Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Specific COVID-19 risk behaviors and the preventive effect of personal protective equipment among healthcare workers in Japan.

As coronavirus disease 2019 (COVID-19) outbreaks in healthcare facilities are a serious public health concern, we performed a case-control study to investigate the risk of COVID-19 infection in healthcare workers. We collected data on participants' sociodemographic characteristics, contact behaviors, installation status of personal protective equipment, and polymerase chain reaction testing results. We also collected whole blood and assessed seropositivity using the electrochemiluminescence immunoassay and microneutralization assay. In total, 161 (8.5%) of 1,899 participants were seropositive between August 3 and November 13, 2020. Physical contact (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.6) and aerosol-generating procedures (1.9, 1.1-3.2) were associated with seropositivity. Using goggles (0.2, 0.1-0.5) and N95 masks (0.3, 0.1-0.8) had a preventive effect. Seroprevalence was higher in the outbreak ward (18.6%) than in the COVID-19 dedicated ward (1.4%). Results showed certain specific risk behaviors of COVID-19; proper infection prevention practices reduced these risks.

SARS-CoV-2 Omicron-neutralizing memory B cells are elicited by two doses of BNT162b2 mRNA vaccine.

Multiple SARS-CoV-2 variants have mutations in the spike receptor binding domain (RBD) with potential to evade neutralizing antibody. In particular, the Beta and Omicron variants escape from antibody neutralizing activity in those who received two doses of BNT162b2 mRNA vaccine. Nonetheless, boosting with a third vaccine dose or by breakthrough infection improves the overall breadth of the neutralizing antibodies, but the mechanism remains unclear. Here, we longitudinally profiled the cellular composition of RBD-binding memory B cell subsets and their antibody binding and neutralizing activity against SARS-CoV-2 variants after the second dose of mRNA vaccine. Two doses of the mRNA vaccine elicited plasma neutralizing antibodies with a limited activity against Beta and Omicron but induced an expanded antibody breadth overtime, up to 4.9 months after vaccination. In contrast, more than one-third of RBD-binding IgG+ memory B cells with a resting phenotype initially bound the Beta and Omicron variants and steadily increased the B cell receptor breadth overtime. As a result, a fraction of the resting memory B cell subset secreted Beta and Omicron-neutralizing antibody when stimulated in vitro. The neutralizing breadth of the resting memory B cell subset helps us understand the prominent recall of Omicron-neutralizing antibodies after an additional booster or breakthrough infection in fully vaccinated individuals.

A Perspective from a Case Conference on Comparing the Diagnostic Process: Human Diagnostic Thinking vs. Artificial Intelligence (AI) Decision Support Tools.

Artificial intelligence (AI) has made great contributions to the healthcare industry. However, its effect on medical diagnosis has not been well explored. Here, we examined a trial comparing the thinking process between a computer and a master in diagnosis at a clinical conference in Japan, with a focus on general diagnosis. Consequently, not only was AI unable to exhibit its thinking process, it also failed to include the final diagnosis. The following issues were highlighted: (1) input information to AI could not be weighted in order of importance for diagnosis; (2) AI could not deal with comorbidities (see Hickam's dictum); (3) AI was unable to consider the timeline of the illness (depending on the tool); (4) AI was unable to consider patient context; (5) AI could not obtain input information by themselves. This comparison of the thinking process uncovered a future perspective on the use of diagnostic support tools.

Birt-Hogg-Dubé syndrome and familial adenomatous polyposis: an association or a coincidence?

An association between Birt-Hogg-Dubé syndrome (BHDS) and colon cancer remains conjectural, but herein we describe a case who may illustrate a significant link between them. The 60-year-old woman was diagnosed at 28 years of age with colon carcinoma and familial adenomatous polyposis (FAP). She also had repeated pneumothoraces, and was diagnosed with BHDS following the finding of pneumothorax in her son. We confirmed the presence of germline mutations in both her folliculin (FLCN) and adenomatous polyposis coli (APC) genes. The family pedigree suggested that a de novo FLCN mutation might have contributed to the development of colon carcinoma at a younger age than her family members.

[A case of clopidogrel-induced eosinophilic pneumonia].

An 83-year-old man had been prescribed clopidogrel for pontine infarction since 8 months previously, and had had a cough for the last 2 weeks of this period. Laboratory examinations on admission showed a marked increase in eosinophils and elevated serum immunoglobulin E levels. Chest radiography showed bilateral ground-glass opacities, mild reticulation, and interlobar pleural effusion in the minor fissure. After clopidogrel was discontinued his symptoms resolved, and his laboratory tests showed normal results. Bronchoalveolar lavage also showed an increase in eosinophils, and transbronchial biopsy revealed infiltration of eosinophils in the subepithelium of the bronchial mucosa. On the basis of these findings, we diagnosed eosinophilic pneumonia induced by clopidogrel. Reports on cases of lung diseases caused by anti-platelet drugs are rare. To the best of our knowledge, this case is the first report on clopidogrel-induced eosinophilic pneumonia.

