Comorbidities, pharmacologic interventions, and mechanical interventions associated with mortality in isolated diastolic left heart failure: lessons from a national database.

BACKGROUND: Diastolic heart failure may be noted in paediatric patients with CHD, cardiomyopathy, or malignancies requiring chemotherapy, but the available data are scarce, and often derived from adult trials or based on theoretic or anecdotal evidence. METHODS: Data between 2016 and 2021 were obtained from Pediatric Health Information System database. Patients <18 years of age with isolated diastolic heart failure admitted to ICU at some point during admission were included. They were divided into patients with and without inpatient mortality. Patients' demographics, comorbidities using ICD-10 codes, and pharmacologic interventions were also recorded. Univariate analysis was done in demographics, comorbidities, pharmacologic interventions, and mechanical interventions between admissions with and without mortality. Multivariable logistic regression was done for inpatient mortality and multivariable linear regression was done for total hospital length of stay in survivors. RESULTS: Isolated diastolic heart failure comprised 0.5% of critically ill paediatric patients. A total of 121 (5%) experienced mortality among the 2,273 admissions in the final analyses. Milrinone and angiotensin converting enzyme inhibitor were found to be associated with decreased mortality. Increasing age and diuretics were associated with decreased total hospital length of stay in survivors. CONCLUSION: In the cohort studied, isolated diastolic left heart failure has a 5% mortality. Several comorbidities and interventions are associated with increased mortality with milrinone and angiotensin converting enzyme inhibitors being associated with decreased risk of mortality. When only admissions with survival to discharge are considered, older age and diuretics are associated with lower total hospital length of stay.

Acute Effects of Sacubitril/Valsartan with Initial Initiation in Pediatric Patients in the Cardiac Intensive Care Unit.

There are very few objectively studied and proven medical interventions for the management of pediatric heart failure. Due to improvement in morbidity and mortality in the adult heart failure population, sacubitril/valsartan has started to be used in pediatric patients. The aim of this study was to characterize the acute cardiovascular effects of sacubitril/valsartan in the first 48 h after initiation. Single center retrospective study of pediatric patients in the cardiac intensive care unit who were initiated on sacubitril/valsartan for the first time over a three-year period. Clinical data was collected immediately prior to and within 48 h following initiation. A total of 16 patients with a mean age of 9.6 years were started on sacubitril/valsartan with a mean daily dose of 1.6 mg/kg/day in the first 48 h. Significant decreases were noted in N-terminal brain natriuretic peptide and vasoactive-inotrope score. No significant changes were noted in other clinical variables. The initiation of sacubitril/valsartan in a small cohort of pediatric patients with heart failure in the cardiac intensive care unit is associated with a significant decrease in N-terminal brain natriuretic peptide with a concurrent decrease in vasoactive-inotrope score and without significant change venous oxygen extraction ratio or other hemodynamic variables.

Effect of Carnitine Supplementation in Pediatric Patients with Left Ventricular Dysfunction.

Carnitine is an essential amino acid involved in transporting fatty acids across the mitochondrial membrane. Fatty acids are a primary source of energy for the myocardium. Studies in adults demonstrated decreased carnitine levels in the ischemic myocardium, but subsequent exogenous carnitine supplementation showed improvement of myocardial metabolism and left ventricular function. However, only limited data regarding carnitine are available in pediatrics. A single-center retrospective, paired data study was conducted. Patients < 18 years, left ventricular ejection fraction (LVEF) < 55% by echocardiography, and had received at least 7 days of oral or intravenous carnitine supplementation between January 2018 and March 2021 are included in the study. Several endpoints and covariates were collected for each patient: before, one week after, one month after, and 6 months after carnitine supplementation. Univariate analysis consisted of an analysis of variance (ANOVA), followed by an analysis of covariance (ANCOVA) to model LVEF while adjusting for other variables. 44 patients included in the final analyses. LVEF significantly improved from 50.5 to 56.6% (p < 0.01). When LVEF was adjusted for other interventions (mechanical ventilation, afterload reduction, diuretic therapy, spironolactone), the estimated means demonstrated a significant increase from 45.7 to 58.0% (p < 0.01). Free carnitine level increased significantly (p = 0.03), and N-terminal-pro-brain natriuretic peptide (p = 0.03), creatinine (p < 0.01), and lactate (p < 0.01) all significantly decreased over the study period. Carnitine supplementation in pediatric patients with left ventricular systolic dysfunction may be associated with an increase in LVEF and improvement in laboratory markers of myocardial stress and cardiac output.

