Clinical impact of COVID-19 in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

The aim of this study was to evaluate the impact of coronavirus disease 2019 (COVID-19) on treatment outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This single-centre, retrospective cohort study was conducted in a 1,048-bed university-affiliated tertiary hospital in the Republic of Korea from January 2021 to March 2022. The study participants included consecutive hospitalised adult patients (aged ≥18 years) in the intensive care unit with CRAB monomicrobial BSI. During the study period, a total of 70 patients were included in our study, and 24 (34.3%) were diagnosed with COVID-19. The 28-day mortality rate was 64.3%. In the multivariate Cox proportional hazard regression analysis, diagnosis of COVID-19 (hazard ratio (HR), 2.91; 95% confidence interval (CI): 1.45-5.87), neutropenia (HR, 2.76; 95% CI: 1.04-7.29), Pitt bacteraemia score (per point; HR, 1.30; 95% CI: 1.19-1.41), and appropriate definite antibiotic therapy (HR, 0.31; 95% CI: 0.15-0.62) were independent predictors of 28-day mortality in patients with CRAB BSI. In conclusion, our findings suggested that COVID-19 has a negative prognostic impact on patients with CRAB BSI. Further study is needed to investigate the specific mechanisms of how COVID-19 worsens the prognosis of CRAB infection.

LINC00162 regulates cell proliferation and apoptosis by sponging PAQR4-targeting miR-485-5p.

Growing evidence indicates that long intergenic noncoding RNAs play an important role in cancer progression by affecting gene regulation at the transcriptional and posttranscriptional levels. Recent studies have shown that long intergenic noncoding RNA functions as a competitive endogenous RNA, which can interact with and mitigate the function of microRNA. In this study, we investigated the molecular mechanism by which LINC00162 regulates cell proliferation and apoptotic cell death. By analyzing RNA sequencing data, LINC00162 was identified to be a target of heterogeneous nuclear ribonucleoprotein K (hnRNPK). HnRNPK positively regulated LINC00162 expression through p38 mitogen-activated protein kinase. Lowering the level of either hnRNPK or LINC00162 decreased proliferation and colony formation while it increased apoptotic cell death. Small RNA sequencing followed by the antisense oligonucleotide pulldown, revealed that LINC00162 interacts directly with miR-485-5p which exhibited tumor-suppressing effects by suppressing cell proliferation and colony formation, and increasing apoptotic cell death. Through the bioinformatic approaches, progestin and adipoQ receptor 4 (PAQR4) was selected as a common target of LINC00162 and miR-485-5p. miR-485-5p decreased the expression of PAQR4 by directly binding to the 3'-untranslated region of PAQR4 messenger RNA. Knockdown of hnRNPK and LINC00162 increased the level of functional miR-485-5p, indicating that LINC00162 may compete for miR-485-5p, thereby derepressing PAQR4 expression. Overexpression of either hnRNPK or LINC00162, or inhibition of miR-485-5p, protected cells against etoposide-induced apoptotic death. Our findings demonstrate that a regulatory paradigm implicating hnRNPK, LINC00162, miR-485-5p, and PAQR4 plays an important role in cell proliferation and apoptosis, and is a promising target for cancer therapeutics.

Two circPPFIA1s negatively regulate liver metastasis of colon cancer via miR-155-5p/CDX1 and HuR/RAB36.

BACKGROUND: Circular RNAs (circRNAs) play a critical role in colorectal cancer (CRC) progression, including metastasis. However, the detailed molecular mechanism is not fully understood. METHODS: Differentially expressed circRNAs between primary KM12C and liver metastatic KM12L4 colon cancer cells were identified by microarray. The expression of circRNAs was measured by semi-quantitative (semi-qPCR) and real time-quantitative PCR (RT-qPCR). Metastatic potential including invasive and migratory abilities, and liver metastasis were examined by transwell assays and intrasplenic injection, respectively. CircPPFIA1-associated microRNA (miRNA) and RNA-binding protein (RBP) were screened by an antisense oligonucleotide (ASO) pulldown experiment. The effects of circPPFIA1 on target gene expression were evaluated by RT-qPCR and western blot analyses. RESULTS: By analyzing circRNA microarray data, we identified two anti-metastatic circRNAs generated from PPFIA1 with different length, which named circPPFIA1-L (long) and -S (short). They were significantly downregulated in liver metastatic KM12L4 cells compared to primary KM12C cells. The knockdown of circPPFIA1s in KM12C enhanced metastatic potential and increased liver metastasis. Conversely, overexpression of circPPFIA1s weakened metastatic potential and inhibited liver metastasis. circPPFIA1s were found to function as sponges of oncogenic miR-155-5p and Hu antigen R (HuR) by an ASO pulldown experiment. circPPFIA1s upregulated tumor-suppressing CDX1 expression and conversely downregulated oncogenic RAB36 by decoying miR-155-5p and by sequestering HuR, respectively. CONCLUSION: Our findings demonstrate that circPPFIA1s inhibit the liver metastasis of CRC via the miR-155-5p/CDX1 and HuR/RAB36 pathways.

