Systemic Hypoxemia Induces Cardiomyocyte Hypertrophy and Right Ventricular Specific Induction of Proliferation.

BACKGROUND: A recent study suggests that systemic hypoxemia in adult male mice can induce cardiac myocytes to proliferate. The goal of the present experiments was to confirm these results, provide new insights on the mechanisms that induce adult cardiomyocyte cell cycle reentry, and to determine if hypoxemia also induces cardiomyocyte proliferation in female mice. METHODS: EdU-containing mini pumps were implanted in 3-month-old, male and female C57BL/6 mice. Mice were placed in a hypoxia chamber, and the oxygen was lowered by 1% every day for 14 days to reach 7% oxygen. The animals remained in 7% oxygen for 2 weeks before terminal studies. Myocyte proliferation was also studied with a mosaic analysis with double markers mouse model. RESULTS: Hypoxia induced cardiac hypertrophy in both left ventricular (LV) and right ventricular (RV) myocytes, with LV myocytes lengthening and RV myocytes widening and lengthening. Hypoxia induced an increase (0.01±0.01% in normoxia to 0.11±0.09% in hypoxia) in the number of EdU+ RV cardiomyocytes, with no effect on LV myocytes in male C57BL/6 mice. Similar results were observed in female mice. Furthermore, in mosaic analysis with double markers mice, hypoxia induced a significant increase in RV myocyte proliferation (0.03±0.03% in normoxia to 0.32±0.15% in hypoxia of RFP+ myocytes), with no significant change in LV myocyte proliferation. RNA sequencing showed upregulation of mitotic cell cycle genes and a downregulation of Cullin genes, which promote the G1 to S phase transition in hypoxic mice. There was significant proliferation of nonmyocytes and mild cardiac fibrosis in hypoxic mice that did not disrupt cardiac function. Male and female mice exhibited similar gene expression following hypoxia. CONCLUSIONS: Systemic hypoxia induces a global hypertrophic stress response that was associated with increased RV proliferation, and while LV myocytes did not show increased proliferation, our results minimally confirm previous reports that hypoxia can induce cardiomyocyte cell cycle activity in vivo.

Histological and functional assessment of a Takotsubo cardiomyopathy model established by immobilization stress.

INTRODUCTION: Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, resembles acute heart failure syndrome but lacks disease-specific diagnosis and treatment strategies. TTC accounts for approximately 5-6% of all suspected cases of acute coronary syndrome in women. At present, animal models of TTC are often created by large amounts of exogenous catecholamines such as isoproterenol. However, isoproterenol injection cannot fully simulate the onset of stress-induced cardiomyopathy in humans since stress is not an instantaneous event. METHODS: Rats were immobilized for 6 h per day for 1-14 days. To examine whether the TTC model was successful, echocardiography was employed; Elisa detected serum sympathetic activation markers; and the Open-Field test (OFT) was used to analyze behavioral changes in rats after stress. Western blot and histology were used to assess sympathetic remodeling, inflammation levels, and fibrosis; qRT-PCR was used to explore the levels of fibrosis and myocardial hypertrophy. The electrical stability of ventricular was determined by electrophysiological testing. RESULTS: The rats showed severe stress behavior and local sympathetic remodeling of the heart after only 1 day of stress. After 3 days of stress, the induction of ventricular tachyarrhythmia increased prominently. The highest incidence of TTC in rats was at 5 days of immobilization stress. The pathological left ventricular remodeling caused by immobilization (IMO) stress includes inflammatory infiltration, fibrosis, and myocardial hypertrophy. CONCLUSIONS: Our study confirms the hypothesis that IMO stress can mimic Takotsubo cardiomyopathy, and the various effects on the heart depending on the duration of IMO stress. We observed the highest incidence of TTC occurred after 5 days of stress. Furthermore, there is a gradual occurrence of electrical and structural remodeling as the stress duration prolongs.

Treatment of hypopigmented burn hypertrophic scars with short-term topical tacrolimus does not lead to repigmentation.

OBJECTIVES: Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls. METHODOLOGY: Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Sídák's multiple comparisons test was used to compare groups. RESULTS: Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment. CONCLUSION: Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

Echocardiographic findings following renal sympathetic denervation for treatment resistant hypertension, the ReShape CV-risk study.

