Nationwide survey in Japan of the causative diseases of bloody sputum and hemoptysis in departments of respiratory medicine at university hospitals and core hospitals.

BACKGROUND: The Guidelines for the Management of Cough and Sputum (2019) of the Japanese Respiratory Society (JRS) were the first internationally published guidelines for the management of sputum. However, the data used to determine the causative diseases of bloody sputum and hemoptysis in these guidelines were not obtained in Japan. METHODS: A retrospective analysis was performed using the clinical information of patients with bloody sputum or hemoptysis who visited the department of respiratory medicine at a university or core hospital in Japan. RESULTS: Included in the study were 556 patients (median age, 73 years; age range, 21-98 years; 302 males (54.3%)). The main causative diseases were bronchiectasis (102 patients (18.3%)), lung cancer (97 patients (17.4%)), and non-tuberculous mycobacterial disease (89 patients (16%)). Sex and age differences were observed in the frequency of causative diseases of bloody sputum and hemoptysis. The most common cause was lung cancer in males (26%), bronchiectasis in females (29%), lung cancer in patients aged <65 years (19%), and bronchiectasis in those aged >65 years (20%). CONCLUSIONS: The present study is the first to investigate the causative diseases of bloody sputum and hemoptysis using data obtained in Japan. When investigating the causative diseases of bloody sputum and hemoptysis, it is important to take the sex and age of the patients into account.

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition).

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.

A long-term survivor keeping in a complete response without treatment after pemetrexed maintenance therapy for advanced non-squamous non-small cell lung cancer.

Pemetrexed has significant efficacy for some non-squamous non-small cell lung cancer cases, as demonstrated in the current case. For those patients, pemetrexed administration should be carefully considered.

Use of steroids to treat anti-tumor necrosis factor α induced tuberculosis-associated immune reconstitution inflammatory syndrome: Case report and literature review.

INTRODUCTION: Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge. PATIENT CONCERNS: A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. DIAGNOSIS: A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB. INTERVENTIONS: Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)]. OUTCOMES: After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later. CONCLUSION: We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.

Acute Hypertriglyceridaemia Caused by Tocilizumab in a Patient with Severe COVID-19.

Treatment with tocilizumab (TCZ) to block interleukin-6 (IL-6) signalling is predicted to mitigate cytokine release syndrome (CRS) caused by coronavirus disease 2019 (COVID-19). However, the adverse effects of TCZ on patients with COVID-19 remain unclear. We herein report a patient with COVID-19 treated with TCZ who developed acute hypertriglyceridaemia. Despite favipiravir treatment, acute respiratory distress syndrome developed in a 45-year-old patient with COVID-19; thus, TCZ was initiated. The triglyceride levels greatly increased after TCZ administration. Physicians should consider the negative impact of TCZ on the lipid profile in patients with COVID-19, although COVID-19-induced CRS itself may be an aggravating factor.

The First Case of Community-Acquired Pneumonia Due to Capsular Genotype K2-ST86 Hypervirulent Klebsiella pneumoniae in Okinawa, Japan: A Case Report and Literature Review.

Hypervirulent Klebsiella pneumoniae (HV-KP) typically causes pyogenic liver abscess and bacteremia with metastatic infections. Community-acquired pneumonia (CAP) due to HV-KP is uncommon and details of its clinical and microbiological features are limited. We report the first case of CAP due to capsular genotype K2-ST86 HV-KP in Okinawa, Japan and review infections caused by the K2-ST86 strain. A 79-year-old woman presenting with fever and productive cough persisting for the past three days was admitted to hospital. Her vital signs indicated septic shock. Lung examination by auscultation revealed holo-crackle and lobar pneumonia in chest radiography, and Streptococcus pneumoniae was suspected. However, sputum and blood cultures revealed Gram-negative coccus identified as K. pneumoniae. Genetic analysis identified the isolated strain as the K2 serotype harboring rmpA, iutA, entB, and mrkD. Therefore, we identified the isolated strain as hypervirulent. The isolate belonged to ST86 as determined by multilocus sequence typing. The case was not complicated by predisposing factors such as diabetes mellitus and malignancy related to HV-KP infection; thus, this CAP-causing HV-KP strain may differ from the typical HV-KP strain that induces liver abscess. A literature review identified only nine cases with CAP due to HV-KP. In all cases, the disease mainly occurred in older males with diabetes mellitus, which makes the present case unusual, and had high rates of septic shock and death. No case, including ours, was complicated by metastatic infection, suggesting that CAP due to HV-KP poses little distant metastasis risk, even in patients with bloodstream infection. In our review, consistent with our case, K2-ST86 was the most common strain of HV-KP in patients with CAP. Therefore, studies are needed to elucidate the clinical and microbiological features of HV-KP CAP, with a focus on the K2-ST86 strain. Physicians should always consider K. pneumoniae in cases of sepsis CAP with lobar pneumonia.