The utility of a structured, interactive cardiac anatomy teaching session for resident education.

BACKGROUND: Paediatric residents are often taught cardiac anatomy with two-dimensional images of heart specimens, or via imaging such as echocardiography or computed tomography. This study aimed to determine if the use of a structured, interactive, teaching session using heart specimens with CHD would be effective in teaching the concepts of cardiac anatomy. METHODS: The interest amongst paediatric residents of a cardiac anatomy session using heart specimens was assessed initially by circulating a survey. Next, four major cardiac lesions were identified to be of interest: atrial septal defect, ventricular septal defect, tetralogy of Fallot, and transposition. A list of key structures and anatomic concepts for these lesions was developed, and appropriate specimens demonstrating these features were identified by a cardiac morphologist. A structured, interactive, teaching session was then held with the paediatric residents using the cardiac specimens. The same 10-question assessment was administered at the beginning and end of the session. RESULTS: The initial survey demonstrated that all the paediatric residents had an interest in a cardiac anatomy teaching session. A total of 24 participated in the 2-hour session. The median pre-test score was 45%, compared to a median post-test score of 90% (p < 0.01). All paediatric residents who completed a post-session survey indicated that the session was a good use of educational time and contributed to increasing their knowledge base. They expressed great interest in future sessions. CONCLUSION: A 2-hour hands-on cardiac anatomy teaching session using cardiac specimens can successfully highlight key anatomic concepts for paediatric residents.

Left Ventricular Pseudoaneurysm Following Surgical Repair of Ventricular Septal Defect in an Infant.

Left ventricular pseudoaneurysm (LV-PSA) is a rare complication following cardiac surgery, let alone in the pediatric population. Other known causes of LV-PSA are trauma, percutaneous cardiac intervention, and infections. This report describes the development of LV-PSA following surgical repair of ventricular septal defect (VSD) and coarctation of aorta (CoA) in an infant.

Identification of gibberellin-regulated protein as a new allergen in orange allergy.

BACKGROUND: To date, three orange allergens have been reported. However, it is still unclear whether gibberellin-regulated proteins (GRPs), identified as new allergens in other fruit allergies, are also involved in orange allergy. OBJECTIVE: To investigate the allergenicity of orange GRP and to determine the clinical characteristics of patients with orange allergy who are sensitized to orange GRP. METHODS: We enrolled 14 patients (four men, 10 women, mean age: 29.6 years) who were diagnosed with orange allergy based on relevant clinical history, positive skin test, and/or positive challenge test. Orange GRP (molecular weight: 6941.6 Da) was purified by ion-exchange column chromatography. To test for orange GRP-specific IgE, we performed ELISA, basophil activation tests, and skin prick tests. Cross-reactivity of orange GRP with native peach allergen nPru p 7 and Japanese apricot nPru m 7 was analysed by ELISA inhibition assays. IgE specific for orange, grapefruit, and peach allergens rPru p 1, rPru p 3, and rPru p 4 was measured using ImmunoCAP. RESULTS: Twelve of the 14 patients (85.7%) were positive for orange GRP allergy in at least one test: 71.4% (10/14) were positive by ELISA, 50% (3/6) were positive in the basophil activation test, and 100% (4/4) were positive in the skin prick test. ELISA inhibition assays revealed cross-reactivity of orange GRP with both nPru p 7 and nPru m 7. The patients showed variable positivity for specific IgE against orange, grapefruit, rPru p 1, rPru p 3, and rPru p 4 (57.1%, 71.4%, 7.1%, 0%, and 21.4%, respectively). The most frequent symptoms of orange GRP allergy were facial swelling and oropharyngeal symptoms. CONCLUSIONS AND CLINICAL RELEVANCE: Orange GRP may be involved in orange allergy and may be a cross-reactive allergen between citrus fruits and the Rosaceae family of fruits.

Inhibitory effects of fluoxetine, an antidepressant drug, on masseter muscle nociception at the trigeminal subnucleus caudalis and upper cervical spinal cord regions in a rat model of psychophysical stress.

