One-year survival in recipients older than 50 bridged to heart transplant with Impella 5.5 via axillary approach / 老年心脏病学杂志（英文版）

BACKGROUND@#Optimizing patients with advanced heart failure before orthotopic heart transplantation (OHT), especially in patients greater than 50 years old, is imperative to achieving successful post-transplant outcomes. Complications are well-described for patients bridged to transplant (BTT) with durable left ventricular assist device (LVAD) support. Given the lack of data available in older recipients after the recent increase in mechanical support use, we felt it crucial to report our center's one-year outcomes in older recipients after heart transplantation with percutaneously placed Impella 5.5 as a BTT.@*METHODS@#Forty-nine OHT patients were supported with the Impella 5.5 intended as a bridge between December 2019 and October 2022 at Mayo Clinic in Florida. Data were extracted from the electronic health record at baseline and during their transplant episode of care after Institutional Review Boards approval as exempt for retrospective data collection.@*RESULTS@#Thirty-eight patients aged 50 or older were supported with Impella 5.5 as BTT. Ten patients underwent heart and kidney transplantation within this cohort. The median age at OHT was 63 (58-68) years, with 32 male (84%) and six female patients (16%). Etiology was divided into ischemic (63%) and non-ischemic cardiomyopathy (37%). The baseline median ejection fraction was 19% (15-24). Most patients were in blood group O (60%), and 50% were diabetic. The average duration of support was 27 days (range 6-94). The median duration of follow-up is 488 days (185-693). For patients that have reached the 1-year follow-up timeframe (22 of 38, 58%), the 1-year post-transplant survival is 95%.@*CONCLUSION@#Our single-center data provides awareness for using the Impella 5.5 percutaneously placed axillary support device in older heart failure patients in cardiogenic shock as a bridge to transplantation. One-year survival outcomes after heart transplantation are excellent despite the older recipient's age and prolonged pre-transplant support.

Novel Effect of Hyaluronan and Proteoglycan Link Protein 1(HAPLN1) on Hair Follicle Cells Proliferation and Hair Growth

Hair loss is a common condition that can have a negative impact on an individual’s quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

A Novel Role of Hyaluronic Acid and Proteoglycan Link Protein 1(HAPLN1) in Delaying Vascular Endothelial Cell Senescence

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

Development of a Label-Free LC-MS/MS-Based Glucosylceramide Synthase Assay and Its Application to Inhibitors Screening for Ceramide-Related Diseases

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.

Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and 150 muM), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.

A Case of Pulmonary Edema by Idiopathic Rupture of Mitral Chordae Tendinae / 결핵및호흡기질환

The typical radiographic findings of pulmonary edema from the increased hydrostatic pressure shows centrally localized consolidation, which is known as a "butterfly or bat's wing" pattern. These terms describe the anatomic distribution of edema that uniformly involve the hilum and medulla of the lung but not the peripheral region of the lung parenchyma (cortex). We present a case of butterfly wing-like pulmonary edema on a chest radiograph by mitral regurgitation due to an idiopathic chordal rupture.

Wilms' tumor with polydipsia, polyuria, hyponatremic hypertension and congestive heart failure: a case report / 소아과

A 3-year-old girl presented with polydipsia, polyuria, hyponatremia, hypertension and congestive heart failure. Her polyuria was unresponsive to water restriction and vasopressin challenge tests, and her blood pressure was not effectively controlled by antihypertensive drugs. Radiologic examinations revealed a Wilms' tumor in the right kidney. Her plasma renin activity and aldosterone concentration were greatly increased. After surgical removal of the tumor, the congestive heart failure disappeared. Congestive heart failure due to Wilms' tumor is very rare and we report here on such a case, with a brief review of the literature.

A case of Kikuchi's disease with skin involvement / 소아과

Histiocytic necrotizing lymphadenitis, which is also commonly referred to as Kikuchi's disease (KD), is a self-limiting disease of unknown etiology. It affects individuals of all ages, although it is usually seen in young women. However, only a few descriptions of this disease are available in the pediatric literature. KD is clinically characterized by cervical lymphadenopathy, high fever, myalgia, neutropenia and, rarely, cutaneous eruptions. Cutaneous manifestations have been reported in 16-40 percent of KD cases. The specific skin changes occurring in cases of KD have yet to be completely characterized. In most of the reported cases thus far, the lesions have been located on the face and upper extremities. In this report, we describe a case of pediatric Kikuchi's disease, occurring in a 9-year-old boy. The boy exhibited transient erythematous maculopapular skin lesions over the entirety of his body, including his lower extremities.

