Outcome and etiology of fetal pleural effusion, fetal ascites and hydrops fetalis after fetal intervention: retrospective observational cohort from a single institution.

OBJECTIVES: Non-immune hydrops fetalis (NIHF) is the pathological accumulation of fluids in fetal compartments, without maternal isoimmunization. Fetal interventions (e.g. shunting, fetal paracentesis, fetal thoracocentesis, fetal pleurodesis) are used to alleviate fluid accumulations, but the outcome is uncertain because the underlying causes of NIHF vary. We aimed to explore the etiology and long-term outcome of NIHF after fetal intervention. METHODS: This was a retrospective review of fetuses with NIHF, defined by the presence of fetal ascites, pleural or pericardial effusion, skin edema or cystic hygroma, or a combination of these features, who underwent intervention at our institution during the period 2012-2021. Clinical surveillance, genetic analysis and viral infection screening were used to define the etiology. Chart reviews and telephone interviews were conducted to assess the long-term outcomes. RESULTS: In total, 55 fetuses were enrolled and 46 cases had final follow-up data after delivery. Etiology was identified in 33 cases, including four for which the underlying causes were not identified initially using small-gene-panel tests but which were later diagnosed with monogenic disorders by whole-exome sequencing (WES). Twenty-three cases with follow-up survived, having a follow-up period of 2-11 years at the time of writing, of which 17 were healthy. All 11 cases initially presenting as congenital chylothorax survived with favorable outcome. CONCLUSIONS: The etiologies of NIHF are heterogeneous, and the long-term (spanning 2-11 years) outcome of fetal intervention varies, according to the underlying etiology, with cases caused by congenital chylothorax having the best prognosis. Genome-wide tests, such as WES, may be helpful in determining the underlying condition in cases caused by a genetic disorder, and this may affect fetal therapy approaches in the future. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Isolation of Streptomycin-Resistant Erwinia pyrifoliae in Korea.

As a black shoot blight disease-causing agent, Erwinia pyrifoliae was first reported in 1995 in Korea. A total of 101 isolates of E. pyrifoliae were isolated from samples showing bacterial symptoms collected from apple and pear orchards between 2020 and 2021. These isolates were screened for streptomycin resistance, with one from an orchard in Gwangju showing resistance at 100 µg/ml streptomycin. This streptomycin-resistant E. pyrifoliae (EpSmR) isolate was identified via polymerase chain reaction amplification of the strA/strB gene and an internal region of the ribosomal rpsL gene containing codon 43. EpSmR has a point mutation that altered this codon from lysine (AAA) to threonine (ACA). The strA and strB genes were not identified in EpSmR. EpSmR showed a high resistance to streptomycin (>50,000 µg/ml). This is the first study reporting EpSmR, which emerged due to a mutation in codon 43 of the rpsL gene.

A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy.

BACKGROUND: Up to 40% of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) present with disease progression in the central nervous system (CNS), either as brain metastases (BM) or leptomeningeal metastases (LM). Osimertinib (80 mg), a third-generation, irreversible, oral EGFR TKI, has shown efficacy in active CNS metastases. However, efficacy of osimertinib 160 mg in BM or LM is unclear. PATIENTS AND METHODS: This prospective, single-arm, two cohort study evaluated the efficacy of osimertinib 160 mg in T790M-positive BM or LM NSCLC patients who progressed on prior EGFR TKI (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H1 = 30%) for the BM cohort and overall survival (OS) (H1 = 5 months) for the LM cohort. RESULTS: The median follow-up duration was 10.1 months and 9.6 months for the BM and LM cohorts, respectively. In the BM cohort, intracranial ORR and disease control rate were 55.0% and 77.5%, respectively. The median progression-free survival (PFS) was 7.6 months [95% confidence interval (CI) 5.0-16.6]; the median OS was 16.9 months [95% CI 7.9-not reached (NR)]. In the LM cohort, intracranial disease control rate was 92.5% and complete response rate was 12.5%. The median OS was 13.3 months (95% CI 9.1-NR); the median PFS was 8.0 months (95% CI 7.2-NR). Subgroup analyses based on previous exposure to T790M-targeting agents, including osimertinib 80 mg or other third-generation EGFR TKIs, showed no difference in PFS in both the BM (n = 18, P = 0.39) and LM (n = 17, P = 0.85) cohorts. Previous radiotherapy favored PFS in the BM cohort (hazard ratio 0.42, P = 0.04). The most common adverse events were decreased appetite, diarrhea, and skin rash; however, most were grade 1-2. CONCLUSION: Thus, osimertinib 160 mg demonstrated promising ORR and survival benefit with a tolerable safety profile in EGFR T790M-positive NSCLC patients with CNS metastasis who progressed on prior EGFR TKIs.