This study aimed to determine whether psychophysical stress conditionings had facilitatory effects on masseter muscle nociception in the central nervous system via serotonergic mechanisms in rats. Two experiments were conducted to assess: (1) whether repeated forced swim stress for 3 days increased the number of Fos-positive neurons evoked by masseter muscle injury due to formalin injection; and (2) whether serotonin-reuptake inhibitor, fluoxetine, administered daily after each stress conditioning, had modulatory roles on Fos expression. The number of Fos-positive cells was quantified in several areas within the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord regions (Vc areas), including the ventrolateral area of the trigeminal subnucleus interpolaris/Vc transition, and the middle or caudal portion of the Vc regions, since nociceptive neural activity in the Vc region could play critical roles in deep craniofacial nociception. We found that forced swim stress conditionings increased depression-like behaviors, which was prevented by fluoxetine. Repeated forced swim stress significantly increased Fos expression in all Vc areas compared with those of non-stressed rats, while systemic administration of fluoxetine significantly decreased Fos expression in all areas, but mainly in the caudal Vc region, in stressed rats. Fluoxetine had no effect on Fos expression in non-stressed rats. These results indicate that repeated forced swim stress conditionings increase Fos expression in the Vc areas, and the contribution of serotonergic mechanisms to masseter muscle nociception could be greater in stressed rats than in sham rats. These results support the hypothesis that changes in brain function, including serotonergic mechanisms, in the Vc areas play critical roles in enhanced masseter muscle nociceptive responses under psychophysical stress conditions.

Aortic arch shape after arch repair predicts exercise capacity: a multicentre analysis.

Aims: Coarctation of the aorta is associated with long-term morbidity including decreased exercise capacity, despite successful repair. In the absence of discrete recoarctation, the haemodynamic mechanism remains unknown. This multicentre study evaluated the relationship between aorta shape, flow, and exercise capacity in patients after arch repair, specifically through the lens of aortic size mismatch and descending aortic (DAo) flow and their association with exercise. Methods and results: Cardiac magnetic resonance, cardiopulmonary exercise test, and echocardiogram data within 1 year were analysed from 58 patients (age 28 ± 10 years, 48% male) across four centres with history of isolated arch repair. Aortic arch measurements were correlated with % predicted VO2max with subgroup analyses of those with residual arch obstruction, bicuspid aortic valve, and hypertension. Ascending aorta (AAo) to DAo diameter ratio (DAAo/DDAo) was negatively correlated with % predicted VO2max. %DAo flow positively correlated with VO2max. Sub-analyses demonstrated that the negative correlation of DAAo/DDAo with VO2max was maintained only in patients without arch obstruction and with a bicuspid aortic valve. Smaller aortic arch measurements were associated with both hypertension and exercise-induced hypertension. Conclusion: Aorta size mismatch, due to AAo dilation or small DAo, and associated decreased %DAo flow, correlated significantly with decreased exercise capacity after aortic arch repair. These correlations were stronger in patients without arch obstruction and with a bicuspid aortic valve. Aorta size mismatch and %DAo flow capture multiple mechanisms of altered haemodynamics beyond blood pressure gradient or discrete obstruction and can inform the definition of a successful repair.

ITGA3 and ITGB4 expression biomarkers estimate the risks of locoregional and hematogenous dissemination of oral squamous cell carcinoma.