Detailed distribution of acute pulmonary thromboemboli: direct evidence for reduction of acquisition length and radiation dose for triple rule-out CT angiography.

PURPOSE: To reduce the redundant acquisition range and total radiation dose for planning appropriate "triple rule-out" CT angiography (CTA) for acute chest pain, we evaluated the detailed distribution of pulmonary thromboemboli (PTE) in subjects with acute PTE. MATERIALS AND METHODS: Retrospective review of CTA n 75-subjects (48-females; 57 ± 16 years) with proven acute PTE was performed to determine whether PTE was present solely above the aortic arch or below the heart. RESULTS: 77% had PTE in the right upper lobe but none had PTE that were solely located higher than the aortic arch; 73% had PTE in the right middle lobe; 80% had PTE in the right lower lobe, but none had PTE that were solely located lower than the heart. 81% had PTE in the left upper lobe and 3% of them had PTE solely located higher than the aortic arch; both had PTE in the right upper, middle, and lower, and the left lower lobes. 75% had PTE in the left lower lobe, but none had PTE that were solely located lower than the heart. The acquisition length in limited CTPA in this population was reduced on average by 21.9% compared with full CTPA. CONCLUSIONS: In subjects with acute PTE, there were none whose PTE was located solely in the upper lobes which were higher than the aortic arch, nor solely in the lower lobes which were lower than the heart. A limited range triple rule-out CTA protocol would decrease effective doses approximately 22% relative to full chest CTA and may help the physician find all PE present.

[A case of anaphylactic reaction after pleurodesis with OK-432].

A 60-year-old woman had received adjuvant chemotherapy after abdominal hysterectomy for clear cell carcinoma of the endometrium. She had no history of allergy. She was admitted to our hospital because of massive pleural effusion. She underwent drainage of left-side malignant pleural effusion followed by chemical pleurodesis with OK-432 via a chest tube. Ten minutes after administration of OK-432 to the thoracic cavity, she complained of dyspnea and showed general flushing. Since the clinical course suggested drug-induced anaphylactic reaction, she was immediately treated with an adrenaline subcutaneous injection and methylprednisolone sodium succinate intravenous injection. However, the respiratory insufficiency progressively deteriorated and mechanical ventilation was needed for the next 3 days. This is the first published case of anaphylactic reaction to OK-432 pleurodesis. In Japan, OK-432 is a key drug used for pleurodesis and we should consider possible serious adverse reactions include anaphylactic reaction.

[Racemose hemangioma of the bronchial artery].

Racemose hemangioma of the bronchial arteries is a rare abnormality and is characterized by enlarged and convoluted bronchial arteries arranged segmentally along the longitudinal axis of bronchus. Primary racemose hemangioma may arise from inborn malformation, and secondary one may develop following primary inflammatory, stenosing or deforming diseases of the bronchus, the peribronchial tissues and the surrounding lung tissues. The symptom at onset is usually hemoptysis. Although the typical treatments have not been established, various treatments, like embolization or ligation of the bronchial arteries and surgical resection of the involved area of lung, were reported. However the term 'Racemose hemangioma' seems to be used only in Japan, so it is favorable to make a consensus of its definition among countries.

Gender differences in chronic thromboembolic pulmonary hypertension in Japan.

BACKGROUND: The predominance of chronic thromboembolic pulmonary hypertension (CTEPH) in females and association of HLA-B*5201 with CTEPH have been reported in Japan. However, the clinical characteristics of female CTEPH remain uncertain. The purpose of the present study is to clarify the clinical phenotype of female CTEPH in Japan. METHODS AND RESULTS: The 150 consecutive patients (female 103, male 47; age 52.8+/-12.4 years SD) were admitted to Chiba University Hospital, and diagnosis was confirmed using right cardiac catheterization and pulmonary angiography. Among these patients, 78 underwent pulmonary endarterectomy. Clinical characteristics, pulmonary hemodynamics, extent of central disease and surgical outcome in females were compared with those in males. The female patients were elderly and had less deep vein thrombosis, less acute embolic episodes, better cardiac function, lower arterial oxygen tension and more peripheral thrombi, and showed less improvement through surgery than males. When the patients were identified using HLA-B*5201, HLA-B*5201-positive female patients had less embolic episodes and better cardiac function with lower operative mortality. In contrast, HLA-B*5201-negative female patients had less embolic episodes, and more peripheral thrombi, resulting in less improvement by surgery. CONCLUSION: The clinical phenotype of female CTEPH differed from that of male CTEPH. Additionally, gender differences of HLA-B*5201-positive type were dissimilar to those of HLA-B*5201-negative type.

[Case of metachronous mucosa-associated lymphoid tissue (MALT) lymphoma originated from a distinct B-cell clone].