Diagnostic sensitivity and specificity of 2-mSv CT vs. conventional-dose CT in adolescents and young adults with suspected appendicitis: post hoc subgroup analysis of the LOCAT data.

OBJECTIVES: To test whether the difference in sensitivity or specificity between 2-mSv CT and conventional-dose CT (CDCT) for the diagnosis of appendicitis differs across subgroups of adolescents and young adults with suspected appendicitis. MATERIALS AND METHODS: We used the per-protocol analysis data of a trial conducted between Dec 2013 and Aug 2016, including 2773 patients (median age [interquartile range], 28 [21-35] years) and 160 radiologists from 20 hospitals. We defined subgroups by sex, body size, clinical risk scores for appendicitis, time of CT examination (i.e., working vs. after hours), CT machines, radiologists' experience, previous site experience in 2-mSv CT, and site practice volume. We drew forest plots and tested for additive or multiplicative interaction between radiation dose and subgroup attributes. If any subgroup had fewer than 200 patients, we considered the results from that subgroup not meaningful. RESULTS: For most subgroups, the 95% CIs for the differences in sensitivity and specificity were 4.0 percentage points or narrower and contained the minute overall between-group differences. There was no significant interaction on sensitivity or specificity. A few subgroups, including those of extreme body sizes, high appendicitis inflammatory response scores, and hospitals with small appendectomy volume, were regarded to have insufficient numbers of patients. CONCLUSIONS: There was no notable subgroup heterogeneity, which implies that 2-mSv CT can replace CDCT in diverse populations. Further studies are needed for the subgroups for which we had only small data. KEY POINTS: • The minute difference in sensitivity or specificity between the 2-mSv CT and conventional-dose CT (typically 7 mSv) groups were consistent across various patient or hospital characteristics. • These results indicate that 2-mSv CT can replace conventional-dose CT in diverse populations. • Further studies are needed to confirm whether 2-mSv CT can replace conventional-dose CT in patients of extreme body sizes, high appendicitis inflammatory response scores, or hospitals with small appendectomy volume, as those subgroups in our data included limited numbers of patients.

Toxicological assessments of an ethanol extract complex of Descurainia sophia and Peucedanum praeruptorum: Subacute oral toxicity and genotoxicity studies.

An ethanol extract complex of Descurainia sophia seeds and Peucedanum praeruptorum roots, called BP10A, has antitumor potential against colorectal cancer. In the present study, we evaluated the 28-day oral toxicity and the genotoxicity of BP10A. The subacute toxicity test was done through oral administration to mice. ICR mice (n = 10) received daily oral BP10A doses of 0, 500, 1000 and 2000 mg/kg for 28 consecutive days. During administration, general clinical signs, food consumption, organ weights, and hematologic, biochemical and histopathological parameters in male and female mice were assessed. No significant adverse effects up to the highest dose (2000 mg/kg) were found. The genotoxicity was evaluated using a battery of tests, including an in vitro bacterial reverse mutation (Ames) test, an in vivo micronucleus test using bone marrow cells in ICR mice and a chromosomal aberration test using CHL/IU cells. BP10A did not show any genotoxic signs in the Ames (up to 5000 µg/plate), micronucleus (up to 5000 mg/kg) and the chromosomal aberration tests (550-1750 µg/mL). Therefore, BP10A was considered safe based on the subacute toxicity and genotoxicity results, indicating that it is a useful pharmaceutical material with no adverse toxicity.

