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.

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.

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.

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.

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.

hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2.

Malignant characteristics of cancers, represented by rapid cell proliferation and high metastatic potential, are a major cause of high cancer-related mortality. As a multifunctional RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) is closely associated with cancer progression in various types of cancers. In this study, we sought to identify hnRNPK-regulated long intergenic non-coding RNAs (lincRNAs) that play a critical role in the regulation of cancer malignancy. We found that hnRNPK controlled malignant phenotypes including invasiveness, proliferation, and clonogenicity. RNA sequencing and functional studies revealed that LINC00263, a novel target of hnRNPK, is involved in the oncogenic functions of hnRNPK. Knockdown of LINC00263 mitigated the malignant capabilities. Conversely, increased malignant phenotypes were observed in LINC00263-overexpressing cells. Since LINC00263 was mainly localized in the cytosol and highly enriched in Argonaute 2-immunoprecipitation (Ago2-IP), we hypothesized that LINC00263 acts as a competitive endogenous RNA (ceRNA), and thus sought to identify LINC00263-associated microRNAs. Using small RNA sequencing followed by antisense oligonucleotide pull-down, miR-147a was selected for further study. We found that miR-147a negatively regulates LINC00263 via direct interaction, thus suppressing malignant capabilities. Moreover, knockdown of hnRNPK and LINC00263 upregulated miR-147a, indicating that LINC00263 serves as a ceRNA for miR-147a. By analyzing RNA sequencing data and miRNA target prediction, calpain 2 (CAPN2) was identified as a putative target of miR-147a. Ago2-IP and luciferase reporter assay revealed that miR-147a suppressed CAPN2 expression by directly binding to the 3'UTR of CAPN2 mRNA. In addition, we found that the weakened malignant capabilities following knockdown of hnRNPK or LINC00263 were restored by miR-147a inhibition or CAPN2 overexpression. Furthermore, our findings were validated in various other types of cancer cells including lung cancer, colorectal cancer, neuroblastoma, and melanoma. Collectively, we demonstrate that hnRNPK-regulated LINC00263 plays an important role in cancer malignancy by acting as a miR-147a decoy and thus upregulating CAPN2.

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.

Dual-strand tumor suppressor miR-193b-3p and -5p inhibit malignant phenotypes of lung cancer by suppressing their common targets.

Emerging studies suggest that microRNAs (miRNAs) play multiple roles in cancer malignancy, including proliferation and acquisition of metastatic potential. Differentially expressed miRNAs responsible for the malignancy of lung cancer were searched by miRNA microarray using a previously established brain metastatic lung cancer model. Twenty-five miRNAs were down-regulated in brain metastatic lung cancer cells. Among those, miR-193b-3p and -5p were chosen for further studies. Their function in metastatic potential and proliferation was examined using Transwell invasion, wound healing, and colony forming assays. The underlying mechanism of tumor-suppressor miR-193b-3p and -5p was explored using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), Western blot, Argonaute 2-RNA immunoprecipitation (Ago2-RIP), and reporter assays. Both strands of miR-193b were down-regulated in brain metastatic lung cancer cells and in tissues from lung cancer patients. Overexpression of miR-193b-3p and -5p inhibited invasive and migratory activities and diminished clonogenic ability. Conversely, inhibition of miR-193b-3p or -5p increased the metastatic potential and colony forming ability. Cyclin D1 (CCND1), Ajuba LIM Protein (AJUBA), and heart development protein with EGF like domains 1 (HEG1) were identified as common target genes of miR-193b-3p and -5p. A reporter assay and an Ago2-RIP experiment showed that both miRNAs directly bind to the 3' untranslated region (3'UTR) of the target mRNA. Knockdown of target gene reduced the proliferative and metastatic potential of primary and metastatic lung cancer cells. Our results demonstrate miR-193b is a dual-strand tumor suppressor and a novel therapeutic target for lung cancer.

