Grainyhead-like 2, encoded by GRHL2, is a member of a highly conserved family of transcription factors that play essential roles during epithelial development. Haploinsufficiency for GRHL2 has been ...implicated in autosomal-dominant deafness, but mutations have not yet been associated with any skin pathology. We investigated two unrelated Kuwaiti families in which a total of six individuals have had lifelong ectodermal defects. The clinical features comprised nail dystrophy or nail loss, marginal palmoplantar keratoderma, hypodontia, enamel hypoplasia, oral hyperpigmentation, and dysphagia. In addition, three individuals had sensorineural deafness, and three had bronchial asthma. Taken together, the features were consistent with an unusual autosomal-recessive ectodermal dysplasia syndrome. Because of consanguinity in both families, we used whole-exome sequencing to search for novel homozygous DNA variants and found GRHL2 mutations common to both families: affected subjects in one family were homozygous for c.1192T>C (p.Tyr398His) in exon 9, and subjects in the other family were homozygous for c.1445T>A (p.Ile482Lys) in exon 11. Immortalized keratinocytes (p.Ile482Lys) showed altered cell morphology, impaired tight junctions, adhesion defects, and cytoplasmic translocation of GRHL2. Whole-skin transcriptomic analysis (p.Ile482Lys) disclosed changes in genes implicated in networks of cell-cell and cell-matrix adhesion. Our clinical findings of an autosomal-recessive ectodermal dysplasia syndrome provide insight into the role of GRHL2 in skin development, homeostasis, and human disease.
Objective
Post‐traumatic growth typically refers to enduring positive psychological change experienced as a result of adversity, trauma, or highly challenging life circumstances. Critics have ...challenged insights from much of the prior research on this topic, pinpointing its significant methodological limitations. In response to these critiques, we propose that post‐traumatic growth can be more accurately captured in terms of personality change—an approach that affords a more rigorous examination of the phenomenon.
Method
We outline a set of conceptual and methodological questions and considerations for future work on the topic of post‐traumatic growth.
Results
We provide a series of recommendations for researchers from across the disciplines of clinical/counseling, developmental, health, personality, and social psychology and beyond, who are interested in improving the quality of research examining resilience and growth in the context of adversity.
Conclusion
We are hopeful that these recommendations will pave the way for a more accurate understanding of the ubiquity, durability, and causal processes underlying post‐traumatic growth.
Epidermal growth factor receptor (EGFR) signaling is fundamentally important for tissue homeostasis through EGFR/ligand interactions that stimulate numerous signal transduction pathways. Aberrant ...EGFR signaling has been reported in inflammatory and malignant diseases, but thus far no primary inherited defects in EGFR have been recorded. Using whole-exome sequencing, we identified a homozygous loss-of-function missense mutation in EGFR (c.1283G>A; p.Gly428Asp) in a male infant with lifelong inflammation affecting the skin, bowel, and lungs. During the first year of life, his skin showed erosions, dry scale, and alopecia. Subsequently, there were numerous papules and pustules—similar to the rash seen in patients receiving EGFR inhibitor drugs. Skin biopsy demonstrated an altered cellular distribution of EGFR in the epidermis with reduced cell membrane labeling, and in vitro analysis of the mutant receptor revealed abrogated EGFR phosphorylation and EGF-stimulated downstream signaling. Microarray analysis on the patient’s skin highlighted disturbed differentiation/premature terminal differentiation of keratinocytes and upregulation of several inflammatory/innate immune response networks. The boy died at the age of 2.5 years from extensive skin and chest infections as well as electrolyte imbalance. This case highlights the major mechanism of epithelial dysfunction following EGFR signaling ablation and illustrates the broader impact of EGFR inhibition on other tissues.
We described care received by hospitalized children with COVID-19 or multi-system inflammatory syndrome (MIS-C) prior to the 2021 COVID-19 Omicron variant surge in the US. We identified hospitalized ...children <18 years of age with a COVID-19 or MIS-C diagnosis (COVID-19 not required), separately, from February 2020-September 2021 (n = 126 hospitals). We described high-risk conditions, inpatient treatments, and complications among these groups. Among 383,083 pediatric hospitalizations, 2,186 had COVID-19 and 395 had MIS-C diagnosis. Less than 1% had both COVID-19 and MIS-C diagnosis (n = 154). Over half were >6 years old (54% COVID-19, 70% MIS-C). High-risk conditions included asthma (14% COVID-19, 11% MIS-C), and obesity (9% COVID-19, 10% MIS-C). Pulmonary complications in children with COVID-19 included viral pneumonia (24%) and acute respiratory failure (11%). In reference to children with COVID-19, those with MIS-C had more hematological disorders (62% vs 34%), sepsis (16% vs 6%), pericarditis (13% vs 2%), myocarditis (8% vs 1%). Few were ventilated or died, but some required oxygen support (38% COVID-19, 45% MIS-C) or intensive care (42% COVID-19, 69% MIS-C). Treatments included: methylprednisolone (34% COVID-19, 75% MIS-C), dexamethasone (25% COVID-19, 15% MIS-C), remdesivir (13% COVID-19, 5% MIS-C). Antibiotics (50% COVID-19, 68% MIS-C) and low-molecular weight heparin (17% COVID-19, 34% MIS-C) were frequently administered. Markers of illness severity among hospitalized children with COVID-19 prior to the 2021 Omicron surge are consistent with previous studies. We report important trends on treatments in hospitalized children with COVID-19 to improve the understanding of real-world treatment patterns in this population.
