Mortality after cardiac arrest in children less than 2 years: relevant factors.

BACKGROUND: There are only scant studies of predicting outcomes of pediatric resuscitation due to lack of population-based data. This study aimed to determine variable factors that may impact the survival of resuscitated children aged under 24 months. METHODS: This is a retrospective study of 66 children under 24 months. Cardiopulmonary resuscitation (CPR) with pediatric advanced life support guideline was performed uniformly for all children. Linear regression analysis with variable factors was conducted to determine impacts on mortality. RESULT: Factors with statistically significant increases in mortality were the number of administered epinephrine (p value < 0.001), total CPR duration (p value < 0.001), in-hospital CPR duration of out-hospital cardiac arrest (p value < 0.001), and changes in cardiac rhythm (p value < 0.040). However, there is no statistically significant association between patient outcomes and remaining factors such as age, sex, underlying disease, etiology, time between last normal to CPR, initial CPR location, initial cardiac rhythm, venous access time, or inotropic usage. CONCLUSION: More than 10 times of epinephrine administration and CPR duration longer than 30 minutes were associated with a higher mortality rate, while each epinephrine administration and prolonged CPR time increased mortality. IMPACT STATEMENT: This study analyzed various factors influencing mortality after cardiac arrest in patients under 24 months. Increased number of administered epinephrine and prolonged cardiopulmonary resuscitation duration do not increase survival rate in patients under 24 months. In patients with electrocardiogram rhythm changes during CPR, mortality increased when the rhythm changed into asystole in comparison to no changes occurring in the rhythm.

Establishment and characterization of matched immortalized human frontal and occipital scalp dermal papilla cell lines from androgenetic alopecia.

Androgenetic alopecia (AGA), also known as male pattern baldness, is a common hair loss condition influenced by genetic and hormonal factors. Variations in gene expression and androgen responsiveness have been observed between the frontal and occipital regions of AGA patients. However, obtaining and cultivating frontal hair follicles is challenging. Therefore, no matched frontal and occipital dermal papilla (DP) cell lines have been reported yet. This study aimed to establish matched immortalized human frontal and occipital scalp DP cell lines from AGA patients. Simian virus 40 large T antigen (SV40T-Ag) and human telomerase reverse transcriptase (hTERT) were introduced into primary human DP cells. The obtained cell lines were characterized by assessing their gene expression patterns, androgen receptor (AR) levels, and the presence of 5-alpha reductase (5αR). Additionally, we examined their response to dihydrotestosterone (DHT) and evaluated cell viability. The conditioned medium from the frontal DP cell line inhibited human hair follicle growth, leading to reduced keratinocyte proliferation and increased apoptosis. Furthermore, when the cells were cultured in a 3D environment mimicking in vivo conditions, the 3D cultured frontal DP cell line exhibited weaker sphere aggregation than the occipital DP cell line due to the increased expression of matrix metalloproteinase 1 (MMP1), MMP3, and MMP9. Additionally, the expression of DP signature genes was inhibited in the 3D cultured frontal DP cell line. These matched frontal and occipital DP cell lines hold significant potential as valuable resources for research on hair loss. Their establishment allows us to investigate the differences between frontal and occipital DP cells, contributing to a better understanding of the molecular mechanisms underlying AGA. Furthermore, these cell lines may be valuable for developing targeted therapeutic approaches for hair loss conditions.

The role of dexamethasone in mediating the contradictory effects of Wnt antagonists SFRP2 and SFRP3 on human hair follicle growth.

