Treatment of ZC4H2 Variant-Associated Spastic Paraplegia with Selective Dorsal Rhizotomy and Intensive Postoperative Rehabilitation: A Case Report.

Selective dorsal rhizotomy (SDR) has been used to treat children with spastic cerebral palsy (CP), and its beneficial effect on quality of life and ambulation has been confirmed in long-term follow-up studies. However, the role of SDR in the treatment of spasticity in patients with hereditary spastic paraplegia (HSP) and related disorders is not well-established. Here, we report the first patient with the ZC4H2 variant who underwent SDR to treat spastic paraplegia. Abnormal gait was discovered during a regular checkup at the age of 3 years and 9 months, and she was diagnosed with spastic paraplegia. She was heterozygous for the ZC4H2 variant and underwent SDR at the age of 5 years and 11 months, which alleviated the spasticity. The patient underwent inpatient postoperative rehabilitation for 4 months and continued outpatient physiotherapy after discharge. The Gross Motor Function Measure-88 score and maximum walking speed decreased transiently 1 month postoperatively, but gradually recovered, and continuously improved 6 months postoperatively. SDR and postoperative intensive rehabilitation were effective in improving motor and walking functions up to 6 months after surgery, although long-term follow-up is needed to draw conclusions.

Developing an Educational Program for Ultrasound Hip Screening during Newborn and Infant Home Visits: A Protocol Paper.

Ultrasound hip screening is suitable for the early identification of developmental dysplasia of the hip (DDH). Newborn and infant home visits are good opportunities for hip screening in the community, but studies focusing on nurse-led screenings are lacking. Based on a pre-post design, this study aims to develop and evaluate an ultrasound training program to improve nurses' assessment skills in detecting DDH cases during newborn and infant home visits. Said educational program will include e-learning, hands-on seminars, and clinical training. The primary outcome will be the success rate of imaging standard planes (standardized images for hip assessment) in clinical training. The secondary outcomes will include knowledge test results, objective structured clinical examination scores, time required for imaging, and inter-rater reliability between nurses and physicians. The educational program will address the issue of missed and late detection of DDH cases in resource-limited communities. This study will demonstrate the feasibility of procedures and the effectiveness of the educational program in 2024. The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry before starting the study (no. UMIN000051929, 16 August 2023).

Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity.

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen-antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6-8 months regardless of the subsequent change in the antibody levels.

Effect of voluntary human mobility restrictions on vector-borne diseases during the COVID-19 pandemic in Japan: A descriptive epidemiological study using a national database (2016 to 2021).

The coronavirus disease 2019 (COVID-19) pandemic not only encouraged people to practice good hygiene but also caused behavioral inhibitions and resulted reduction in both endemic and imported infectious diseases. However, the changing patterns of vector-borne diseases under human mobility restrictions remain unclear. Hence, we aimed to investigate the impact of transborder and local mobility restrictions on vector-borne diseases through a descriptive epidemiological study. The analysis was conducted using data from the National Epidemiological Surveillance of Infectious Diseases system in Japan. We defined the pre-pandemic period as the period between the 1st week of 2016 to the 52nd week of 2019 and defined the pandemic period as from the 1st week of 2020 to the 52nd week of 2021, with the assumption that human mobility was limited throughout the pandemic period. This study addressed 24 diseases among notifiable vector borne diseases. Datasets were obtained from weekly reports from the National Epidemiological Surveillance of Infectious Diseases, and the incidence of each vector-borne disease was examined. Interrupted time series analysis was conducted on the epidemic curves for the two periods. Between the pre- and post-pandemic periods, the incidence of dengue fever and malaria significantly decreased, which may be related to limited human transboundary mobility (p = 0.003/0.002). The incidence of severe fever with thrombocytopenia syndrome, scrub typhus, and Japanese spotted fever did not show changes between the two periods or no association with human mobility. This study suggests that behavioral control may reduce the incidence of new mosquito-borne diseases from endemic areas but may not affect tick-borne disease epidemics within an endemic area.

Rebound mortality rate of Legionella pneumonia in Japan.

