Effect of cisplatin on respiratory activity in neonatal rats.

One side effect of cisplatin, a cytotoxic platinum anticancer drug, is peripheral neuropathy; however, its central nervous system effects remain unclear. We monitored respiratory nerve activity from the C4 ventral root in brainstem and spinal cord preparations from neonatal rats (P0-3) to investigate its central effects. Bath application of 10-100 µM cisplatin for 15-20 min dose-dependently decreased the respiratory rate and increased the amplitude of C4 inspiratory activity. These effects were not reversed after washout. In separate perfusion experiments, cisplatin application to the medulla decreased the respiratory rate, and application to the spinal cord increased the C4 burst amplitude without changing the burst rate. Application of other platinum drugs, carboplatin or oxaliplatin, induced no change of respiratory activity. A membrane potential analysis of respiratory-related neurons in the rostral medulla showed that firing frequencies of action potentials in the burst phase tended to decrease during cisplatin application. In contrast, in inspiratory spinal motor neurons, cisplatin application increased the peak firing frequency of action potentials during the inspiratory burst phase. The increased burst amplitude and decreased respiratory frequency were partially antagonized by riluzole and picrotoxin, respectively. Taken together, cisplatin inhibited respiratory rhythm via medullary inhibitory system activation and enhanced inspiratory motor nerve activity by changing the firing property of motor neurons.

Comparison of COVID-19 disease between young and elderly patients: Hidden viral shedding of COVID-19.

OBJECTIVES: The symptoms of Coronavirus disease 2019 (COVID-19) vary among patients. The aim of this study was to investigate the clinical manifestation and disease duration in young versus elderly patients. METHODS: We retrospectively analyzed 187 patients (87 elderly and 100 young patients) with confirmed COVID-19. The clinical characteristics and chest computed tomography (CT) extent as defined by a score were compared between the two groups. RESULTS: The numbers of asymptomatic cases and severe cases were significantly higher in the elderly group (elderly group vs. young group; asymptomatic cases, 31 [35.6%] vs. 10 [10%], p < 0.0001; severe cases, 25 [28.7%] vs. 8 [8.0%], p = 0.0002). The proportion of asymptomatic patients and severe patients increased across the 10-year age groups. There was no significant difference in the total CT score and number of abnormal cases. A significant positive correlation between the disease duration and patient age was observed in asymptomatic patients (ρ = 0.4570, 95% CI 0.1198-0.6491, p = 0.0034). CONCLUSIONS: Although the extent of lung involvement did not have a significant difference between the young and elderly patients, elderly patients were more likely to have severe clinical manifestations. Elderly patients were also more likely to be asymptomatic and a source of COVID-19 viral shedding.

A case of COVID-19 pneumonia successfully treated with favipiravir (Avigan) in which serum SARS-CoV-2 RNA detected by LAMP method was clinically useful.

A 49-year-old Japanese male was managed by mechanical ventilation due to coronavirus disease 2019 (COVID-19) pneumonia. Favipiravir as an antiviral therapy, and anti-inflammatory treatment were administered. SARS-CoV-2 RNA was detected in serum by the loop-mediated isothermal amplification (LAMP) method on Day 9; favipiravir treatment was continued. On Day 13, negative serum RNA was confirmed, followed by mechanical ventilation was removed. On Day 23, LAMP negative was confirmed in nasopharynx, after that the patient discharged on Day 27. We could treat successfully for severe COVID-19 pneumonia based on the LAMP method. We consider this method will be useful in COVID-19 treatment.

Primary cardiac rhabdomyosarcoma successfully treated with eribulin: a case report.