Stress can be one of the leading causes of hair loss. Stress related hormones, glucocorticoids (GCs), secretion by hair follicle have been mentioned in literature and proven to exert an inhibitory effect on hair follicle cells growth by modulating the expression of target genes related to cell proliferation and cycling. The gene modulating effect of the synthetic GC, dexamethasone (DEX), in human dermal papilla (DP) cells has been outlined in this study by mediating a contradictory effect on the expression of secreted frizzled related protein 2 (SFRP2) and SFRP3. The SFRP2 and SFRP3 possess a regulating effect on wnt signaling pathway. Their structural similarities to the cysteine-rich-domain of the frizzled receptors (FZD) allow their binding to the wnt ligands causing the blocking of the wnt ligands-receptors complex. The SFRP family members have been known as inhibitors of the wnt signaling modulating the proliferation and development of various cells. In hair follicle cells, SFRP2 activity has been reported positively on the proliferation of keratinocytes. However, the SFRP3 effect hasn't been well addressed. Under stress, the investigation of the mRNA and protein expressions of SFRP members in human DP cells revealed opposite expressions where SFRP2 decreased while SFRP3 increased by DEX. The proliferation rate of hair keratinocytes outer root sheath was detected via immunofluorescence highlighting the stimulatory effect of SFRP2 and the inhibitory effect of SFRP3. Here, we sought to determine the effect of GC agonist on SFRPs expression and their effect on hair follicle growth.

Dexamethasone, a Synthetic Glucocorticoid, Induces the Activity of Androgen Receptor in Human Dermal Papilla Cells.

Psychosocial stress stimulates the secretion of glucocorticoids (GCs), which are stress-related neurohormones. GCs are secreted from hair follicles and promote hair follicle regression by inducing cellular apoptosis. Moreover, the androgen receptor (AR) is abundant in the balding scalp, and androgens suppress hair growth by binding to AR in androgenetic alopecia. First, by using immunofluorescence, we investigated whether the treatment of dermal papilla (DP) cells with dexamethasone (DEX), a synthetic GC, causes the translocation of the glucocorticoid receptor (GR) into the nucleus. DEX treatment causes the translocation of the GR into the nucleus. Next, we investigated whether stress-induced GCs affect the AR, a key factor in male pattern baldness. In this study, we first assessed that DEX increases the expression of AR mRNA in non-balding DP cells, which rarely express AR without androgen. RU486, a GR antagonist, attenuated DEX-inducible AR mRNA expression and AR activation in human non-balding DP cells. In addition, AR translocated into the nucleus after DEX treatment. Furthermore, we indeed showed that the expression of AR was induced in the nucleus by DEX in DP cells of human and mouse hair follicles. Our results first suggest that stress-associated hair loss may be due to increased AR expression and activity induced by DEX. These results demonstrate that hair loss occurs in non-balding scalps with low AR expression.

Delayed Influenza Treatment in Children With False-Negative Rapid Antigen Test: A Retrospective Single-Center Study in Korea 2016-2019.

BACKGROUND: We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. METHODS: This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016-2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. RESULTS: A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2-100.1, P < 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7-187.3/ILI patient. CONCLUSION: Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.

Versatile Usage of the Modified Lateral Mass Screw as an Alternative to Cervical Pedicle Screw Fixation.

OBJECTIVE: Posterior subaxial cervical screw fixation is commonly performed using the cervical pedicle screws (CPS) and lateral mass screws (LMS); however, their compatibility is low. Modified lateral mass screws (mLMS, also called paravertebral foramen screw) fixation was introduced as a salvage technique for LMS fixation and has features of both LMS and CPS techniques. In the present study, the use of mLMS as an alternative to CPS was analyzed based on clinical results. METHODS: Seventy-eight screws (38 CPSs and 40 mLMSs) were inserted into 12 patients. The misplacement of the screws was evaluated by computed tomography (CT). The failure of instrumentation and instability were evaluated using plain radiographs. RESULTS: The total number of CPS misplacements was 3 (10.5%); however, neurologic complications were not observed. mLMSs were used in the middle segments of the fusion in 10 patients and 2 patients had mLMS fixation for single-level fusion. An additional bridging implant was not required for connecting both CPSs and mLMSs. Instability was not observed during the observation period (4-51 months). Complete fusion was seen in 10 patients. CONCLUSIONS: The alternative mLMS fixation can decrease the risk of screw misplacement compared with CPS fixation alone and achieves adequate stability leading to fusion.