Factors affecting quality of life in patients with vitiligo: a nationwide study.

BACKGROUND: Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. OBJECTIVES: To explore the QoL of patients with vitiligo and to identify factors affecting QoL. METHODS: A nationwide questionnaire-based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex-29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex-29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. RESULTS: Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20-84). The median duration of disease was 3·0 years (range 0-60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex-29. Additionally, the QoL of patients aged 20-59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. CONCLUSIONS: A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.

Positivity rates of antithyroid antibody, antinuclear antibody and thyroid peroxidase antibody in different types of vitiligo.

BACKGROUND: Vitiligo is associated with various autoimmune disorders, and organ-specific autoantibodies are frequently found in patients with this disorder. Vitiligo is classically divided into segmental vitiligo (SV) and nonsegmental vitiligo (NSV), and it is believed that the pathogenesis differs between these two types. As the NSV type is related to an autoimmune mechanism, autoantibody detection rates are likely to be higher in the NSV type than in the segmental type; however, no comparative studies have been performed. AIM: To analyse the rates of autoantibody positivity according to the clinical features in patients with vitiligo. METHODS: Rates of antithyroid antibody (Tg Ab), antinuclear antibody (ANA) and thyroid peroxidase antibody (TPO Ab) positivity were analysed and compared according to the sex, clinical type and age of onset of 807 patients with vitiligo. RESULTS: There were 106 patients with SV (13.1%) and 701 patients with NSV (86.9%). Tg Ab and ANA positivity did not differ between the SV and NSV types. A positive TPO Ab result was obtained in 16 patients with SV (15.1%) and 173 patients with NSV (24.7%). The TPO Ab positivity rate was significantly higher in NSV (χ² = 4.14, P < 0.05). The positivity rates of the three autoantibodies differed significantly according to age of onset (P = 0.001, P = 0.02 and P < 0.001 for Tg Ab, ANA and TPO Ab positivity, respectively). The TPO Ab positivity rate also showed a sex difference (P < 0.001). CONCLUSIONS: The positivity rates for the three autoantibodies showed differences according to age of onset and sex. The rates of Tg Ab and ANA positivity showed no significant differences according to clinical type, but the TPO Ab positivity rate was significantly different between SV and NSV. It appears likely that an autoimmune mechanism contributes to the pathogenesis of SV.

The association of diabetes and anti-diabetic medications with clinical outcomes in multiple myeloma.