Rhabdomyosarcoma is the most common soft tissue sarcoma that typically occurs in children and adolescents and is rare in adults. Furthermore, as cardiac tumor is rare, adult cardiac rhabdomyosarcoma is a very rare entity. Here, we report the case of a 68-year-old woman with cardiac rhabdomyosarcoma who was successfully treated with eribulin. She presented with sudden loss of consciousness, which was attributed to the cardiac tumor. The tumor was resected by emergency surgery and was diagnosed as embryonal rhabdomyosarcoma. Although surgical treatment alleviated her symptoms, the residual tumor increased in size after surgery and required multimodal treatment. First-line chemotherapy with the vincristine, actinomycin D, and cyclophosphamide regimen had to be discontinued owing to adverse events, and thus eribulin was used as a second-line treatment. Eribulin was better tolerated and helped maintain a stable disease status for >18 months. This reported case of cardiac rhabdomyosarcoma is the first case to be successfully treated with eribulin over a relatively long period. Eribulin therapy may thus be a viable treatment alternative for rhabdomyosarcoma.

Serial serum SARS-CoV-2 RNA results in two COVID-19 cases with severe respiratory failure.

Coronavirus disease 2019 (COVID-19) is spreading worldwide and poses an imminent threat to public health. We encountered 2 cases of COVID-19 with progression resulting in severe respiratory failure and improvement without any specific treatment. To examine the course of infection, we performed reverse-transcription (RT) polymerase chain reaction assay with serum specimens, and serum SARS-CoV-2 RNA was detected in both cases when body temperature increased and respiratory status deteriorated. We, then examined, retrospectively and prospectively, the clinical course during hospitalization by performing serial examinations of serum SARS-CoV-2 RNA status. The findings from our cases suggest that not only is detection of viremia useful as a predictive marker of severity, but also serial serum SARS-CoV-2 RNA results can be helpful for predicting the clinical course.

[Experience with Pulmonary Resection under Thoracoscopic Surgery for Lung Cancer Patient with Abnormal Left A4b+5 and A8+9 Branching].

The case was a 56-year-old man. A nodular shadow of the left upper lobe was found in the chest computed tomography, and a diagnosis of adenocarcinoma was obtained by bronchoscopy. Preoperative 3-dimensional computed tomography (3D-CT) angiography indicated an extremely rare pulmonary artery bifurcation abnormality in which A4b+5 and A8+9 bifurcate from the left main pulmonary artery. Thoracoscopic left upper lobectomy and lymph node dissection were performed. Pathological diagnosis was adenocarcinoma with pStage I B. The mediastinal basal pulmonary artery is extremely rare, and to our knowledge, the bifurcation pattern of this case has not been reported elsewhere. The 3D-CT angiography was useful to detect the anatomical vascular abnormalities of the pulmonary artery before surgery, for the safe performance of the thoracoscopic surgery.

[Schloffer Tumor that Appeared and Increased 40 Months after Resection of Lung Cancer and was Suspected of Recurrence of Pleural Dissemination].

The case is a 50-year-old woman. Video-assisted thoracic surgery (VATS) left upper division segmentectomy was performed for adenocarcinoma through a postero-lateral incision. The pathological result was stage ⅠA. A chest computed tomography (CT) examination 40 months after the operation revealed a nodule in contact with the left 6th rib. A recurrence due to pleural dissemination was suspected in the PET/CT examination, but the possibility of reactive granulation was also considered. Two months later, chest CT reexamination showed an enlargement of the nodule, and reoperation was performed. A fibrous structure that appears to be a silk thread for closing chest at the 1st operation was found on the chest wall. The pathological examination revealed chronic suppurative pleuritis and organizing pneumonia without malignancy, leading to a diagnosis of Schloffer tumor.

[Dumbbell-shaped Intercostal Neurilemmoma of the Anterior Chest Wall;Report of a Case].

A 18-year-old man was referred to our hospital complaining of chest abnormal shadow of the left upper lung field in mass screening chest X-ray. Although his left anterior chest wall swelled, he did not recognize that. Computed tomography and magnetic resonance imaging demonstrated a dumbbell shaped tumor of the left 1st intercostal space which had grown both inside and outside the thoracic cavity. As a possibility of solitary fibrous tumor or myxoma was not excluded, the patient underwent tumor resection. A solid tumor connected to the 1st intercostal nerve was easily dissected from surrounding tissue. Pathological examination revealed the tumor was consisted of spindle shaped cells without atypia, and diagnosed as neurilemmoma without malignancy. Based on anatomical pathway of intercostal nerves, we speculate that the tumor originated from anterior cutaneous nerve.