Age-adjusted quick Sequential Organ Failure Assessment score for predicting mortality and disease severity in children with infection: a systematic review and meta-analysis.

We assessed the diagnostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) for predicting mortality and disease severity in pediatric patients with suspected or confirmed infection. We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and Web of Science. Eleven studies with a total of 172,569 patients were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of the age-adjusted qSOFA for predicting mortality and disease severity were 0.69 (95% confidence interval [CI] 0.53-0.81), 0.71 (95% CI 0.36-0.91), and 6.57 (95% CI 4.46-9.67), respectively. The area under the summary receiver-operating characteristic curve was 0.733. The pooled sensitivity and specificity for predicting mortality were 0.73 (95% CI 0.66-0.79) and 0.63 (95% CI 0.21-0.92), respectively. The pooled sensitivity and specificity for predicting disease severity were 0.73 (95% CI 0.21-0.97) and 0.72 (95% CI 0.11-0.98), respectively. The performance of the age-adjusted qSOFA for predicting mortality and disease severity was better in emergency department patients than in intensive care unit patients. The age-adjusted qSOFA has moderate predictive power and can help in rapidly identifying at-risk children, but its utility may be limited by its insufficient sensitivity.

Paediatric Trauma Score as a non-imaging tool for predicting intracranial haemorrhage in patients with traumatic brain injury.

To identify a useful non-imaging tool to screen paediatric patients with traumatic brain injury for intracranial haemorrhage (ICH). We retrospectively analysed patients aged < 15 years who visited the emergency department with head trauma between January 2015 and September 2020. We divided patients into two groups (ICH and non-ICH) and compared their demographic and clinical factors. Among 85 patients, 21 and 64 were in the ICH and non-ICH groups, respectively. Age (p = 0.002), Pediatric trauma score (PTS; p < 0.001), seizure (p = 0.042), and fracture (p < 0.001) differed significantly between the two groups. Factors differing significantly between the groups were as follows: age (odds ratio, 0.84, p = 0.004), seizure (4.83, p = 0.013), PTS (0.15, p < 0.001), and fracture (69.3, p < 0.001). Factors with meaningful cut-off values were age (cut-off [sensitivity, specificity], 6.5 [0.688, 0.714], p = 0.003) and PTS [10.5 (0.906, 0.81), p < 0.001]. Based on the previously known value for critical injury (≤ 8 points) and the cut-off value of the PTS identified in this study (≤ 10 points), we divided patients into low-risk, medium-risk, and high-risk groups; their probabilities of ICH (95% confidence intervals) were 0.16-12.74%, 35.86-89.14%, and 100%, respectively. PTS was the only factor that differed significantly between mild and severe ICH cases (p = 0.012). PTS is a useful screening tool with a high predictability for ICH and can help reduce radiation exposure when used to screen patient groups before performing imaging studies.

Comparative Graft Survival Study of Follicular Unit Excision Grafts With or Without Minor Injury.

BACKGROUND: Various types of follicular trauma occur during follicular unit excision (FUE). However, the effects of different types of follicular injury on graft survival have not been reported. OBJECTIVE: This study was performed to evaluate the differences in hair follicle survival by the type of follicular injury, including paring, fracture, and bulb injury. METHODS: Seven healthy patients who underwent hair transplant surgery by FUE were enrolled in the study. For each patient, 10 single-hair follicular unit grafts per injury group (paring, fracture, bulb injury, or intact) were differentiated. Using sharp implanters, 10 grafts of each of the 4 injury types were transplanted into mice, and the mice were sacrificed 5 months after transplantation. The skin was excised at each of the 4 locations, and newly formed follicular units were counted and photographed under a microscope. RESULTS: Of 70 hair follicles in each group, the number of successfully engrafted follicles was 50 (71.43%) in the intact group, 36 (51.43%) in the paring injury group, 9 (12.86%) in the fracture injury group, and 31 (44.29%) in the bulb injury group. CONCLUSION: Grafts with minor injury had a lower survival rate than intact grafts. Fractured follicles showed the lowest survival rate.

