Despite low viral titer in saliva samples, Sanger-based SARS-CoV-2 spike gene sequencing is highly applicable for the variant identification.

BACKGROUND: This study aimed to compare the performance of Sanger-based SARS-CoV-2 spike gene sequencing and Next Generation Sequencing (NGS)-based full-genome sequencing for variant identification in saliva samples with low viral titer. METHODS: Using 241 stocked saliva samples collected from confirmed COVID-19 patients between November 2020 and March 2022 in Hiroshima, SARS-CoV-2 spike gene sequencing (nt22735-nt23532) was performed by nested RT-PCR and Sanger platform using in-house primers. The same samples underwent full-genome sequencing by NGS using Illumina NextSeq2000. RESULTS: Among 241 samples, 147 were amplified by both the Sanger and the Illumina NextSeq2000 NGS, 86 by Sanger only, and 8 were not amplified at all. The overall amplification rates of Illumina NextSeq2000 NGS and Sanger were 61% and 96.7%, respectively. At low viral titer (< 103 copies/mL), Illumina NextSeq2000 NGS provided 19.2% amplification, while Sanger was 89.7% (p < 0.0001). Both platforms identified 38 wild type, 54 Alpha variants, 84 Delta variants, and 57 Omicron variants. CONCLUSIONS: Our study provided evidence to expand the capacity of Sanger-based SARS-CoV-2 spike gene sequencing for variants identification over full-genome by Illumina NextSeq2000 NGS for mass screening. Therefore, the feasible and simple Sanger-based SARS-CoV-2 spike gene sequencing is practical for the initial variants screening, which might reduce the gap between the rapid evolution of SARS-CoV-2 and its molecular surveillance.

Variant-specific symptoms after COVID-19: a hospital-based study in Hiroshima.

BackgroundSymptoms after COVID-19 recovery by SARS-CoV-2 strains are unspecified.MethodsThis self-administered questionnaire-based study was conducted to investigate symptoms after COVID-19 recovery at one of the main hospitals for COVID-19 treatment in Hiroshima, Japan, from September 2020 to March 2022 for patients who visited follow-up consultations after COVID-19. Study subjects were divided into four groups (Wild-type, Alpha, Delta, and Omicron periods) according to COVID-19 onset date. Hierarchical cluster analysis was performed to determine symptom clusters and investigate risk factors for each symptom cluster using multivariate analysis.ResultsAmong 385 patients who enrolled in this study, 249 patients had any persistent symptoms at a median of 23.5 [IQR, 20-31] days after COVID-19 onset. Among patients with any persistent symptoms, symptom clusters including olfactory or taste disorders, respiratory symptoms, and cardiac symptoms were found. Respiratory symptoms were more frequent among patients infected in the Omicron period compared to the Wild-type period (AOR, 3.13; 95% CI, 1.31-7.48; p=0.0101). Compared to patients who recovered from mild COVID-19, patients who needed for oxygen or ventilation support suffered fewer post-COVID-19 respiratory symptoms (AOR, 0.46; 95% CI, 0.22-0.97; p=0.0415) but more post-COID-19 cardiac symptoms among them (AOR, 2.67; 95% CI, 1.26-5.65; p=0.0103). Olfactory or taste disorders were fewer among patients infected in the Omicron period compared to the Wild-type period (AOR, 0.14; 95% CI, 0.04-0.46; p=0.0011).ConclusionThis study revealed that symptoms after COVID-19 may vary depending on the infected strain.

Concurrent lung adenocarcinoma hidden among multiple shadows of COVID-19 pneumonia: A rare and instructive case report.

A 40-year-old man was admitted with a diagnosis of COVID-19 pneumonia. Although most of multiple ground-glass opacities and consolidations on computed tomography improved, a round ground-glass opacity with consolidation remained unchanged and was suspected to be a part-solid nodule of lung adenocarcinoma. Pathologic diagnosis of resected tumor was papillary adenocarcinoma.

The role of discrimination in the relation between COVID-19 sequelae, psychological distress, and work impairment in COVID-19 survivors.