Legionella pneumonia is a fatal disease caused by Legionella pneumophila, a bacterium belonging to the genus Legionella. The incidence of this disease has been increasing since 2005 and has continued to increase following the COVID-19 pandemic in Japan. Furthermore, Legionella pneumonia mortality rates have increased slightly since the pandemic due to some plausible reasons. The increased proportion of older patients with legionellosis might affect it because advanced age is a major risk factor for disease mortality. Additionally, physicians were focused on COVID-19 while examining febrile patients; therefore, they might have missed the early diagnosis of other respiratory infections, including Legionella pneumonia.

Respiratory virus infections of the lower respiratory tract elevate bronchoalveolar lavage eosinophil fraction: a clinical retrospective study and case review.

BACKGROUND: Eosinophilic airway inflammation caused by respiratory virus infection has been demonstrated in basic research; however, clinical investigations are lacking. To clarify the extent to which respiratory virus infection induces airway eosinophilic inflammation, we reviewed the results of bronchoalveolar lavage (BAL) and respiratory virus testing performed at our hospital. METHODS: Among the BAL procedures performed at the University of the Ryukyu Hospital from August 2012 to September 2016, we collected cases of acute respiratory disease in which multiplex polymerase chain reaction (PCR) was used to search for respiratory viruses. The effect of respiratory virus detection on BAL eosinophil fraction was analyzed using statistical analysis. A case study was conducted on respiratory virus detection, which showed an elevated BAL eosinophil fraction. RESULTS: A total of 95 cases were included in this study, of which 17 were PCR-positive. The most common respiratory virus detected was parainfluenza virus (eight cases). The PCR-positive group showed a higher BAL eosinophil fraction than the PCR-negative group (p = 0.030), and more cases had a BAL eosinophil fraction > 3% (p = 0.017). Multivariate analysis revealed that being PCR-positive was significantly associated with BAL eosinophil fraction > 1% and > 3%. There were nine PCR-positive cases with a BAL eosinophil fraction > 1%, of which two cases with parainfluenza virus infection had a marked elevation of BAL eosinophil fraction and were diagnosed with eosinophilic pneumonia. CONCLUSIONS: Cases of viral infection of the lower respiratory tract showed an elevated BAL eosinophil fraction. The increase in eosinophil fraction due to respiratory virus infection was generally mild, whereas some cases showed marked elevation and were diagnosed with eosinophilic pneumonia. Respiratory virus infection is not a rare cause of elevated BAL eosinophil fraction and should be listed as a differential disease in the practice of eosinophilic pneumonia.

Impact of G29179T mutation on two commercial PCR assays for SARS-CoV-2 detection.

Nucleic acid amplification test (NAAT) is the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. However, genetic mutations in the virus can affect the result. Cycle threshold (Ct) values of N genes and their association with mutations using SARS-CoV-2 positive specimens diagnosed by the Xpert Xpress SARS-CoV-2 were examined in this study. In total, 196 nasopharyngeal swab specimens were tested for SARS-CoV-2 infection using the Xpert Xpress SARS-CoV-2, and 34 were positive. WGS was performed for four outlier samples with increased ΔCt identified by Scatterplot analysis as well as seven control samples without increased ΔCt in the Xpert Xpress SARS-CoV-2. The presence of the G29179T mutation was identified as a cause of increased ΔCt. PCR using the Allplex™ SARS-CoV-2 Assay did not show a similar increase in ΔCt. Previous reports focusing on N-gene mutations and their effects on SARS-CoV-2 testing including the Xpert Xpress SARS-CoV-2 were also summarized. While a single mutation that impacts one target of a multiplex NAAT is not a true detection failure, mutation compromising NAAT target region can cause confusion of the results and render the assay susceptible to diagnostic failure.

Characteristics of patients with viral infections of the lower respiratory tract: A retrospective study.