OBJECTIVE: The aim of this study was to describe and compare echocardiographic findings before renal sympathetic denervation (RDN) and 6 and 24 months after the procedure. MATERIALS AND METHODS: Patients with treatment resistant hypertension (TRH) were included in this non-randomised intervention study. RDN was performed by a single experienced operator using the Symplicity Catheter System. Echocardiographic measurements were performed at baseline, and after 6 and 24 months. RESULTS: The cohort consisted of 21 patients with TRH, with a mean systolic office blood pressure (BP) of 163 mmHg and mean diastolic BP 109 mmHg. Mixed model analysis showed no significant change in left ventricular (LV) mass index (LVMI) or left atrium volume index (LAVI) after the RDN procedure. Higher LVMI at baseline was significantly associated with greater reduction in LVMI (p < 0.001). Relative wall thickness (RWT) increased over time (0.48 mm after two years) regardless of change in BP. There was a small but significant reduction in LV end-diastolic (LVIDd) and end-systolic (LVIDs) diameters after RDN, with a mean reduction of 2.6 and 2.4 mm, respectively, after two years. Progression to concentric hypertrophy was observed only in in patients who did not achieve normal BP values, despite BP reduction after RDN. CONCLUSION: There was no reduction of LV mass after RDN. We found a small statistically significant reduction in LVIDd and LVIDs, which together with increase in RWT can indicate progression towards concentric hypertrophy. BP reduction after RDN on its own does not reverse concentric remodelling if target BP is not achieved.

Analysis of the cause of retrolingual obstruction in patients with moderate-severe obstructive sleep apnea.

PURPOSE: To evaluate the percentage of obstructive sleep apnea (OSA) patients with retrolingual obstruction in all moderate-severe OSA patients and the proportions of different causes in all moderate-severe OSA patients with retrolingual obstruction and to discuss the accuracy of the Friedman tongue position (FTP) and retrolingual cross-sectional area (RCSA) in assessing the retrolingual obstruction. METHODS: Two hundred and twenty moderate-severe OSA patients were enrolled. After retrolingual obstruction was diagnosed, the percentage of OSA patients with retrolingual obstruction in all moderate-severe OSA patients was calculated. After that, the different causes of retrolingual obstruction were diagnosed based on different diagnostic criteria, and the proportions of different causes in all moderate-severe OSA patients with retrolingual obstruction were calculated. Finally, the correlations between FTP, RCSA, and apnea-hypopnea index after nasopharyngeal tube insertion (NPT-AHI) were analyzed, and the proportions of different causes of retrolingual obstruction based on different FTP and RCSA were observed. RESULTS: There were 128 patients with retrolingual obstruction, accounting for 58.2% of all moderate-severe OSA patients. In 128 patients with retrolingual obstruction, the proportions of glossoptosis (48.4%), palatal tonsil hypertrophy (28.1%), and lingual hypertrophy (8.6%) were relatively high. Both FTP and RCSA did not correlate with NPT-AHI. The proportion of lingual hypertrophy increased gradually with the increase of FTP and the proportions of glossoptosis in all FTP classifications were high. The patients with RCSA > 180 mm2 were mainly affected by glossoptosis and palatal tonsil hypertrophy, while patients with RCSA ≤ 180 mm2 were mainly affected by lingual hypertrophy. CONCLUSION: The percentage of patients with retrolingual obstruction in all moderate-severe OSA patients is relatively high, mainly glossoptosis, palatal tonsil hypertrophy, and lingual hypertrophy. FTP classification and RCSA can only reflect the retrolingual anatomical stenosis, but cannot fully reflect the retrolingual functional stenosis, especially the presence of glossoptosis.

Efficacy and safety of turbinate reduction surgery in children: a systematic review.