Assessment of the 4-week repeated-dose oral toxicity and genotoxicity of GHX02.

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non-clinical safety testing comprised a single-dose oral toxicity study and a 28-day repeated-dose oral toxicity study with a 14-day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single-dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28-day repeated-dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single-dose study. The no-observed-adverse-effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague-Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

CT in Differentiating Complicated From Uncomplicated Appendicitis: Presence of Any of 10 CT Features Versus Radiologists' Gestalt Assessment.

OBJECTIVE. The purpose of this study is to propose a sensitive CT criterion (the presence of any of 10 CT features) for complicated appendicitis that could be used in the nonoperative management of appendicitis and to compare the diagnostic performance of this sensitive CT criterion with that of gestalt assessment. MATERIALS AND METHODS. This retrospective study, which was conducted in a tertiary teaching hospital, included 100 patients with suspected appendicitis on CT. Complicated appendicitis, defined as gangrenous or perforated appendicitis, was pathologically or surgically confirmed in 32 patients. Six radiologists independently determined the presence of 10 previously reported CT features of complicated appendicitis (contrast enhancement defect of the appendiceal wall, abscess, extraluminal air, intraluminal air, extraluminal appendicolith, intraluminal appendicolith, moderate-to-severe periappendiceal fat stranding, periappendiceal fluid, ileus, and ascites) and rated the likelihood score for complicated appendicitis using gestalt assessment. The sensitivity and specificity of CT for complicated appendicitis were measured by the presence of any of 10 CT features (the any-of-10-features criterion) and by the radiologists' gestalt assessment. Pooled sensitivity and specificity were compared using a generalized linear mixed model. RESULTS. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment (92% vs 64%; difference, 28% [95% CI, 10-46%]; p < 0.001), although the pooled specificity was lower (43% vs 76%; difference, -33% [95% CI, -48% to -17%]; p < 0.001). CONCLUSION. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment, at the cost of lower specificity. For prudent selection of patients who should receive nonoperative treatment of appendicitis, the any-of-10-features criterion may be used to decrease treatment failure associated with a false-negative diagnosis of complication.

An Evaluation of Active Case Detection in Malaria Control Program in Kiyuni Parish of Kyankwanzi District, Uganda.

Malaria remains one of the leading health burdens in the developing world, especially in several sub-Saharan Africa countries; and Uganda has some of the highest recorded measures of malaria transmission intensity in the world. It is evident that the prevalence of malaria infection, the incidence of disease, and mortality from severe malaria remain very high in Uganda. Although the recent stable political and economic situation in the last few decades in Uganda supported for a fairly good appreciation of malaria control, the declines in infection, morbidity, and mortality are not sufficient to interrupt transmission and this country is among the top 4 countries with cases of malaria, especially among children under 5 years of age. In fact, Uganda, which is endemic in over 95% of the country, is a representative of challenges facing malaria control in Africa. In this study, we evaluated an active case detection program in 6 randomly selected villages, Uganda. This program covered a potential target population of 5,017 individuals. Our team screened 12,257 samples of malaria by active case detection, every 4 months, from February 2015 to January 2017 in the 6 villages (a total of 6 times). This study assessed the perceptions and practices on malaria control in Kiyuni Parish of Kyankwanzi district, Uganda. Our study presents that the incidence of malaria is sustained high despite efforts to scale-up and improve the use of LLINs and access to ACDs, based on the average incidence confirmed by RDTs.

Clinical Features and Risk Factors for Development of Breakthrough Gram-Negative Bacteremia during Carbapenem Therapy.