Perceived discrimination and work impairment are commonly observed in COVID-19 survivors, but their relationship has not been well understood. We aimed to evaluate the role of discrimination in the development of psychological distress and work impairment in COVID-19 survivors. From April 2020 to November 2021, 309 patients were recruited at two designated COVID-19 hospitals in Japan. Participants completed a standardized questionnaire including COVID-19 sequelae, psychological distress, impairments in work performance and perceived discrimination. The majority of participants (62.5%) experienced one or more COVID-19 sequelae. Psychological distress was observed in 36.9% and work impairment in 37.9%. In multivariate logistic regression analyses, COVID-19 sequelae and discrimination were associated with both psychological distress and work impairment. Mediation analysis demonstrated that the direct effect of sequelae on work impairment was non-significant after accounting for psychological distress, suggesting that the effect of sequelae on work impairment was mainly mediated through psychological distress. These findings were replicated in a subgroup analysis limited to patients with mild COVID-19. We conclude that discrimination plays an important role in the development of psychological distress and work impairment, and that both discrimination and psychological distress should be targets of intervention in COVID-19 survivors.

Comparison of COVID-19 pneumonia during the SARS-CoV-2 Omicron wave and the previous non-Omicron wave in a single facility.

BACKGROUND: The characteristics of coronavirus disease 2019 (COVID-19) pneumonia caused by the severe acute respiratory syndrome coronavirus 2 Omicron variant have not been fully described. Unlike other variants, the Omicron variant replicates rapidly in the bronchus. Therefore, we hypothesized that it would have different computed tomography (CT) findings from non-Omicron variants. METHODS: We enrolled patients with COVID-19 who visited our hospital and underwent chest CT during the first month of the Omicron wave (January 2022; N = 231) and the previous non-Omicron wave (July 2021; N = 87). We retrospectively evaluated the differences in the prevalence rate and CT characteristics of COVID-19 pneumonia between the two waves. RESULTS: The prevalence of pneumonia was significantly lower in the Omicron wave group (79/231, 34.2%) compared to the previous wave group (67/87, 77.0%) (P < 0.001). For the predominant distribution pattern of pneumonia, the Omicron wave group revealed a significantly lower rate of the peripheral pattern and a higher rate of the random pattern than the previous wave group. In addition, the Omicron wave group had a significantly lower rate of consolidation than the previous wave group. The ground-glass opacities (GGOs) rate was similar between the two wave groups. For GGOs patterns, cluster-like GGOs along the bronchi on chest CT were more frequently observed during the Omicron wave than during the previous wave. CONCLUSION: The Omicron wave group had a lower COVID-19 pneumonia prevalence than the previous wave group. Cluster-like GGOs should be noted as a characteristic CT finding of pneumonia during the Omicron wave.

Concurrent coronavirus disease 2019 and primary syphilis in a young man: A rare case report.

INTRODUCTION: The global rise of syphilis infections and the ongoing coronavirus disease 2019 (COVID-19) pandemic are causes for concern. We herein report a rare case of concurrent primary syphilis and COVID-19. CASE REPORT: A 29-year-old man was admitted with a diagnosis of COVID-19. Although COVID-19 pneumonia appeared during ciclesonide and favipiravir treatment, his symptoms improved without developing severe hypoxemia. A small, red ulcer on the left-side of his glans penis was noted and left inguinal lymph node swellings were detected on computed tomography (CT). He reported that his last engagement in sexual intercourse had been 3 months previously, and that his partner had subsequently been diagnosed with syphilis. Although both serum Treponema pallidum (TP) antibody and rapid plasma reagin (RPR) quantitative tests were negative on the day of admission, we clinically diagnosed a suspected case of primary syphilis and started treatment with amoxicillin (1500 mg/day). We subsequently learned that the TP antibody and RPR quantitative tests had been positive 4 days before starting syphilis treatment. Amoxicillin treatment was continued for 61 days, and the ulcer gradually improved. One year later, the RPR quantitative test was negative, and CT revealed a reduction in size of the inguinal lymph nodes and no residual signs of COVID-19 pneumonia. CONCLUSION: The prevalence of syphilis has been increasing even during the COVID-19 pandemic, and the incidence of concurrent syphilis and COVID-19 might be higher than is recognized. Asking patients with COVID-19 about high-risk sexual behavior and genital lesions could help with early diagnosis of syphilis.

Risk factors for progression to acute respiratory failure after casirivimab and imdevimab administration: A retrospective study.

