Ocular candidiasis in a tertiary hospital in Japan: A 10-year single-center retrospective study.

Ocular candidiasis is a major complication of candidemia that is sometimes sight-threatening. Although prompt ophthalmologic consultation and antifungal medication have been emphasized, recent changes in the causative species and drug susceptibilities make the picture unclear. This study aimed to determine whether there are trends among patients with ocular candidiasis and included 80 patients with candidemia who underwent ophthalmological screening at our hospital between 2010 and 2020. Data on the clinical characteristics, comorbidities, biochemical test results, causative Candida species, treatment, outcomes, visual acuity, and antifungal susceptibility were collected and analyzed. Statistical analyses were performed by comparing two groups, namely, the ocular candidiasis (n = 29) and non-ocular candidiasis (n = 51) groups. In the ocular candidiasis group, there were significantly more cases of central venous catheter insertion (82.8%, p = 0.026) and Candida albicans candidemia (72.4%, p < 0.001). Regarding ocular involvement, the majority of patients were asymptomatic. Most cases improved with antifungal therapy, but one case underwent vitrectomy. Between 2016 and 2020, there was a diversification of species, with a decrease in Candida parapsilosis and the emergence of Candida glabrata and Candida tropicalis. Regarding drug susceptibility, the minimum inhibitory concentrations of echinocandin and 5-fluorocytosine against Candida albicans, Candida parapsilosis, and Candida glabrata were slightly increased. In conclusion, in addition to appropriately performing ophthalmologic examinations, it is beneficial to select antifungal agents according to the diversity of species and drug susceptibilities.

No significant changes in preterm birth, low-birth-weight, and small-for-gestational-age infants during the first year of the COVID-19 pandemic in a rural area in Japan.

AIMS: To evaluate the coronavirus disease 2019 pandemic's impact on pregnancy outcomes in a Japanese rural area. METHODS: This retrospective study focused on the periods between March 1, 2020, and February 28, 2021 (during the coronavirus disease 2019 pandemic), and January 1, 2017, and December 31, 2019. Singleton pregnancies delivered at or after 22 gestational weeks were included. Preterm delivery, low-birth-weight, and small-for-gestational-age infant rates during the pandemic were compared to those in the preceding 3 years. RESULTS: In the pandemic and control groups, 1650 and 5762 pregnant women were included, respectively. Two pregnant women with coronavirus disease 2019 were identified (0.1%). There were no significant intergroup differences in preterm delivery rates (control, 4% vs. pandemic, 3.3%; difference: -0.7% [95% confidence interval: -1.7%-0.3%], p = 0.22). The low-birth-weight rate tended to decrease; however, the difference was insignificant (7.9% vs. 6.5%; difference: -1.4% [95% confidence interval: -2.8-0%], p = 0.06). The small-for-gestational-age infant rate was significantly lower in the pandemic than in the control group (7.3% vs. 5.2%; difference: -2.1% [95% confidence interval: -3.3-0.8%], p < 0.01). However, the interrupted time series analysis showed no significant trend. CONCLUSIONS: There were no significant changes in the rates of preterm delivery, low-birth-weight infants, and small-for-gestational-age infants during the pandemic's first year compared to those in the preceding 3 years. Behavioral changes, such as "stay-at-home" measures, may not improve pregnancy outcomes in Japan.

Development of intravascular large B-cell lymphoma during prophylactic antibiotic treatment for anti-interferon-gamma autoantibody syndrome: A case report.