BACKGROUND: Insulin/insulin-like growth factor-1 signalling may underlie the promoting effect of type 2 diabetes on cancer. This study examined the association of diabetes, including steroid-induced diabetes (SID), and the impact of anti-diabetic medication on clinical outcomes of multiple myeloma (MM). METHODS: A retrospective review was conducted of 1240 MM patients. Overall survival (OS) and MM disease status prior to death were analysed. RESULTS: Diabetic patients had a significantly shorter OS than non-diabetic patients (median: 65.4 vs 98.7 months). In multivariate analysis, SID was a significant predictor of decreased OS, along with age, comorbidity, MM stage, and cytogenetic abnormalities. Analyzing only the diabetic MM patients, Cox regression showed that metformin predicted an increased OS, whereas use of insulin/analogues predicted a decreased OS. Competing risk analysis showed that DM was associated with increased cumulative incidence of death with progressive MM. Among the diabetics, multivariate regression showed that insulin/analogues were associated with increased, but metformin with decreased death with progressive MM. Potential immortal time bias was evaluated by landmark analyses. CONCLUSIONS: DM, SID in particular, is associated with poor clinical outcomes in MM. Insulin/analogues are associated with poor outcomes, whereas metformin is associated with improved outcomes. No conclusion about causal relationships can be made at this time. Managing hyperglycaemia with non-insulin regimens should be investigated in randomised trials.

Alendronate and risk of lower limb ischemic vascular events: a population-based cohort study.

UNLABELLED: While alendronate inhibits atherosclerosis experimentally, its effect on lower limb ischemia risk is unknown. Our results suggest that alendronate reduces the risk of lower limb ischemic vascular events requiring surgical interventions, including amputation. Our results are relevant for patients at risk of lower limb ischemia undergoing fragility fracture treatment. INTRODUCTION: This study aimed to determine the association between alendronate therapy and the risk of lower limb ischemic vascular events (i.e., bypass surgery, endovascular stenting, and major lower limb amputation for lower limb ischemia). METHODS: We used a nationwide population-based cohort of patients aged over 50 years diagnosed with a vertebral or hip fracture between January 1999 and June 2010. We compared the risk of lower limb ischemic vascular events between patients undergoing treatment with alendronate (n = 3,731) and an age- and sex-matched comparison group (n = 7,462) over 5 years of follow-up. Hazard ratios (HR) were estimated using Cox proportional regression analysis with adjustment for treatment status, comorbidities, and other variables. RESULTS: Ten patients (0.3 %) in the alendronate treatment group had a lower limb ischemic vascular event compared with 51 patients (0.7 %) in the comparison group. The incidence of lower limb ischemic vascular events was 8.4 (95 % CI, 4.0-15.5) per 10,000 person-years in the alendronate group and 21.8 (95 % CI, 16.2-28.7) per 10,000 person-years in the comparison group. The risk of a lower limb ischemic vascular event in the alendronate treatment group was lower (adjusted HR, 0.41; 95 % CI, 0.21-0.82). CONCLUSION: Alendronate treatment was associated with a reduced risk of lower limb ischemic vascular events among hip or vertebral fragility fracture patients.

Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010.

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n = 517) exhibited MICs of 2 µg/ml and 0.3 % (n = 6) demonstrated intermediate susceptibility (MICs of 4 µg/ml). Nearly all isolates (≥ 99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC90 values were 2 µg/ml for ceftobiprole and 1 µg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12 and 4 µg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 µg/ml, the MIC90 values were 2 µg/ml for teicoplanin, 0.5 µg/ml for daptomycin, and 0.5 µg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 µg/ml (2, 0.06, and 0.12 µg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n = 6), teicoplanin (n = 1), daptomycin (n = 2), or tigecycline (n = 1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 µg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.

First Report of Bacterial Leaf Blight of Carrot Caused by Xanthomonas hortorum pv. carotae in Korea.

