Cyanosis and myocardial hypertrophy frequently occur in combination. Hypoxia or cyanosis can be potent inducers of angiogenesis, regulating the expression of hypoxia-inducible factors (HIF), vascular endothelial growth factors (VEGF), and VEGF receptors (VEGFR-1 and 2); in contrast, pressure overload hypertrophy is often associated with impaired pro-angiogenic signaling and decreased myocardial capillary density. We hypothesized that the physiological pro-angiogenic response to cyanosis in the hypertrophied myocardium is blunted through differential HIF and VEGF-associated signaling.

Background: Cardiopulmonary disorders are the most common cause of central cyanosis, and methemoglobinemia is often overlooked in the differential diagnosis of patients with central cyanosis. In most cases, methemoglobinemia is acquired and hereditary congenital methemoglobinemia is rare. Only a few case reports of congenital methemoglobinemia can be found in PubMed. To date, only four cases of congenital methemoglobinemia diagnosed after the age of 50 years have been reported. Case Presentation: A 79-year-old Japanese woman presented at our hospital with the chief complaints of dyspnea and cyanosis. She exhibited cyanosis of the lips and extremities, and her SpO2 was 80%, with oxygen administration at 5 L/min. Blood gas analysis revealed a PaO2 of 325.4 mmHg and methemoglobin level of 36.9%. The SpO2 and PaO2 values were dissociated, and methemoglobin levels were markedly elevated. Genetic analysis revealed a nonsynonymous variant in the gene encoding nicotinamide adenine dinucleotide cytochrome (NADH) B5 reductase 3 (CYB5R3), and the patient was diagnosed with congenital methemoglobinemia. Conclusions: It is important to consider methemoglobinemia in the differential diagnosis of patients with central cyanosis. At 79 years of age, our patient represents the oldest patient with this diagnosis. This report indicates that it is crucial to consider the possibility of methemoglobinemia regardless of the patient's age.

Neonatal respiratory distress syndrome (RDS) is one of the most common problems for preterm infants, and symptoms include tachypnoea, grunting, retractions and cyanosis, which occur immediately after birth. Treatment with surfactants has reduced morbidity and mortality rates associated with neonatal RDS.

Chronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized.

Cyanosis in an apparently healthy newborn baby may be caused by hemoglobin variants associated with the formation of methemoglobin, collectively known as M hemoglobins. They should not be confused with genetic alterations in methemoglobin reductase enzyme systems of red cells since treatment and prognosis are completely different. A newborn male child was noted to be significantly cyanotic at birth and is the basis for this report. Hemoglobin isoelectric focusing, acid and alkaline gel electrophoresis, and HBA/HBB gene sequencing were performed for the child, both parents and a sister. The newborn child was treated with methylene blue in an intensive care unit fearing that he had a defective reductase system and exposure to oxidant drugs or toxins. Newborn hemoglobin screening with high performance liquid chromatography was abnormal on the 10th and 45th days but no conclusive diagnosis was reached. Cyanosis persisted up to four years of age with no other symptoms. Hemoglobin M Iwate [alpha2 87(F8) His>Tyr, HBA2:c.262C>T] was detected. It was not present in the child's presumed mother, father, sister, and brother. The analysis of 15 short tandem repeats in the trio demonstrated a de novo mutation occurrence (p-value<1×10(-8)). The family was reassured that no further action was necessary and genetic counseling was provided. Methemoglobins should be considered for differential diagnosis of cyanosis in newborns even if no familial cases are detected. Except for cosmetic consequences, the clinical course of patients with hemoglobin M Iwate is unremarkable.

Congenital Heart Diseases (CHD) involves a wide range of pathological conditions, such as Pulmonary Atresia with Ventricle Septal Defect (PA/VSD). This disorder leads to the systemic circulation of oxygen-poor blood (cyanosis), with associated features and consequences in the oral cavity.

