Cardiac problems in the fetus: a review for pediatric providers.

PURPOSE OF REVIEW: The aim of this study was to provide pediatric providers with a review of the diagnosis and management of fetal cardiac disease in the current era. RECENT FINDINGS: Prenatal detection of congenital heart disease (CHD) has improved but is still imperfect. In experienced hands, fetal echocardiography can detect severe CHD as early as the first trimester and a majority of more subtle conditions in the second and third trimesters. Beyond detection, a prenatal diagnosis allows for lesion-specific counseling for families as well as for development of a multidisciplinary perinatal management plan, which may involve in-utero treatment. Given the diversity of cardiac diagnoses and the rarity of some, collaborative multicenter fetal cardiac research has gained momentum in recent years. SUMMARY: Accurate diagnosis of fetal cardiac disease allows for appropriate counseling, pregnancy and delivery planning, and optimization of immediate neonatal care. There is potential for improving fetal CHD detection rates. Fetal interventions are available for certain conditions, and fetal and pediatric cardiac centers have developed management plans specific to the expected postnatal physiology.

Precise Measurement of Differential Cross Sections of the Σ

The differential cross sections of the Σ^{-}p→Λn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise angular information about the Σ^{-}p→Λn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 [statistical error(stat.)] ±0.65 [systematic error(syst.)] mb and 15.8±0.83(stat)±0.52(syst) mb for 470

Current State of Fetal Heart Disease Counseling and Training: Room for Improvement? : Endorsed by the Fetal Heart Society.

We sought to describe the fellowship experiences and current practice habits of pediatric cardiologists who counsel patients with fetal heart disease (FHD) and to identify fellowship experiences related to FHD counseling perceived as valuable by respondents as well as opportunities for improvement. A cross-sectional survey of attending pediatric cardiologists who care for patients with FHD was performed. The respondents' demographics, fellowship experiences related to FHD counseling, reflections on fellowship training, and current practice habits were collected. The Fetal Heart Society endorsed this survey. There were 164 survey responses. 56% of respondents did not have 4th-year subspecialty training in fetal cardiology. Observing and performing FHD counseling were the most commonly used methods of training, with the highest perceived effectiveness. The number of counseling sessions observed and performed correlated moderately with confidence in FHD counseling skills at fellowship graduation. Extracardiac pathology and neurodevelopment were the least frequently addressed topics in fellowship training and in current practice. Fewer than 50% of respondents received formal education and feedback in counseling techniques during fellowship training. A significant proportion of practicing pediatric cardiologists provide FHD counseling with only standard categorical training. This highlights the potential importance of expanding FHD counseling education into categorical fellowship curricula. We suggest increasing opportunities for fellows to perform FHD counseling and receive feedback as this is a valued and beneficial experience during training. A formalized curriculum including extracardiac pathology and neurodevelopment and the use of evidence-based workshops in counseling techniques may address identified gaps in fellowship education.

High Output Cardiovascular Physiology and Outcomes in Fetal Diagnosis of Vein of Galen Malformation.

Vein of Galen aneurysmal malformation (VGAM) is a rare anomaly associated with poor outcomes from high output cardiac failure and neurologic complications. Studies addressing fetal cardiovascular status and outcomes in this population are limited. A single-center retrospective review was conducted on patients with a prenatal diagnosis of VGAM who underwent a fetal echocardiogram between January 2015 and July 2019. Fetal echocardiographic data, brain magnetic resonance imaging (MRI) findings and outcomes were collected. Nine fetuses [median gestational age at echocardiogram 34 (1.1) weeks] were included. All patients had superior vena cava dilation and reversal of diastolic flow in the transverse aortic arch. Median cardiothoracic (CT) ratio was 0.39 (0.09). Right ventricular (RV) and left ventricular (LV) dysfunction was present in 66% and 11% fetuses, respectively. Four out of five patients that underwent postnatal endovascular neurosurgical interventions at our center were alive at follow-up (mean 2.7 years). Of the non-survivors (n = 5), 3 received comfort care because of severe brain damage and died in the neonatal period. Non-survivors more commonly had > mild tricuspid regurgitation (TR) (40% vs. 25%) and > mild RV dilation (60% vs. 25%). Combined cardiac index (CCI) was higher in non-survivors when compared to survivors (672.7 vs. 530.2 ml/kg/min, p = 0.016). Fetuses with significant parenchymal damage on brain MRI tended to have a higher CCI than those without (979.8 vs. 605.0 ml/kg/min, p = 0.047). RV dysfunction, TR and elevated CCI are more commonly seen in non-survivors with VGAM. A higher CCI is seen in those deemed untreatable due to significant parenchymal volume loss. Future multicenter studies are needed to assess for prenatal prediction of outcomes in this high-risk population.

