Anti-MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis Associated With Multiple Heterologous Carcinomas: A Case Report.

Dermatomyositis (DM), an autoimmune disorder, is linked to increased malignancy risk. A 53-year-old man with anti-melanoma differentiation-associated gene 5 (MDA5)-positive clinically amyopathic dermatomyositis (CADM) and rapidly progressing interstitial lung disease (RP-ILD) developed heterochronous gastric and colorectal cancers. Early endoscopic screenings led to successful curative resections, preventing recurrence. Despite low cancer incidence assumptions in patients with anti-MDA5-positive RP-ILD, this case advocates for reevaluation and periodic cancer screenings to enhance management, considering the improved survival with intensive therapy. Vigilance for multiple carcinomas at various time points is vital in CADM management.

Clarithromycin-induced eosinophilic granulomatosis with polyangiitis: A case report.

A 75-year-old man presented to our hospital with chronic sinusitis, bronchiectasis, and chronic lower respiratory tract infections. He began taking erythromycin in August, X-2. The chronic lower respiratory tract infection gradually worsened, and clarithromycin was started on May 11, X. He became aware of fever and numbness in his lower legs on June 4, X. The sign occurred soon after oral clarithromycin and blood tests showed an elevated eosinophil count and C-reactive protein (CRP) levels, positive MPO-ANCA antibodies, and positive for drug-induced lymphocyte stimulation test (DLST); we diagnosed eosinophilic granulomatosis with polyangiitis (EGPA) associated with clarithromycin administration.

Clinical characteristics of patients with coronavirus disease 2019-associated pulmonary aspergillosis on mechanical ventilation: A single-center retrospective study in Japan.

BACKGROUND: Aspergillus is one of the important pathogens that contribute to high mortality in patients with coronavirus disease 2019 (COVID-19) in intensive care units (ICUs). Although incidence rates of Aspergillus coinfection are high globally, a Japanese national survey reported a low incidence. This study aimed to describe the clinical characteristics of patients with COVID-19-associated pulmonary aspergillosis at our institute. METHODS: We identified patients with microbiologically confirmed COVID-19 on mechanical ventilation in the ICU. Of these patients, we identified patients in whom Aspergillus was cultured from the respiratory specimen. RESULTS: Of a total of 169 patients, seven had aspergillosis (4.1%), which included three patients, three patients, and one patient with possible, probable, and proven aspergillosis, respectively, according to the criteria of the European Confederation of Medical Mycology International Society. All patients received systemic steroid therapy. Two patients (one each with proven and probable aspergillosis) had tracheobronchitis diagnosed by bronchoscopy. All patients in whom Aspergillus was repeatedly isolated from samples died. The mortality rates for all cases and probable and proven cases were 57% (4/7) and 75% (3/4), respectively. CONCLUSIONS: The incidence rate of aspergillosis in patients with COVID-19 in the ICU was higher in our institute than that reported by a Japanese national survey (4.1% vs. 0.5%). Repeated detection of Aspergillus might suggest a true Aspergillus infection, such as chronic aspergillosis, rather than colonization. In patients with severe COVID-19 patients, it is important to always keep CAPA in mind.

A case of thoracic SMARCA4-Deficient undifferentiated tumor successfully treated with combination Ipilimumab-Nivolumab.

Thoracic SMARCA4-deficient undifferentiated tumors are rare, with poor prognosis. A 73-year-old man presented to our hospital with dyspnea. Computed tomography-guided biopsy revealed a SMARCA4-deficient undifferentiated tumor. The patient was treated with combination ipilimumab-nivolumab. The tumor reduced in size after two courses.

Guillain-Barré Syndrome Associated with COVID-19 in a Japanese Male.