While the impact of respiratory virus infections has been well researched in some respiratory diseases, no clinical studies have discussed the subject of who would be more likely to develop respiratory virus infections among patients with various respiratory illnesses who come from different backgrounds. This study aimed to identify respiratory diseases that are frequently associated with respiratory virus infections along with the characteristics of patients who develop such infections in clinical settings. Tested specimens were obtained from the lower respiratory tract by bronchoscopy to provide more accurate data. Data of bronchoscopies at Ryukyu University Hospital between August 2012 and September 2016 were reviewed, and patients who underwent multiplex polymerase chain reaction (PCR) tests for detecting respiratory viruses in bronchoscopy specimens were retrospectively recruited for descriptive statistics. Differences among patients' primary pulmonary diseases and backgrounds were compared between the PCR-positive and -negative patients, and multivariate statistical analysis was performed to analyze factors associated with a positive PCR test result. Overall, 756 bronchoscopies were performed during the study period and PCR tests were performed for 177 patients. Of them, 27 tested positive for respiratory viruses, mainly parainfluenza virus and rhinovirus, and out of those, 7 were hospitalized for >1 month. Overall, all patients did not experience typical upper respiratory infection symptoms. In positive patients, 13 and 7 had diagnoses of interstitial lung disease and bacterial pneumonia, respectively. The diagnoses of 3 bacterial pneumonia cases were changed to viral pneumonia after receiving their PCR-positive tests. Respiratory virus infections were confirmed in 14 patients on immunosuppressant therapy and 4 on maintenance dialysis. Multivariate analysis revealed that immunosuppressant therapy and maintenance dialysis were independently associated with respiratory virus infections. Viruses were commonly detected in patients with interstitial lung diseases and bacterial pneumonia, while few patients were diagnosed with pure viral pneumonia. These illnesses were considered to be induced by respiratory infections. Immunosuppressant therapy and maintenance dialysis were associated with respiratory virus infections. Multiplex PCR testing is an essential diagnostic tool for respiratory virus infections in immunocompromised patients.

Radiological findings in nontuberculous mycobacterial pulmonary diseases: A comparison between the Mycobacterium avium complex and the Mycobacterium abscessus complex.

The Mycobacterium abscessus complex (MABC) comprises rapidly growing mycobacteria and has received increasing attention recently, with an increasing number of associated infections reported worldwide. However, the clinical features of MABC pulmonary disease (MABC-PD), especially in terms of the chest computed tomography (CT) findings, are not fully understood. Thus, this retrospective, cross-sectional study aimed to evaluate the clinical background and chest high-resolution CT (HRCT) findings of MABC-PD in comparison with those of Mycobacterium avium complex PD (MAC-PD). Accordingly, 36 patients with MABC-PD and 65 patients with MAC-PD (defined according to the American Thoracic Society criteria), who were newly diagnosed at four major hospitals in Okinawa (Japan) between January 2012 and December 2017, were analyzed. With respect to their clinical background, only cardiovascular diseases were significantly more common in patients with MABC-PD than in those with MAC-PD (38.9% vs. 18.5%, p = 0.0245). HRCT revealed a significantly higher incidence of low attenuation in patients with MABC-PD than in those with MAC-PD (63.9% vs. 10.8%, p<0.0001). On analyzing only never-smokers (20 and 47 patients with MABC-PD and MAC-PD, respectively), this significant difference remained (65.0% vs. 8.5%, p<0.0001), suggesting MABC infection itself caused low attenuation. In terms of the distribution of abnormal shadows, the involvement of the right lower, left upper, and left lower lobes was more common in patients with MABC-PD than in those with MAC-PD. Furthermore, the mean number of involved lung lobes was significantly higher in patients with MABC-PD than in those with MAC-PD (5.6 vs. 4.7, p<0.001). Although further studies are needed, we assume that the aforementioned radiological features of MABC-PD are due to the high virulence of MABC.

Molecular Epidemiological Characteristics of Mycobacterium abscessus Complex Derived from Non-Cystic Fibrosis Patients in Japan and Taiwan.