Knockdown of FOXA2 Impairs Hair-Inductive Activity of Cultured Human Follicular Keratinocytes.

Reciprocal interactions between hair-inductive dermal cells and epidermal cells are essential for de novo genesis of hair follicles. Recent studies have shown that outer root sheath (ORS) follicular keratinocytes can be expanded in vitro, but the cultured cells often lose receptivity to hair-inducing dermal signals. In this study, we first investigated whether the hair-inductive activity (trichogenicity) of cultured human ORS follicular keratinocytes was correlated with the cultivation period. ORS follicular keratinocytes from the scalp were cultured for 3, 4, 5, or 6 weeks and were then implanted into nude mice along with freshly isolated neonatal mouse dermal cells. We observed that the trichogenicity of the implanted ORS cells was inversely correlated with their cultivation period. These initial findings prompted us to investigate the differentially expressed genes between the short-term (20 days) and long-term (42 days) cultured ORS cells, trichogenic and non-trichogenic, respectively, by microarray analysis. We found that forkhead box protein A2 (FOXA2) was the most up-regulated transcription factor in the trichogenic ORS cells. Thus, we investigated whether the trichogenicity of the cells was affected by FOXA2 expression. We found a significant decrease in the number of induced hair follicles when the ORS cells were transfected with a FOXA2 small interfering RNA versus control small interfering RNA. Taken together, our data strongly suggest that FOXA2 significantly influences the trichogenicity of human ORS cells.

Ectodysplasin-A2 induces dickkopf 1 expression in human balding dermal papilla cells overexpressing the ectodysplasin A2 receptor.

Androgenetic alopecia (AGA) is a common genetic disorder, and a X-chromosomal locus that contains the androgen receptor (AR) and ectodysplasin A2 receptor (EDA2R) genes represents a major susceptibility locus for AGA. In our previous study, we reported that ectodysplasin-A2 (EDA-A2) induces apoptosis in cultured human hair follicle (HF) cells and promotes the regression of HFs in mice. However, the role of the EDA-A2/EDA2R in AGA remains unknown, as the causative gene in this pathway has not yet been identified and potential functional connections between EDA-A2 signaling and the androgen pathway remain unclear. In this study, we investigated the expression of EDA2R in balding HFs and matched with non-balding HFs. The EDA2R level was upregulated in the balding dermal papilla (DP) cells compared with non-balding DP cells derived from patients with AGA. However, EDA2R was strongly expressed in both balding and non-balding outer root sheath (ORS) cells. We screened EDA-A2-regulated genes in balding DP cells and identified dickkopf 1 (DKK-1) as catagen inducer during the hair cycle. The mRNA and protein expression levels of DKK-1 were both upregulated by EDA-A2. In addition, DKK-1 expression was induced by EDA-A2 both in cultured human HFs and in mouse HFs. Moreover, the EDA-A2-induced apoptosis of DP and ORS cells was reversed by the antibody-mediated neutralization of DKK-1. Collectively, our data strongly suggest that EDA-A2 induces DKK-1 secretion and causes apoptosis in HFs by binding EDA2R, which is overexpressed in the bald scalp. EDA-A2/EDA2R signaling could inhibit hair growth through DKK-1 induction, and an inhibitor of EDA-A2/EDA2R signaling may be a promising agent for the treatment and prevention of AGA.

Predictive factors for bacteremia in febrile infants with urinary tract infection.

