hepatic coma, according to Japanese diagnostic criteria. The patient also exhibited elevated creatine kinase (9498 U/L) and a mild increase in creatinine (1.25 mg/dL) levels, but both values improved with intravenous fluid support and molnupiravir administration. To our knowledge, this is the first reported case presenting with both ALF and rhabdomyolysis associated with COVID-19. In addition, we review the existing literature to summarize previously reported cases of ALF triggered by SARS-CoV-2. This case report underscores the significance of recognizing COVID-19 as a significant contributing factor in the development of multiorgan failure. Furthermore, it suggests that COVID-19 can lead to severe illness, irrespective of the absence of respiratory failure.

Rapid Multiplex RT-PCR for Influenza A and B by Genesoc®, a Microfluidic PCR System.

Background: Rapid antigen tests are widely used to diagnose influenza. However, despite their simplicity and short turnover time, the sensitivity of these tests is relatively low, and molecular tests with greater sensitivity are being sought. In this study, we developed and clinically evaluated a protocol for the rapid multiplex testing of influenza A and B, using a rapid real-time PCR system, GeneSoC®, that is based on microfluidic thermal cycling technology. Methods: The specificity of the developed assay was validated using cultured viral strains of influenza A/B, human metapneumovirus, and respiratory syncytial virus. Analytical sensitivity was evaluated using serially diluted RNA synthesized via in vitro transcription and nasopharyngeal swab samples collected from consecutive patients seeking medical attention for a combination of upper respiratory and general symptoms. Cross-validation of GeneSoC® based on comparisons with conventional real-time RT-PCR and rapid antigen tests was performed by parallel testing of influenza-positive clinical specimens. Results: The GeneSoC® assay detected the target sequences of influenza A and B at minimum concentrations of 38 and 65 copies/µL in reaction, respectively. For the analysis of clinical specimens, the positive, negative, and overall agreement between GeneSoC® RT-PCR and a conventional real-time RT-PCR was in all cases 100%, whereas for the comparison between GeneSoC® RT-PCR and the rapid antigen test, the agreements for positive, negative, and overall findings were 100%, 90.9%, and 95.7%, respectively. The mean time for completing GeneSoC® RT-PCR was 16 min 29 s (95% confidence interval, 16 min 18 s to 16 min 39 s). Conclusion: The microfluidic real-time PCR system, GeneSoC®, has an analytical performance comparable to that of conventional real-time RT-PCR with rapid turnover time, and represents a promising alternative to rapid antigen tests for diagnosing influenza A and B.

Characteristics and potential quality indicators for evaluating pre-travel consultations in Japan hospitals: the Japan Pretravel consultation registry (J-PRECOR).

BACKGROUND: Awareness of pre-travel consultations (PTCs) and prevention methods for overseas travel-related diseases, and the understanding of PTCs among Japanese travelers and medical professionals remains low in Japan. A multicenter registry was established to examine PTCs in Japan. This study assessed the PTC implementation rate and examined the indicators of PTCs that can be used as criteria for evaluating quality. METHODS: Clients who presented for their PTCs at 17 facilities and were registered between February 1, 2018, and May 31, 2020, were included. Medical information was extracted retrospectively via a web-based system. Correlations between vaccination risk categories and advice/intervention proportions by the facility were evaluated using Spearman's ordered phase relations (α = 0.05). RESULTS: Of the 9700 eligible clients (median age, 32 years; 880 [9.1%] aged < 16 years and 549 [5.7%] aged ≥65 years), the most common travel duration was ≥181 days (35.8%); higher among younger clients. The most common reason for travel was business (40.5%); the US (1118 [11.5%]) and Asia (4008 [41.3%]) were the most common destinations and continents, respectively. The vaccine number (median three per person) increased after the PTCs except for the tetanus toxoid. Only 60.8% of the clients recommended for malaria prophylaxis received anti-malarial agents. The gross national income; the incidence of human rabies, typhoid fever, falciparum malaria; and dengue risk category were associated with the percentage of hepatitis-A vaccines; explaining rabies post-exposure prophylaxis, typhoid-fever vaccinations, malaria-prophylaxis prescriptions; and mosquito repellants, respectively. CONCLUSIONS: Although the characteristics of the travelers differed, the quality of the PTCs should be improved to address, for example, the lower rate of acceptance of malaria prophylaxis in Japan.

Peritoneal dialysis-associated peritonitis caused by Mycobacteroides massiliense: the first case and review of the literature.