PURPOSE: Inferior turbinate hypertrophy is not a rare problem in children, it causes chronic nasal obstruction which can severely impact the quality of life. This study aimed to investigate the efficacy and safety of turbinate reduction surgery in children with impaired nasal breathing due to hypertrophied inferior turbinate that's refractory to medical treatment. METHODS: We included 23 articles with various study designs: randomized controlled trials, single-arm clinical trials, and prospective and retrospective cohort studies. We searched PubMed, Scopus, Cochrane Library, and Web of Science with the relevant keywords till April 9th, 2023. The inclusion criteria were studied with the three prespecified study design that addressed children under 18 years who underwent turbinate reduction with any technique and evaluating the improvement whether by objective or subjective methods. RESULTS: Studies used objective measures favor turbinate surgery except two that showed no significant difference between pre and postoperative results. All studies used subjective measures showed an improvement postoperatively except one study. Complication rates are rare, with crust formation is being the commonest (6.03%), however, the procedure is generally safe in children. In addition, follow-up periods varied widely between 2 weeks and more than 5 years. CONCLUSION: Turbinate reduction in children is an effective as a treatment method for nasal blockage due to inferior turbinate hypertrophy which is resistant to medical treatment. It is a safe procedure with low rates of complications, however, due to the heterogenicity of the study designs, with a possible risk of bias we could not conduct a meta-analysis besides our systematic review.

Individualized Homeopathic Medicines in the Management of Symptomatic Adenotonsillar Hypertrophy in Children: A Prospective Observational Study.

BACKGROUND: Globally, adenotonsillar hypertrophy (ATH) is one of the most prevalent upper respiratory tract disorders of children, with associated troublesome symptoms such as sleep apnea and cognitive disturbances. In this study, we evaluated the potential role of individualized homeopathic medicines in the management of symptomatic ATH in children. METHODS: A multicenter prospective observational study was conducted at five institutes under the Central Council for Research in Homoeopathy, India. Primary and secondary outcomes (symptom score for adenoids, other symptoms of ATH, Mallampati score, tonsillar size, Sleep-Related Breathing Disorder of the Paediatric Sleep Questionnaire [SRBD-PSQ]) were assessed through standardized questionnaires at baseline and at 3, 6, 9 and 12 months. Radiological investigations for assessing the adenoid/nasopharyngeal (A/N) ratio were carried out at baseline, 6 and 12 months. All analyses were carried out using an intention-to-treat approach. RESULTS: A total of 340 children were screened and 202 children suffering from ATH were enrolled and followed up monthly for 12 months. Each patient received individualized homeopathic treatment based on the totality of symptoms. Statistically significant reductions in adenoid symptom score, Mallampati score (including tonsillar size), SRBD-PSQ sleep quality assessment and A/N ratio were found over time up to 12 months (p < 0.001). Homeopathic medicines frequently indicated were Calcarea carbonicum, Phosphorus, Silicea, Sulphur, Calcarea phosphoricum, Pulsatilla, Lycopodium and Tuberculinum. No serious adverse events were recorded during the study period. CONCLUSION: This study suggests that homeopathic medicines may play a beneficial role in the management of symptomatic ATH in children. Well-designed comparative trials are warranted.

The effects of adenoid hypertrophy and oral breathing on maxillofacial development: a review of the literature.

According to modern epidemiological surveys, the prevalence of adenoid hypertrophy in children and adolescents ranges from 42% to 70%. Adenoid hypertrophy can lead to airway obstruction; thus forces a child to breathe through their mouth, thus affecting the normal development of the dental and maxillofacial area, and can lead to malocclusion. Long-term mouth breathing can cause sagittal, vertical and lateral changes in the maxillofacial area. In this article, we review the current research status relating to the association between adenoid hypertrophy, oral breathing and maxillofacial growth and development in children and adolescents. We also discuss the personalized formulation of treatment plans.

Outcome of clinical experience of introducing a patient with secondary systemic AL-amyloidosis associated with multiple myeloma.