Anti-interferon (IFN)-γ autoantibody-positive syndrome is one of the acquired non-HIV cellular immunodeficiencies, caused by abnormalities in the IFN-γ/interleukin (IL)-12 pathways. It is often diagnosed alongside the onset of disseminated mycobacterium infection, and requires continuous antimycobacterial chemotherapy; however, the detailed pathological mechanisms underlying this syndrome, including its prognosis, are not known. To the best of our knowledge, this is the first reported case of intravascular large B-cell lymphoma complicated by anti-IFN-γ autoantibody syndrome, presented in an 82-year-old woman. The patient had been diagnosed with anti-IFN-γ autoantibody immunodeficiency ten years ago. She had repeated subacute fever of undetermined origin for 13 months that made us suspect infections, such as disseminated mycobacterium disease and other viral and fungal infections, despite receiving prophylactic antimycobacterial chemotherapy with rifampicin and clarithromycin. However, all the screenings performed showed no evidence of infectious diseases; thus, she was finally diagnosed with intravascular large B-cell lymphoma via a random skin biopsy. Unfortunately, the patient debilitated rapidly and died. Evidence supporting a correlation between anti-IFN-γ autoantibody syndrome and carcinogenesis is still lacking, although it is known that patients with anti-IFN-γ autoantibody syndrome are at risk of persistent viral infection-related and T-cell lineage-related carcinogenesis. This case demonstrated that patients with anti-IFN-γ autoantibody syndrome are also at risk of developing B-cell lymphoma, such as intravascular lymphoma. This emphasizes that caution should be paid to increased risk of developing malignancy during the long-term management of anti-IFN-γ autoantibody syndrome with cellular immunodeficiency.

Histological severity of maternal and fetal inflammation is correlated with the prevalence of maternal clinical signs.

AIM: To evaluate whether there is a stepwise increase in the prevalence of maternal clinical signs according to the severity of histological inflammation in the chorioamniotic membranes, placenta, and umbilical cord in preterm deliveries. METHODS: This retrospective study, conducted between January 2007 and May 2017, included patients with preterm delivery between 22 and 33 weeks. The histological findings of maternal/fetal inflammatory responses were staged and graded according to the Amsterdam Placental Workshop Group consensus statement. Correlations between the histological severity of maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and clinical signs were evaluated using the Cochran-Armitage trend test. RESULTS: A total of 138 patients were included. The stage and grade of the maternal inflammatory response were correlated with earlier gestational weeks at delivery and lighter birth weight. The prevalence of clinical chorioamnionitis was significantly correlated with a higher stage and grade of the maternal inflammatory response (Gibbs/Lencki criteria: 15.8%/15.8% in Stage 3, 16.3%/14% in Grade 2). No significant correlations were observed between gestational weeks at delivery and birth weight and stage/grade of fetal inflammatory response. The prevalence of clinical chorioamnionitis was significantly correlated with higher stage and grade of fetal inflammatory response (Gibbs/Lencki criteria: 25%/25% in Stage 3 and 29.4%/29.4% in Grade 2). CONCLUSION: Correlations exist between the severity of histological maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and positive maternal clinical signs in preterm deliveries. However, the prevalence of clinical chorioamnionitis was 20%-30% even in the most severe fetal inflammatory responses.

Zosteriform skin metastasis caused by retrograde lymphatic migration of metastatic squamous cell lung carcinoma.

BACKGROUND: Zosteriform skin metastasis (ZSM) is rare, and its etiology is not well understood. ZSM is possibly derived from the retrograde movement of cancer cells through the lymphatic vessels during disease development. However, it has been difficult to demonstrate it, as no specific findings have been observed. CASE PRESENTATION: A 68-year-old man presented to our department with neck lymphadenopathy. After detailed examinations, squamous cell lung carcinoma (cT2aN3M1c) was diagnosed. Although cisplatin combined with gemcitabine was administered, his cancerous lymphangiopathy was exacerbated, and ZSM was observed on his right chest. Pembrolizumab was initiated as a second-line chemotherapy; however, the patient died 7 months after the initial presentation. In this case, fluorodeoxyglucose-positron emission tomography indicated the presence of skin metastasis and cancerous lymphangiopathy. Similarly, after performing an autopsy, tumor-cell filled lymph ducts were observed in the right subclavian and the cutaneous lymphatic vessel from the right hilar lymph nodes. CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate that the localization of ZSM in the cutaneous lymphatics was caused by the retrograde movement of cancer cells through the lymphatic vessels, using radiographical and pathological analysis. In addition, fluorodeoxyglucose-positron emission tomography may help predict skin metastasis induced by cancerous lymphangiopathy.

Hepatitis A virus-associated fulminant hepatitis with human immunodeficiency virus coinfection.