With the increasing use of carbapenems, carbapenem-resistant Gram-negative bacteria have become a major concern in health care-associated infections. The present study was performed to evaluate the clinical and microbiological features of breakthrough Gram-negative bacteremia (GNB) during carbapenem therapy and to assess risk factors for development of breakthrough GNB. A case-control study was performed at a tertiary hospital from 2005 to 2014. Case patients were defined as individuals whose blood cultures grew Gram-negative bacteria while the patients were receiving carbapenems for at least 48 h before breakthrough GNB. Age-, sex-, and date-matched controls were selected from patients who received carbapenem for at least 48 h and did not develop breakthrough GNB during carbapenem treatment. A total of 101 cases of breakthrough GNB were identified and compared to 100 controls. The causative microorganisms for breakthrough GNB were Stenotrophomonas maltophilia (n = 33), Acinetobacter baumannii (n = 32), Pseudomonas aeruginosa (n = 21), and others (n = 15). Approximately 90% of S. maltophilia isolates were susceptible to levofloxacin and trimethoprim-sulfamethoxazole. The most common infection types were primary bacteremia (38.6%) and respiratory infections (35.6%). More than half of the patients died within a week after bacteremia, and the 30-day mortality rate was 70.3%. In a multivariate analysis, a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization by causative microorganisms were significantly associated with breakthrough GNB. Our data suggest that S. maltophilia, A. baumannii, and P. aeruginosa are the major pathogens of breakthrough GNB during carbapenem therapy, in association with a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization.

Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients.

BACKGROUND: Cytomegalovirus (CMV) colitis is a common manifestation of CMV end-organ disease, which has typically been described in immunocompromised hosts. Recently, it has been noted that this also occurs in immunocompetent patients. To gather relevant data about clinical presentation, prognosis, and risk factors for development of CMV colitis in immunocompetent hosts, we analyzed all cases that occurred during a 19-year period at our institution. METHODS: A case-control study was performed to identify risk factors for CMV colitis in immunocompetent hosts. Electronic medical records of individuals who were admitted and diagnosed with CMV colitis between January 1995 and February 2014 at a tertiary care university hospital were reviewed. Two non-CMV colitis patients who were age- and sex-matched were selected as controls for each case. RESULTS: A total of 51 patients with CMV colitis were included in this study along with 102 control patients. Certain conditions including renal disease on hemodialysis, neurologic disease, rheumatologic disease, intensive care unit admission, and exposure to antibiotics, antacids, steroids, or red blood cell (RBC) transfusions within 1 month of diagnosis of colitis were associated with CMV colitis on univariate analysis. Among these, steroid use and RBC transfusion within 1 month were identified as independent risk factors for developing CMV colitis on multivariate analysis. The 30-day mortality rate was 7.8% without any attributable mortality. CONCLUSIONS: Steroid use and RBC transfusion within 1 month of the diagnosis of colitis were independent risk factors for development of CMV colitis in immunocompetent hosts.

Case-control study of the risk factors for acquisition of Pseudomonas and Proteus species during tigecycline therapy.

Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp.

Clinical features and risk factors for development of Bacillus bacteremia among adult patients with cancer: a case-control study.

PURPOSE: Bacillus species have been frequently reported in recent decades as true pathogens among cancer patients. The purpose of this study was to evaluate the clinical features and risk factors of Bacillus bacteremia among adult patients with cancer. METHODS: A case-control study was performed to identify the risk factors of Bacillus bacteremia among adult patients with cancer at a 1,950-bed tertiary care university hospital. Electronic medical records were reviewed for individuals who were diagnosed with Bacillus bacteremia during the period of January 1995 through December 2012. Each case was matched to two controls with cancer and non-Bacillus bacteremia. Logistic regression model was used to identify independent risk factors for Bacillus bacteremia development. RESULTS: A total of 86 patients with Bacillus bacteremia were included and compared with 172 control patients. The presence of a central venous catheter and use of extended-spectrum cephalosporin within 1 month were identified to be independent risk factors for the development of Bacillus bacteremia. Hospital stays longer than 14 days, a history of hematopoietic stem cell transplantation, and prior use of glycopeptides had a negative association. CONCLUSIONS: The presence of a central venous catheter and prior use of extended-spectrum cephalosporin within 1 month were independent risk factors for the development of Bacillus bacteremia in adult cancer patients.

Bacteremic meningitis caused by Parvimonas micra in an immunocompetent host.

A 61-year-old man with chronic hepatitis B and dyslipidemia visited the emergency department with a fever and severe headache. He was diagnosed with bacterial meningitis after a lumbar puncture, and blood culture revealed Parvimonas micra bacteremia. Although he had a history of extraction of a molar two weeks before symptom onset, there was no evidence of abscess formation on physical examination or imaging studies. He was successfully treated with oral metronidazole for 12 days after 9 days of treatment with IV ceftriaxone and vancomcycin. This is the first report of primary bacterial meningitis caused by this organism, which indicates that this organism is capable of being a bacterial meningitis pathogen.