This research is relevant, as AL-amyloidosis refers to a systemic type of disease characterized by aggregation of an improperly folded light chain of an immunoglobulin, mainly in the heart and kidneys, causing organ failure. This study describes the clinical experience of introducing a patient with cardiac amyloidosis associated with multiple myeloma (MM). A clinical case of a patient diagnozed with amyloidosis was considered. Magnetic resonance imaging signs of cardiac amyloidosis were confirmed due to the presence of concentric biventricular hypertrophy without dilation, atrial septal hypertrophy, a tendency to atrial dilation, thickening of valve flaps and atrial walls. Upon admission to the research institute, the patient had an anasarca. More accurate recognition of AL-amyloidosis by cardiologists allows for prescribing earlier treatment and improving results. Conventional treatment of MM and AL-amyloidosis includes a combination of dexamethasone with bortezomib and endoxan. Haematopoietic stem cell transplantation after taking high doses of melphalan has become another treatment option and has led to remission in some patients. The novelty of the study is that an example of a timely complete diagnosis and treatment of a combination of these two diseases was presented, as a result of which the patient has achieved a complete haematological and partial organ response to the underlying disease.

M-type pyruvate kinase 2 (PKM2) tetramerization alleviates the progression of right ventricle failure by regulating oxidative stress and mitochondrial dynamics.

BACKGROUND: Right ventricle failure (RVF) is a progressive heart disease that has yet to be fully understood at the molecular level. Elevated M-type pyruvate kinase 2 (PKM2) tetramerization alleviates heart failure, but detailed molecular mechanisms remain unclear. OBJECTIVE: We observed changes in PKM2 tetramerization levels during the progression of right heart failure and in vitro cardiomyocyte hypertrophy and explored the causal relationship between altered PKM2 tetramerization and the imbalance of redox homeostasis in cardiomyocytes, as well as its underlying mechanisms. Ultimately, our goal was to propose rational intervention strategies for the treatment of RVF. METHOD: We established RVF in Sprague Dawley (SD) rats by intraperitoneal injection of monocrotaline (MCT). The pulmonary artery pressure and right heart function of rats were assessed using transthoracic echocardiography combined with right heart catheterization. TEPP-46 was used both in vivo and in vitro to promote PKM2 tetramerization. RESULTS: We observed that oxidative stress and mitochondrial disorganization were associated with increased apoptosis in the right ventricular tissue of RVF rats. Quantitative proteomics revealed that PKM2 was upregulated during RVF and negatively correlated with the cardiac function. Facilitating PKM2 tetramerization promoted mitochondrial network formation and alleviated oxidative stress and apoptosis during cardiomyocyte hypertrophy. Moreover, enhancing PKM2 tetramer formation improved cardiac mitochondrial morphology, mitigated oxidative stress and alleviated heart failure. CONCLUSION: Disruption of PKM2 tetramerization contributed to RVF by inducing mitochondrial fragmentation, accumulating ROS, and finally promoted the progression of cardiomyocyte apoptosis. Facilitating PKM2 tetramerization holds potential as a promising therapeutic approach for RVF.

Mechanisms of adaptive hypertrophic cardiac remodeling in a large animal model of premature ventricular contraction-induced cardiomyopathy.

Frequent premature ventricular contractions (PVCs) promoted eccentric cardiac hypertrophy and reduced ejection fraction (EF) in a large animal model of PVC-induced cardiomyopathy (PVC-CM), but the molecular mechanisms and markers of this hypertrophic remodeling remain unexplored. Healthy mongrel canines were implanted with pacemakers to deliver bigeminal PVCs (50% burden with 200-220 ms coupling interval). After 12 weeks, left ventricular (LV) free wall samples were studied from PVC-CM and Sham groups. In addition to reduced LV ejection fraction (LVEF), the PVC-CM group showed larger cardiac myocytes without evident ultrastructural alterations compared to the Sham group. Biochemical markers of pathological hypertrophy, such as store-operated Ca2+ entry, calcineurin/NFAT pathway, ß-myosin heavy chain, and skeletal type α-actin were unaltered in the PVC-CM group. In contrast, pro-hypertrophic and antiapoptotic pathways including ERK1/2 and AKT/mTOR were activated and/or overexpressed in the PVC-CM group, which appeared counterbalanced by an overexpression of protein phosphatase 1 and a borderline elevation of the anti-hypertrophic factor atrial natriuretic peptide. Moreover, the potent angiogenic and pro-hypertrophic factor VEGF-A and its receptor VEGFR2 were significantly elevated in the PVC-CM group. In conclusion, a molecular program is in place to keep this structural remodeling associated with frequent PVCs as an adaptive pathological hypertrophy.