A case of Epstein-Barr virus-negative human immunodeficiency virus-related primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus-8. Most cases are co-infected with Epstein-Barr virus (EBV). The prognosis of PEL is extremely poor and no optimal treatment regimen has been established. We report a case of EBV-negative PEL in a 49-year-old human immunodeficiency virus-positive man, presenting with massive bilateral pleural effusion.

Diagnosis of imported Ugandan typhoid fever based on local outbreak information: A case report.

Re-emerging multidrug-resistant typhoid fever is becoming a worldwide threat, especially in East Africa. At the beginning of 2015, an outbreak of typhoid fever started in the capital city of Uganda, and 1940 suspected cases were reported by 5 March 2015. In this report, we describe a case of typhoid fever caused by a MDR strain with HIV infection and hemoglobin S-syndrome thalassemia in an Ugandan from Kampala City. It is essential to consider MDR strains of Salmonella enterica serovar Typhi infections, including fluoroquinolone-resistant strains, in patients from Africa and Southeast Asia.

Nonepisodic angioedema with eosinophilia following a rose-thorn prick injury.

Background: Nonepisodic angioedema with eosinophilia (NEAE) is a condition marked by angioedema and significant eosinophilia and often linked with atopic dermatitis. It predominantly affects young Asian women and occurs more frequently in the autumn and winter. Despite over 100 reported cases, its etiology and pathogenesis remain unclear. Case presentation: A 23-year-old Japanese female florist presented with acute arm swelling following rose-thorn pricks to her hands and fingers in spring. One week later, she developed progressive symmetrical non-pitting edema in her lower legs and a 3 kg weight gain without any rash. She had a history of oral allergy syndrome to apples and pears for which allergen-specific IgE were previously detected. Blood tests showed significant eosinophilia (14,930 cells/µL) and elevated thymus and activation-regulated chemokine (TARC) levels (12,864 pg/mL). Thyroid disease, autoimmune disorders, and hematologic malignancies were ruled out. Normal cardiac markers and a whole-body computed tomography excluded visceral organ involvement. She was diagnosed with NEAE and treated with oral prednisolone, which resolved the edema within 10 days. Prednisolone was tapered gradually on an outpatient basis without recurrence. Conclusion: A review of the literature indicates that NEAE triggered by subcutaneous antigen exposure may not follow the typical age or seasonal patterns. Direct subcutaneous antigen exposure, including rose-thorn pricks, can trigger NEAE. Clinicians should consider NEAE in atypical presentations and thoroughly investigate preceding episodes.

Effectiveness and duration of additional immune defense provided by SARS-CoV-2 infection before and after receiving the mRNA COVID-19 vaccine BNT162b2.

Background: Our investigation focused whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before or after receiving the mRNA COVID-19 vaccine can increase immune protection. And we also investigated relationship of infection acquired. Methods: Three shots of the mRNA coronavirus disease 2019 (COVID-19) vaccine BNT162b2 were administered to 736 healthcare workers at Tokyo Shinagawa Hospital. Serum samples were collected before the first shot (P1), at one month (P2), and at six months (P3) after the second shot and at one month after the third shot (P4). The presence of infection was assessed using IgG against the nucleocapsid (IgG (N) and RBD in the spike protein of SARS-CoV-2. We defined infection before P2 as natural infection (NI) and infection between P2 and P3 as breakthrough infection (BI) and compared susceptibility to further infection between the NI (-) and NI (+) groups and between BI (-) and BI (+) groups. Events in 485 participants who had a complete dataset of IgG (N) and IgG (RBD) from P1 to P4 were analyzed. Results: The presence of SARS-CoV-2 infection before P2 were examined by examining the titers of IgG (N)P1, IgG (N) P2, and IgG (RBD) P1 that exceeded the cutoff values. Consequently, 35 participants (7.22 %) were categorized into the NI (+) group, whereas 450 (92.8 %) were categorized into the NI (-) group. Between P2 and P3, the NI (-) group showed a higher rate of SARS-CoV-2 infection than the NI (+) group; however, there was no significant difference in the infection rate between P3 and P4. The infection rate was significantly lower in the BI (+) group than in the BI (-) group. Pre-primary vaccination infection significantly increased IgG (RBD) levels between P1 and P3. Post-primary vaccination infection significantly increased IgG (RBD) levels between P3 and P4. Conclusions: Infection with SARS-CoV-2 before or after receiving the mRNA COVID-19 vaccine can increase immune protection; however, the duration of this effect may be limited.