Background and Objective: Mutations in the CYB5R3 gene cause reduced NADH-dependent cytochrome b5 reductase enzyme function and consequently lead to recessive congenital methemoglobinemia (RCM). RCM exists as RCM type I (RCM1) and RCM type II (RCM2). RCM1 leads to higher methemoglobin levels causing only cyanosis, while in RCM2, neurological complications are also present along with cyanosis. Materials and Methods: In the current study, a consanguineous Pakistani family with three individuals showing clinical manifestations of cyanosis, chest pain radiating to the left arm, dyspnea, orthopnea, and hemoptysis was studied. Following clinical assessment, a search for the causative gene was performed using whole exome sequencing (WES) and Sanger sequencing. Various variant effect prediction tools and ACMG criteria were applied to interpret the pathogenicity of the prioritized variants. Molecular dynamic simulation studies of wild and mutant systems were performed to determine the stability of the mutant CYB5R3 protein. Results: Data analysis of WES revealed a novel homozygous missense variant NM_001171660.2: c.670A > T: NP_001165131.1: p.(Ile224Phe) in exon 8 of the CYB5R3 gene located on chromosome 22q13.2. Sanger sequencing validated the segregation of the identified variant with the disease phenotype within the family. Bioinformatics prediction tools and ACMG guidelines predicted the identified variant p.(Ile224Phe) as disease-causing and likely pathogenic, respectively. Molecular dynamics study revealed that the variant p.(Ile224Phe) in the CYB5R3 resides in the NADH domain of the protein, the aberrant function of which is detrimental. Conclusions: The present study expanded the variant spectrum of the CYB5R3 gene. This will facilitate genetic counselling of the same and other similar families carrying mutations in the CYB5R3 gene.

To evaluate if the functional grading system (Cambridge classification) of brachycephalic obstructive airways syndrome (BOAS) and the temperament score can be useful tools in predicting the feasibility of echocardiographic examination in lateral recumbency. The hypothesis is that the temperament of the dog, rather than the severity of BOAS alone, can exacerbate respiratory symptoms (dyspnea, stertor, stridor and/or cyanosis) during lateral containment.

During oxygen therapy in preterm infants, targeting oxygen saturation is important for avoiding hypoxaemia and hyperoxaemia, but this can be very difficult and challenging for neonatal nurses. We systematically reviewed the qualitative and quantitative studies investigating the compliance in targeting oxygen saturation in preterm infants and factors that influence this compliance. We searched PubMed, Embase, Web of Science, Cochrane, CINAHL and ScienceDirect from 2000 to January 2015. Sixteen studies were selected, which involved a total of 2935 nurses and 574 infants. The studies varied in methodology, and we have therefore used a narrative account to describe the data. The main finding is that there is a low compliance in oxygen targeting; the upper alarm limits are inappropriately set, and maintaining the saturation (SpO2) below the upper limit presented particular difficulties. Although there is little data available, the studies indicate that training, titration protocols and decreasing workload could improve awareness and compliance. Automated oxygen regulations have been shown to increase the time that SpO2 is within the target range.

Antihaemophilic factor (recombinant) (rAHF; ADVATE® ) is approved for prophylaxis and treatment of bleeding in children and adults with haemophilia A. Reconstitution in 2 mL sterile water for injection instead of 5 mL allows for a 60% reduction in infusion volume and administration time, but could increase the likelihood of hypersensitivity and infusion-related reactions, especially in children.

A cardiopulmonary exercise test (CPET) is essential for lung resection. However, performing a CPET can be challenging. This study aimed to develop a machine learning model to estimate maximal oxygen consumption (VO2max) using data collected through a patch-type single-lead electrocardiogram (ECG) monitoring device in candidates for lung resection. This prospective, single-center study included 42 patients who underwent a CPET at a tertiary teaching hospital from October 2021 to July 2022. During the CPET, a single-lead ECG monitoring device was applied to all patients, and the results obtained from the machine-learning algorithm using the information extracted from the ECG patch were compared with the CPET results. According to the Bland-Altman plot of measured and estimated VO2max, the VO2max values obtained from the machine learning model and the FRIEND equation showed lower differences from the reference value (bias: -0.33 mL·kg-1·min-1, bias: 0.30 mL·kg-1·min-1, respectively). In subgroup analysis, the developed model demonstrated greater consistency when applied to different maximal stage levels and sexes. In conclusion, our model provides a closer estimation of VO2max values measured using a CPET than existing equations. This model may be a promising tool for estimating VO2max and assessing cardiopulmonary reserve in lung resection candidates when a CPET is not feasible.