Down-regulation of the mitochondrial fusion protein Opa1/Mfn2 promotes cardiomyocyte hypertrophy in Su5416/hypoxia-induced pulmonary hypertension rats.

BACKGROUND: Maladaptive right ventricular (RV) remodeling is the most important pathological feature of pulmonary hypertension (PH), involving processes such as myocardial hypertrophy and fibrosis. A growing number of studies have shown that mitochondria-associated endoplasmic reticulum membranes (MAMs) are involved in various physiological and pathological processes, such as calcium homeostasis, lipid metabolism, inflammatory response, mitochondrial dynamics, and autophagy/mitophagy. The abnormal expression of MAMs-related factors is closely related to the occurrence and development of heart-related diseases. However, the role of MAM-related factors in the maladaptive RV remodeling of PH rats remains unclear. METHODS AND RESULTS: We first obtained the transcriptome data of RV tissues from PH rats induced by Su5416 combined with hypoxia treatment (SuHx) from the Gene Expression Omnibus (GEO) database. The results showed that two MAMs-related genes (Opa1 and Mfn2) were significantly down-regulated in RV tissues of SuHx rats, accompanied by significant up-regulation of cardiac hypertrophy-related genes (such as Nppb and Myh7). Subsequently, using the SuHx-induced PH rat model, we found that the downregulation of mitochondrial fusion proteins Opa1 and Mfn2 may be involved in maladaptive RV remodeling by accelerating mitochondrial dysfunction. Finally, at the cellular level, we found that overexpression of Opa1 and Mfn2 could inhibit hypoxia-induced mitochondrial fission and reduce ROS production in H9c2 cardiomyocytes, thereby retarded the progression of cardiomyocyte hypertrophy. CONCLUSIONS: The down-regulation of mitochondrial fusion protein Opa1/Mfn2 can accelerate cardiomyocyte hypertrophy and then participate in maladaptive RV remodeling in SuHx-induced PH rats, which may be potential targets for preventing maladaptive RV remodeling.

Analysis of Multimorbidity of Moderate to Severe Allergic Rhinitis in Children: A Real-World Study.

INTRODUCTION: Allergic rhinitis (AR) in children is associated with various comorbidities, posing challenges for treatment and management. There have been few investigations of these multimorbidities in Chinese children with AR. Here, we investigated the prevalence of multimorbidities in children with moderate to severe AR and analyzed the influencing factors using real-world data. METHODS: In total, 600 children who visited the outpatient clinic of our hospital and were diagnosed with moderate-severe AR were prospectively enrolled. All children underwent allergen detection and electronic nasopharyngoscopy. Parents or guardians completed a questionnaire that included age, sex, mode of delivery, feeding pattern, and familial history of allergy. The multimorbidities investigated included atopic dermatitis (AD), asthma, allergic conjunctivitis (AC), chronic rhinosinusitis (CRS), adenoid hypertrophy (AH), tonsil hypertrophy (TH), recurrent epistaxis, and recurrent respiratory tract infections (RRTIs). RESULTS: The AR multimorbidities reported in children were as follows: recurrent epistaxis (46.5%), AC (46.3%), AD (40.7%), asthma (22.5%), RRIs (21.3%), CRS (20.5%), AH (19.7%), and TH (12.5%). In univariate logistic regression analysis, age (<6 years), birth mode, familial history of allergy, and single dust mite allergy were associated with AR multimorbidity (p < 0.05). Multivariate logistic regression revealed that a familial history of allergy was an independent risk factor for AC (odds ratio [OR] = 1.539, 95% confidence interval [CI]: 1.104-2.145) and AH (OR = 1.506, 95% CI: 1.000-2.267) (p < 0.05). Age (<6 years) was independently associated with the risk of AD (OR = 1.405, 95% CI: 1.003-1.969) and RRTIs (OR = 1.869, 95% CI: 1.250-2.793) (p < 0.05), cesarean section with AR and CRS risk (OR = 1.678, 95% CI: 1.100-2.561), and single dust mite allergy with asthma (OR = 1.590, 95% CI: 1.040-2.432) and CRS (OR = 1.600, 95% CI: 1.018-2.515) risk (p < 0.05). Further, non-dust mite allergy was independently associated with AR and CRS (OR = 2.056, 95% CI: 1.084-3.899). CONCLUSION: AR was found to be accompanied by different comorbidities, including both allergic and non-allergic comorbidities, complicating disease treatment. These findings demonstrated that age (<6 years), familial history of allergy, types of allergens, and cesarean section were risk factors for different multimorbidities associated with AR.