Burden of respiratory syncytial virus, human metapneumovirus and influenza virus infections in Japanese adults in the Hospitalized Acute Respiratory Tract Infection study.

BACKGROUND: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus are responsible for acute respiratory tract infections (ARTIs) in adults. We assessed the clinical burden of RSV, hMPV and influenza virus infection among Japanese adults hospitalized with ARTIs. METHODS: The Hospitalized Acute Respiratory Tract Infection (HARTI) study was a multinational, prospective cohort study in adults with ARTIs across the 2017-2019 epidemic seasons. Enrolment in Japan began in Sept 2018 and ran until Oct 2019. The clinical diagnosis of ARTI and the decision to hospitalize the patient were made according to local standard of care practices. Viral testing was performed by reverse transcription polymerase chain reaction. RESULTS: Of the 173 adults hospitalized with ARTI during this period at the Japan sites, 7 (4.0%), 9 (5.2%), and 11 (6.4%) were positive for influenza virus, RSV, and hMPV, respectively. RSV season was observed from Oct 2018 to Jan 2019, followed by influenza from Dec 2018 to Apr 2019. hMPV was detected across both the RSV and influenza seasons. Two patients with RSV and 1 patient with hMPV required ICU admission whereas none with influenza. Use of antibiotics, bronchodilators and inhaled corticosteroids was high amongst patients with RSV and hMPV at 1, 2, and 3 months' post-discharge compared with patients with influenza, with few exceptions. CONCLUSION: These findings highlight the need for a high degree of clinical suspicion for RSV and hMPV infection in adults hospitalized with ARTIs.

Comparison of liver fibrosis scores and fatty liver on computed tomography as risk factors for severity of COVID-19.

Background and Aim: Increased liver fibrosis scores (LFS), such as fibrosis-4 index (FIB-4) or non-alcoholic fatty liver disease fibrosis score (NFS), and fatty liver are known risk factors for severe coronavirus disease 2019 (COVID-19). The purpose of this study was to identify the best scores, which predict the prognosis of COVID-19. Methods: Participants comprised consecutive Japanese COVID-19 patients admitted to our hospital between February 14, 2020, and April 14, 2021. Multivariate logistic regression analysis was performed to evaluate the relationships between LFS (FIB-4, NFS, aspartate aminotransferase-to-platelet ratio index [APRI], BARD score, and hepatic steatosis index [HSI]) or fatty liver on computed tomography (CT), and severity of COVID-19. Results: Of the 415 patients (mean age, 59 years), 177 patients (42.7%) needed oxygen therapy, 90 patients (21.7%) worsened to severe COVID-19, and 45 patients (10.8%) died during admission. Multivariate logistic regression analysis showed that increased FIB-4 and NFS were risk factors for death, severe COVID-19, and oxygen demand; that increased BARD was a risk factor for severe COVID-19 and oxygen demand; and that increased APRI and HSI were not risk factors for any status of COVID-19. Furthermore, increased NFS or BARD and fatty liver were independent risk factors for severe COVID-19 and oxygen demand. Conclusions: This study showed that FIB-4 and NFS were the best liver fibrosis scores that predicted worse prognosis for COVID-19, and that increased NFS or BARD and fatty liver evident on CT represented independent risk factors for severe COVID-19 and oxygen demand.

Surveillance of seasonal influenza viruses during the COVID-19 pandemic in Tokyo, Japan, 2018-2023, a single-center study.