BACKGROUND: Casirivimab and imdevimab are effective in preventing hospitalization in outpatients with coronavirus disease 2019 (COVID-19); however, disease progression after casirivimab and imdevimab administration has been reported. This study aimed to elucidate the risk factors for disease progression after casirivimab and imdevimab administration. METHODS: This retrospective study included patients with COVID-19 who received casirivimab and imdevimab at Hiroshima City Funairi Citizens Hospital between August 6, 2021, and October 10, 2021. All patients had at least one risk factor for severe disease and were treated on admission. The patients' background characteristics and test results at the first visit were analyzed. The patients were divided into two groups (progressed and improved) based on whether they progressed to acute respiratory failure during hospitalization. RESULTS: Sixty-seven patients were included: 9 patients in the progressed group (median age, 56 years) and 58 patients in the improved group (median age, 51 years). Age, coexistence rate of diabetes, cycle threshold value of polymerase chain reaction test, rate of detectable pneumonia on chest radiographs or chest computed tomography images, lymphocyte count, and the levels of C-reactive protein, interleukin-6, glucose, and glycated hemoglobin were significantly different between the two groups. Multivariate logistic regression analysis revealed that the coexistence of diabetes and the presence of detectable pneumonia on chest radiographs were independent factors predicting the progression to acute respiratory failure. CONCLUSION: Acute respiratory failure after antibody therapy with casirivimab and imdevimab may develop in patients with diabetes or detectable pneumonia on chest radiographs at the first visit.

Can the Omicron variant of COVID-19 cause pneumonia in young patients without risk factors?

The Omicron variant (B.1.1.529) of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide since December 2021. In daily medical practice, pneumonia does not often appear as a complication of the Omicron variant. We present a case of COVID-19 pneumonia by the Omicron variant in young patients without obvious risk factors.

Pneumonia and Meningoencephalitis Due to Varicella-zoster Virus Reinfection and Epstein-Barr Virus Reactivation in a Patient with Rheumatoid Arthritis.

A 72-year-old woman with rheumatoid arthritis was treated with methotrexate (MTX) and iguratimod. Upon examination of a liver tumor, blisters due to varicella-zoster virus (VZV) infection were observed. Despite oral administration of valacyclovir, she developed varicella pneumonia and meningoencephalitis. A VZV antibody test revealed reinfection. The liver tumor shrank after discontinuance of MTX, and polymerase chain reaction revealed the reactivation of the Epstein-Barr virus (EBV). Therefore, we were unable to deny MTX-associated lymphoproliferative disorder (MTX-LPD). This is the first case of a complication of pneumonia and meningoencephalitis due to VZV reinfection and EBV reactivation.

First-line osimertinib treatment in a patient with lung adenocarcinoma with coexisting epidermal growth factor receptor G719S and de novo T790M mutations.

Osimertinib is the standard treatment for non-small cell lung cancer (NSCLC) with an active epidermal growth factor receptor (EGFR) mutation and a T790M mutation-present in cases of acquired resistance. However, there have been no reports on the efficacy of osimertinib in patients with EGFR G719S and de novo T790M mutations. Here, we present the case of a 71-year-old woman who received first-line osimertinib for lung adenocarcinoma with G719S and de novo T790M mutations. A partial response was observed after osimertinib initiation; however, the disease progressed 5 months after. Next-generation sequencing using a rebiopsy sample from the brain metastases revealed no newly acquired resistance mutations, including EGFR C797S. From experience, the efficacy of osimertinib in NSCLC with G719S and T790M compound mutations may be poor. Therefore, optimal treatment for these cases should be determined.

Pneumatosis Intestinalis following Radiation Esophagitis during Chemoradiotherapy for Lung Cancer: A Case Report.

Pneumatosis intestinalis (PI) is a rare disease that forms emphysema lesions under the mucosa and serosa of the gastrointestinal tract. We present the first case of PI following radiation-induced esophagitis during chemoradiotherapy (CRT) for lung cancer. A 74-year-old man with severe chronic obstructive pulmonary disease (COPD) was treated with CRT for lung cancer. During the treatment, he presented with vomiting and abdominal distention. CT showed pneumatosis from the esophagus to the small intestine. Severe radiation-induced esophagitis was observed, and gastrointestinal endoscopy revealed a circumferential esophageal ulcer. From these observations, this case was diagnosed as PI following severe esophagitis. A nasogastric tube was inserted, and conservative treatment with fasting, fluid replacement, and antibiotic was performed. Four days after the onset of PI, CT showed marked improvement of the pneumatosis. When CRT is performed for lung cancer patients, we should not only consider esophagitis but also PI. The presence of COPD may be considered a specific factor for the development of severe esophagitis and the consequent PI in this case.

Tolerability and efficacy of IMpower133 regimen modified for dialysis patients with extensive-stage small cell lung cancer: Two case reports.