Hepatitis B virus reactivation during anti-cancer chemotherapy in patients with past hepatitis B virus infection.

BACKGROUND/AIMS: The necessity of preemptive antiviral therapy in patients with past HBV infection is uncertain. We evaluated the incidence and risk factors of HBV reactivation in cancer patients with past HBV infection who received anti-cancer chemotherapy. METHODOLOGY: Between Jan. 2009 and Dec. 2011, we reviewed 675 HBsAg negative and anti-HBc positive patients who had solid cancers or hematologic malignancies that were treated with intravenous cytotoxic chemotherapy. RESULTS: Among 675 patients, 321 (47.6%) patients had solid cancer and 354 (52.4%) had hematologic malignancy. HBV reactivation was observed in 13 patients (1.9%). In solid cancer patients, 1 (0.3%) patient had HBV reactivation, whereas 12 out of 365 (3.3%) patients with hematologic malignancy experienced HBV reactivation. Among the 12 HBV-reactivated patients with hematologic malignancy, 11 patients had lymphoma. Lymphoma carried a significantly higher risk for HBV reactivation than solid cancer in patients with past HBV infection (OR, 24.134; 95% CI, 3.027-192.406; P = 0.003). Among HBV-reactivated lymphoma patients, 2 patients experienced fulminant liver failure. The absence of anti- HBs was identified as a risk factor for HBV reactivation (OR, 22.446; 95% CI, 4.816-104.609; P < 0.001). CONCLUSIONS: Preemptive antiviral therapy should be considered in lymphoma patients with past HBV infection before starting anti-cancer chemotherapy

Acute myocardial infarction after radiofrequency catheter ablation of typical atrial flutter.

A 53-yr-old man underwent radiofrequency ablation to treat persistent atrial flutter. After the procedure, the chest pain was getting worse, and the electrocardiogram showed ST-segment elevation in inferior leads with reciprocal changes. Immediate coronary angiography showed total occlusion with thrombi at the distal portion of the right coronary artery, which was very close to the ablation site. Intervention with thrombus aspiration and balloon dilatation was successful, and the patient recovered without any kind of sequelae. Although the exact mechanism is obscure, the most likely explanation is a thermal injury to the vascular wall that ruptured into the lumen and formed thrombus. Vasospasm and thromboembolism can also be other possibilities. This case raise the alarm to cardiologists who perform radiofrequency ablation to treat various kinds of cardiac arrhythmias, in that myocardial infarction has been rarely considered one of the complications.

Diabetic Neuropathy and Minimum Effective Anesthetic Concentration of Mepivacaine for Axillary Brachial Plexus Block: A Prospective Observational Study.

Nerves in patients with diabetic neuropathy (DN) show increased susceptibility to local anesthetics, potentially requiring a decreased dose. We investigated whether the minimum effective anesthetic concentration (MEAC) of mepivacaine for successful axillary block is lower in patients with DN than in those without. This prospective observational study included patients with DN (n = 22) and without diabetes (n = 22) at a tertiary care center. Patients received an ultrasound-guided axillary block with 30 mL of mepivacaine for anesthesia. The mepivacaine concentration used in each patient was calculated using Dixon's up-and-down method. A block was considered successful if all four sensory nerves had a score of 1 or 2 within 30 min with no pain during surgery. The primary outcome was the MEAC of mepivacaine, and the secondary outcomes included the minimal nerve stimulation intensity for the musculocutaneous nerve and the occurrence of adverse events. The MEAC50 was 0.55% (95% CI 0.33-0.77%) in patients without diabetes and 0.58% (95% CI 0.39-0.77%) in patients with DN (p = 0.837). The MEAC90 was 0.98% (95% CI 0.54-1.42%) in patients without diabetes and 0.96% (95% CI 0.57-1.35%) in patients with DN (p = 0.949). The stimulation threshold for the musculocutaneous nerve was significantly different between groups (0.49 mA vs. 0.19 mA for patients with vs. without diabetes; p = 0.002). In conclusion, the MEAC of mepivacaine for a successful axillary block is not lower in patients with DN.

Immunoglobulin g4 non-related sclerosing disease with intracardiac mass mimicking mitral stenosis: case report.

