Research on the Clinical Practical Use of Pivoxil-Conjugated Antibodies and the Risk of Carnitine Deficiency Using Real-World Data.

In Japan, pivoxil-conjugated antibodies (PVs) are commonly used to treat infections. However, carnitine deficiency is a known adverse drug reaction associated with PV treatment. This study aimed to research the practical use of PV and assess the risk of carnitine deficiency in patients receiving PV compared to their amoxicillin (AM)-treated counterparts. The Pediatric Medical Information Collection System (P-MICS) served as the data source for this study. The study cohort comprised patients aged 0-15 years prescribed PV between April 2016 and March 2021. Data on the actual PV prescriptions were extracted for each patient. To evaluate the risk of carnitine deficiency, adverse events (AEs) were defined as carnitine deficiency and its associated symptoms. Propensity score matching was employed to compare the AE incidence between the PV and AM groups. The number of cases of PV prescriptions decreased year-on-year between 2016 and 2021, and >80% of prescriptions were dispensed in the clinic. The propensity score matching analysis demonstrated no statistically significant difference in the incidence of carnitine deficiency and its associated symptoms between the PV and AM groups. Our findings suggest that the risk of carnitine deficiency in children treated with PV is not significantly higher than that associated with other antibiotics.

Transitions in sense of coherence among middle-aged women raising adolescents before and during the COVID-19 pandemic.

Objective: A longitudinal study was conducted among Japanese women raising adolescents to determine how the COVID-19 pandemic has affected their sense of coherence (SOC) and to provide suggestions for supporting them. Methods: The SOC scores of 138 pairs of middle-aged women and their children (junior high school students) were compared at two time points: 2019 (before the pandemic, T1) and 2020 (during the pandemic, T2). Results: Overall, the women's SOC did not change, whereas the adolescents' SOC increased. In contrast, 44% of the women's SOC scores decreased during the pandemic; no differences were detected between the SOC maintenance and increase group (G1) and the SOC decrease group (G2) in mental health, subjective physical health, social capital, and job status, and the child variables were not related. Multiple regression analysis of G1 and G2 with SOC at T2 as the dependent variable showed that for G2, at T1, having good mental and physical health conditions, a rich social capital, and having a job were positively associated with SOC during the pandemic. Conclusion: Middle-aged Japanese women, who often work as informal workers, are easily laid off and are involved in care work. Thus, the change in their socioeconomic status due to the pandemic may have been severe. Given the long-term social impact of the pandemic, it is necessary to consider support for women, including economic and social support such as employment and building human connections.

A Sense of Belonging and Help Seeking: Examining Factors Related to the Mental Health of High School Students with High Autistic Traits without Diagnosis.

Certain individuals are clinically undiagnosed for Autism Spectrum Disorder (ASD) but exhibit strong ASD characteristics. This study examined the differences between a control group and a "high autistic traits" group involving individuals who scored 9 or higher on the Autism-Spectrum Quotient-16 Japanese Version, based on their sense of belonging, help-seeking style, and relationship with mental health. The participants were 608 Japanese public high school students. Of them, 129 (21.2%) and 479 (78.8%) were in the high autistic traits and control groups, respectively. A multiple regression analysis was performed using the General Health Questionnaire (GHQ) as the dependent variable for the groups. The analysis revealed no differences between the two groups regarding grade, gender, physical illness, insomnia, or mental health status; however, they differed regarding avoidant help-seeking style and teacher acceptance. Moreover, avoidant help-seeking scores in the high autistic traits group and teacher acceptance showed a significantly positive and significantly negative association with GHQ, respectively. The results indicated that children with autistic traits internally suppress them, experiencing distress. Teachers are aware that these students seek support from them, but the students seem reluctant to ask them for help. This can negatively impact the mental health of children with high autistic traits.

Difficulties and distress experienced by Japanese public health nurses specializing in quarantine services when dealing with COVID-19: A qualitative study in peri-urban municipality.