Hepatitis A virus (HAV) commonly causes acute hepatitis in humans and is transmitted through the fecal-oral route or by ingestion of contaminated food or water. HAV infection generally follows a self-limiting course; it can seldom cause fulminant hepatitis that increases the risk of mortality. To the best of our knowledge, this is the first reported fatal case of fulminant hepatitis caused by HAV in a 40-year-old male with human immunodeficiency virus (HIV) infection. The HAV genotype in this case was IA, which has recently become common globally among people living with HIV (PLWHIV), intravenous drug users, and homeless people especially in developed countries. His HIV infection was stabilized by antiretroviral drugs and his CD4 values were stable. He developed acute hepatic encephalopathy, did not respond to repeated plasma exchange therapy, and died rapidly. It is known that HIV co-infection sometimes leads to fulminant non-HAV hepatitis, although evidence supporting a correlation between fulminant hepatitis A risk and HIV infection is still lacking. This case demonstrated the fatal risk of HAV infection in PLWHIV; it was suggested that education about appropriate preventive measures and vaccination are important for preventing HAV infections among PLWHIV.

Characteristics and influence of Mycoplasma/Ureaplasma cultures in amniotic fluid on perinatal outcomes.

AIM: To investigate the effects of Mycoplasma/Ureaplasma cultured in amniotic fluid on perinatal characteristics in preterm delivery between 22 and 33 weeks of gestation. METHODS: The study was conducted in a tertiary perinatal center and involved 38 pregnant women who had undergone amniocentesis to evaluate intrauterine infection due to preterm labor or premature rupture of membranes. The subjects were divided into three groups based on the culture results: negative (Negative Group, n = 24), positive for Mycoplasma/Ureaplasma (M/U Group, n = 6), and positive for other pathogens (Other Pathogens Group, n = 8). One-way analysis of variance was used to compare the three groups. RESULTS: The incidence of histological chorioamnionitis and neonatal sepsis was significantly different among the three groups (the Negative Group and the Other Pathogens Group, P < 0.01; the M/U Group and the Other Pathogens Group, P = 0.03). In the M/U Group, no infants had sepsis, severe intraventricular hemorrhage, cystic periventricular leukomalacia, or poor neurological outcomes, but one infant developed bronchopulmonary dysplasia and needed home oxygen treatment. Although one died of gastrorrhexis, the remaining five patients had normal brain magnetic resonance imaging findings and developed normally. CONCLUSION: The presence of Mycoplasma/Ureaplasma isolated from amniotic fluid did not cause neonatal sepsis or poor prognosis. In some infants, there was no histological chorioamnionitis in the placenta. These pathogens thus seem to be less invasive than any other microbes with respect to perinatal outcomes.

Maternal Undernourishment in Guinea Pigs Leads to Fetal Growth Restriction with Increased Hypoxic Cells and Oxidative Stress in the Brain.

BACKGROUND: We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for brain hypoxia and oxidative stress. METHODS: Guinea pigs were fed ad libitum (control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1) was injected into pregnant sows. Fetuses were then necropsied and brain tissues were processed for HP-1 (hypoxia marker) and 4HNE, 8-OHdG, and 3-nitrotyrosine (oxidative stress markers) immunoreactivity (IR). RESULTS: FGR-MNR fetal and brain weights were decreased 38 and 12%, respectively, with brain/fetal weights thereby increased 45% as a measure of brain sparing, and more so in males than females. FGR-MNR HP-1 IR was increased in most of the brain regions studied, and more so in males than females, while 4HNE and 8-OHdG IR were increased in select brain regions, but with no sex differences. CONCLUSIONS: Chronic hypoxia is likely to be an important signaling mechanism in the FGR brain, but with males showing more hypoxia than females. This may involve sex differences in adaptive decreases in growth and normalizing of oxygen, with implications for sex-specific alterations in brain development and risk for later neuropsychiatric disorder.

Maternal nutrient restriction in guinea pigs leads to fetal growth restriction with increased brain apoptosis.

BACKGROUND: We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts cell death in the brain with implications for neurodevelopmental adversity. METHODS: Guinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Fetuses were necropsied near term and brain tissues processed for necrosis (H&E), apoptosis (TUNEL), and pro- (Bax) and anti- (Bcl-2 and Grp78) apoptotic protein immunoreactivity. RESULTS: FGR-MNR fetal and brain weights were decreased 38% and 12%, respectively, indicating brain sparing but with brains still smaller. While necrosis remained unchanged, apoptosis was increased in the white matter and hippocampus in the FGR brains, and control and FGR-related apoptosis were increased in males for most brain areas. Bax was increased in the CA4 and Bcl-2 was decreased in the dentate gyrus in the FGR brains supporting a role in the increased apoptosis, while Grp78 was increased in the FGR females, possibly contributing to the sex-related differences. CONCLUSIONS: MNR-induced FGR results in increased brain apoptosis with regional and sex-related differences that may contribute to the reduction in brain area size reported clinically and increased risk in FGR males for later neurodevelopmental adversity.