The cardiovascular system may be one of the target organs of both immunoglobulin G4 related and non-related systemic multifocal fibrosclerosis. We present a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis on echocardiography. For a more detailed differential diagnosis, we used multimodal imaging techniques. After surgical biopsy around the abdominal aortic area in the retroperitoneum, histological examination revealed IgG4 non-related systemic multifocal fibrosclerosis. We describe the multimodal imaging used to diagnose IgG4 non-related systemic multifocal fibrosclerosis and a positive response to steroid treatment. There have been no previous case reports of IgG4 non-related systemic multifocal fibrosclerosis with intracardiac involvement. Here, we report a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis.

Clinical Features and Outcomes of Invasive Fusariosis: A Case Series in a Single Center with Literature Review.

Fusarium species, which are commonly found in soil, water, and organic substrates, can cause serious infections especially in immunocompromised patients. Fusarium infection is notoriously difficult to treat, because of their inherently high minimum inhibitory concentrations (MICs) to most antifungal agents. There have been limited data on invasive fusariosis in Korea. We identified 57 patients with culture-proven fusariosis at Samsung Medical Center, Seoul, Korea, from September 2003 through January 2017. Invasive fusariosis was defined as any case with at least one positive blood culture or with concurrent involvement of 2 or more non-contiguous sites. Superficial infections such as keratitis and onychomycosis were excluded. We reported 14 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, of which 6 cases were fusarium fungemia. Hematologic malignancies (7/14, 50%), solid organ transplantation (2/14, 14.2%), or immunosuppressive therapy (2/14, 14.2%), were the predominant underlying conditions. The overall mortality rate was 37%, however, that of disseminated fusariosis was up to 83%. Antifungal treatment with voriconazole or liposomal amphotericin B was commonly administered. In this report, we described the clinical characteristics and treatment outcomes of invasive fusariosis in Korea. Given the high mortality in disseminated cases, invasive fusariosis is becoming a therapeutic challenge to clinicians treating immunocompromised patients.

Rosacea Granulomatosis in a Neutropenic Leukemic Patient.

Rosacea granulomatosis is a common, chronic skin disorder that primarily affects the central face, namely the cheek, nose, chin, and central forehead. Although rosacea is mainly a disorder of innate and adaptive immunity, a variety of endogenous and exogenous triggers such as Demodex may stimulate it. Often found as commensal organisms in human skin, Demodex ​​​​​​​can be parasitic if there is a change in the host's cutaneous environment. This is especially relevant for immunosuppressed patients, who need prompt treatment to prevent further complications. We review the literature regarding rosacea granulomatosis in immunosuppression and present an acute myelogenous leukemia patient with severe neutropenia, which may have promoted the development of rosacea due to Demodex ​​​​​​​mite proliferation. This local proliferation of the ectoparasite on the face can cause an atypical skin rash that mimics severe infections in the setting of neutropenia.

Local lymph node assay: 5-bromo-d-deoxyuridine-ELISA method for comparative study in assessing chemical potencies and skin sensitization in BALB/c and CBA/J strains.

Local lymph node assay (LLNA) is a predictive in vivo method to provide estimates of relative potency and to contribute to risk assessment/risk management regarding skin sensitizing potency of chemicals and formulations as a stand-alone alternative test. In addition, LLNA is relatively rapid and cost-effective compared to the Buehler method (Guinea pig test), and confers important animal welfare benefits. CBA/J and BALB/c strains are widely commercially available and have been evaluated by formal LLNA validation studies. However, the LLNA method using BrdU with ELISA, unlike other LLNA methods (OECD TG 429, 442 A, 442B), has not been previously validated. Therefore, in this study a validation method was performed to evaluate if the LLNA:BrdU-ELISA method could also be used to identify sensitizers among chemicals listed in OECD TG 429 using CBA/J and BALB/c strains. Here, we newly found that the LLNA:BrdU-ELISA validation method correctly identified 12 of 13 sensitizers in the BALB/c, 11 of 13 sensitizers in the CBA/J, and 3 of 5 non-sensitizers were identified in the two strains. Collectively, we found that the results of LLNA:BrdU-ELISA method provide a similar level of performance for accuracy and sensitivity in two mouse strains BALB/c and CBA/J.