BACKGROUND: Molecular biomarkers are essential for monitoring treatment effects, predicting prognosis, and improving survival rate in oral squamous cell carcinoma. This study sought to verify the effectiveness of two integrin gene expression ratios as biomarkers. METHODS: Gene expression analyses of integrin α3 (ITGA3), integrin ß4 (ITGB4), CD9 antigen (CD9), and plakoglobin (JUP) by quantitative real-time PCR were conducted on total RNA from 270 OSCC cases. The logrank test, Cox proportional hazards model, and Kaplan-Meier estimates were performed on the gene expression ratios of ITGA3/CD9 and ITGB4/JUP and on the clinicopathological parameters for major clinical events. RESULTS: A high rate (around 80%) of lymph node metastasis was found in cases with a high ITGA3/CD9 ratio (high-ITGA3/CD9) and invasive histopathology (YK4). Primary site recurrence (PSR) was associated with high-ITGA3/CD9, T3-4 (TNM class), and positive margin, indicating that PSR is synergistically influenced by treatment failure and biological malignancy. A high ITGB4/JUP ratio (high-ITGB4/JUP) was revealed to be a primary contributor to distant metastasis without the involvement of clinicopathological factors, suggesting intervention of a critical step dependent on the function of the integrin ß4 subunit. Kaplan-Meier curves revealed positive margin as a lethal treatment consequence in high-ITGA3/CD9 and YK4 double-positive cases. CONCLUSION: Two types of metastatic trait were found in OSCC: locoregional dissemination, which was reflected by high-ITGA3/CD9, and distant metastasis through hematogenous dissemination, uniquely distinguished by high-ITGB4/JUP. The clinical significance of the integrin biomarkers implies that biological mechanisms such as cancer cell motility and anchorage-independent survival are vital for OSCC recurrence and metastasis.

Aortic Thrombosis and Subsequent Myocardial Infarction in a Previously Healthy 12-Year-Old Male.

Aortic thrombus formation in children is uncommon, particularly in an otherwise healthy pediatric patient. Thromboembolism of such thrombi resulting in subsequent ST-segment elevation myocardial infarction is, thus, exceedingly rare. (Level of Difficulty: Intermediate.).

Adenosquamous Carcinoma with the Acantholytic Feature in the Oral Cavity: A Case Report and Comprehensive Literature Review.

Adenosquamous carcinoma (ASC) is an aggressive subtype of squamous cell carcinoma (SCC). Due to its poor prognosis, a precise pathological diagnosis of ASC is essential but challenging because its pathological criteria are still unclear. Here, we present a rare case of oral ASC accompanied by acantholytic features. The tumor was raised in the mandibular gingiva and recurred locally approximately 13 months after the initial surgery with cervical lymph node metastasis. Pathological specimens of the primary lesion showed acantholysis in a large area of the SCC. Mucous cells, the characteristic finding indicating glandular differentiation, were imperceptible in the initial surgical specimen but increased in the locally recurrent and metastatic lymph node specimens. In a comprehensive literature review of oral ASC cases, the present case was the only case of ASC with acantholytic features. We reconfirmed that ASC has poor prognoses, such as low 5-year overall survival and disease-free survival, high locoregional recurrence, and high distant metastasis rates. A precise diagnosis of ASC is required for estimating prognosis and undergoing close follow-up, even if the adenocarcinomatous component is limited to a small area in the lesion.

Anomalous Origin of the Left Coronary Artery From the Right Pulmonary Artery of an Infant.

A female presented 2 weeks after birth with an unbalanced atrioventricular canal, double outlet right ventricle, mild pulmonary stenosis, and patent ductus arteriosus that eventually caused pulmonary over circulation. After pulmonary artery banding, she experienced myocardial ischemia, suggesting interference with coronary blood flow by the band that had been placed on the main pulmonary trunk. The band was removed and revised to bilateral branch pulmonary artery banding, and cardiac function improved. An anomalous left coronary artery from the underside of the right pulmonary artery was identified. Eight weeks later, the patient underwent coronary transfer and reimplantation of the left coronary artery into the aorta followed by main pulmonary artery banding. She subsequently underwent bidirectional Glenn.

[Effectiveness of low dose PCEA for postoperative pain after laparoscopic gynecological surgeries--a comparison of laparoscopic ovarian cystectomy and myomectomy].