First Determination of the Level Structure of an sd-Shell Hypernucleus, _{Λ}

We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}→1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}→1/2^{+}), E1(1/2^{-}→1/2^{+}), and E1(1/2^{-}→3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.

Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia.

BACKGROUND AND PURPOSE: Mixed neurogenerative and vascular dementia has emerged as the leading cause of dementia in the elderly. Inflammation is implicated in atherosclerosis, cerebral small-vessel disease (SVD) as well as cognitive impairment. However, longitudinal data on the predictive value of circulating inflammatory markers including gene variants and magnetic resonance imaging (MRI) findings in incident dementia are scarce. It was investigated whether circulating interleukin-6 (IL-6), C-reactive protein (CRP) and gene variants increase dementia risk. METHODS: In a cohort of Japanese participants with vascular risk factors in an observational study from 2001, the association between baseline IL-6, CRP levels, gene variants [interleukin-6 receptor (IL-6R), rs2228145; IL-6, rs2097677; CRP, rs3093059] and incident all-cause dementia was evaluated. Baseline MRI was used to determine SVD (lacuna, white matter hyperintensities) and atrophy (medial-temporal lobe atrophy, bicaudate ratio). Cox proportional hazards analyses were performed for predictors of dementia, adjusting for age, sex, apolipoprotein Eε4, education, cerebrovascular events, vascular risk factors and MRI findings. RESULTS: Of 803 subjects (mean 67.0 ± 8.5 years, males 59%), during a mean of 7.5 ± 3.2 years follow-up, 60 incident dementia patients (Alzheimer's disease 31; vascular dementia 17; mixed-type six; other six) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, MRI findings and IL-6R variant (rs2228145), IL-6 levels (relative risk 1.68, P = 0.048) or highest tertile (relative risk 2.38, P = 0.031) for all-cause dementia remained significant. Although subjects with rs2228145 carrier had significantly higher IL-6 levels, a significant association between rs2228145 and dementia was not observed. Conversely, CRP and remaining gene variants were not associated with dementia. CONCLUSIONS: The deleterious effect of higher IL-6 on dementia remains consistent irrespective of conventional risk factors, MRI findings and IL-6R variant.

Serum high-molecular-weight adiponectin level and incident dementia in patients with vascular risk factors.

BACKGROUND AND PURPOSE: The involvement of metabolic factors in the development of dementia has received much attention. However, previous studies have yielded conflicting results regarding how blood adipocytokine level impacts cognitive decline and dementia. This study aimed to clarify whether serum high-molecular-weight (HMW) adiponectin level is related to incident dementia. METHODS: Data were from 466 patients (mean age 67.8 years, male 57%)--who had normal cognitive function and received brain magnetic resonance imaging--from amongst the 1106 patients in the Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, a prospective cohort study of cardiovascular events and dementia amongst patients with vascular risk factors enrolled between 2001 and 2009. Baseline HMW adiponectin levels were measured using frozen serum. Dementia occurrence was examined in June 2013. RESULTS: Serum HMW adiponectin level was 4.33 ± 2.95 µg/ml; the levels were lower in men than in women and negatively correlated with body mass index. During the follow-up period (median 6.9 years), 47 patients had incident dementia including Alzheimer's disease dementia (27), vascular dementia (13), mixed dementia (four), other dementia (three). Risks of dementia in patients with high versus low HMW adiponectin levels were almost identical (P = 0.689). No association was found between adiponectin levels and Alzheimer's disease dementia or vascular dementia in the whole group or amongst men and women separately. CONCLUSIONS: This study demonstrated that serum HMW adiponectin level has little association with future dementia. Determination of metabolic factors involved in dementia requires evaluation of other biomarkers or parameters.