The IMpower133 regimen, composed of atezolizumab/etoposide (VP-16)/carboplatin (CBDCA), is the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, the safety and efficacy of triplet therapy in patients receiving dialysis have not been sufficiently evaluated. Here, we report two cases of dialysis patients with ES-SCLC who received the modified IMpower133 regimen. Patient 1 was a 69-year-old man, and patient 2 was a 73-year-old man who received dialysis because of end-stage renal failure caused by diabetic nephropathy. Both patients received a modified IMpower133 regimen in the following order: atezolizumab (1200 mg/body) on day 1, VP-16 (50 mg/m2 ) on days 1 and 3, and CBDCA (300 mg/m2 ) on day 1. Four hours of dialysis was performed 1 hour after completing the administration of CBDCA on Day 1 and 2 hours after completing the administration of VP-16 on Day 3. Both patients achieved a partial response and received atezolizumab maintenance therapy after four cycles of triplet therapy without uncontrollable adverse events. By modifying the dosage, the order of drugs, and the timing of dialysis, the IMpower133 regimen may be tolerable and effective for patients receiving dialysis.

Autoantibody Positivity Is a Risk Factor for Chemotherapy-induced Exacerbation of Interstitial Pneumonia in Lung Cancer.

BACKGROUND: No study has yet investigated the incidence of chemotherapy-induced acute exacerbation of interstitial pneumonia (AE-IP) in patients with autoantibody-positive IP and lung cancer. Herein, we retrospectively compared the incidence of chemotherapy-induced AE-IP in patients with lung cancer between those with autoantibody-positive and -negative IP. PATIENTS AND METHODS: Between October 2003 and December 2018, patients with lung cancer who received chemotherapy, underwent serological test of antinuclear antibody or rheumatoid factor, and were diagnosed with IP were enrolled. RESULTS: A total of 81 patients were enrolled; autoantibody-positive cases were observed in 23.5%. Autoantibody positivity was an independent risk factor for chemotherapy-induced AE-IP at 6 months after initiation of chemotherapy for lung cancer. The time to onset of AE-IP was significantly shorter in autoantibody-positive patients than in the seronegative patients. CONCLUSION: Chemotherapy-induced AE-IP developed earlier in patients with autoantibody than in those without. Therefore, the potential development of AE-IP in autoantibody-positive patients warrants monitoring.

The STOP-Bang Test Is Useful for Predicting the Severity of Obstructive Sleep Apnea.

INTRODUCTION: The STOP-Bang test was used to detect patients at high risk of obstructive sleep apnea (OSA). We evaluated the usefulness of the STOP-Bang test for predicting the severity of OSA in Japanese patients. METHODS: We retrospectively evaluated the patients who performed full polysomnography at the Mihara Medical Association Hospital. We evaluated the correlation between the STOP-Bang score and the apnea hypopnea index (AHI) using Spearman's rank correlation analysis. We then used multivariate analyses to examine the independent risk factor for severe OSA (AHI ≥ 30/hr). RESULTS: One hundred seven patients were diagnosed as no (n = 5), mild (n = 17), moderate (n = 30), and severe (n = 55) OSA. The median age was 67 years old (range: 35-84), and 73 of the 107 patients were males. The correlation coefficient between the STOP-Bang score and AHI was 0.701 (P < 0.001). A STOP-Bang score ≥ 5 had sensitivity of 80.0% and specificity of 76.9% for detecting severe OSA. A STOP-Bang score ≥ 5 and BMI ≥ 30 kg/m2 were the independent risk factor for severe OSA. CONCLUSIONS: The STOP-Bang score correlates with AHI and is useful for predicting OSA severity. Polysomnography should be performed actively for the patients with high STOP-Bang scores.

[Development of Pulmonary Pleomorphic Carcinoma after Treatment for Infectious Bulla].

A 54-year-old man with a history of smoking developed infectious bullae at the apex of his left lung and underwent long-term antimicrobial treatment. The bullae gradually reduced in size along with a slight left pleural thickening. Left back pain relapsed after a year, and CT revealed a rapid increase in pleural thickening. Left upper lobectomy led to the diagnosis of pulmonary polymorphic carcinoma. Chronic inflammation due to infection could contribute to carcinogenesis; therefore, post-inflammatory changes should be carefully followed-up.

[A Case of Lung Cancer Discovered Due to Unresponsive Course of Corticosteroids for Rheumatoid-Associated Interstitial Lung Disease].