BACKGROUND: We evaluated the effectiveness of low-dose patient-controlled epidural analgesia (PCEA) in the patients undergoing laparoscopic gynecological surgery, and investigated the difference of postoperative pain between patients for laparoscopic ovarian cystectomy and those for myomectomy. METHODS: Thirteen patients (ASA PS 1 or 2), scheduled for laparoscopic surgery, were enrolled in this study. They were divided into two groups of ovarian cystectomy (group C, n=17) and myomectomy (group M, n=13). After administering epidural bolus of 0.2% ropivacaine 6 ml, droperidol 2.5 mg, and buprenorphine hydrochloride 0.1 mg, PCEA was started: 1 ml x hr(-1) background infusion; 0.2% ropivacaine 54 ml, droperidol 5 mg, and buprenorphine hydrochloride 0.3 mg; 1 ml epidural bolus with a 30-minute lockout interval. We evaluated postoperative pain using visual analogue scale (VAS) at rest and on movement, adverse effects such as respiratory and cardiovascular depression, nausea and vomiting for 48 hours after surgery. RESULTS: VAS at rest with group M was significantly higher than that of group C (11 +/- 2 vs. 6 +/- 2, P=0.048), and VAS on movement of group M was also higher than that of group C (25 +/- 3 vs. 18 +/- 2, P=0.023): however, we found good analgesic effect of less than VAS 3 in both groups. Severe adverse effects were not observed. CONCLUSIONS: These findings suggest that low dose PCEA is effective for patients who undergo laparoscopic gynecological surgery.

Modulatory effects of repeated psychophysical stress on masseter muscle nociception in the nucleus raphe magnus of rats.

Psychophysical stress can cause neural changes that increase nociception in the orofacial region, particularly the masseter muscle (MM). The nucleus raphe magnus (NRM), which is located in the brain stem, serves the crucial role of regulating nociception through descending modulatory pain control. However, it remains unclear if neural activities in the NRM are affected under psychophysical stress conditions. This study conducted experiments to assess (1) whether neural activity, indicated by Fos expression in an NRM that has experienced MM injury, is affected by the stress of repeated forced swim tests (FST); and (2) whether the selective serotonin reuptake inhibitor fluoxetine administered daily after an FST could affect the number of Fos-positive neurons in the NRM. Results revealed that the stress from repeated FSTs significantly increased the number of Fos-positive neurons in an NRM that had been affected by MM injury. Fluoxetine inhibited increases in the number of Fos-positive neurons in the NRM that occurred as a result of FSTs, but this was not observed in sham rats. These findings indicate that the stress from FSTs could increase nociceptive neural activity in an NRM that has experienced MM injury. This could be due, in part, to changes in serotonergic mechanisms.

Conductive polymer-carbon-imidazolium composite: a simple means for constructing solid-state dye-sensitized solar cells.

A clay-like conductive material comprising polyaniline-loaded carbon black particles and an ethyleneoxide-substituted imidazolium iodide was prepared. The material was sandwiched between dye-coated porous TiO2 and counter-electrode to form a solid-state dye-sensitized solar cell, which works with overall conversion efficiencies of 3.48% and 4.07% for AM 1.5, 100 mW cm(-2) and 23 mW cm(-2) irradiation, respectively.

Mitochondrial microsatellite variability in common wheat and its ancestral species.

On the basis of the entire mitochondrial DNA sequence of common wheat, Triticum aestivum, 21 mitochondrial microsatellite loci having more than ten mononucleotide repeats were identified. The mitochondrial microsatellite variability at all loci was examined with 43 accessions from 11 Triticum and Aegilops species involved in wheat polyploidy evolution. Polymorphic banding patterns were obtained at 15 out of 21 mitochondrial microsatellite loci. The number of alleles per polymorphic microsatellite ranged from 2 to 5 with an average of 3.07, and the diversity values (H) ranged from 0.09 to 0.50 with an average of 0.29. These values are almost two third of wheat chloroplast microsatellite values, indicating that variability of mitochondrial microsatellite is much less than that of chloroplast microsatellite. Based on the allele variation at all loci, a total of seven mitochondrial haplotypes were identified among common wheat and its ancestral species. Three diploid species showed their own specific haplotypes and timopheevi group (11 accessions) had three types, whereas 29 accessions of emmer and common wheat groups shared the same haplotype. These results indicate that a single mitochondrial haplotype determined by microsatellite analysis has conservatively been maintained in the evolutionary lineage from wild tetraploid to cultivated hexaploid species.

A solid-state dye-sensitized photovoltaic cell with a poly(N-vinyl-carbazole) hole transporter mediated by an alkali iodide.

A polymer-based dye-sensitized solar cell in dry solid state was constructed using poly(N-vinyl-carbazole)(PVK) as a hole-transporting layer; the cell attained the highest power efficiencies of 2.4% and 2.0% at 1/4 sun and 1 sun (AM1.5), respectively, by incorporation of a solid intermediate layer (LiI, KI) at the dye-PVK interface.