Mycobacterium abscessus complex (MABC) is a group of emerging, highly antimicrobial-resistant non-tuberculous mycobacteria. Specific MABC clones are spreading globally in patients with cystic fibrosis (CF); however, associated genomic epidemiology is lacking in East Asia, with very few patients with CF. Here, we investigated MABC populations derived from non-CF patients in Japan and Taiwan. Analysis of whole-genome sequencing data of 220 MABC isolates revealed that 112, 105, and 3 were M. abscessus subsp. abscessus (ABS), M. abscessus subsp. massiliense (MAS), and M. abscessus subsp. bolletii (BOL), respectively. Moreover, >50% of ABS and >70% of MAS were related to four predominant clones in the region. Known mutations conferring macrolide resistance were rare (1.4%) and were not enriched in the predominant clones. Conversely, the macrolide-susceptible erm(41) T28C mutation was significantly enriched in one predominant ABS clone. The most predominant ABS clone was genetically related to the previously described dominant circulating clone (DCC)1 in patients with CF, whereas no isolates were related to DCC2; isolates related to DCC3 were not necessarily predominant in our sample set. We found that the erm(41) T28C mutants spread globally, and some of them reacquired the functional erm(41) gene through both point mutation and recombination. This study revealed predominant MABC clones in Japan and Taiwan and their relationship with the globally superadding clones in the patient community with CF. Our study provides insights into the genetic characteristics of globally dominant and area-specific strains isolated from patients with or without CF and differences between globally spread and regionally specific strains. IMPORTANCE Members of Mycobacterium abscessus complex (MABC) are frequently isolated from patients. Studies have reported that predominant clones of MABC (known as dominant circulating clones; DCCs) are distributed worldwide and transmitted from humans to humans in patients with cystic fibrosis (CF). However, associated genomic epidemiology has not yet been conducted in East Asia, including Japan and Taiwan, where there are only a few patients with CF. Using whole-genome sequencing data derived from non-CF patients in Japan and Taiwan, we revealed prevalent clones and the incidence of macrolide resistance-associated mutations in the MABC population in this region. We also clarified the associations between these predominant clones and DCCs in the global CF patient community. Our results would assist further studies in elucidating the genetic characteristics of strains isolated from patients with or without CF, the differences between globally spread and regionally specific strains, and the adaptive evolution of MABC within the host.

Unilateral digital clubbing in hemiplegia due to a putaminal hemorrhage.

Digital clubbing usually occurs bilaterally; however, unilateral clubbing can be seen in hemiplegia and local vascular lesions. We highlight a case of unilateral digital clubbing due to putaminal hemorrhage. Further accumulation of cases will enable exploration of the mechanisms of clubbing.

Incidence of common infectious diseases in Japan during the COVID-19 pandemic.

Recent reports indicate that respiratory infectious diseases were suppressed during the novel coronavirus disease-2019 (COVID-19) pandemic. COVID-19 led to behavioral changes aimed to control droplet transmission or contact transmission. In this study, we examined the incidence of common infectious diseases in Japan during the COVID-19 pandemic. COVID-19 data were extracted from the national data based on the National Epidemiological Surveillance of Infectious Diseases (NESID). Common infectious diseases were selected from notifiable infectious diseases under the NESID. The epidemic activity of the diseases during 2015-2020 was evaluated based on the Infectious Disease Weekly Reports published by the National Institute of Infectious Diseases. Each disease was then categorized according to the route of transmission. Many Japanese people had adopted hygienic activities, such as wearing masks and hand washing, even before the COVID-19 pandemic. We examined the correlation between the time-series of disease counts of common infectious diseases and COVID-19 over time using cross-correlation analysis. The weekly number of cases of measles, rotavirus, and several infections transmitted by droplet spread, was negatively correlated with the weekly number of cases of COVID-19 for up to 20 weeks in the past. According to the difference-in-differences analysis, the activity of influenza and rubella was significantly lower starting from the second week in 2020 than that in 2015-2019. Only legionellosis was more frequent throughout the year than in 2015-2019. Lower activity was also observed in some contact transmitted, airborne-transmitted, and fecal-oral transmitted diseases. However, carbapenem-resistant Enterobacteriaceae, exanthema subitum, showed the same trend as that over the previous 5 years. In conclusion, our study shows that public health interventions for the COVID-19 pandemic may have effectively prevented the transmission of most droplet-transmitted diseases and those transmitted through other routes.

Community-acquired Respiratory Virus Cases Mimic COVID-19 on Lung Computed Tomography.