This study aimed to investigate the predictive factors of concomitant bacteremia occurring in febrile infants who initially presented with pyuria and fever, and were subsequently diagnosed with culture-proven urinary tract infection (UTI). We conducted a retrospective cohort study for January 2010-October 2018 that included infants younger than six months with febrile UTI at a tertiary hospital. The study included 463 patients, of whom 34 had a concomitant bacteremic UTI. Compared to those in the non-bacteremic urinary tract infection (UTI) group, the bacteremic UTI group had a lower mean age; higher levels of C-reactive protein (CRP), delta neutrophil index (DNI, reflects the fraction of immature granulocytes) and blood urea nitrogen (BUN); lower levels of hemoglobin (Hb) and albumin; and a lower platelet count. Vesicoureteral reflux (VUR) was detected nearly twice as often in patients with bacteremic UTI compared to those with non-bacteremic UTI (59.3% vs. 30.6%; P = 0.003). Univariate logistic analyses showed that age ≤90 days; higher DNI, CRP, and creatinine levels; lower Hb and albumin levels; and the presence of VUR were predictors for bacteremic UTI. On multivariate logistic regression analysis, age ≤90 days, higher DNI and CRP levels, and the presence of VUR were independent predictors of bacteremic UTI. The area under the receiver operating characteristic curve of the multivariate model was 0.859 (95% CI, 0.779-0.939; P < 0.001). Age ≤90 days, higher DNI and CRP values may help predict bacteremia of febrile infants younger than 6 months with UTI. Vesicoureteral reflux imaging is also recommended in infants with bacteremic UTI to evaluate VUR.

Correction to: Long-term Outcome of Angioplasty Using a Wingspan Stent, Post-Stent Balloon Dilation and Aggressive Restenosis Management for Intracranial Arterial Stenosis.

Correction to: Clin Neuroradiol 2019 https://doi.org/10.1007/s00062-019-00793-1The original version of this article unfortunately contained some mistakes. The Institutional Review Board number was given wrongly in the Methods/Participants section and in the Compliance with ethical guidelines/Ethical.

Prognostic value of the delta neutrophil index in pediatric cardiac arrest.

The delta neutrophil index (DNI), which reflects the ratio of circulating immature neutrophils, has been reported to be highly predictive of mortality in systemic inflammation. We investigated the prognostic significance of DNI value for early mortality and neurologic outcomes after pediatric cardiac arrest (CA). We retrospectively analyzed the data of eligible patients (<19 years in age). Among 85 patients, 55 subjects (64.7%) survived and 36 (42.4%) showed good outcomes at 30 days after CA. Cox regression analysis revealed that the DNI values immediately after the return of spontaneous circulation, at 24 hours and 48 hours after CA, were related to an increased risk for death within 30 days after CA (P < 0.001). A DNI value of higher than 3.3% at 24 hours could significantly predict both 30-day mortality (hazard ratio: 11.8; P < 0.001) and neurologic outcomes (odds ratio: 8.04; P = 0.003). The C statistic for multivariable prediction models for 30-day mortality (incorporating DNI at 24 hours, compression time, and serum sodium level) was 0.799, and the area under the receiver operating characteristic curve of DNI at 24 hours for poor neurologic outcome was 0.871. Higher DNI was independently associated with 30-day mortality and poor neurologic outcomes after pediatric CA.

Particulate Matters Induce Apoptosis in Human Hair Follicular Keratinocytes.

BACKGROUND: Particulate matters (PM) comprise a heterogeneous mixture of particles suspended in air. A recent study found that urban PMs may penetrate into hair follicles via transfollicular and transdermal routes in dorsal skin. OBJECTIVE: To investigate the effects of PM on ex vivo cultured human scalp hair follicles and hair follicular keratinocytes in vitro. METHODS: TUNEL staining was employed to check cells undergoing apoptosis in cultured hair follicles after PM treatment. MTT assay was employed to check cell viability after PM treatment. Quantitative real-time PCR analysis was employed to quantitate the expression of inflammatory genes, matrix metalloproteinases (MMPs), and Duox1. Inflammatory cytokine levels were measured by ELISA after PM treatment. The level of reactive oxygen species (ROS) production was measured using a chemical fluorescent probe by a fluorescence plate reader. RESULTS: Abundant TUNEL-positive cells were observed in the keratinocyte region of hair including the epidermis, sebaceous gland, outer root sheath (ORS), inner root sheath (IRS), and bulb region. The viability of follicular cells, including the ORS, was found to be decreased upon PM exposure. mRNA expression and protein levels of inflammatory response genes and MMPs were upregulated in a dose-dependent manner by PM treatment. ROS levels were also increased by PM. CONCLUSION: These data strongly suggest that penetrated PMs from air pollution may cause apoptotic cell death to follicular keratinocytes by increased production of ROS and inflammatory cytokines, which could impair hair growth.