Determinants of awake oropharyngeal volume reduction between sitting and supine positions in children evaluated for snoring.

Pharyngeal collapsibility is a major determinant of obstructive sleep apnea (OSA) pathophysiology, but its anatomical predictors in children are largely unknown. We hypothesised that anatomical (tonsillar hypertrophy, narrow palate, nasal obstruction, dental/skeletal malocclusion, obesity) and OSA-related (apnea-hypopnea index, AHI) parameters could be related to a measure of awake pharyngeal collapsibility. We performed acoustic pharyngometry in children evaluated for suspected OSA, allowing us to measure the reduction of oropharyngeal volume in supine versus sitting position normalised for the volume in supine position (ΔV%), a measure of pharyngeal collapsibility. In addition to polysomnography and a clinical examination (anatomical parameters), acoustic rhinometry was used to assess nasal obstruction. A total of 188 snoring children were included, 118 (63%) of whom were obese and 74 (39%) of whom had moderate to severe OSA (AHI ≥5/h). The median (25th-75th percentiles) ΔV% in the whole population was 20.1% (4.7; 43.3). ΔV% was independently and positively associated with AHI (p = 0.023), z-score of BMI (p = 0.001), tonsillar hypertrophy (p = 0.007), narrow palate (p = 0.035), and African (p < 0.001) ancestry. By contrast, ΔV% was not modified by dental or skeletal malocclusion, Friedman palate position class or nasopharyngeal obstruction. Tonsillar hypertrophy, obesity, narrow palate and African ancestry are independently associated with an increase in pharyngeal collapsibility in snoring children, thus increasing the risk of OSA. Increased pharyngeal compliance in African children may explain the increased risk of residual OSA after adenotonsillectomy observed in this population.

Hypertrophic neuropathy: a possible cause of pain in children with Noonan syndrome and related disorders.

This study is aimed at describing the findings of high-resolution nerve ultrasound in children with Noonan syndrome (NS) and related disorders experiencing pain in their legs. This retrospective cohort study was conducted in the NS expert center of the Radboud University Medical Center in the Netherlands. Patients were eligible if they were younger than 18 years, clinically and genetically diagnosed with NS or a NS related disorder, and experienced pain in their legs. Anamneses and physical examination were performed in all children. In addition, high-resolution nerve ultrasound was used to assess nerve hypertrophy and, if needed, complemented spinal magnetic resonance imaging was performed. Over a period of 6 months, four children, three with NS and one child with NS with multiple lentigines, who experienced pain of their legs were eligible for inclusion. Muscle weakness was found in two of them. High-resolution nerve ultrasound showed (localized) hypertrophic neuropathy in all patients. One child underwent additional spinal magnetic resonance imaging, which showed profound thickening of the nerve roots and plexus.  Conclusion: In the four children included with a NS and related disorders, pain was concomitant with nerve hypertrophy, which suggests an association between these two findings. The use of high-resolution nerve ultrasound and spinal magnetic resonance imaging might result in better understanding of the nature of this pain and the possible association to nerve hypertrophy in patients with NS and related disorders. What is Known: • Children with Noonan syndrome and related disorders may report pain in their legs, which is often interpreted as growing pain. • Some adults with Noonan syndrome and related disorders have hypertrophic neuropathy as a possible cause of neuropathic pain. What is New: • This is the first study using high-resolution nerve ultrasound in children with Noonan syndrome and related disorders experiencing pain in their legs. • Hypertrophic neuropathy was diagnosed as possible cause of pain in four children with Noonan syndrome and related disorders.