We herein report four patients with community-acquired respiratory virus (CRV) infection. Although they had no history of contact with any individual with coronavirus disease 2019 (COVID-19), they were suspected of having COVID-19 based on findings of high-resolution computed tomography (CT) of the lungs. Among the four patients, two were infected with rhinovirus, one with metapneumovirus, and one with influenza A. Their chest CT findings were similar to those of COVID-19 patients reported in previous studies. Both CRV infection and COVID-19 can show various patterns on chest CT. CRV infection is thus indistinguishable from COVID-19 based on CT findings alone.

Clinical and bacterial features of Group B streptococci with reduced penicillin susceptibility from respiratory specimens: a case-control study.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an invasive pathogen that causes sepsis and meningitis among infants, elderly adults, and immunosuppressed patients. Generally, GBS is susceptible to penicillin; however, GBS with reduced penicillin susceptibility (PRGBS) has been reported. PRGBS are commonly isolated from respiratory specimens, but clinical features of patients with PRGBS remain unclear. In this case-control study, clinical features of patients with PRGBS and bacterial characteristics of these isolates from respiratory specimens were investigated. Patients with GBS at the University of the Ryukyus Hospital between January 2017 and June 2018 were retrospectively investigated. GBS were further classified into penicillin-susceptible GBS (PSGBS) and PRGBS using a drug susceptibility test. Moreover, serotypes, genotypes, and drug resistance genes of PRGBS isolates were determined. In total, 362 GBS were isolated, of which 46 were collected from respiratory specimens, which had the highest rate of PRGBS (24%). Compared to patients with PSGBS, those with PRGBS were more likely to have neuromuscular disease, poor performance status, risk of multidrug-resistant pathogen infection, prior pneumonia history within 1 year, and prior penicillin use within 1 year. Among eight PRGBS isolates, multilocus sequence typing revealed that five isolates were sequence type (ST) 358, two were ST3 and ST10, respectively, and one isolate was ST1404. All PRGBS isolates belonged to the ST1/ST19/ST10 group. This study reveals clinical characteristics of patients with PRGBS from respiratory specimens. Because invasive GBS infection cases are increasing, especially in the elderly, more attention should be paid to this infection.

National survey of physicians in Japan regarding their use of diagnostic tests for legionellosis.

INTRODUCTION: Bacterial culture remains the gold standard for the diagnosis of legionellosis. However, past reports indicate that most physicians use the urinary antigen test (UAT) alone. Combining it with other tests is important, especially in patients with negative UAT results. The aim of this study was to investigate the current situation of legionellosis diagnostics and clarify the issues that need to be addressed. METHODS: Between March 1, 2021 and April 30, 2021, a questionnaire survey was conducted in an anonymous manner among physicians working in Japan. Questionnaires were generated on a website and asked questions in a multiple-choice format. RESULTS: Valid responses were received from 309 physicians during the study period. Most (92.9%) physicians reported using UAT as the initial test for patients suspected of having legionellosis, and <10% reported using other tests (e.g., culture, nucleic acid amplification test [NAAT], Gimenez staining, and serum antibody titer measurement [ATM]). When the initial test result was negative, 63% of physicians reported not conducting additional tests. Even when they chose to run additional tests, at most 27.8%, 23.6%, 12.3%, and 10.4% of all physicians used NAAT, culture, Gimenez staining, and serum ATM, respectively. The major reasons for not using tests other than UAT were "unavailability in the medical facility," "long turn-around time," and "difficult to collect sputum." CONCLUSIONS: The present survey revealed that most physicians in Japan used UAT alone for diagnosing legionellosis. Eliminating barriers to creating a reasonable environment and edification of physicians are needed to improve the current situation.

Tuberculous shadow in Klebsiella oxytoca pneumonia: An unexpected denouement.

Urgent response is required in suspected pulmonary tuberculosis (PTB) cases for infection control, and chest image is the first step to suspect PTB. This case shows an unexpected exception and importance of molecular testing for definite diagnosis.

Spontaneously shrinking lung mass due to Mycobacterium avium mimicking lung cancer.

NTM-SPN is often indistinguishable from malignancy. Although surgical resection is sometimes chosen for the diagnosis and treatment, the mass in this case shrank spontaneously. Careful observation is required to avoid unnecessary interventions.