Case Report of Primary Lung Abscesses Due to Hypervirulent Klebsiella pneumoniae (Serotype K2, Sequence Type 375): an Emerging Isolate in Okinawa, Japan.

Hypervirulent Klebsiella pneumoniae (HV-KP) is typically associated with community-acquired liver abscess and bacteremia with metastatic infection; however, primary lung abscess (PLA) caused by HV-KP is rare, with only one such case report to date. A 69-year-old man with a history of diabetes mellitus (DM) was admitted to hospital complaining of slight bloody sputum. Chest imaging showed multiple consolidations with cavities in both lung fields. A culture of bronchoalveolar lavage fluid confirmed the presence of K. pneumoniae. Genetic analyses identified the isolate as serotype K2 and sequence type 375 (K2-ST375), and that it harbored the rmpA gene. The patient was an Asian middle-aged male with DM, all of which are risk factors for HV-KP infection. Although complicating DM and the presence of the rmpA gene are more likely to induce disseminated infection, metastatic infections were not found in this patient. The clinical and microbiological characteristics of our patient were different from those of a previous reported case, although in both cases the patient was from Asia and had DM. Therefore, DM appears to be one of the predisposing factors for HV-KP lung abscesses and physicians should pay attention to emerging HV-KP lung abscess infection, particularly in Asian countries. Previous studies have also revealed that K2-ST375 is one of the major clones causing HV-KP infection, and that it is mainly isolated from patients with liver abscess. Interestingly, including the present case, most of the infectious cases caused by K2-ST375 have been reported from Okinawa Prefecture in Japan. Therefore, the trend of the K2-ST375 strain should be carefully monitored, particularly in Okinawa, Japan. The serotype of HV-KP that causes PLA is still unknown and further study is needed to elucidate the etiology of PLA due to HV-KP and the relationship between the strain K2-ST375 and PLA.

Comparison of two screening tests for HIV-Associated Neurocognitive Disorder suspected Japanese patients with respect to cART usage.

In this study, we demonstrated the pervasiveness of HIV-associated neurocognitive disorders (HAND) among a selection of Japanese patients as well as evaluated and compared the Mini Mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) for use as a screening tool among combination anti-retroviral therapy (cART)-naïve and cART experienced patients. The MMSE and the IHDS have both been used as HAND screening tests around the world with variable success. It has been reported the increased usage of cART the utility of these screening tests may have been diminished due to the decreased severity of impairment and the altered pattern of neurocognitive impairments in cART era HAND patients. It is therefore possible the MMSE and the IHDS may still be useful among cART-naïve patients even in the cART era. However, only one study has investigated and compared the screening results of the IHDS among cART-naïve and cART experienced patients. All HIV positive patients who visited, or were admitted, to the Ryukyu University Hospital between January 2009 and March 2014 were evaluated for inclusion. Selected patients (n = 49) had data without omission for all tests. The overall prevalence of HAND in our cohort was 44%. The area under the curve (AUC), for all subjects using the MMSE and the IHDS, were 0.60 and 0.69, respectively. However, the AUC among cART-naïve patients were 0.58 and 0.76 for the MMSE and the IHDS, respectively. Whereas, cART experienced patients had an AUC of 0.60 and 0.61, respectively. Overall, the MMSE demonstrated a poor screening ability for HAND, regardless of cART usage (the cut-off value of 27 had a Youden's J-Index of 0.1, in all groups). Alternatively, the IHDS was moderately useful for HAND screening among cART-naïve patients (the cut-off value of 11 had a Youden's J-Index of 0.4), but performed poorly as a screening test among cART experienced patients (the cut-off value of 11 had a Youden's J-Index of 0.1).

Evaluation of Anyplex™ II RV16 and RB5 real-time RT-PCR compared to Seeplex® RV15 OneStep ACE and PneumoBacter ACE for the simultaneous detection of upper respiratory pathogens.

This prospective study was performed to evaluate and compare the performance of the multiplex PCR Seeplex® assays and Anyplex™ II assays. From May 2014 until April 2016, a total of 247 respiratory samples were collected in Okinawa, Japan. Multiple respiratory pathogens were detected in 37% of patients with positive results. The most prevalent pathogens were influenza A virus and respiratory syncytial virus B. Despite minor differences in capabilities, both the Seeplex® assays and Anyplex™ II assays can be easily implemented in diagnostic or research laboratories to optimize the detection and management of respiratory pathogen induced diseases.

Etiological analysis and epidemiological comparison among adult CAP and NHCAP patients in Okinawa, Japan.