The Epidemiologic Characteristics and Infection Control Measures for an Outbreak of Rotavirus Infection in the Neonatal Unit / 감염과화학요법

BACKGROUND: The purpose of the study is to investigate an outbreak of rotavirus infection in a neonatal unit and to study the effectiveness of the infection control measures implemented. MATERIALS AND METHODS: We investigated an outbreak of rotavirus infection in a neonatal unit equipped with 4 newborn nursery rooms (NNRs) from Dec. 2002 through May 2003. After performing initial surveillance study in all 11 newborns and 21 staffs for stool rotavirus shedding, we observed the course of the outbreak by assessing week incidence and introducing reinforced control measures. P (VP4) genotypes of rotavirus isolates were determined to investigate the link between NNRs and the pediatric ward. RESULTS: Initial surveillance showed that 2 newborns from NNRs were infected, but none of staffs were infected. Despite initial intervention (70% alcohol based gel for hand hygiene, cohorting of the neonates, and education for staffs), new cases increased up to 9.2 cases per 100 neonate week. Even after further control measures such as using commercialized milk and recruiting new staffs, cases continued to occur with 22.2 cases per 100 neonate week. Finally, a temporary NNR was set up and disinfection of surfaces and equipments from the neonatal unit was performed, after which the outbreak ceased. All rotaviruses isolated during the outbreak from newborns in NNRs were genotype P2A, whereas isolates from the pediatric ward were genotype P1A, P1B, and P3. CONCLUSIONS: This study indicates that rotaviral diarrhea is highly transmissible and when outbreak occurs in the neonatal unit, excessive control measures such as the ward closure may be needed.

The Epidemiologic Characteristics and Infection Control Measures for an Outbreak of Rotavirus Infection in the Neonatal Unit / 감염과화학요법

BACKGROUND: The purpose of the study is to investigate an outbreak of rotavirus infection in a neonatal unit and to study the effectiveness of the infection control measures implemented. MATERIALS AND METHODS: We investigated an outbreak of rotavirus infection in a neonatal unit equipped with 4 newborn nursery rooms (NNRs) from Dec. 2002 through May 2003. After performing initial surveillance study in all 11 newborns and 21 staffs for stool rotavirus shedding, we observed the course of the outbreak by assessing week incidence and introducing reinforced control measures. P (VP4) genotypes of rotavirus isolates were determined to investigate the link between NNRs and the pediatric ward. RESULTS: Initial surveillance showed that 2 newborns from NNRs were infected, but none of staffs were infected. Despite initial intervention (70% alcohol based gel for hand hygiene, cohorting of the neonates, and education for staffs), new cases increased up to 9.2 cases per 100 neonate week. Even after further control measures such as using commercialized milk and recruiting new staffs, cases continued to occur with 22.2 cases per 100 neonate week. Finally, a temporary NNR was set up and disinfection of surfaces and equipments from the neonatal unit was performed, after which the outbreak ceased. All rotaviruses isolated during the outbreak from newborns in NNRs were genotype P2A, whereas isolates from the pediatric ward were genotype P1A, P1B, and P3. CONCLUSIONS: This study indicates that rotaviral diarrhea is highly transmissible and when outbreak occurs in the neonatal unit, excessive control measures such as the ward closure may be needed.

Usefulness of B-type Natriuretic Peptide Assay as a Biochemical Marker of Cardiovascular Manifestations in Children with Kawasaki Disease

PURPOSE: The purpose of our study is to investigate the usefulness of B-type natriuretic peptide(BNP) assay as a biochemical marker of cardiovascular manifestations in children with Kawasaki disease(KD). METHODS: Blood was obtained to measure and compare plasma BNP concentrations in the acute phases of typical KD(n=56), atypical KD(n=25), viral febrile disease(n=30), Henoch-Shonlein purpura(n=20) and in the subacute phase of typical KD. Plasma BNP concentrations were measured using a commercial kit, Triage(R) BNP test kit. RESULTS: The mean BNP concentration in the acute phase of KD was significantly higher than in the acute phase of atypical KD, viral febrile disease and Henoch-Shonlein purpura(198.7+/-49.6 vs 55.9+/-10.4, 27.0+/-5.7, 13.7+/-3.1 pg/mL, P<0.001). In KD patients, the mean BNP concentration in the subacute phase was decreased significantly after the treatment with intravenous immunoglobulin and high-dose aspirin(78.0+/-23.5 pg/mL, P<0.001). The area under the Receiver Operating Characteristic curve using BNP level to differentiate KD from viral febrile disease was high: 0.826(95% CI, 0.735 to 0.918, P<0.001). A best cutoff of BNP concentrations for the differential diagnosis of Kawasaki disease was determined to be 30.8 pg/mL(sensitivity 76.8%, specificity 76.7%). CONCLUSION: This study shows the possibility that the rapid BNP assay is useful to detect cardiovascular manifestations associated with KD. Further studies are needed to clarify the mechanism by which the elevated levels of plasma BNP occur in the acute phase of KD.