Manual removal of placenta in women having unpredictable adherent placenta.

AIM: Our aim is to provide expected outcomes for undergoing manual removal of placenta (MROP) following vaginal delivery in women having an unpredictable adherent placenta (AP). METHODS: The data were obtained from four hospitals in Miyazaki Prefecture, Japan. We used propensity score-matched (1:1) analysis to match women who underwent MROP with women who did not undergo MROP (control). Total blood loss and hemorrhagic rate used as a ratio of women who reached a certain amount of blood loss were compared. Subgroup analysis was undertaken and was dependent on the presence of AP. We found the cut-off value of blood loss for detecting AP. RESULTS: Thirty-seven MROP cases were identified. Total blood loss and hemorrhagic rate differed significantly between MROP cases and controls; 95% of controls had blood loss of 1000 mL or less, whereas for the MROP cases, it was 14%. Fourteen MROP cases were diagnosed with AP. The hemorrhagic rate differed significantly between MROP cases with and without AP (n = 19); 79% of MROP cases without AP had blood loss of 2000 mL or less, whereas for the MROP cases with AP, it was 7%. There were seven incidents of hysterectomy and two of arterial embolization in MROP cases with AP. Through receiver operating characteristic curve analysis, 2035 mL of blood loss was determined to be the optimal cut-off value for detecting AP. CONCLUSION: The incidence of unpredictable AP in MROP cases was as high as 38%. The morbidity of MROP cases with unpredictable AP was severe. MROP should be prohibited in the absence of appropriate hemostatic preparations.

Maternal nutrient restriction in guinea pigs as an animal model for studying growth-restricted offspring with postnatal catch-up growth.

We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs with fetal growth restriction (FGR) on offspring body and organ weights, hypothesizing that FGR-MNR animals will show catch-up growth but with organ-specific differences. Guinea pig sows were fed ad libitum (Control) or 70% of the control diet from 4 weeks preconception, switching to 90% at midpregnancy (MNR). Control newborns >95 g [appropriate for gestational age (AGA); n = 37] and MNR newborns <85 g (FGR; n = 37) were monitored until neonatal (~25 days) or adult (~110 days) necropsy. Birth weights and body/organ weights at necropsy were used to calculate absolute and fractional growth rates (FRs). FGR-MNR birth weights were decreased ~32% compared with the AGA-Controls. FGR-MNR neonatal whole body FRs were increased ~36% compared with Controls indicating catch-up growth, with values negatively correlated to birth weights indicating the degree of FGR leads to greater catch-up growth. However, the increase in organ FRs in the FGR-MNR neonates compared with Controls was variable, being similar for the brain and kidneys indicating comparable catch-up growth to that of the whole body and twofold increased for the liver but negligible for the heart indicating markedly increased and absent catch-up growth, respectively. While FGR-MNR body and organ weights were unchanged from the AGA-Controls by adulthood, whole body growth rates were increased. These findings confirm early catch-up growth in FGR-MNR guinea pigs but with organ-specific differences and enhanced growth rates by adulthood, which are likely to have implications for structural alterations and disease risk in later life.

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.

Maternal nutrient restriction in guinea pigs leads to fetal growth restriction with evidence for chronic hypoxia.

BackgroundWe determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.MethodsGuinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR).ResultsFGR-MNR fetuses were 36% smaller with asymmetrical growth restriction compared to controls. EPO and VEGF protein levels were increased in the female FGR-MNR fetuses, providing support for hypoxic stimulus and linkage to increased erythropoiesis, but not in the male FGR-MNR fetuses, possibly reflecting a weaker link between oxygenation and erythropoiesis. HP-1 IR was increased in the liver and kidneys of both male and female FGR-MNR fetuses as an index of local tissue hypoxia, but with no changes in the placenta.ConclusionChronic hypoxia is likely to be an important signaling mechanism for the decreased fetal growth seen with maternal undernutrition and appears to be post-placental in nature.