Public health nurses (PHNs) are among the few municipal civil servants who lead community infection control and prevention initiatives in Japanese public health centers (PHCs). This study aims to investigate the distress faced by PHNs and clarify their difficulties and working environment relative to infection prevention control activities during the COVID-19 pandemic. We adopted a qualitative description methodology in this study of 12 PHNs who were involved in COVID-19 prevention and control in PHCs in Prefecture A. The distress during the early phase of the pandemic was due to the uncertainty of the SARS-CoV-2 related disease, which caused panic in medical institutions and among residents. PHNs were overwhelmed, distressed and exhausted by their inability to control the 'pandemic', lack of patient cooperation for prevention control and the unsustainable organizational environment. They were also distressed because they were one of the specialized personnel responsible for saving residents' lives with limited medical resources and while having identity crises due to an inability to carry out the PHN's role of controlling infection in the community. For future crises, rapid, drastic innovation defying conventional organizational systems is critical to reform sustainable organizations so that they play an effective role in the community. Innovation in crisis communication and strengthening the medical system will help achieve a resilient community in a health crisis.

A study on the examination of sense of coherence-related factors in Japanese junior high school students and their mothers.

This study examined the relationship between the sense of coherence (SOC), which is conceptually the ability to successfully cope with stress, of Japanese junior high school students and their mothers, and investigated SOC-related factors among the students. We analyzed self-reported data from 134 junior high school students (aged 12-14 years) and their mothers (average age: 45.5 ± 4.1 years), based in an urban area of Japan. We found a weak correlation between the SOC total scores of female students and their mothers; further, few subscales showed weak correlations. However, the SOC of male students was not correlated with that of their mothers, including the three subcomponents that constitute the SOC. The results of multiple regression analysis indicated that the SOC of female students was negatively associated with ASD-related characteristics, sensitivity to evaluation, and avoidant help-seeking style, and positively associated with a sense of belonging to the school. However, male students' SOC showed a negative relationship with excessive response to evaluation and a strong sense of parental control. To improve SOC in adolescents, it is necessary to consider their gender differences and support them, both at home and school.

Changes in Japanese Junior High School Students' Sense of Coherence Before and After the Onset of the COVID-19 Pandemic: A Longitudinal Study of Children and Mothers.

We conducted a longitudinal study to clarify the changes in the sense of coherence (SOC); that is, the ability to cope with stress successfully, of 166 Japanese junior high school students and their mothers before and after the onset of the COVID-19 pandemic. First, we analyzed changes in SOC at three time points for all students and divided them into two groups: Group 1 included students with SOC scores that increased or maintained before and after the onset of the pandemic and Group 2 included students with decreased SOC scores after the onset of the pandemic. Second, we conducted a comparative analysis between the two groups. Overall, results indicated that student's SOC scores increased. Additionally, interpersonal stress scores were lower after the onset of the pandemic than before. There were almost no differences in family relationships, financial conditions, or personality tendencies between the two groups. However, Group 2 did not regain their sense of belonging to school. In this group, the frequency of stress experiences in club activities after the onset of the pandemic, troubles with the opposite gender, and inability to catch up with the contents of the subject lecture were high. The accumulation of small stressors may have hindered the maintenance of a sense of school affiliation. Mothers of students in Group 2 either were full-time employees at baseline or had started a new job after the onset of the pandemic. Their children may have been affected by the household's damaged financial budget and changes in mother's working styles. As COVID-19 reduced the number of days students went to school, students' SOC could have reduced had they not felt a sense of presence or belonging due to the lack of participation in club activities, school events, etc. Teachers and mothers should communicate carefully with their students and children, respectively, to develop a sense of belonging.

Factors Influencing Sense of Coherence: Family Relationships, High School Life and Autism Spectrum Tendency.