COVID-19 is less serious in children than in adults. However, respiratory management dominates the clinical picture of hospitalized COVID-19 even in children. In some case series, deterioration of the clinical picture wherein dyspnea, cyanosis, and the onset of acute respiratory distress syndrome (ARDS) emerged ~8-10 days after the onset of SARS-CoV-2 infection, which could rapidly progress to multiple organ failure and death. This review aimed to evaluate the characteristics of COVID-19 pneumonia in pediatric populations, beginning from its etiology and pathological mechanisms and closing with its clinical management.

Over the years, forensic pathology has registered the spread of new methods of suicide, such as the ingestion of sodium nitrite. Sodium nitrite causes increased methemoglobin, resulting in systemic hypoxia, metabolic acidosis, and cyanosis. Since sodium nitrite is a preservative, the ingestion of foods containing an excessive amount of this substance can also cause acute intoxication up to death. The present review is aimed at guiding health professionals in the identification and management of sodium-nitrite-related intoxications and deaths.

Jaw dystonia and laryngospasm in the context of subacute brainstem dysfunction have been described in a small number of diseases, including antineuronal nuclear antibody type 2 (ANNA-2, also known as anti-Ri) paraneoplastic neurologic syndrome. Severe episodes of laryngospasms causing cyanosis are potentially fatal. Jaw dystonia can also cause eating difficulty, resulting in severe weight loss and malnutrition. In this report, we highlight the multidisciplinary management of this syndrome associated with ANNA-2/anti-Ri paraneoplastic neurologic syndrome and discuss its pathogenesis.

Raynaud's phenomenon (RP) describes the phenomenon of recurrent vasospasm of digital arteries, associated with skin colour changes: pallor, cyanosis and erythema. Twin studies have indicated a genetic predisposition for RP; however, the precise aetiology of RP remains unknown. It is thought that genetic variation in temperature-responsive or vasospastic genes might underlie RP so performed a candidate gene study in a large, population based sample. We assessed the association between RP and single nucleotide polymorphisms (SNPs) in the TRPA1, TRPM8, CALCA, CALCB and NOS1 genes.

The increasing incidence of bronchopulmonary dysplasia in premature babies may be due in part to immature ventilatory control, contributing to hypoxemia. The latter responds to ventilation and/or oxygen therapy, treatments associated with adverse sequelae. This is an overview of the Prematurity-Related Ventilatory Control Study which aims to analyze the under-utilized cardiorespiratory continuous waveform monitoring data to delineate mechanisms of immature ventilatory control in preterm infants and identify predictive markers.

Respiratory syncytial virus (RSV) pneumonia is a leading cause of hospitalization and mortality among neonates worldwide, and there are currently no specific clinical treatments for RSV infection. Interferons (IFNs) possess broad-spectrum antiviral properties, and the present study aimed to evaluate the efficacy and safety of IFN-α1b for the treatment of neonatal RSV pneumonia. Neonates with RSV pneumonia were divided into the treatment (126 neonates) and control (160 neonates) groups, the former of which were treated with IFN. Aside from IFN administration, both groups received the same routine treatments. There were no significant differences in patient characteristics between the two groups. All neonates in the two groups displayed symptoms such as a cough (93.0%), tachypnea (90.1%), perilabial cyanosis (67.8%), choking on milk (62.9%) and moist rales (58.4%), and no significant differences in the occurrence of these symptoms were observed between the groups (P>0.05). The percentage of cases with bacterial co-infection was 66.8% (191/286), and the bacterial species in the spectrum primarily included Escherichia coli (21.5%), Klebsiella pneumonia (20.4%), Staphylococcus aureus (17.2%), Acihetobacter baumanii (13.1%) and Pseudomonas aeruginosa (9.9%). There were no significant differences in the co-infection rate or bacterial spectrum between the two groups. The remission time of cough, tachypnea, choking on milk, perilabial cyanosis, moist rales and oxygen inhalation in the treatment group was significantly lower compared with the control group (P<0.05). Although the hospitalization time in the treatment group was shorter compared with the control group, the difference was not significant. There were two patients in the treatment group that developed fever within 2-6 h after receiving IFN-α1b, though no other adverse effects were observed. In conclusion, IFN-α1b treatment improved the symptoms associated with neonatal RSV pneumonia with minimal adverse effects.