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN Interaction: Gamma-Ray Spectroscopy of _{Λ}

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

Association between carotid stenosis or lacunar infarction and incident dementia in patients with vascular risk factors.

BACKGROUND AND PURPOSE: The association between vascular risk factors and dementia is of interest. Several studies have shown that cerebral small vessel disease (SVD) is associated with dementia. However, the association between cerebral large vessel disease (LVD) and dementia has not been thoroughly examined. METHODS: The Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, was a prospective cohort study of cardiovascular events and dementia in which patients (n = 1106) with vascular risk factors underwent carotid ultrasound. Of these patients, 600 who had normal cognitive function were included and underwent brain magnetic resonance imaging. The presence of lacunar infarction and carotid stenosis served as markers for SVD and LVD, respectively. RESULTS: Amongst 600 patients (mean 68 years, 57% men), 261 (44%) showed lacunar infarction and 94 (16%) showed carotid stenosis. During the follow-up period (median 8.0 years), 57 patients had incident dementia. Patients with carotid stenosis and lacunar infarction were significantly more likely to be diagnosed with dementia (log-rank test, P = 0.037 and P < 0.001, respectively). The association between lacunar infarction and dementia remained significant after adjusting for risk factors including stroke history, apolipoprotein E genotype and years of education (hazard ratio 2.64, 95% confidence interval 1.22-6.09). However, the presence of carotid stenosis was not associated with incident dementia after adjusting for age and sex (P = 0.477). CONCLUSIONS: This study demonstrated that carotid stenosis had little association with dementia, but lacunar infarction had a significant association. The impact of SVD on dementia could be much greater than that of LVD.

Search for the Θ+ pentaquark via the π(-)p→K(-)X reaction at 1.92 GeV/c.

The Θ(+) pentaquark baryon was searched for via the π(-)p→K(-)X reaction with a missing mass resolution of 1.4 MeV/c(2) (FWHM) at the Japan Proton Accelerator Research Complex (J-PARC). π(-) meson beams were incident on the liquid hydrogen target with a beam momentum of 1.92 GeV/c. No peak structure corresponding to the Θ(+) mass was observed. The upper limit of the production cross section averaged over the scattering angle of 2° to 15° in the laboratory frame is obtained to be 0.26 µb/sr in the mass region of 1.51-1.55 GeV/c(2). The upper limit of the Θ(+) decay width is obtained to be 0.72 and 3.1 MeV for J(Θ)(P)=1/2(+) and J(Θ)(P)=1/2(-), respectively, using the effective Lagrangian approach.

Myalgic encephalomyelitis: International Consensus Criteria.

The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand.

Fas ligand is a well-characterized apoptosis inducer. Here we demonstrate that Fas ligand induces the processing and secretion of interleukin-1beta (IL-1beta) in peritoneal exudate cells. This IL-1beta secretion is independent of IL-1beta converting enzyme (caspase 1), yet it is inhibited by caspase inhibitors, indicating that a caspase(s) in addition to IL-1beta converting enzyme can process IL-1beta. Inoculation of tumor cells expressing Fas ligand into wild-type mice induces a massive neutrophil infiltration that is, in contrast, suppressed in IL-1alpha/beta knockout mice. These results demonstrate a newly discovered role for Fas ligand in inflammation, and challenge the dogma that apoptosis does not induce inflammation.