BACKGROUND: Etiological epidemiology and diagnosis are important issues for CAP and NHCAP. Despite the availability of effective therapies, significant morbidity and mortality ensues. METHODS: We retrospectively analyzed the etiology of 200 pneumonia patients at the University of the Ryukyus Hospital. Patients were categorized into CAP (n = 97) or NHCAP (n = 103), according to the Japanese Respiratory Society guidelines. Diagnoses were made using clinical tests including, Gram stain, bacterial culture, serum and urinary tests. RESULTS: Pathogens were detected in 71% of patients, and identified as the source of infection in 52% (104/200). The majority of patients suffered from Streptococcus pneumoniae (32/200), Haemophilus influenzae (22/200), and Moraxella catarrhalis (16/200). Gram stain guided pathogen-oriented therapy decisions for 38 of 96 patients with unknown pathogens. Atypical pathogens were only diagnosed in CAP patients (n = 5). Severity of pneumonia was related to male sex (p = 0.006), and preexisting conditions, such as chronic heart failure (p < 0.001) and COPD (p < 0.001). Risk factors associated with increased length of stay included chronic heart failure, chronic renal failure, other pulmonary diseases and diabetes. Mortality for NHCAP patients was associated with lung cancer and bronchiectasis. CAP patients were more frequently admitted during winter months, while NHCAP patients were admitted during all other seasons. Seasonal patterns for individual pathogens could not be determined. CONCLUSION: Gram staining remains useful to guiding diagnostics. Pathogens affecting CAP and NHCAP patients were not significantly different; as such, attention should be focused on the management of underlying conditions. Clinical outcomes were not affected by guideline discordant therapy.

The clinical and phylogenetic investigation for a nosocomial outbreak of respiratory syncytial virus infection in an adult hemato-oncology unit.

Although many reports have already shown RSV outbreaks among hemato-oncology patients, genomic studies detecting similar RSV strains prior to an outbreak in the hospital are rare. In 2014, the University of the Ryukyus hospital hemato-oncology unit experienced, and successfully managed, a respiratory syncytial virus (RSV) nosocomial outbreak. During the outbreak investigation, genotyping and phylogenetic analysis was used to identify a potential source for the outbreak. Nasopharyngeal swabs were tested for RSV using three tests: (1) rapid antigen test (RAT); (2) reverse transcriptase polymerase chain reaction (PCR); or (3) quantitative PCR (RT-qPCR); a positive PCR reaction was considered a confirmed case of RSV. Phylogenetic analysis of the G protein was performed for outbreak and reference samples from non-outbreak periods of the same year. In total, 12 confirmed cases were identified, including 8 hemato-oncology patients. Patient samples were collected weekly, until all confirmed RSV cases returned RSV negative test results. Median time of suspected viral shedding was 16 days (n = 5, range: 8-37 days). Sensitivity and specificity of the RAT compared with RT-qPCR were 30% and 91% (n = 42). Phylogenetic analysis revealed nine genetically identical strains; eight occurring during the outbreak time period and one strain was detected 1 month prior. A genetically similar RSV detected 1 month before is considered one potential source of this outbreak. As such, healthcare providers should always enforce standard precautions, especially in the hemato-oncology unit.

Bacteremia due to Citrobacter braakii: A case report and literature review.

Among the Citrobacter genus, the most commonly isolated bacteria from human specimens are Citrobacter freundii and Citrobacter koseri, and previous cases of infection due to Citrobacter braakii have been rarely reported. We present a case of bacteremia due to C. braakii in a 38-year-old woman with cervical cancer. She was admitted to our hospital with complaints of a fever, chills, and nausea. Blood culture results showed gram-negative bacilli identified as C. braakii via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, although biochemical testing findings were suggestive of C. freundii. Since a rare pathogen was detected in the present case and the results of additional biochemical studies were suggestive of both C. braakii and Citrobacter farmeri, genetic analysis was conducted. Finally, the gram-negative bacilli were confirmed as C. braakii, a member of the C. freundii complex since 1993, by 16S ribosomal RNA gene sequencing analysis. The gastrointestinal tract was considered the portal of entry, because the patient had a rectal fistula and other cultures such as urine and vaginal discharge incubated species other than C. braakii. The patient recovered after receiving treatment with ciprofloxacin for 14 days. The epidemiology and clinical characteristics of C. braakii infection are still unknown because of the limitations in accurate identification by using currently available commercial biochemical testing and previously, only 6 cases of C. braakii infection have been reported. Physicians should focus on this species, because it causes community-acquired infections, although further studies are needed to clarify the clinical characteristics of C. braakii infections.

Bacteremia due to Streptococcus tigurinus: A case report and literature review.