Although mucosa-associated lymphoid tissue (MALT) lymphoma is classified as an indolent lymphoma, it frequently disseminates and recurs to make the disease difficult to cure. The present case had metachronous lesions in the skin, orbit and pleura, and all of them were diagnosed as derived from the same monoclonal tumor cell. A 65-year-old woman was admitted to our hospital because of a pleural tumor with pleural effusion. Two years before, she had undergone surgical resection for skin erythematous lesion and an ocular adnexa tumor, which were diagnosed as lymphoid hyperplasia by histological examination at that time. On admission, thoracoscopy-guided biopsy of the pleural tumor with local anesthesia established a diagnosis of MALT lymphoma. The rearranged immunoglobulin heavy chain of the skin tumor, ocular adnexa tumor, pleural tumor and lymphocytes in the pleural effusion were analyzed using a polymerase chain reaction (PCR)-based assay. This analysis revealed the metachronous MALT lymphoma originated from a distinct B-cell clone. After rituximub and CHOP therapy, complete remission was obtained. Although MALT lymphoma occurs in a wide variety of body sites, the pleural presentation of MALT lymphoma is very rare. Lifelong observation of all patients treated for MALT lymphoma is required because of the high frequency of dissemination and recurrence.

Dilatation of bronchial arteries correlates with extent of central disease in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Dilatation of the bronchial arteries is a well-recognized feature in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of the current study was to use computed tomography (CT) to assess the relationship between dilated bronchial arteries and the extent of thrombi, and to evaluate the predictive value of the former for surgical outcome. METHODS AND RESULTS: Fifty-nine patients with CTEPH and 16 with pulmonary arterial hypertension (PAH) were retrospectively evaluated. The total cross-sectional area of bronchial arteries was measured by CT and its relationship with the central extent of thrombi or surgical outcome was assessed. The total area of the bronchial arteries in CTEPH patients was significantly larger than that in PAH patients (median [range], 6.9 [1.7-29.5] mm(2) vs 3.2 [0.8-9.4] mm(2)), with the total area of bronchial arteries correlating with the central extent of thrombi. In patients who had undergone pulmonary thromboendarterectomy (PTE) (n=22), the change in PaO(2) after surgery had a tendency to correlate with the total area of the bronchial arteries. CONCLUSION: The total cross-sectional area of the bronchial arteries correlated with the extent of central disease in patients with CTEPH, and it might predict gas exchange improvement after PTE.

Survival and quality of life for patients with peripheral type chronic thromboembolic pulmonary hypertension.

BACKGROUND: The validity of pulmonary thromboendarterectomy for treatment of relatively peripheral type of chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. The survival and quality of life (QOL) of patients with relatively peripheral type of CTEPH was investigated at follow up. METHODS AND RESULTS: Between April 1999 and March 2006, 83 consecutive patients with CTEPH were evaluated for surgical indication and underwent computed tomography angiography. The extent of central disease was scored (ie, CD score), and a CD score of

Multidetector-row computed tomography management of acute pulmonary embolism.

BACKGROUND: The purpose of this study was to evaluate the usefulness and safety of multidetector-row computed tomography (MDCT) pulmonary angiography and indirect venography management of acute pulmonary embolism (PE), including indication for inferior vena cava (IVC) filter. METHODS AND RESULTS: Seventy-one consecutive patients who were clinically suspected of PE and underwent 16-slice MDCT pulmonary angiography and indirect venography were enrolled. Management included indication of IVC filter for patients with extensive deep venous thrombosis (DVT) in submassive or massive PE. A right ventricular to left ventricular short-axis diameter by MDCT>1.0 was judged as submassive PE. All patients were followed for 1 year. MDCT identified 50 patients with venous thromboembolism and 47 patients had acute PE: 4 were judged as massive, 14 as submassive, and 29 as non-massive by MDCT; 3 patients had DVT alone and 7 patients had caval or iliac DVT. Only 1 patient with massive PE and DVT near the right atrium died of recurrence. No other patients died of PE. CONCLUSION: Management based on MDCT pulmonary angiography combined with indirect venography is considered to be safe and reliable in patients with suspected acute PE.

[A case of intractable hemoptysis originating from the branches of the right subclavian artery, successfully treated with arterial coil embolization].

A 30-year-old woman was admitted because of persistent and severe hemoptysis in November 2005. She had been given a diagnosis of interstitial pneumonia (IP) and pulmonary aspergilloma in 2001, and she was treated with oral prednisolone and itraconazole. However she had persistent and intractable hemoptysis. Multi-detector row computed tomography (MDCT) revealed that hemoptysis from the right upper lobe did not originate in bronchial arteries, but the abnormal branches of the right subclavian artery. Surgery was not performed because of her pulmonary function, but she was successfully treated by non-bronchial arterial coil embolization. At 10 months after the embolization, hemoptysis has not recurred. MDCT was very useful for diagnosing the cause of hemoptysis and selective nonbronchial arterial coil embolization might be helpful in treating intractable or refractory hemoptysis.