Candida Chorioamnionitis Leads to Preterm Birth and Adverse Fetal-Neonatal Outcome.

Candida chorioamnionitis is rare but can lead to neonatal infection, high mortality, and neurodevelopmental impairment. We aimed to investigate maternal clinical features and perinatal outcomes and discuss future management strategies. We reviewed the medical records of women with Candida chorioamnionitis at our hospital over a 10-year period (n = 9) and previous published case reports and case series. The most prevalent Candida species was C. albicans (71.3% of the all cases). The most prevalent predisposing condition was preterm premature rupture of membranes (31/123, 25.2%), followed by pregnancy with a retained intrauterine contraceptive device (26/123, 21.1%) and pregnancy after in vitro fertilization (25/123, 20.3%). Preterm labor was the most common symptom (52/123, 42.3%), and only 13% of cases involved fever. Of the infants, 27% of the singletons and 23.8% of the twins were born before 22 gestational weeks, while 60% of the singletons and 76.2% of the twins were born at 22-36 weeks. The median birth weight of the babies born after 22 weeks was 1230 g. The mortality rates of the singletons and twins born after 22 weeks of gestation in the year 2000 or later were 28.6% and 52.4%, respectively. Antenatal treatment for Candida chorioamnionitis has not been established.

Preterm labor and neonatal sepsis caused by intrauterine Helicobacter cinaedi infection.

Helicobacter cinaedi is a rare pathogen but known to cause bacteremia, cellulitis and enterocolitis. Recently, cases of involving various organs are increasingly reported such as endocarditis, meningitis, and kidney cyst infection. We report a case of intrauterine H. cinaedi infection leading preterm birth and neonatal sepsis. A 29-year-old pregnant women who was no underlying disease hospitalized due to threatened preterm labor at 22 weeks of gestation. Clinical findings showed uterine tenderness, fever, leukocytosis and elevated C-reactive protein. H. cinaedi was isolated from amniotic fluid obtained by transabdominal amniocentesis. We diagnosed as intrauterine H. cinaedi infection and administered intravenous ampicillin followed by oxytocin to terminate pregnancy. A live 446 g male infant was delivered. The patient was no signs of infection throughout postpartum course and discharged on post-delivery day 5. The neonate was admitted in neonatal intensive care unit and administered ampicillin and amikacin. H. cinaedi was isolated from umbilical cord blood culture. He has no signs of infection on day 5 but died from uncontrollable hyperglycemia and ketoacidosis on 15 days of age. H. cinaedi can cause intrauterine infection during pregnancy and lead preterm labor and neonatal sepsis.

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.

Independent uterine contractions in simultaneous twin pregnancy in each horn of the uterus didelphys.

The mechanism of synchronizing uterine contractions is not fully understood. We present a case of twin pregnancy in a uterus didelphys and objectively analyze the synchrony of bilateral uterine contractions. A 32-year-old woman, with a history of vaginal septal resection during her previous vaginal delivery, became pregnant with twins in a uterus didelphys in which each uterine horn had one fetus. At 37 weeks and 6 days, the first baby was delivered vaginally. The second baby was delivered by cesarean section due to recurrent late decelerations. Operative findings confirmed the didelphys uterus. We retrospectively reviewed the timing of contractions of both uteruses. The timing was determined by visual analysis as synchronous if both uteruses contracted within 5 s. Otherwise, contractions were considered solitary. Both uterine horns contracted independently in 90% of the incidence throughout labor and delivery. From this rare case of an 'experiment by nature', we speculated that the myometrium must be histologically connected in order to synchronize uterine contractions.

Association between Empirical Anti-Pseudomonal Antibiotics and Progression to Thoracic Surgery and Death in Empyema: Database Research.