In December 2012, symptoms of typical bacterial leaf blight were observed on carrot plants (Daucus carota L. subsp. sativus) cultivated in commercial fields in Kujwa, Jeju, Korea. The disease was detected in 40% of 50 fields surveyed with an incidence of 10% on average. The bacterial leaf blight lesions on leaf blades were elongated, dark brown to black with water-soaked edges and chlorotic halos. Lesions were also crescent-shaped to V-shaped on leaflets. Four bacterial isolates were recovered on trypticase soy agar from leaf lesions that were surface-sterilized in 70% ethyl alcohol for 20 s. Identity of the isolates was confirmed by PCR product (1,266-bp) using a specific primer set for Xanthomonas hortorum pv. carotae (Kendrick 1934) Vauterin et al. 1995, XhcPP03 (1). All isolates were gram-negative, aerobic rods with a single polar flagellum. Isolates were positive for catalase and negative for oxidase. In phenotypic tests for differentiation of Xanthomonas (2), the isolates positive for mucoid growth on yeast extract-dextrose-calcium carbonate agar, growth at 35°C, hydrolysis of esculin, protein digestion, alkaline in litmus milk, acid production from arabitol, and utilization of glycerol and melibiose. The isolates were negative for growth on SX medium, hydrolysis of starch, and ice nucleation. The gyrB gene (863 bp) and the rpoD gene (870 bp) were sequenced to aid identification of the original isolates using published PCR primer sets, Xgyr1BF/Xgyr1BR and XrpoD1F/XrpoD1R (4), respectively. Sequences of the gyrB gene (GenBank accessions KC920729 to KC920732) from the carrot isolates shared 100% sequence identity with that of the X. hortorum pv. carotae strain NCPPB 425 (EU285243). In phylogenetic analyses based on the partial sequences of the gyrB and the rpoD genes for Xanthomonas spp. available at NCBI (4), and sequences of the carrot isolates (KC920734 to KC920737 for rpoD gene) using the Neighbor-joining method in MEGA Version 5.1 (3), the isolates were clustered in the X. hortorum-cynarae-garnderi group. Pathogenicity of the isolates was tested by spray inoculation with a bacterial suspension (106 CFU/ml) prepared in sterile distilled water at 6 to 7 true-leaf stage (three plants per isolate). Sterile distilled water was used as negative control. The inoculated plants were incubated in a growth chamber (25°C and 95% relative humidity [RH]) for 15 hr, and then transferred to a greenhouse at 24 to 28°C and 65% RH. Characteristic leaf blight symptoms developed on inoculated carrot plants, while no symptoms were observed on the negative control plants 14 days after inoculation. The bacterium was re-isolated from symptomatic tissue and the identity confirmed through gyrB gene sequence analysis (4). Based on PCR, morphological and phenotypic tests, sequence analysis, and pathogenicity assays, the isolates were identified as X. hortorum pv. carotae. To our knowledge, this is the first report of bacterial leaf blight of carrot caused by X. hortorum pv. carotae in Korea. The detection of this pathogen could have a significant economic impact due to yield losses from disease development. Consolidation of quarantine inspection on imported carrot seeds needs to control an outbreak of the disease. Crop rotation and plowing are recommended to reduce incidence of the disease in the infested fields. References: (1) J. A. Kimbrel et al. Mol. Plant Pathol. 12:580, 2011. (2) N. W. Schaad et al. Page 189 in: Laboratory Guide for Identification of Plant Pathogenic Bacteria. 3rd ed. N. W. Schaad et al., eds. The American Phytopathological Society, St. Paul, MN, 2001. (3) K. Tamura et al. Mol. Biol. Evol. 28:2731, 2011. (4) J. M. Young et al. Syst. Appl. Microbiol. 31:366, 2008.

Effect of Paget's disease of bone (osteitis deformans) on the progression of prostate cancer bone metastasis.

BACKGROUND: Patients with prostate cancer tend to die from bone metastases. Until now, no evidence has shown that Paget's disease of bone (PDB) affects the progression of bone metastasis or overall survival of patients with prostate cancer. METHODS: We searched our patient database for men who had presented with prostate cancer and PDB between June 1993 and March 2009, and identified best-matched control patients according to stage, grade, age, date of diagnosis, treatment, and race. RESULTS: Among 1346 consecutive patients with prostate cancer diagnosed before 2008, 15 were confirmed to have comorbid PDB. Twenty-six more were identified from the institutional billing search. Including the 41 best-matched controls, our total study population was 82 patients. In the Kaplan-Meier analysis, we estimated median times from diagnosis of prostate cancer to bone metastasis to be 21.5 years for those with PDB and 9.4 years for those without PDB (P=0.044). Median overall survival times were 11.8 and 9.2 years for the two groups, respectively (P=0.008). CONCLUSION: For the first time, we have obtained evidence that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival than do patients with prostate cancer alone.

Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer.

BACKGROUND: Insulin/insulin-like growth factor-I (IGF-I) signaling is a mechanism mediating the promoting effect of type 2 diabetes (DM2) on cancer. Human epidermal growth factor receptor (HER2), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer. METHODS: We reviewed 1983 consecutive patients with HER2+ breast cancer treated between 1 January 1998 and 30 September 2010. The overall survival, breast cancer-specific death rate, age, race, nuclear grade, stage, menopausal status, estrogen and progesterone receptor status, body mass index and classes of antidiabetic pharmacotherapy were analyzed. RESULTS: A Cox regression analysis showed that DM2 [P=0.026, hazard ratio (HR)=1.42, 95 % confidence interval (95 % CI) 1.04-1.94] predicted poor survival of stage≥2 HER2+ breast cancer. In Kaplan-Meier analysis, metformin predicted lengthened survival and so did thiazolidinediones. Analyzing only the diabetics, Cox regression showed that metformin (P=0.041, HR=0.52, 95 % CI 0.28-0.97) and thiazolidinediones (P=0.036; HR=0.41, 95% CI 0.18-0.93) predicted lengthened survival, and competing risk analysis showed that metformin and thiazolidinediones were associated with decreased breast cancer-specific mortality (P=0.023, HR=0.47, 95% CI 0.24-0.90 and P=0.044, HR=0.42, 95 % CI 0.18-0.98, respectively). CONCLUSIONS: Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.

Prurigo pigmentosa: a clinicopathologic study of 16 cases.

BACKGROUND: Prurigo pigmentosa is a rare inflammatory disease of unknown origin. It is characterized by the sudden onset of pruritic erythematous papules, usually involving the trunk and neck, which coalesce to form reticulated, mottled patches. METHODS: We studied 16 patients with prurigo pigmentosa. The patients were selected from those attending the outpatient Department of Dermatology at the Kyung Hee University Hospital from January 2002 to January 2010. All clinical information was retrospectively collected from medical records. The serum concentrations of ketones (acetoacetic acid, 3-hydroxybutyrate acid [3-OHBA]) were examined in four patients, and a test for ketone in the urine was performed in 10 patients. RESULTS: The age at the time of diagnosis ranged from 18 to 36 years (mean age: 23.5 years), and the female : male ratio was 14 : 2. Skin lesions were almost always characterized by recurrent pruritic erythematous papules that had resolved, leaving a peculiar, reticulate hyperpigmentation. Eight of 16 patients showed a chronological relationship between a prurigo pigmentosa appearance of skin lesions and dieting or fasting. Histopathological findings were either of fully developed lesions (4/16) or late lesions (12/16). Most patients responded well to minocycline treatment. Ketosis was observed in six patients. CONCLUSIONS: In conclusion, we propose that ketosis was caused by fasting, and that diet may contribute to the pathogenesis of prurigo pigmentosa. Thus, physicians need to warn that excessive fasting can cause prurigo pigmentosa.

Performance of the new biological small- and wide-angle X-ray scattering beamline 13A at the Taiwan Photon Source.

Recent developments in the instrumentation and data analysis of synchrotron small-angle X-ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small- and wide-angle X-ray scattering (SAXS-WAXS or SWAXS). The endstation features an in-vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size-exclusion chromatography system incorporating several optical probes including a UV-Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS-WAXS data collection and data reduction for high-throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal-model fittings to the data in the q range ∼0.005-2.0 Å-1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration-dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.