Comparison of the surgical outcomes of thoracoscopic lobectomy, segmentectomy, and wedge resection for clinical stage I non-small cell lung cancer.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) for clinical stage I non-small cell lung cancer (NSCLC) has been widely used as a less invasive surgical procedure, but the resection method is still controversial. We retrospectively compared the surgical outcomes of lobectomy, segmentectomy and wedge resection. PATIENTS AND METHODS: A total of 411 patients with clinical stage I NSCLC who underwent VATS (218 males and 193 females, aged 69.3 years; 345 adenocarcinomas, 57 squamous cell carcinomas, and 9 others) were investigated. The surgical procedure was lobectomy in 289, segmentectomy in 38, and wedge resection in 84. Surgical outcomes were compared among these 3 groups. RESULTS: Demographic characteristics showed that the rate of elderly and male patients was higher in the wedge resection group. The 5-year survival rates for the lobectomy, segmentectomy, and wedge resection groups were 82.1, 87.2, and 55.4%, respectively. In the wedge resection group, the 5-year survival rate was 83.3% in patients undergoing intentional low-risk operations for small tumors with ground glass opacity, and 41.1% in those undergoing conservative high-risk operations because of comorbidities. Using Cox's proportional multivariate analysis and sex differences, histology, and tumor size as co-influential factors, the surgical procedure was found to be a significantly poor prognostic factor, and the hazard ratio of wedge resection relative to lobectomy was 4.30. CONCLUSION: The outcomes of VATS lobectomy and segmentectomy procedures for clinical stage I NSCLC were equivalent, while the outcome for VATS wedge resection was inferior. VATS wedge resection for clinical stage I NSCLC should be carefully indicated and requires adequate patient selection.

Outcomes of mitral regurgitation associated with large ventricular septal defect and a normal mitral valve apparatus: does intact atrial septum have an impact?

The hemodynamics of isolated large ventricular septal defect with an intact atrial septum results in greater mitral valve (MV) annular dilation and an increased incidence of mitral regurgitation (MR). MR will resolve in most patients after surgical VSD closure alone without MV repair.

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following carboplatin-paclitaxel administration in a patient with lung cancer.

A 60-year-old female underwent right upper lobectomy of the lung and lymph node dissection under a diagnosis of cancer in the upper lobe of the right lung. Pathological examination showed stage IIIA adenocarcinoma with mediastinal lymph node metastasis. One month after the operation, adjuvant chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) was initiated. Four days after the chemotherapy, hyponatremia progressed, and central nervous system disorder developed. A diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was made. She recovered after fluid intake restriction and electrolyte correction. SIADH was considered to be due to the adverse effects of anticancer drugs. In postoperative adjuvant chemotherapy, attention should be paid to the serum Na level.

Serum inflammatory proteins and frontal lobe dysfunction in patients with cardiovascular risk factors.

BACKGROUND: Recent studies have shown that the levels of circulating inflammatory markers are associated with cognitive decline and cerebral small-vessel disease. Frontal lobe dysfunction is believed to be a relatively characteristic neuropsychological symptom in vascular cognitive impairment caused by cerebral small-vessel disease. The purpose of this study was to investigate whether the levels of serum inflammatory markers are associated with frontal lobe dysfunction, particularly executive dysfunction. METHODS: Between January 2003 and September 2007, 388 patients who had one or more atherosclerotic risk factors and subsequently underwent brain MRI and neuropsychological testing including mini-mental state examination (MMSE), frontal assessment battery (FAB), and modified Stroop test were enrolled in this study. We evaluated the effect of serum levels of inflammatory markers and white matter lesions on frontal lobe function. RESULTS: The FAB score was negatively correlated with serum inflammatory marker levels (hsCRP; r = -0.170, IL-6; r = -0.143, IL-18; r = -0.175) and white matter lesions. In the modified Stroop test, interference measure was positively correlated with the levels of hsCRP (r = -0.198), and IL-18 (r = -0.152), and white matter lesions. However, the MMSE score was not correlated with either inflammatory marker levels. The association between hsCRP and FAB score or interference measure remained significant when controlling for other confounding factors and MRI findings. CONCLUSIONS: The circulating level of hsCRP is associated with frontal lobe dysfunction in patients with cardiovascular risk factors independent of white matter lesions in brain MRI.

Mediastinal tuberculous lymphadenitis with intractable fistula to the neck.

A 62-year-old female consulted our hospital due to an ulceration on the skin of her neck and a mediastinal tumor. Chest CT scan and MRI revealed a mediastinal tumor-like lesion with direct progression to the neck skin lesion. En bloc resection of the tumor including the neck skin ulcer was performed under a median sternotomy. Mediastinal tuberculous lymphadenitis was diagnosed histologically. This is a case of a very rare type of mediastinal tuberculous lymphadenitis that progressed to the neck with an intractable fistula.

A case of G-CSF-producing invasive apical cancer resected following preoperative adjuvant therapy.