Congenital myasthenic syndromes (CMSs) are a group of inherited disorders caused by genetic defects in neuromuscular junctions. Mutations in CHAT, encoding choline acetyltransferase, cause congenital myasthenic syndrome with episodic apnea (CMS-EA), a rare autosomal recessive disease characterized by respiratory insufficiency with cyanosis and apnea after infections, fever, vomiting, or excitement. To date, no studies have reported deletions comprised of multiple exons. Here, using next generation sequencing, we identified compound heterozygous mutations, namely a large maternally inherited deletion, including exons 4, 5, and 6, and a paternally inherited missense variant (c.914T>C [p.Ile305Thr]) in CHAT in a Chinese patient with a severe phenotype of CMS-EA. Furthermore, the large deletion was also validated by real-time fluorescence quantitative polymerase chain reaction. The patient was a 10-month-old boy, who presented with a weak cry and feeding difficulties soon after birth, ptosis at 4 months old, episodic apnea after fever at 9 months old, and respiratory insufficiency with cyanosis and apnea that required intubation after a respiratory tract infection at 10 months old. Unfortunately, he died in the Pediatric Intensive Care Unit soon after hospitalization. The patient's elder sister had similar clinical manifestations, and she died prior to the age of 2 months old without a diagnosis. Genotype-phenotype correlation analysis revealed that loss-of-function mutations in exons 4-6 of CHAT might cause more severe CMS-EA. To our knowledge, this is the first study to show compound heterozygous CHAT mutations consisting of a large deletion and missense mutation in a patient with CMS-EA.

Data on the impact of arterial stiffness on autonomic function are limited. We sought to investigate whether heart rate recovery (HRR), a predictor of autonomic function, is impaired in patients with increased arterial stiffness. A total of 475 participants (mean age 55.8 ± 11.1 years, 34.3% women) who underwent a treadmill exercise test (TET) for the evaluation of chest pain were retrospectively analyzed. All patients underwent brachial-ankle pulse wave velocity (baPWV) measurement on the same day. HRR was defined as the difference in heart rate from maximal exercise to 1 min of recovery. Participants with the lowest HRR tertile were older and had more cardiovascular risk factors than those with the highest HRR tertile. Simple correlation analysis showed that baPWV was negatively correlated with HRR (r =  - 0.327, P < 0.001). In multiple linear regression analysis, there was a significant association between baPWV and HRR, even after adjusting for potential confounders (β =  - 0.181, P < 0.001). In participants who underwent TET, baPWV was negatively correlated with HRR. The results of our study indicate a potential relationship between arterial stiffness and the autonomic nervous system.

Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins (ACDMPV) is a fatal congenital disease resulting from a pulmonary vascular endothelial deficiency of FOXF1, producing abnormal morphogenesis of alveolar capillaries, malpositioned pulmonary veins and disordered development of lung lobes. Affected neonates suffer from cyanosis, severe breathing insufficiency, pulmonary hypertension, and death typically within days to weeks after birth. Currently, no treatment exists for ACDMPV, although recent murine research in the Kalinichenko lab demonstrates nanoparticle delivery improves survival and reconstitutes normal alveolar-capillary architecture. The aim of the present study is to investigate the safety of intravenous administration of FOXF1-expressing PEI-PEG nanoparticles (npFOXF1), our pioneering treatment for ACDMPV.