April 2021 saw a widespread outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Osaka, Japan. We encountered the case of a 52-year-old man who had Guillain-Barré syndrome associated with coronavirus disease 2019 (COVID-19). After the relief of the respiratory symptoms owing to COVID-19, the patient experienced muscle weakness, which spread from his fingers to his extremities, and was unable to walk. Further examinations revealed mild protein elevation in the cerebrospinal fluid. In addition, nerve conduction studies showed demyelinating polyneuropathy, leading to the diagnosis of Guillain-Barré syndrome. After the administration of intravenous immunoglobulin and intravenous methylprednisolone, his symptoms drastically improved, and he was able to walk unaided 21 days after the onset of symptoms. On day 40, the patient was discharged with minimal muscle fatigue. Because Guillain-Barré syndrome associated with COVID-19 is expected to have a good prognosis, early diagnosis and treatment are important. Therefore, Guillain-Barré syndrome should be considered as a possible factor for muscle weakness during and after COVID-19 treatment.

Persistent viral shedding of severe acute respiratory syndrome coronavirus 2 after treatment with bendamustine and rituximab: A case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12-20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.

Acute worsening of glycemic control in a patient with type 2 diabetes and non-small cell lung cancer after administration of lorlatinib.

A patient with non-small cell lung cancer (NSCLC) exhibited extreme hyperglycemia after lorlatinib treatment. The present case highlights the importance of glucose monitoring during lorlatinib administration and intensifying hyperglycemia treatment.

Corynebacterium pseudodiphtheriticum as a Pathogen in Bacterial Co-Infection in COVID-19 Patients on Mechanical Ventilation.

Many studies have been conducted on ventilator-associated complications (VACs) in patients with coronavirus 2019 (COVID-19). However, in these studies, the causative organisms were similar, and there were no reports on VAC corresponding with Corynebacteria. Coryneforms are frequently cultured in cases of polymicrobial infections and are usually considered contaminants in respiratory specimens. However, Corynebacterium pseudodiphtheriticum or C. striatum is known to be a pathogen in lower respiratory tract infections. We report three cases of VAC, probably due to C. pseudodiphtheriticum, in patients with COVID-19. If purulent lower respiratory tract specimens showed coryneform predominantly upon Gram staining, empirical therapy should be started. Furthermore, species identification and drug susceptibility testing should be performed.

Assessing the effects of exposure to a SARS-CoV-2 re-positive patient in healthcare personnel.

OBJECTIVE: To evaluate whether patients with COVID-19 who have tested re-positive with the PCR test for the SARS-CoV-2 virus are infectious is a challenge in the current circumstances. A follow-up survey was conducted with healthcare personnel (HCP) who were exposed to a patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative PCR results. RESULTS: We studied a total of 15 HCP who had contact exposures (15/15) and aerosol exposures (7/15). None of them tested positive for IgG against SARS-CoV-2 on blood examination. None of them had any symptoms during 10 days of active isolation. All PCR tests conducted using the nasopharyngeal swabs collected from the HCP on day 10 were negative. No apparent infection was found in any of the HCP who had contact exposure with and/or aerosol exposure to the patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative results of PCR tests for SARS-CoV-2. CLINICAL TRIAL: Trial Registration: No. 170, approved June 10th, 2020 by the ethics committee of Sakai City Medical Center.

Analysis of the predictive factors for a critical illness of COVID-19 during treatment － relationship between serum zinc level and critical illness of COVID-19.

OBJECTIVES: Because most severely ill patients with COVID-19 in our hospital showed zinc deficiency, we aimed to examine the relationship between the patient's serum zinc level and severe cases of COVID-19. METHODS: Serum zinc <70 µg/dL was defined as the criterion for hypozincemia, and patients continuously with serum zinc <70 µg/dL were classified in the hypozincemia cohort. To evaluate whether hypozincemia could be a predictive factor for a critical illness of COVID-19, we performed a multivariate analysis by employing logistic regression analysis. RESULTS: Prolonged hypozincemia was found to be a risk factor for a severe case of COVID-19. In evaluating the relationship between the serum zinc level and severity of patients with COVID-19 by multivariate logistic regression analysis, critical illness can be predicted through the sensitivity and false specificity of a ROC curve with an error rate of 10.3% and AUC of 94.2% by only two factors: serum zinc value (P = 0.020) and LDH value (P = 0.026). CONCLUSIONS: Proper management of the prediction results in this study can contribute to establishing and maintaining a safe medical system, taking the arrival of the second wave, and the spread of COVID-19 in the future into consideration.

Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial.

BACKGROUND: Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP. METHODS: In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP. RESULTS: We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0). CONCLUSIONS: Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.Trial registration numberUMIN000014969, date: 28 August 2014.

Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. METHODS: For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. RESULTS: The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. CONCLUSION: Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.

Molecular characteristics of serotype 3 Streptococcus pneumoniae isolates among community-acquired pneumonia patients in Japan.

In order to understand the spread of the erythromycin-resistant serotype 3 Streptococcus pneumoniae clone in Japan, we have assessed the molecular characteristics of this clone. Among 156 S. pneumoniae isolates recovered from adults with community-acquired pneumonia between 2003 and 2005, 42 were serotype 3 and 40 were sequence type (ST) 180/Netherlands(3)-31 by multilocus sequence typing. Thirty-eight of the 40 ST 180 isolates had acquired resistance to erythromycin via the ermB gene. Although the ermB-positive ST180 clone isolates were more susceptible to penicillin and trimethoprim-sulfamethoxazole than ermB-positive non-ST180 isolates and contained a less mutated pbp1a or pbp2b gene, without a mefA gene, the ST180 clone was highly prevalent among ermB-positive isolates. Routine surveillance for the ST180 S. pneumoniae clone may soon become necessary.

Antimicrobial susceptibilities of Streptococcus pneumoniae isolated from adult patients with community-acquired pneumonia in Japan.

BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae (S. pneumoniae) is the most common pathogen associated with community-acquired pneumonia and its resistance to antimicrobials is a worldwide problem. The aim of this study was to investigate the current drug susceptibilities of S. pneumoniae isolated from adult patients with community-acquired pneumonia in Japan. METHODS: S. pneumoniae strains isolated from adult patients with pneumococcal pneumonia from 10 institutions were collected prospectively between May 2003 and October 2004 and tested for drug susceptibilities. Clinical data were analysed and the risk factors for drug resistance investigated. RESULTS: A total of 141 isolates of S. pneumoniae were analysed. Of these S. pneumoniae isolates, 46.1% had intermediate penicillin resistance and the minimum inhibitory concentration (MIC) occurring in the greatest number of isolates and MIC90 value was 2 microg/mL. The prevalence of resistance to macrolides was 80%, with the MIC90 values being greater than or equal to 16 microg/mL. Approximately 40% of the strains were resistant to oral third-generation cephems. Penicillin and erythromycin resistance were both associated with the pre-existing chronic disease states. CONCLUSIONS: The cephem and macrolide resistance of S. pneumoniae was higher than penicillin resistance in adult patients with community-acquired pneumococcal pneumonia in Japan. We recommend that bacterial identification and sensitivities are determined in areas where the macrolide resistance to S. pneumoniae is high.

Genotypes and related factors reflecting macrolide resistance in pneumococcal pneumonia infections in Japan.

Although macrolide-resistant Streptococcus pneumoniae strains possessing either the ermB or mefA gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by S. pneumoniae was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with ermB and mefA genotyping. Independent relationships between tested variables and possession of either the ermB or the mefA gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes: ermB alone (50.0%), mefA alone (23.7%), and both ermB and mefA (7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for ermB-positive pneumococcal pneumonia (odds ratio [OR]=11.1; 95% confidence interval [CI]=1.30 to 95.0; P=0.03), but there were no associations with mefA or with ermB mefA positivity. Penicillin nonsusceptibility was associated with mefA-positive and with ermB- and mefA-positive isolates (OR=14.2; 95% CI=4.27 to 46.9; P<0.0001 and P<0.0001, respectively) but not with ermB-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan, S. pneumoniae with erythromycin resistance or possession of ermB, mefA, or both genes was highly prevalent in patients with CAP. The risk factors for ermB-positive, mefA-positive, and double ermB-mefA-positive pneumococcal pneumonia were different, but the clinical outcomes did not differ.