Distribution of serum uric acid concentration and its association with lipid profiles: a single-center retrospective study in children aged 3 to 12 years with adenoid and tonsillar hypertrophy.

BACKGROUND: Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy. METHODS: Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were collected. SUA concentrations were scaled to standard deviation (SD), and SUA deviations were expressed as SD from the mean SUA of children without dyslipidemia. RESULTS: The mean SUA concentration of the participants was 4.27 ± 1.01 mg/dL, and the prevalence of hyperuricemia was 1.6% when it was defined using an SUA of ≥ 7.0 mg/dL. Participants with dyslipidemia (856, 17.4%) had a higher prevalence of hyperuricemia (3.4% vs. 1.2%, P < 0.001) and higher SUA concentrations (4.51 ± 1.15 vs. 4.22 ± 0.97 mg/dL, P < 0.001) than those with ortholiposis. The circulating lipid status of participants with SUAs < 1 SD below the mean value for the participants with ortholiposis (range 1.80-3.28 mg/dL) was more normal. Each 1-SD increase in SUA was associated with a 27% increase in the risk of dyslipidemia (OR = 1.270, 95% CI, 1.185-1.361). Adjustment for a number of potential confounders reduced the strength of the relationship, but this remained significant (OR = 1.125, 95% CI, 1.042-1.215). The higher risk of dyslipidemia was maintained for participants with SUAs > 1 SD above the mean value of the participants with ortholiposis. CONCLUSIONS: SUA was independently associated with dyslipidemia in children with adenoid and tonsillar hypertrophy, and an SUA < 1 SD below the mean value for patients with ortholiposis was associated with a healthy lipid profile.

Treatment of burn hypertrophic scar with fractional ablative laser-assisted drug delivery can decrease levels of hyperpigmentation.

BACKGROUND: Laser treatments have been used to treat a variety of scar symptoms, including the appearance of scars following burn injury. One such symptom is hyperpigmentation. There are several qualitative and quantitative measures of assessing improvement in hyperpigmentation over time. The Patient and Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS) are two scales that describe characteristics of scar such as pigmentation level. These scales are limited by their qualitative nature. On the other hand, spectrophotometers provide quantitative measures of pigmentation. Prior studies have reported that laser can change scar pigmentation, but no quantitative values have been reported. The current study examines changes in scar melanin index after CO2 fractional ablative laser scar revision (FLSR) via noninvasive probe measurement in patients of various Fitzpatrick skin types (FST). MATERIALS AND METHODS: Patients with scars of various sizes and etiologies were treated with FLSR. A database was constructed including 189 patients undergoing laser treatment. From this pool, individuals were selected based on the criteria that they completed at least two laser sessions and had Melanin index measurements for both of these sessions and the pre-operative visit. This criteria resulted in 63 patients of various FST in the cohort. Melanin index, POSAS-Observer (O) and -Patient (P) pigmentation and color scores and VSS-pigmentation scores were examined over time. Demographic information (age of patient at time of first treatment, age of scar at time of first treatment, use of laser-assisted drug delivery (LADD), gender, FST, and Ethnicity) were collected from the medical record. Patients were grouped as "responder" if their Melanin index indicated decreased levels of hyperpigmentation after FLSR treatment in more than half of their total number of visits and "nonresponder" if it did not. RESULTS: The majority of patients were responders (41/63). In responder patients, measurements of Melanin index showed significantly improved levels of hyperpigmentation in hypertrophic scars after two FLSR sessions (p < 0.05). Age of patient, gender, FST, age of scar, ethnicity, or type of drug delivered by LADD did not predict responder grouping. POSAS-O and -P pigmentation/color scores showed improved scores after two FLSR sessions within the responder group. POSAS-P color scores showed improved scores after two and three FLSR sessions in the nonresponder group. VSS pigmentation scores showed improved scores after three FLSR sessions in the responder group only. CONCLUSION: Based on Melanin index values, FLSR leads to improvements in hyperpigmentation in certain patients.

Structural phenotypes of knee osteoarthritis: potential clinical and research relevance.