Adolescence is marked by significant life stress. Recently, school refusal and dropouts as well as suicide among Japanese adolescents have increased. Sense of coherence (SOC) is recognized as a competency that helps people deal with stress. The purpose of this study was to examine the factors influencing SOC in male and female high school students. We conducted a survey with 203 pairs of high school students and their mothers, in Tokyo, to explore their SOC, family relationships, school belonging, and autistic traits. Analysis of the data revealed a weak relationship between female students' SOC and that of their mothers, and no relationship between male students' SOC and their mothers' SOC. Feelings of acceptance and recognition from teachers improved students' SOC, irrespective of gender. Low SOC in mothers had a negative impact on female students' SOC, and children's lack of imagination (an autism spectrum tendency) had a negative impact on male students' SOC. This study revealed the importance of support at home and school according to the needs of both genders.

Acetylcholine receptor antibody-positive myasthenia gravis associated with small-cell lung cancer: A case report.

RATIONALE: Only few cases of myasthenia gravis (MG) associated with small-cell lung cancer (SCLC) have been reported, and cases positive for acetylcholine receptor antibody (AChR-ab) are even rarer. The efficacy of standard MG treatment, such as cholinesterase inhibitor therapy, immunosuppressive therapy using steroids and immunosuppressive drugs, plasma exchange, and intravenous immune globulin (IVIg), for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 71-year-old man complained of bilateral eyelid ptosis. He also presented with dysphagia and masticatory muscle fatigue after chewing. The edrophonium test was positive, and the serum AChR-ab level was increased; therefore, the patient was diagnosed with MG. Computed tomography scan showed a nodule on the left upper lobe of the lung and mediastinal lymphadenopathy. Further examination revealed the lesion as SCLC. Finally, he was diagnosed with AChR-ab-positive MG associated with SCLC. INTERVENTIONS AND OUTCOMES: Oral pyridostigmine and tacrolimus were administered to treat MG; however, his symptoms worsened. Therefore, methylprednisolone and IVIg were administrated, which temporarily improved his symptoms. However, they remained uncontrolled. Meanwhile, chemotherapy with carboplatin and etoposide was administered to treat his SCLC. The lesions shrunk, and the MG symptoms and serum AChR-ab level also improved. LESSONS: AChR-ab-positive MG may develop as a comorbidity of SCLC. In such cases, management might require treatment for SCLC in addition to the standard MG treatment to stabilize the MG symptoms.

Putative lung adenocarcinoma with epidermal growth factor receptor mutation presenting as carcinoma of unknown primary site: A case report.

RATIONALE: Only a few cases of putative lung adenocarcinoma presenting as carcinoma of unknown primary site (CUP) with epidermal growth factor receptor (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 67-year-old man complained of paresis of the right lower extremity, dysarthria, and memory disturbance. Computed tomography and magnetic resonance imaging showed multiple brain tumors with brain edema and swelling of the left supraclavicular, mediastinal, and upper abdominal lymph nodes. Moreover, a metastatic duodenal tumor was detected via upper gastrointestinal endoscopy examination. The biopsy specimen of the lesion was examined and was diagnosed as adenocarcinoma with CK7 and TTF-1 positivity. Finally, the case was diagnosed as EGFR mutation-positive putative lung adenocarcinoma presenting as CUP. INTERVENTIONS AND OUTCOMES: Oral erlotinib, an EGFR-TKI, was administered at 150 mg daily. Five weeks later, the brain lesions and several swollen lymph nodes showed marked improvement, and the symptoms of the patient also improved. Three months later, the duodenal lesion was undetected on upper gastrointestinal endoscopy. After an 8-month follow-up, the patient was well with no disease progression. LESSONS: Putative lung adenocarcinoma presenting as CUP may have EGFR mutation, and EGFR-TKI therapy may be effective for such malignancy.

A Rare Combination of Dermatomyositis, Interstitial Pneumonia, and Lung Cancer in a Patient Treated with Immunosuppressive Therapy and Chemotherapy.

We herein report the rare case of co-occurring dermatomyositis (DM), interstitial pneumonia (IP), and lung cancer in a 59-year-old man. Computed tomography (CT) and positron emission tomography-CT showed the presence of a left lung tumor with IP, which was diagnosed as lung adenocarcinoma by a CT-guided tumor biopsy. We diagnosed DM based on the presence of myalgia, Gottron's papules, and anti-aminoacyl-tRNA synthetase antibody positivity in the patient. Co-occurrence of the above-mentioned three diseases is rare, and acute exacerbation of IP is a major cause of death in such cases. These patients can be treated with immunosuppressive therapy followed by chemotherapy.