The patient was a 47-year-old male with the chief complaints of right shoulder pain and fever. A 10-cm mass was found to be present in the right pulmonary apical region on chest X-ray examination. The mass was diagnosed as a G-CSF-producing invasive apical cancer and the patient underwent chemoradiotherapy followed by right upper lobectomy with combined resection of the chest wall, and lymph node dissection. A very small nodule was noted in the right frontal lobe on brain MRI before surgery, and the final diagnosis was pT3N0M1, stage IV lung adenocarcinoma. For the brain metastasis, gamma knife treatment and chemotherapy were performed after surgery, and there was no recurrence during 16 months after surgery. The prognosis for G-CSF-producing lung cancer and invasive apical cancer is poor. This was a rare and difficult case of lung cancer showing both characteristics of lung cancer.

Diagnostic Accuracy of Fetal Echocardiography in Congenital Heart Disease.

BACKGROUND: The accuracy of fetal echocardiography (FE) is not well defined, and reporting of diagnostic discrepancies (DDs) is not standardized. The authors applied a categorization scheme developed by the American College of Cardiology Quality Metric Working Group and applied it to FE. METHODS: A retrospective single-center study was conducted of prenatally diagnosed major structural congenital heart disease, defined as expected need for intervention within the first year of life. DDs between pre- and postnatal findings were identified and categorized. Minor DDs had no clinical impact, moderate DDs had impact without harm, and severe DDs resulted in adverse events. Multivariate regression analysis was used to determine factors associated with discrepancy. RESULTS: From December 2008 to September 2017, 17,096 fetal echocardiograms were obtained, among which 222 fetuses with a median gestational age at first FE of 24 weeks were included. There were 30 DDs (13.5%), of which the majority were false negatives (56.7%). Most were minor or moderate in severity, with one severe DD. The majority were possibly preventable (90%), with the most common contributing factor being technical limitations (43.3%). The most common anatomic segment involved was the ventricular septum (23%), primarily missed septal defects. Comparing cases with DDs versus those without, those with DDs were more likely to have high anatomic complexity (16.7% vs 3.6%, P = .01), maternal comorbidities (40.0% vs 22.1%, P = .03), and a younger maternal age (median, 27 vs 30 years, P = .02). They were also more likely to have later gestation at initial FE (median, 29.5 vs 24 weeks, P = .003), to have fewer total fetal echocardiograms (median, 2 vs 3, P = .002), and to have a fellow as the initial sonographer (36.7% vs 16.7%, P = .03). There were no significant differences in maternal race/ethnicity, fetal comorbidities, and interpreting physician experience between cases with DDs and those without. On multivariate analysis, variables associated with DD included high anatomic complexity, maternal comorbidities, and fellow as initial imager. A greater number of fetal echocardiograms was associated with reduced DD. CONCLUSIONS: FE had a DD rate of 13.5%, mostly minor and moderate in severity. Factors associated with DD included high anatomic complexity, maternal comorbidities, fellow as the initial sonographer, and fewer fetal echocardiograms. Strategies to reduce DD could include a regular secondary review and repeat FE, particularly when anatomic complexity is high.

Fixed dosing and pharmacokinetics of S-1 in Japanese cancer patients with large body surface areas.

BACKGROUND: S-1 is an oral anticancer agent that combines tegafur (FT) with 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate. The recommended initial dose of S-1 is 120 mg/day for patients with a body surface area (BSA) of > or =1.5 m(2) in Japan. METHODS: We examined the effects of using this fixed dose on the pharmacokinetics of FT, CDHP, and active 5-fluorouracil (5-FU) on the basis of actual BSA. The pharmacokinetics was compared between patients with a BSA of 1.5-1.75 m(2) and those with a BSA of > or =1.75 m(2). RESULTS: The median areas under the time-concentration curves (AUCs) of 5-FU and CDHP were significantly lower in patients with a BSA of > or =1.75 m(2) than in those with a BSA of 1.5-1.75 m(2) (P = 0.005 and 0.006, respectively; Mann-Whitney U-test). There was no difference between the groups in the median AUC of FT. CONCLUSION: Systemic exposure to 5-FU is significantly lower in Japanese cancer patients with a large BSA of >1.75 m(2) who received the recommended fixed dose of S-1.