A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting that osteoarthritis (OA) comprises several phenotypes or subpopulations. Consequently, a treatment for OA that targets only one pathophysiologic abnormality is unlikely to be similarly efficacious in preventing or delaying the progression of all the different phenotypes of structural OA. Five structural phenotypes have been proposed, namely the inflammatory, meniscus-cartilage, subchondral bone, and atrophic and hypertrophic phenotypes. The inflammatory phenotype is characterized by marked synovitis and/or joint effusion, while the meniscus-cartilage phenotype exhibits severe meniscal and cartilage damage. Large bone marrow lesions characterize the subchondral bone phenotype. The hypertrophic and atrophic OA phenotype are defined based on the presence large osteophytes or absence of any osteophytes, respectively, in the presence of concomitant cartilage damage. Limitations of the concept of structural phenotyping are that they are not mutually exclusive and that more than one phenotype may be present. It must be acknowledged that a wide range of views exist on how best to operationalize the concept of structural OA phenotypes and that the concept of structural phenotypic characterization is still in its infancy. Structural phenotypic stratification, however, may result in more targeted trial populations with successful outcomes and practitioners need to be aware of the heterogeneity of the disease to personalize their treatment recommendations for an individual patient. Radiologists should be able to define a joint at risk for progression based on the predominant phenotype present at different disease stages.

A closer look: ultrastructural evaluation of high-risk progression IgA nephropathy.

This retrospective, cross-sectional study sought to examine the ultrastructural characteristics of glomerular lesions using Transmission Electron Microscopy (TEM) in IgA nephropathy (IgAN) and their relationship with the high risk of progression phenotype defined by KDIGO guideline as proteinuria ≥1 g/24 hours despite 3 months of optimized supportive care. We analyzed 81 IgAN patients (median age 41 years, 67% male, eGFR 43.8 mL/min, proteinuria 1.04 g/day); 42 (52%) of them had high risk of progression. There were no differences in terms of age, sex, comorbidities, eGFR, and hematuria between the two groups. High-risk patients more often had segmental glomerulosclerosis (29% vs 8%, p 0.01) in optical microscopy, while in TEM had more frequent podocyte hypertrophy (62% vs 26%, p 0.001) and podocyte foot process detachment from the glomerular basement membrane (19% vs 8%, p 0.05), more often thicker (19% vs 5%, p 0.05) and duplicated (26% vs 10%, p 0.05) glomerular basement membrane, and the presence of subendothelial and subepithelial deposits (31% vs 13%, p 0.05). However, in multivariate binary logistic regression analysis, only podocyte hypertrophy (OR 3.14; 95%CI 1.12, 8.79) was an independent risk factor for high-risk progression in IgAN. These findings highlight the importance of podocytopathy in IgAN progression.

Plaque histology and myocardial disease in sudden coronary death: the Fingesture study.

AIMS: At least 50% of deaths due to coronary artery disease (CAD) are sudden cardiac deaths (SCDs), but the role of acute plaque complications on the incidence of sudden death in CAD is somewhat unclear. The present study aimed to investigate plaque histology and concomitant myocardial disease in sudden coronary death. METHODS AND RESULTS: The study population is derived from the Fingesture study, which has collected data from 5869 consecutive autopsy-verified SCD victims in Northern Finland (population ≈600 000) between 1998 and 2017. In this substudy, histological examination of culprit lesions was performed in 600 SCD victims whose death was due to CAD. Determination of the cause of death was based on the combination of medical records, police reports, and autopsy data. Plaque histology was classified as either (i) plaque rupture or erosion, (ii) intraplaque haemorrhage, or (iii) stable plaque. The mean age of the study subjects was 64.9 ± 11.2 years, and 82% were male. Twenty-four per cent had plaque rupture or plaque erosion, 24% had an intraplaque haemorrhage, and 52% had a stable plaque. Myocardial hypertrophy was present in 78% and myocardial fibrosis in 93% of victims. The presence of myocardial hypertrophy or fibrosis was not associated with specific plaque histology. CONCLUSION: Less than half of sudden deaths due to CAD had evidence of acute plaque complication, an observation which is contrary to historical perceptions. The prevalence of concomitant myocardial disease was high and independent of associated plaque morphology.