Introduction: COVID-19 pandemic led to significant reductions in influenza detection worldwide, fueling debates on whether influenza truly ceased circulating in communities. The number of influenza cases decreased significantly in Japan, raising concerns about the potential risk of decreased immunity to influenza in the population. Our single-center study aimed to investigate influenza trends before and during the COVID-19 pandemic in Tokyo, Japan. Materials and Methods: This cross-sectional study included patients of all ages who visited Tokyo Shinagawa Hospital between April 1, 2018, and March 31, 2023. Influenza and COVID-19 tests were conducted using Quick Navi-Flu2 and polymerase chain reaction (PCR). We analyzed data from before and during the COVID-19 epidemic, based on patient background, hospitalization, and deaths, collected from medical records. Results: A total of 12 577 influenza tests were conducted, with approximately 100 tests consistently performed each month even in the influenza off-season. Throughout the observation period, 962 positive cases were identified. However, no cases were observed for 27 months between March 2020 and November 2022. Influenza A cases were reobserved in December 2022, followed by influenza B cases in March 2023, similar to the influenza incidence reports from Tokyo. The positivity rate during the 2022-2023 winter season was lower than before the COVID-19 epidemic and decreased in elderly patients, with no hospitalizations or deaths observed. Conclusion: This single-center study provided actual trend data for influenza patients before and during COVID-19 outbreaks in Tokyo, which could offer insights into the potential impact and likelihood of influenza virus infection in Japan.

High Fever, Wide Distribution of Viral Pneumonia, and Pleural Effusion are More Critical Findings at the First Visit in Predicting the Prognosis of COVID-19: A Single Center, retrospective, Propensity Score-Matched Case-Control Study.

Introduction: Currently, infection control measures for SARS-COV2 are being relaxed, and it is important in daily clinical practice to decide which findings to focus on when managing patients with similar background factors. Methods: We retrospectively evaluated 66 patients who underwent blood tests (complete blood count, blood chemistry tests, and coagulation tests) and thin slice CT between January 1 and May 31, 2020, and performed a propensity score-matched case-control study. Cases and controls were a severe respiratory failure group (non-rebreather mask, nasal high-flow, and positive-pressure ventilation) and a non-severe respiratory failure group, matched at a ratio of 1:3 by propensity scores constructed by age, sex, and medical history. We compared groups for maximum body temperature up to diagnosis, blood test findings, and CT findings in the matched cohort. Two-tailed P-values <0.05 were considered statistically significant. Results: Nine cases and 27 controls were included in the matched cohort. Significant differences were seen in maximum body temperature up to diagnosis (p=0.0043), the number of shaded lobes (p=0.0434), amount of ground-glass opacity (GGO) in the total lung field (p=0.0071), amounts of GGO (p=0.0001), and consolidation (p=0.0036) in the upper lung field, and pleural effusion (p=0.0117). Conclusion: High fever, the wide distribution of viral pneumonia, and pleural effusion may be prognostic indicators that can be easily measured at diagnosis in COVID-19 patients with similar backgrounds.

[Air embolism at the pleurodesis for air leakage after pulmonary resection].

A 61-year-old female who was diagnosed with right lung cancer had right lower lobectomy by videoassisted thoracic surgery in June 2010. At the 7th post operative day( 7POD), the patient complained of dyspnea and chest X-ray showed right pneumothorax which was successfully treated by closed drainage and pleurodesis. Since then repeated right pneumothorax appeared and the same procedures were chosen for treatment. In September 2010, just after the pleurodesis for the 3rd time event, she lost consciousness. Brain computed tomography (CT) demonstrated air density area in bilateral internal carotid arteries and right parietal lobe, establishing the diagnosis of air embolism which was successfully treated by hyperbaric oxygen treatment.

Detection of silent infection of severe acute respiratory syndrome coronavirus 2 by serological tests.