Evidence on the optimal antibiotic strategy for empyema is lacking. Our database study aimed to evaluate the effectiveness of empirical anti-pseudomonal antibiotics in patients with empyema. We utilised a Japanese real-world data database, focusing on patients aged ≥40 diagnosed with empyema, who underwent thoracostomy and received intravenous antibiotics either upon admission or the following day. Patients administered intravenous vasopressors were excluded. We compared thoracic surgery and death within 90 days after admission between patients treated with empirical anti-pseudomonal and non-anti-pseudomonal antibiotics. Cause-specific hazard ratios for thoracic surgery and death were estimated using Cox proportional hazards models, with adjustment for clinically important confounders. Subgroup analyses entailed the same procedures for patients exhibiting at least one risk factor for multidrug-resistant organisms. Between March 2014 and March 2023, 855 patients with empyema meeting the inclusion criteria were enrolled. Among them, 271 (31.7%) patients received anti-pseudomonal antibiotics. The Cox proportional hazards models indicated that compared to empirical non-anti-pseudomonal antibiotics, empirical anti-pseudomonal antibiotics were associated with higher HRs for thoracic surgery and death within 90 days, respectively. Thus, regardless of the risks of multidrug-resistant organisms, empirical anti-pseudomonal antibiotics did not extend the time to thoracic surgery or death within 90 days.

Impact of frequency and duration of freeze-dried inactivated tissue culture hepatitis A vaccine (Aimmugen®) vaccination on antibody titers; a japanese cross-sectional study.

BACKGROUND: The effect of the timing of additional doses and the long-term persistence of lyophilized inactivated tissue culture hepatitis A (HA) vaccine (Aimmugen®) on antibodies is unknown. METHODS: A single-center, cross-sectional, observational study was conducted in collaboration with the Japan Air Self-Defense Force, whose personnel were immunized with Aimmugen® when deployed to endemic areas. Patients who consented to this study after a medical examination with blood sampling between June 2022 and February 2023 were included; HA-IgG level in the residual serum was measured using the chemiluminescent immunoassay method. The exact vaccination history was investigated based on immunization records maintained by the Ministry of Defense, and a questionnaire was used to collect confounding factors. RESULTS: Of the 181 participants observed, 49 were in the unvaccinated group, and 132 were in the vaccinated group. Out of the vaccinated group, 6.8 % received either one or two doses, 40.9 % received three doses, and 52.3 % received more than four doses. IgG antibody titers (S/CO value) in each group (0, 1 or 2, 3, and over 4) increased in a frequency-dependent manner, with those vaccinated over four times showing significantly higher IgG antibody titers than all other groups (0.19 ± 0.10 vs 3.66 ± 3.00 vs 7.63 ± 3.57 vs 10.57 ± 1.86, respectively). When the number of months elapsed from the last vaccination to the date of blood collection in each group was plotted against IgG antibody titer, the slope of the regression line flattened out from a decreasing trend in the order 1 or 2, 3, over 4. CONCLUSIONS: Three doses of Aimmugen® are efficacious, but four or more doses induce more robust and sustained antibody production. Additionally, four or more doses may be effective when there is a need to ensure long-term immunity or risk of prolonged exposure.

Longitudinal changes in radiographic features of pulmonary Mycobacterium avium complex diseases.

Background: The radiographic features of Mycobacterium avium complex pulmonary disease (MAC-PD), a major component of nontuberculous mycobacteria, consist of a variety of lesions; however, the responsiveness of each type of radiographic factor to treatment is unclear. Thus, we evaluated the longitudinal changes of each factor in serial computed tomography (CT) images using a mixed-effects model, and investigated the radiographic transition in patients with MAC-PD whose progress could be followed. Methods: In this retrospective study, eighty-four patients diagnosed with MAC-PD and with yearly CT records were recruited after a review of 328 medical records with culture-positive MAC in respiratory specimens. The study participants were divided into two groups: treatment (n = 43) and no-treatment (n = 41) groups. Radiographic images were scored using the nodule (N), infiltration (I), cavity (C), ectasis (E) scoring system. Longitudinal changes in each radiographic lesion factor were analyzed using a mixed-effects model in treated and untreated patients. Results: All factors tended to progress without treatment, and significant longitudinal changes were observed in the N, I, and E factors (N: p = 0.010, I: p = 0.004, E: p < 0.001). Although treatment tended to improve N and I in radiographic images (N: p = 0.006, I: p = 0.203), cavities and ectasis progressed, regardless of treatment (C: p = 0.057 and E: p = 0.033). Conclusion: Radiographic changes of MAC-PD can be categorized into reversible (nodules and infiltrations) and irreversible (cavities and ectasis) lesions. Early treatment may prevent the accumulation of irreversible factors.