BACKGROUND: Peritoneal dialysis (PD)-associated peritonitis caused by nontuberculous Mycobacterium is rare; however, the number of cases has increased over the past decades. Mycobacteroides massiliense is a subspecies of the Mycobacteroides abscessus complex. It has different clinical characteristics compared to the other subspecies of the complex. Previous case reports of PD-associated peritonitis caused by Mycobacteroides abscessus complex have not distinguished the subspecies in detail. CASE PRESENTATION: A 40-year-old man presented with an exit-site and tunnel infection refractory to antibiotic therapy. Peritonitis occurred after simultaneous catheter removal and reinsertion. The Mycobacteroides abscessus complex was detected in the culture of the dialysis effluent. Removal of the PD catheter combined with antibiotics, including macrolides, resulted in a good clinical course. Further analysis of multiplex PCR and the hsp65 gene sequence identified the bacterium as Mycobacteroides massiliense. CONCLUSIONS: The Mycobacteroides abscessus complex is classified into three subspecies; Mycobacteroides abscessus, Mycobacteroides massiliense, and Mycobacteroides bolletii. These have different characteristics, particularly antibiotic susceptibility. Therefore, clear identification of the subspecies of the Mycobacteroides abscessus complex is necessary for definitive treatment.

Effect of Cetuximab and EGFR Small Interfering RNA Combination Treatment in NSCLC Cell Lines with Wild Type EGFR and Use of KRAS as a Possible Biomarker for Treatment Responsiveness.

BACKGROUND: The epidermal growth factor receptor (EGFR) is a therapeutic target for patients with non-small cell lung cancer (NSCLC). Cetuximab is an anti-EGFR monoclonal antibody that inhibits EGFR signaling and proliferation of colorectal cancer and head and neck cancers. Since only few NSCLC patients benefit from cetuximab therapy, we evaluated a novel combination treatment using cetuximab and EGFR small interfering RNA (siRNA) to strongly suppress EGFR signaling and searched for a biomarker in NSCLC cell lines harboring wild-type EGFR. METHODS: Alterations in EGFR and its downstream genes in five NSCLC cell lines (A549, Lu99, 86-2, Sq19 and Ma10) were assessed through sequencing. The protein expression levels of these molecules were assessed through western blotting. The effect of combination treatment was determined through cell proliferation assay, caspase-3/7 assay, invasion assay, and migration assay. RESULTS: All cell lines were harboring wild-type EGFR, whereas KRAS, PTEN, TP53 and TP53 were mutated in A549 and Lu99; Lu99 and Sq19; Lu99, 86-2, Sq19 and Ma10; and A549, 86-2, and Sq19 cell lines, respectively. PTEN was not expressed in Sq19, and LKB1 was not expressed in both A549 and Sq19. TP53 was not expressed in both A549 and Lu99. The combination of cetuximab and EGFR siRNA significantly suppressed cell proliferation in 86-2, Sq19 and Ma10, which express wild-type KRAS. It induced apoptosis in A549, 86-2 and Ma10 cells, which express wild type PTEN. The combination treatment had no effect either on cell invasion nor migration in all cell lines. CONCLUSION: EGFR targeted therapy using the combination of cetuximab and EGFR siRNA is effective in NSCLC cell lines harboring wild-type EGFR. Wild-type KRAS may act as a potential biomarker for response to combination treatment by the induction of apoptosis in cells with wild-type PTEN.

Calcium Pyrophosphate Deposition Disease Involving a Lumbar Facet Joint Following Urinary Tract Infection.

A 75-year-old woman was admitted with urosepsis due to Escherichia coli infection. After improvement with a ureteral stent and antimicrobial agent, she complained of back pain and showed elevated inflammation marker levels. Arthralgia and arthritis of multiple peripheral joints were noted, and radiography indicated cartilage calcification. Magnetic resonance imaging revealed lumbar facet joint effusion. Her symptoms improved with nonsteroidal anti-inflammatory drug administration. Thus, she was diagnosed with calcium pyrophosphate deposition (CPPD)-related facet joint arthritis (FJA) rather than infectious FJA. CPPD-related FJA is an important differential diagnosis in elderly individuals with a risk of CPPD disease who complain of back pain.

Evaluation of antigen-positive toxin-negative enzyme immunoassay results for the diagnosis of toxigenic Clostridium difficile infection.