BACKGROUND: To control COVID-19 pandemic is of critical importance to the global public health. To capture the prevalence in an accurate and timely manner and to understand the mode of nosocomial infection are essential for its preventive measure. METHODS: We recruited 685 healthcare workers (HCW's) at Tokyo Shinagawa Hospital prior to the vaccination with COVID-19 vaccine. Sera of the subjects were tested by assays for the titer of IgG against S protein's receptor binding domain (IgG (RBD)) or IgG against nucleocapsid protein (IgG (N)) of SARS-CoV-2. Together with PCR data, the positive rates by these methods were evaluated. RESULTS: Overall positive rates among HCW's by PCR, IgG (RBD), IgG (N) with a cut-off of 1.4 S/C (IgG (N)1.4), and IgG (N) with a cut-off of 0.2 S/C (IgG (N)0.2) were 3.5%, 9.5%, 6.1%, and 27.7%, respectively. Positive rates of HCW's working in COVID-19 ward were significantly higher than those of HCW's working in non-COVID-19 ward by all the four methods. Concordances of IgG (RBD), IgG (N)1.4, and IgG (N)0.2 against PCR were 97.1%, 71.4%, and 88.6%, respectively. By subtracting the positive rates of PCR from that of IgG (RBD), the rate of overall silent infection and that of HCW's in COVID-19 ward were estimated to be 6.0% and 21.1%, respectively. CONCLUSIONS: For the prevention of nosocomial infection of SARS-CoV-2, identification of silent infection is essential. For the detection of ongoing infection, periodical screening with IgG (RBD) in addition to PCR would be an effective measure. For the surveillance of morbidity in the population, on the other hand, IgG (N)0.2 could be the most reliable indicator among the three serological tests.

Effects of ANP and BNP on the generation of respiratory rhythms in brainstem-spinal cord preparation isolated from newborn rats.

Natriuretic peptides (NPs) are a family of peptide hormones produced in cardiac muscle cells and consist mainly of three types: atrial NP (ANP), B-type (or brain) NP (BNP), and C-type NP. We herein report the effects of ANP and BNP on central respiratory activity in brainstem-spinal cord preparation isolated from newborn rats. Bath application of these peptides (100 nM) induced a weak transient depression of the respiratory rhythm followed by recovery. Respiratory-related neurons in the rostral ventrolateral medulla showed a tendency for transient hyperpolarization followed by recovery during the application of ANP or BNP. The application of a membrane-permeable cGMP, 8-Br-cGMP (10 or 20 µM), did not induce significant effects on respiratory rhythm, suggesting no involvement of guanylyl cyclase in effects of ANP or BNP. We also examined effects of BNP on respiratory depression induced by the sedative dexmedetomidine, which exerts an inhibitory influence on respiratory rhythm. When pretreated with 50 nM BNP, the inhibitory effect of 100 nM dexmedetomidine was significantly reduced. Our findings suggest that ANP and BNP act as mild excitatory agents with sustained effects on respiratory rhythm after an initial transient depression.

Possibility of underestimation of COVID-19 prevalence by PCR and serological tests.

BACKGROUND: Exact comprehension of the prevalence of SARS-CoV-2 infection is essential for the preventive measures. In the clinical settings, however, patients infected with SARS-CoV-2 may not be fully detected by PCR. In the long-term prevalence study, cut-off of IgG assay may not be appropriate due to waning IgG titer. METHODS: 24 PCR-negative subjects suspected of COVID-19 were categorized into cohorts termed "presumed COVID-19 positive" and "presumed COVID-19 negative" by chest CT images. IgG against nucleocapsid protein of SARS-CoV-2 (IgG (N)) and IgG against receptor biding domain of SARS-CoV-2 (IgG (RBD)) were measured in sera of the subjects and the concordance with the cohort categorization was assessed by receiver operating characteristics (ROC) analyses. RESULTS: Area under the curves (AUC's) by the ROC analyses with the 24 subjects were 0.982 with IgG (N) and 0.854 with IgG (RBD). Even when we excluded the subjects whose initial PCR was performed after five days from symptom onset, the AUC's were 0.967 with IgG (N) and 0.800 with IgG (RBD). The ROC analysis indicated 0.2 S/C as the optimum cut-off forIgG (N). CONCLUSION: Both IgG (N) and IgG (RBD) titers were significantly elevated in subjects whose PCR never showed positive but suggestive of SARS-CoV-2 infection, which indicated the necessity of serological tests in complementing the shortcomings of PCR. For a long-term prevalence study, a cut-off lower than the one used in the ongoing infection phase (e.g. 0.2 S/C vs. 1.4 S/C) was indicated to be more appropriate for IgG (N).