Development of the articular cavity in the rat temporomandibular joint with special reference to the behavior of endothelial cells and macrophages.

Previous developmental studies on the temporomandibular joint (TMJ) have proposed several hypotheses on the formation of its articular cavity. However, detailed information is meager. The present study examined the formation process of the articular cavity in the rat TMJ by immunocytochemistry for CD31, RECA-1, and ED1, which are useful cellular markers for endothelial cells and monocyte/macrophage lineages, respectively. The upper articular cavity formation had begun by embryonic day 21 (E21) and was completed at postnatal day 1 (P1) in advance of the lower cavitation; the latter took place from P1 to P3. The occurrence and distribution pattern of the CD31-, RECA-1-, and ED1-positive cells differed between the upper and lower articular cavity-forming areas: the ED1-positive cells exclusively occurred in the area of the prospective upper articular cavity prior to its formation, while no ED1-positive cell appeared in the lower cavity-forming area. In contrast, the CD31- and RECA-1-positive endothelial cells were restricted to the lower cavity-forming area (never the prospective upper cavity) at E19 and diminished thereafter. Throughout the cavity formation, we failed to find any apoptotic cells in the cavity formation area, indicating no involvement of apoptosis in the cavity formation in TMJ. The present findings on the behaviors of endothelial cells and ED1-positive cells show a possibility of different mechanism in the cavity formation between the upper and lower articular cavities in the rat TMJ. The appearance of ED1-reactive cells and temporal vascularization may play crucial roles in the upper and lower articular cavity formation, respectively.

Naegele Forceps Delivery and Association between Morbidity and the Number of Forceps Traction Applications: A Retrospective Study.

OBJECTIVE: To present the method of Naegele forceps delivery clinically practiced by the lead author, its success rate, and morbidity and to evaluate the relationship between morbidity and the number of forceps traction applications. METHODS: Naegele forceps delivery was performed when the fetal head reached station +2 cm, the forceps were applied in the maternal pelvic application, and traction was slowly and gently performed. In the past two years, Naegele forceps delivery was attempted by the lead author in 87 cases, which were retrospectively reviewed. RESULTS: The numbers of traction applications were one in 64.7% of cases, two in 24.7%, and three or more in 10.7%. The success rate was 100%. No severe morbidity was observed in mothers or neonates. Neonatal facial injury occurred most commonly in cases with fetal head malrotation, elevated numbers of traction applications, and maternal complications. Umbilical artery acidemia most commonly occurred in cases with nonreassuring fetal status. The significant crude odds ratio for three or more traction applications was 20 in cases with malrotation. CONCLUSION: Naegele forceps delivery has a high success rate, but multiple traction applications will sometimes be required, particularly in cases with malrotation. Malrotation and elevated numbers of traction applications may lead to neonatal head damage.

Development of the synovial membrane in the rat temporomandibular joint as demonstrated by immunocytochemistry for heat shock protein 25.

The synovial lining layer of the temporomandibular joint (TMJ) consists of macrophage-like type A cells and fibroblast-like type B cells. Until now, little information has been available on the development of the synovial membrane in TMJ. In the present study we examined the development of the synovial lining layer in the rat TMJ by light- and electron-microscopic immunocytochemistry for heat shock protein (Hsp) 25, which is a useful marker for type B cells. At embryonic day 19 (E19), a few Hsp25-positive cells first appeared in the upper portion of the developing condyle. During the formation of the upper articular cavity (E21 to postnatal day 1 (P1)), a few positive cells were arranged on its surface. Immunoelectron microscopy demonstrated that these cells had ultrastructural features of fibroblast-like type B cells. In addition, some Hsp25-positive cells moved to the deep portion by extending their cytoplasmic processes toward the articular cavity at P3. At that time, the presence of typical macrophage-like type A cells in the lining layer was confirmed by immunoelectron microscopy. The slender processes of Hsp25-positive cells showed a continuous covering with the synovial surface at P7, followed by a drastic increase in the Hsp25-positive cells at P15 and later, when active jaw movement occurred. These findings suggested that the arrangement and morphological maturation of type B cells are closely related to the formation of the articular cavity in the embryonic period and the commencement of active jaw movement after birth, respectively.