Clostridium difficile (C. difficile)-associated diarrhea (CDAD) is a challenging nosocomial infectious disease. C. DIFF Quik Chek Complete assay is widely used to detect glutamate dehydrogenase (GDH) antigen and toxin A/B of C. difficile simultaneously. However, the interpretation of GDH positive/toxin negative results is problematic. We performed a retrospective study of patients with GDH positive/toxin negative results to determine the probability of detecting toxigenic C. difficile and its risk factors. Between April 2012 and March 2017, we investigated cultures of fecal specimens followed by toxin detection tests. The clinical histories of patients with and without toxigenic C. difficile were compared using univariate- and multivariate-analyses. In total, 2675 patients were examined using C. Diff Quik Chek Complete assay. Among 356 GDH positive/toxin negative patients, cultures were performed in 220 cases and toxigenic C. difficile was recovered from 139 (63.2%) specimens. Patients with toxigenic C. difficile had significantly lower body mass index than those without. Over half the GDH positive/toxin negative patients were infected with toxigenic C. difficile. Lower BMI was a CDAD risk factor in this patient population. These data can be utilized to initiate isolation and clinical interventions before confirmatory test results are available. J. Med. Invest. 65:131-135, February, 2018.

Cryptococcus gattii genotype VGIIa infection imported from Vancouver Island to Japan.

A 71-year-old Japanese man with travel history to the Vancouver Island, Canada was diagnosed the pulmonary and central nervous system infections caused by Cryptococcus gattii genotype VGIIa. This is the first imported case of Cryptococcus gattii genotype VGIIa infection from endemic area of North America to Japan. He was recovery with no residual neurological dysfunction by early resection of brain mass and antifungal therapy. Early surgical resection of cerebellar cryptococcoma may shorten the length of induction therapy with antifungal drugs.

Splenic Infarction in Acute Cytomegalovirus and Human Parvovirus Concomitant Infection.

We present a case report of a 35-year-old woman who had splenic infarction. She had persistent high fever, systemic joint pain, and abnormal liver function. She was diagnosed with cytomegalovirus and human parvovirus B19 concomitant infection. Her coagulopathy test revealed no abnormal results. She was treated with intravenous ganciclovir for 13 days; consequently, her splenic infarction improved after 7 weeks. As per our knowledge, this is the first case of cytomegalovirus and parvovirus B19 coinfection complicated by splenic infarction. Cytomegalovirus and parvovirus B19 may induce a hypercoagulation state during the acute phase.

Mucosa-associated Lymphoid Tissue Lymphoma of the Trachea in a Patient with Breast Cancer.

We herein report the case of a 93-year-old woman with breast cancer on the left side. Preoperative computed tomography of the chest showed irregularities and narrowing of the mid-trachea. Bronchoscopy was performed, and the results of a biopsy supported a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. The patient responded to treatment with prednisone alone, with a reduction in the size of the lesion. MALT lymphoma of the trachea is extremely rare, and there are only a few case reports of double cancer, i.e., MALT lymphoma of the trachea and breast cancer.

Effect of Clarithromycin on the Expression of UL16-Binding Protein 2 in Human Cells.

BACKGROUND: Clarithromycin is a macrolide antibiotic that possesses anti-inflammatory and immunomodulatory properties. Although recent data suggests that macrolide antibiotics enhance Pseudomonas aeruginosa clearance from the lung, involving natural killer (NK) T cells in this process by activating the NKG2D-NKG2D ligand system, the precise underlying mechanism is still unclear. In this study, we examined the effect of clarithromycin on a potent NKG2D ligand, UL16-binding protein 2 (ULBP2), in the lung and its shedding mechanism. METHODS: The gene expressions of ULBP2 and the shredder proteinases of ULBP2, a disintegrin and metalloproteinase domain 10 (ADAM10) and ADAM17, were measured using real-time PCR. The cell surface ULBP2 expression was measured by flow cytometry. The amount of solubilized ULBP2 (sULBP2) was measured using an ELISA. The activity of ADAM17 was examined by measurement of fluorescence intensity from the fluorescence resonance energy transfer peptide substrate cleaved by ADAM17. RESULTS: Clarithromycin significantly induced transcription of ULBP2 and ADAM17 in both A549 and LCSC #2 cells, which endogenously express minimal and abundant levels of ULBP2, respectively. However, there was no significant change on transcription of ADAM10. The same tendency was observed when LCSC #2 cells were treated with tumor necrosis factoralpha processing inhibitor-2 to inhibit ADAM17 activity. The amount of sULBP2 was significantly decreased in both A549 and LCSC #2 cells by treatment with clarithromycin. Finally, clarithromycin significantly inhibited the activity of ADAM17 in LCSC #2 cells. CONCLUSION: These findings suggest that clarithromycin induces ULBP2 expression and reduces the amount of sULBP2, by possibly inhibiting the activity of the potent ULBP2-shedding enzyme ADAM17. Because these changes in ULBP2 and sULBP2 levels could activate NKT cells, this finding might indicate a novel mechanism by which clarithromycin improves the clearance of P. aeruginosa in chronic respiratory diseases.