First-Line Treatment with Carboplatin plus nab-Paclitaxel and Maintenance Monotherapy with nab-Paclitaxel for a Thymic Carcinoma: A Case Report.

Thymic carcinomas are rare malignant tumors, located in the anterior mediastinum. For the treatment of these carcinomas, several chemotherapy regimens have been suggested, including carboplatin plus paclitaxel. However, because of the rarity of these tumors, the standard chemotherapy regimen has not yet been established. Here, we report a case of thymic carcinoma that responded to first-line carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) therapy with continuation maintenance nab-paclitaxel monotherapy. A 78-year-old male presented to a hospital with the chief complaint of dyspnea. Cardiomegaly was detected on chest X-ray scans, and marked pericardial effusion was observed by echocardiography. Chest computed tomography scans revealed the presence of a mediastinal mass, pericardial thickening, and pericardial effusion. The serum levels of the tumor marker CYFRA 21-1 (cytokeratin-19 fragment) were elevated. Eventually, he was diagnosed with squamous cell carcinoma of the thymus, which was staged as cT4N3M0 or stage IV (according to the tumor-node-metastasis classification). Chemotherapy with carboplatin on day 1 and nab-paclitaxel on days 1, 8, and 15, every 4 weeks was initiated. After the administration of 4 cycles of this regimen, the tumor diameter appeared reduced, and the serum CYFRA 21-1 levels were normalized. After a 1-month interval, the serum CYFRA 21-1 levels increased again; therefore, maintenance nab-paclitaxel monotherapy was initiated. At the end of the treatment, the patient experienced a progression-free survival of 10.3 months. Carboplatin plus nab-paclitaxel may be an appropriate alternative first-line treatment for thymic carcinomas. Additionally, maintenance nab-paclitaxel monotherapy may prolong the progression-free survivals of patients with thymic carcinomas.

Pulmonary cryptococcosis in a ruxolitinib-treated patient with primary myelofibrosis.

We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT) after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks) with concomitant ruxolitinib administration, but the pulmonary lesions progressed. Subsequently, the patient was treated with voriconazole (300 mg daily for 3 weeks), but the lesions worsened further. The administration of ruxolitinib was therefore discontinued, and the dosage of voriconazole was increased to 400 mg daily. Three months later, the pulmonary lesions diminished in size. The present case of pulmonary cryptococcosis occurred in a patient treated with ruxolitinib. Treatment of pulmonary cryptococcosis with concomitant JAK inhibitor administration may result in poor treatment efficacy. It might be better to stop administration of JAK inhibitors, if possible, in patients being treated for pulmonary cryptococcosis.

Nivolumab Therapy for Synchronous ALK-Positive Lung Cancer and Gastric Cancer.

Nivolumab is an immune checkpoint inhibitor with demonstrated efficacy against several malignant tumors. Alterations in driver oncogenes such as EGFR and ALK are a poor prognostic factor in nivolumab therapy for non-small cell lung cancer (NSCLC), whereas a smoking history is a well-known, favorable prognostic factor. However, an efficacy of nivolumab therapy for multiple primary malignant tumors (MPMTs) has not been reported, and its efficacy for driver oncogene-positive NSCLC in smokers is unclear. Herein, we report the case of a patient with a history of heavy smoking who developed synchronous ALK-positive NSCLC and gastric cancer that responded to nivolumab therapy. A 76-year-old man who was a heavy smoker presented to our hospital with symptoms of hoarseness and dysphagia. He was ultimately diagnosed with ALK-positive advanced NSCLC. An ALK inhibitor (alectinib) was administered, and the lung cancer lesions showed improvement. The alectinib therapy was continued for 5 months. Thereafter, the lesions in the left lower lobe of the lung showed regrowth. During the same period, the patient experienced epigastric pain. Gastrointestinal endoscopy examination revealed gastric cancer. He was administered nivolumab to treat both the lung cancer and the gastric cancer. Two months later, both the lung lesions and the gastric lesions had diminished in size. Nivolumab therapy might be an effective therapy for synchronous MPMTs and NSCLC in heavy smokers, even if the lung cancer possesses driver oncogene mutations.