Bacteremia due to Rahnella aquatilis in a Patient with a Chemoport.

Rahnella aquatilis, a saprophytic organism, is a member of the Enterobacteriaceae family. The natural habitat of this organism is fresh water, and it is rarely found in clinical specimens. Clinical conditions ascribed to this organism include bacteremia, respiratory infection, urinary tract infection, wound infection in an immunocompromised host, and infective endocarditis in patients with congenital heart diseases. Here, we report a case of bacteremia due to R. aquatilis in a woman with breast cancer who had received chemotherapy through a chemoport. To our knowledge, this is the second case of bacteremia caused by this organism in a patient with cancer in Korea.

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.

Development of Epidural and Paraspinal Abscesses after Insufficient Evaluation and Treatment of Acute Pyelonephritis Caused by Staphylococcus aureus.

Diagnoses of pyelonephritis caused by Staphylococcus aureus should be accompanied by investigations of concomitant bladder obstruction and metastatic infections, especially to the spine or heart. Complicated pyelonephritis due to S. aureus requires more than 2 weeks of antibiotics, which is the typically recommended treatment duration for pyelonephritis. We describe a patient who was diagnosed with complicated epidural and paraspinal abscesses after insufficient evaluation and treatment of acute pyelonephritis due to S. aureus. A 62-year-old man with type 2 diabetes was admitted with fever, increased urinary frequency, and left flank pain. He was diagnosed with acute pyelonephritis caused by S. aureus. His fever and flank pain subsided after 3 days of intravenous antibiotics. Evaluation of bladder obstruction and metastatic infection were not performed, as he declined further evaluation. The patient was discharged with oral antibiotics and was requested to attend weekly appointments but was lost to follow-up. One month later, the patient presented at the outpatient clinic with similar symptoms. Computed tomography showed recurrent pyelonephritis and a distended bladder. His flank pain persisted despite administration of an opioid agent. Therefore, magnetic resonance imaging was performed, revealing epidural and paraspinal abscesses. Ultrasound-guided aspiration of the paraspinal muscle layer was performed, and blood and percutaneous aspirated fluid cultures revealed S. aureus growth. The pattern of antimicrobial sensitivity was identical to that at his first admission. Following more than 4 weeks of antibiotics, magnetic resonance imaging showed the abscesses had decreased in size. The patient was discharged without neurologic sequelae and was provided with oral antibiotics.

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 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.

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

Unusual manifestation of intravascular large B-cell lymphoma: severe hypercalcemia with parathyroid hormone-related protein.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/ computed tomography scan and bone marrow examination, which may be useful for early diagnosis.

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.

[Predictive factors of response to medical therapy in Crohn's disease patients with intestinal obstruction].

BACKGROUND/AIMS: Crohn's disease is a chronic inflammatory bowel disease. Stricture is a very important indication for surgical intervention as strictures can lead to intestinal obstruction. Strictures can be divided into inflammatory and fibrous strictures. Intestinal obstruction due to inflammatory stricture is expected to be resolved with medical treatment. However, factors that can predict the response to medical treatments are unknown. In the present study, we aimed to identify the factors that can predict the response to medical treatments in Crohn's disease patients with intestinal obstruction. METHODS: Data were collected by retrospectively reviewing the medical records of patients with Crohn's disease who visited the emergency department at Samsung Medical Center in Seoul from January 1, 2000 to December 31, 2010 because of intestinal obstruction. Based on the response to medical treatments, we classified the patients as responders and non-responders and compared the clinical, biochemical, and radiological findings of the two groups. RESULTS: A total of 39 patients were enrolled. Twenty-nine patients responded to medical treatments whereas 10 patients did not. Significant differences were observed between the two groups in terms of vomiting and duration of disease before the development of obstruction. CONCLUSIONS: Patients who responded to the medical treatments exhibited a higher incidence of vomiting and longer duration of disease before the development of obstruction. However, further prospective studies are needed to identify the factors that can predict the response to medical treatments.