Gene sequence analysis methods, including 16S rRNA identification, allows accurate identification of Streptococcus species, which include phenotypically closely related species that are difficult to differentiate using conventional chemical methods. We report a case of bacteremia due to Streptococcus tigurinus, identified by 16S rRNA, in a 72-year-old woman with gastrointestinal cancer and ascites. She was hospitalized to undergo elective tumor-related surgery. Five days prior to undergoing surgery, she developed a fever with no obvious source of infection. Blood cultures identified gram-positive cocci. The patient's bacteremia was initially thought to be caused by an Enterococcus species, given her underlying gastrointestinal disease. However, alpha-hemolytic, mucoid, circular colonies were observed on sheep blood agar the following day. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and biochemical testing suggested Streptococcus pneumoniae, we conducted further investigation to identify the bacterium, as the patient had no symptoms of infections usually related with S. pneumoniae such as pneumonia, meningitis, or sinusitis, and the bacteremia occurred 30 days after hospitalization. Finally, the gram-positive cocci were identified as S. tigurinus, assigned to the Streptococcus mitis group in 2012. Although the origin of infection was unclear, it was suspected that peritonitis or bacterial translocation from the gastrointestinal tract caused the bacteremia. This novel species was recently reported as being extremely pathogenic and different from other Streptococcus species. It has been reported to occur in cases of infectious endocarditis and bacteremia. In this article, we reviewed previous reports of S. tigurinus infection and summarized the clinical and pathogenetic features.

Pulmonary metastases from angiosarcoma: a spectrum of CT findings.

BACKGROUND: Though a few reports have summarized the computed tomography (CT) findings of pulmonary metastases from angiosarcoma, the detailed CT findings of cysts are not well known, except for their characteristic thin walls. PURPOSE: To retrospectively summarize the CT findings of pulmonary metastases from angiosarcoma, focusing mainly on the CT findings of cysts. MATERIAL AND METHODS: Thirty-three patients with pulmonary metastases from angiosarcoma were selected retrospectively. Two radiologists reviewed and assessed patients' chest CT images on a consensus basis for nodules, cysts, the CT halo sign, pneumothorax, pleural effusion, and enlarged lymph nodes. Cysts were also evaluated by wall thickness and smoothness, air-fluid levels, and vessels or bronchi penetrating the cysts. The relationship between cysts and pneumothorax was assessed using the Chi-square test. RESULTS: Nodules were found in 28 (85%) patients. Cysts were found in 19 (58%) patients; 17 had thin and smooth walls, 10 had thin and irregular walls, and four had thick and irregular walls. In addition, 12 patients showed vessels or bronchi penetrating the cysts, and six showed air-fluid levels. The CT halo sign, pneumothorax, pleural effusion, and mediastinal lymphadenopathy were seen in 19 (58%), 16 (48%), 26 (78.8%), and five (15.2%) patients, respectively. Pneumothorax occurred significantly more frequently in patients with cysts (P = 0.002). CONCLUSION: Cysts showed variability in their walls, and air-fluid levels and vessels or bronchi penetrating the cysts appeared to be characteristic findings, which may be useful for detection and accurate diagnosis in patients with pulmonary metastases from angiosarcoma.

An Autopsy Case of Two Distinct, Acquired Drug Resistance Mechanisms in Epidermal Growth Factor Receptor-mutant Lung Adenocarcinoma: Small Cell Carcinoma Transformation and Epidermal Growth Factor Receptor T790M Mutation.

We herein describe the case of a 63-year-old man who died from relapsed epidermal growth factor receptor gene (EGFR) exon 19 deletion lung adenocarcinoma treated with erlotinib. According to the autopsy results, he was confirmed to have small cell carcinoma without the EGFR T790M mutation in his pancreas and left kidney metastatic specimens, while the adenocarcinoma metastatic lesion in his right kidney had the EGFR T790M mutation; both retained the somatic EGFR exon 19 deletion. We herein report an autopsy case of resistance to an EGFR tyrosine kinase inhibitor via small cell carcinoma transformation and the EGFRT790M mutation in separate metastatic organs.

Acute respiratory distress syndrome due to Strongyloides stercoralis infection in a patient with cervical cancer.

A 62-year-old woman complained of diarrhea and vomiting after receiving chemotherapy for cervical cancer in association with high doses of corticosteroids. Two months later, the patient developed acute respiratory distress syndrome, and numerous Strongyloides stercoralis parasites were found in the intrabronchial discharge. Ivermectin was administered daily until nematodes were no longer detected in the sputum, and the patient's condition was successfully rescued. Antibodies for human T-cell lymphotropic virus-1 (HTLV-1) were positive. HTLV-1 infection and the administration of corticosteroids are known risk factors for strongyloides hyperinfection syndrome. Therefore, physicians should consider this disease in the differential diagnosis of patients from endemic areas who present with gastrointestinal symptoms under these risk factors.