A bronchial fibroepithelial polyp with abnormal findings on auto-fluorescence imaging.

Bronchial fibroepithelial polyps represent a rare type of tumour that displays endobronchial growth. The findings of these lesions on auto-fluorescence imaging (AFI) bronchoscopy have not been reported, despite the usefulness of AFI in detecting early lung cancer. We report the case of a patient with a bronchial fibroepithelial polyp that displayed positivity (magenta colour) on AFI. The patient was a 65-year-old man, in whom an endobronchial polypoid lesion of 10 mm diameter had been detected in the right basal bronchus by chest computed tomography (CT). On bronchoscopic examination, we found a whitish, smooth polypoid lesion. The lesion appeared magenta on AFI. On CT, however, the lesion had been almost stable for 4 years and 4 months. Bronchial fibroepithelial polyps may show AFI positivity, even when the lesion displays benign behaviour. The diagnosis of the lesion should not be confused by AFI positivity, and unnecessary surgical intervention should be avoided.

[Effectiveness of Nivolumab in Large-Cell Neuroendocrine Carcinoma of the Lung - A Report of Two Cases].

BACKGROUND: The anti-programmed death-1 antibody nivolumab is an important treatment option for non-small-cell lung carcinoma.However, its effectiveness for large-cell neuroendocrine carcinomas(LCNEC)is still controversial.Here, we report 2 cases of LCNECs that responded to nivolumab.Case 1: A 62-year-old man received chemotherapy and radiotherapy for stage III A lung adenocarcinoma.One year later, another lung lesion was observed and diagnosed as LCNEC using surgical lung biopsy.Although he subsequently received some chemotherapy regimens, the patient developed new brain metastasis, expanded mediastinal lesion, and increased levels of the tumor marker pro-gastrin releasing peptide(ProGRP).We started nivolumab as the sixth-line treatment.In response, ProGRP levels significantly decreased and the mediastinal lesion became smaller.Case 2: A 55-year-old man was diagnosed with stage III A LCNEC and received chemotherapy and radiotherapy.The primary lesion was controlled; however, lung metastases developed and chemotherapy was unable to control them.We provided treatment with nivolumab as the third-line therapy.The tumor marker ProGRP decreased and the lung metastases became smaller. CONCLUSION: Nivolumab can be a valuable treatment option for LCNEC.

Evaluation of the efficacy and safety of biapenem against pneumonia in the elderly and a study on its pharmacokinetics.

Although biapenem is used in the treatment of pneumonia, the clinical data on elderly patients are yet insufficient. Therefore, the purpose of this study was evaluating the efficacy and safety of biapenem against pneumonia in the elderly and its pharmacokinetics. The subjects were patients 65 years of age or older with pneumonia. Biapenem (300 mg) was administered once to three times per day. For some cases, the drug concentrations in plasma were measured chronologically. The clinical efficacy was evaluated in reference to the improvement in subjective symptoms and objective opinion. The primary outcome was efficacy rate at the end of treatment. Biapenem was effective in 17 of 20 subject cases (85.0 %). Regarding safety, although 4 cases experienced hepatic dysfunction and 1 case had nausea, these effects were not severe in all cases and administration was continued. There was no deterioration of renal function associated with biapenem. In 13 cases in which the trough value of biapenem was measured, there were no unacceptable side effects and the trough values were generally low. It is believed that biapenem (300 mg once to three times a day), even when taken by elderly people, does not accumulate and that the dosage is safe and appropriate. The changes in the predicted concentrations calculated with the pharmacokinetic-pharmacodynamic (PK-PD) software, which is based on previously reported population pharmacokinetic parameters, and those in the measured concentrations approximately matched. It is useful to plan biapenem administration using the PK-PD software when performing antibiotic chemical treatment.