A 76-year-old female was followed up for rheumatoid arthritis-associated interstitial lung disease(RA-ILD). Consolidation and ground-glass opacities were observed in the right lung. When the corticosteroid was restarted due to a relapse of RA-ILD, most of the shadows disappeared. However, ground-glass nodules remained in the apex of the right lung. Thoracoscopic segmentectomy was performed, and lung cancer was diagnosed. Patients with rheumatoid arthritis suffer from complications such as RA-ILD, drug-induced pneumonia, pulmonary infections, and malignancies. A careful assessment of treatment response should be made in case of a differential diagnosis.

[A Case of Small Cell Lung Cancer Diagnosed with Metastasis-Induced Acute Pancreatitis].

A 56-year-old man was admitted to our hospital for management of acute epigastric abdominal pain and elevation of pancreatic enzymes. The CT scan revealed enlargement ofthe pancreatic body as well as the lung tumor ofthe right hilar and superior mediastinum. Therefore, bronchoscopy was performed and a diagnosis of small cell lung cancer with metastasisinduced acute pancreatitis(MIAP)was made. Prompt improvement in pancreatic findings was observed following chemotherapy. MIAP, which is a rare complication of lung cancer may affect the prognosis and quality of life of the patients; therefore, rapid diagnosis and appropriate treatment are important.

Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5.

Augmented AMP-activated protein kinase (AMPK) activity inhibits cell migration, possibly contributing to the clinical benefits of chemical AMPK activators in preventing atherosclerosis, vascular remodelling and cancer metastasis. However, the underlying mechanisms remain largely unknown. Here we identify PDZ and LIM domain 5 (Pdlim5) as a novel AMPK substrate and show that it plays a critical role in the inhibition of cell migration. AMPK directly phosphorylates Pdlim5 at Ser177. Exogenous expression of phosphomimetic S177D-Pdlim5 inhibits cell migration and attenuates lamellipodia formation. Consistent with this observation, S177D-Pdlim5 suppresses Rac1 activity at the cell periphery and displaces the Arp2/3 complex from the leading edge. Notably, S177D-Pdlim5, but not WT-Pdlim5, attenuates the association with Rac1-specific guanine nucleotide exchange factors at the cell periphery. Taken together, our findings indicate that phosphorylation of Pdlim5 on Ser177 by AMPK mediates inhibition of cell migration by suppressing the Rac1-Arp2/3 signalling pathway.

Effect of exercise on frequency of stent fracture in the superficial femoral artery.

Stent fracture has emerged as a new problem in the percutaneous transluminal angioplasty of the superficial femoral artery (SFA). The aim of our study was to delineate the factors influencing nitinol stent fracture in the SFA. Forty consecutive patients with peripheral artery disease who underwent rescue stenting with a nitinol stent (Luminexx, Bard) in the SFA were enrolled between May 2004 and January 2005. Follow-up angiography was performed 13.6+/-1.0 months later to detect stent fracture. Stent fracture occurred in 11 patients (28%). Lesion length>100 mm, the number of stents used, the lesion involving the distal SFA, chronic total occlusion, and walking>5,000 steps per day were more frequently observed in those with stent fracture than in those without fracture. Of these variables, walking>5,000 steps per day was the strongest independent determinant associated with stent fracture by discriminant analysis (p=0.0027). Vigorous exercise adversely affects stent fracture in patients implanted with a nitinol stent in the SFA.

Cilostazol reduces target lesion revascularization after percutaneous transluminal angioplasty in the femoropopliteal artery.

BACKGROUND: Although percutaneous transluminal angioplasty (PTA) is being widely used for the treatment of stenosis of peripheral arteries, the high in-stent restenosis rate (50-60%) in the femoropopliteal artery still remains an unsolved issue. Cilostazol is a unique antiplatelet drug that has vasodilatory effects and inhibits smooth muscle cell proliferation. METHODS AND RESULTS: A total of 141 consecutive patients scheduled for PTA in the femoropopliteal artery between September 1999 and April 2004 were retrospectively analyzed for the use of cilostazol. Target lesion revascularization (TLR) was defined as repeated PTA in patients who had a recurrence of symptoms with diameter stenosis >50% by angiography. Patient and lesion characteristics were similar between the cilostazol (+) and cilostazol (-) groups. Use of other medications was similar between the groups, except for ticlopidine, which was more frequently used in the cilostazol (-) than in the cilostazol (+) group (15% vs 61%, p<0.01). TLR was significantly reduced in the cilostazol (+) group (12% [8/68] vs 32% [23/73], p<0.01). CONCLUSIONS: Although this study was retrospective and nonrandomized, the results suggest that cilostazol reduces TLR after PTA in the femoropopliteal artery.