Long-term Outcome of Angioplasty Using a Wingspan Stent, Post-Stent Balloon Dilation and Aggressive Restenosis Management for Intracranial Arterial Stenosis.

PURPOSE: To investigate the long-term outcome of stent angioplasty for symptomatic severe intracranial artery stenosis. METHOD: In this study 95 consecutive patients with intracranial atherosclerotic stenosis (>70%) underwent stent angioplasty using Wingspan stents. The primary endpoints were stroke or death within 30 days of the procedure and subsequent stroke attributed to the stented vessel. Disabling stroke was defined as stroke with a modified Rankin scale > 3. Secondary endpoints included transient ischemic attacks, contralateral stroke, nonstroke death, and other events. Patients underwent prestent balloon dilation with or without poststent balloon dilation, close restenosis follow-up, and selective retreatment, as required. RESULT: The mean follow-up duration was 34.9 ± 23.3 months. Primary endpoint events occurred in 23% of the patients. The median infarction volume was 2.6 ml, and 11 (68%) of 16 infarctions were <5 ml in volume. Disabling stroke occurred in 3% of patients. The primary endpoint rates were 17.9% within 30 days and 2.1% from 30 days to 1 year. Secondary endpoint events occurred in 27.3% of the patients. Mean stenosis was reduced from 76.8 ± 6.1% to 7.5 ± 13.4%. Of 80 patients who underwent angiographic follow-up, 11 (14%) experienced restenosis (≥50%) and 7 (9%) exhibited restenosis-related symptoms of transient ischemic attack. The rate of symptomatic restenosis was significantly higher in patients who underwent prestent balloon dilation alone than in patients who underwent prestent and poststent balloon dilation (p = 0.016). CONCLUSION: The postprocedural stroke rate was similar to that observed in the SAMMPRIS study. Symptomatic restenosis may be reduced by poststent dilation, close angiographic follow-up, and retreatment.

Mesenteric venous thrombosis as a complication of appendicitis in an adolescent: A case report and literature review.

RATIONALE: Mesenteric venous thrombosis is an uncommon but potentially fatal condition that can cause bowel ischemia. It results from a systemic hypercoagulable state or abdominal infection draining into the portal venous system. Several cases regarding portomesenteric venous thrombosis as a complication of appendicitis were reported in adults, but there are far fewer reports in pediatric patients. The mortality rate of the condition is high if untreated, especially in children, reaching up to 50%. PATIENT CONCERNS: A healthy 15-year-old male with no significant past medical history presented with right lower quadrant pain, lethargy, and fever. The computed tomography scan showed a focal thrombosis at the superior mesenteric vein branch and an inflamed appendix. DIAGNOSES: Mesenteric venous thrombosis complicating acute appendicitis. INTERVENTIONS: Intravenous antibiotics along with anticoagulants and laparoscopic appendectomy OUTCOMES:: After 1 month, a follow-up ultrasonography revealed full resolution of the thrombosis. LESSONS: Appendicitis is one of the most frequently encountered causes of pediatric surgical emergencies; therefore, physicians should be conscious of mesenteric venous thrombosis as a possible complication of acute appendicitis, irrespective of whether patients have thrombophilic conditions or not.