Interferon (alpha, beta and omega) receptor 2 is a prognostic biomarker for lung cancer.

OBJECTIVES: It has been reported that the type I interferon receptor subunit, interferon (alpha, beta and omega) receptor 2 (IFNAR2), is overexpressed in several malignancies, primarily adenocarcinomas (ADCs); however, the biological significance of IFNAR2 in human lung cancer has not yet been studied. METHODS: Immunohistochemical analysis of 113 surgically resected lung specimens was performed, and the results were evaluated in association with clinical variables, including survival. Serum concentrations of IFNAR2 were also determined by an enzyme-linked immunosorbent assay in 157 lung cancer patients and 164 healthy volunteers. RESULTS: IFNAR2 overexpression was observed in all histological types of lung cancer examined. Furthermore, strong IFNAR2 expression was associated with shorter progression-free survival (PFS) and overall survival (OS) (p < 0.0001 and p = 0.0110, respectively) in non-small cell lung cancer patients. Multivariate analyses confirmed its independent prognostic value for PFS and OS (p < 0.0001 and p = 0.0222, respectively). IFNAR2 serum levels were also significantly higher in lung cancer patients than in healthy volunteers (p < 0.0001). CONCLUSIONS: IFNAR2 overexpression was observed in various histological types of lung cancer, and appears to be associated with lung cancers that behave aggressively. The results of this study strongly support the potential of IFNAR2 to be a prognostic biomarker for lung cancer.

[Study of autonomic dysfunction in patients with obstructive sleep apnea syndrome to head-up tilt test].

Although it is well known that autonomic dysfunction in obstructive sleep apnea syndrome (OSAS) is associated with hypertension, its relationship to hypotension and orthostatic dysregulation is still unclear. We examined the response of blood pressure (BP) and cardiovascular autonomic function to head-up tilt (HUT) test in patients with OSAS. In this study, 14 patients(mean age: 65+/-2 years old, male/female: 11/3) with diagnosed OSAS by overnight polysomnography and 84 healthy subjects(mean age: 62+/-1 years old, male/female: 46/38) underwent HUT test(from 5 to 10 min at 45 degrees). Autonomic functions were evaluated by spectrum analysis of blood pressure and heart rate variability. In healthy subjects, systolic BP was unchanged by HUT test due to the enhancement of sympathetic nerve activity and the inhibition of parasympathetic nerve activity. In contrast, autonomic responses were unchanged and systolic BP tended to be decreased by HUT test in OSAS patients. In conclusion, the results of this study suggest that baroreflex function is impaired in patients with OSAS. Furthermore, HUT test with spectrum analysis may be useful to evaluate autonomic functions in OSAS patients.

[A case of primary mediastinal choriocarcinoma].

A 30-year-old man presented with cough and bloody sputum. He brought a chest radiogram showing abnormal findings. His chest computed tomography revealed a large mediastinal mass and multiple nodular shadows in both lungs. The serum beta-HCG level was remarkably elevated, and physical examination revealed bilateral gynecomastia and right supraclavicular lymph node swelling. His lymph node was biopsied and choriocarcinoma was diagnosed. After 3 cycles of BEP therapy (cisplatin, etoposide, bleomycin), the tumors regressed and the serum beta-HCG level decreased. Although there were residual tumors and serum beta-HCG was mildly elevated, he refused additional therapy. The choriocarcinoma progessed rapidly again and he died seven months after his first visit. Primary mediastinal germ cell tumors are rare, and in particular the pure type of choriocarcinoma arising in the mediastinum is even rarer. Patients with mediastinal choriocarcinoma are mostly young men. The prognosis of primary mediastinal choriocarcinoma is still very poor despite the introduction of combination chemotheraphy including cisplatin. We report a case of primary mediastinum pure choriocarcinoma. Chemotherapy was effective for the patient, but he died because of recurrence after refusal of future treatment. Establishment of more effective treatment is necessary.