A new rapid method for detecting epidermal growth factor receptor mutations in non-small cell lung cancer.

Mutations in the epidermal growth factor receptor (EGFR) gene are associated with a favorable clinical response to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib in non-small cell lung cancer (NSCLC). We present here, a new method for the rapid detection of the two most common EGFR mutations (delE746-A750 and L858R) from clinical samples. The methodology involves the combination of newly designed mutation-specific primers and a novel real-time PCR machine with an innovative thermo-control mechanism that enables ultrarapid PCR. We evaluated this method using a cell mixture composed of various ratios of lung cancer cells harboring mutated or wild-type EGFR, lung cancer tissues obtained by surgery, and a cytology sample obtained by bronchoscopy from a lung cancer patient. In the cell mixture analysis, our method detected 0.1% of cells with delE746-A750 and 1% of cells with L858R among cells with wild-type EGFR. In 143 lung cancer tissues, the result of this assay was concordant with those of direct sequencing in 138 samples. The five samples with discordant results were tested using a PCR-Invader assay and the result matched those of our method at 100%. We also successfully detected EGFR mutations in the lavage obtained from a lung cancer patient. The turnaround time for this method was <10 min, and all steps could be accomplished in <50 min after sample collection. Thus, our novel PCR method offers a rapid, simple, and less expensive test for EGFR mutations and can be applied as a point-of-care diagnostic test.

[A case of lung abscess due to Aspergillus viridinutans in a patient with aplastic anemia].

A 75-year-old woman with aplastic anemia was admitted to our university hospital because of a dry cough that had persisted for a month. Chest computed tomography showed a mass shadow with a central low attenuation area in the lower lobe of the left lung. Filamentous fungus resembling Aspergillus fumigatus was cultured from the specimens obtained by transthoracic needle aspiration biopsy and bronchoalveolar lavage. The initial diagnosis was a lung abscess due to A. fumigatus, although the patient did not respond well to antifungal agents. Subsequently, the filamentous fungus was identified as Aspergillus viridinutans by sequence analysis of the ß-tubulin gene, and the patient was successfully treated with combination therapy along with granulocyte colony-stimulating factor. The incidence of A. viridinutans infection is very rare. A. viridinutans is morphologically similar to A. fumigatus; however, the response to antifungal agents is generally worse than that observed in A. fumigatus infections. Therefore, the selection of agents and supplemental therapy is of vital importance in cases of A. viridinutans infection.

Positive Predictive Value of True Bacteremia according to the Number of Positive Culture Sets in Adult Patients.

BACKGROUND: Performing multiple blood culture sets simultaneously is a standard blood culture methodology, although it is often difficult to distinguish true bacteremia from contamination when only one of several blood culture sets is positive. This study clarified the relationship between the number of positive blood culture sets and clinical significance in patients with positive blood culture. METHODS: Patients aged 18 years and over with at least 1 positive blood culture were enrolled. Positive blood culture episodes were categorized from clinical records as true bacteremia, contamination, or unknown clinical significance. The associations among episodes of true bacteremia, isolated bacteria, the number of positive blood culture sets from among the performed sets, and the clinical background of patients were analyzed. RESULTS: Among a total of 407 episodes, 262, 67 and 78 were true bacteremia, contamination and unknown clinical significance, respectively. The positive predictive values (PPVs) of 1 out of 1, 1 out of 2 and 2 out of 2 positive sets in cases of Staphylococcus aureus, were 81.3%, 50% and 100% respectively; those in cases of coagulase-negative Staphylococci were 20.5%, 10.8% and 63.5%, respectively. Almost all cases of Escherichia coli, Pseudomonas aeruginosa, Klebsiella species and Candida species were true bacteremia. The probability of true bacteremia was strongly associated with recent surgery in multivariate analysis (P < 0.05). CONCLUSION: The probability of true bacteremia based on the number of positive culture sets from among the performed sets varies by microorganism. Therefore, PPVs calculated using this method may help physicians distinguish true bacteremia from contamination.