To determine risk factors for mortality among COVID-19 patients admitted to a system of community hospitals in the United States.
Retrospective analysis of patient data collected from the routine ...care of COVID-19 patients.
System of >180 acute-care facilities in the United States.
All admitted patients with positive identification of COVID-19 and a documented discharge as of May 12, 2020.
Determination of demographic characteristics, vital signs at admission, patient comorbidities and recorded discharge disposition in this population to construct a logistic regression estimating the odds of mortality, particular for those patients characterized as not being critically ill at admission.
In total, 6,180 COVID-19+ patients were identified as of May 12, 2020. Most COVID-19+ patients (4,808, 77.8%) were admitted directly to a medical-surgical unit with no documented critical care or mechanical ventilation within 8 hours of admission. After adjusting for demographic characteristics, comorbidities, and vital signs at admission in this subgroup, the largest driver of the odds of mortality was patient age (OR, 1.07; 95% CI, 1.06-1.08; P < .001). Decreased oxygen saturation at admission was associated with increased odds of mortality (OR, 1.09; 95% CI, 1.06-1.12; P < .001) as was diabetes (OR, 1.57; 95% CI, 1.21-2.03; P < .001).
The identification of factors observable at admission that are associated with mortality in COVID-19 patients who are initially admitted to non-critical care units may help care providers, hospital epidemiologists, and hospital safety experts better plan for the care of these patients.
Aim
Diabetes has been identified as a risk factor for poor outcomes in patients with COVID‐19. We examined the association of hyperglycaemia, both in the presence and absence of pre‐existing ...diabetes, with severity and outcomes in COVID‐19 patients.
Methods
Data from 74,148 COVID‐19‐positive inpatients with at least one recorded glucose measurement during their inpatient episode were analysed for presence of pre‐existing diabetes diagnosis and any glucose values in the hyperglycaemic range (>180 mg/dl).
Results
Among patients with and without a pre‐existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70–180 mg/dl) in both groups (non‐diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). When adjusting for patient age, BMI, severity on admission and oxygen saturation on admission, this increased risk of mortality persisted and varied by diabetes diagnosis. Among patients with a pre‐existing diabetes diagnosis, any hyperglycaemic value during the episode was associated with a substantial increase in the odds of mortality (OR: 1.77, 95% CI: 1.52–2.07); among patients without a pre‐existing diabetes diagnosis, this risk nearly doubled (OR: 3.07, 95% CI: 2.79–3.37).
Conclusion
This retrospective analysis identified hyperglycaemia in COVID‐19 patients as an independent risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. This indicates that the extent of glucose control could serve as a mechanism for modifying the risk of COVID‐19 morality in the inpatient environment.
This retrospective analysis identified hyperglycaemia in COVID‐19 patients as a risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. Among nearly 75,000 COVID‐19 patients with and without a pre‐existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70–180 mg/dl) in both groups (non‐diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). This indicates that effective glucose control could serve as a mechanism for modifying the risk of COVID‐19 morality.
Coronavirus disease 2019 (COVID-19) has migrated to regions that were initially spared, and it is likely that different populations are currently at risk for illness. Herein, we present our ...observations of the change in characteristics and resource use of COVID-19 patients over time in a national system of community hospitals to help inform those managing surge planning, operational management, and future policy decisions.
Young children have an impressive amount of mathematics knowledge, but past psychological research has focused primarily on their number knowledge. Preschoolers also spontaneously engage in a form of ...early algebraic thinking-patterning. In the current study, we assessed 4-year-old children's knowledge of repeating patterns on two occasions (N = 66). Children could duplicate and extend patterns, and some showed a deeper understanding of patterns by abstracting patterns (i.e., creating the same kind of pattern using new materials). A small proportion of the children had explicit knowledge of pattern units. Error analyses indicated that some pattern knowledge was apparent before children were successful on items. Overall, findings indicate that young children are developing an understanding of repeating patterns before school entry.
•Unique expressions of adversarial growth were identified in individuals’ narratives of challenging life experiences.•Adversarial growth coded from narratives correlated positively with widely used ...questionnaires of adversarial growth.•Narrative growth did not predict incremental validity in well-being outcomes compared to standard questionnaires.
After adversity, individuals sometimes report adversarial growth - positive changes in their identity, relationships, and worldviews. We examined how narrative methods enhanced understanding of adversarial growth compared to standard questionnaires. Participants (N = 411) from college and community samples reported on their well-being, wrote a narrative about a highly challenging experience, and answered questionnaires on adversarial growth. Results showed that adversarial growth coded in narratives was positively associated with widely used self-report questionnaires of adversarial growth. Unexpectedly, narrative growth did not predict incremental validity in well-being outcomes compared to standard questionnaires. We found unique expressions of adversarial growth in a qualitative analysis of the narratives. We discuss the added value of using narratives for the assessment of adversarial growth.
Non-ventilator-associated hospital-acquired pneumonia (NV-HAP) is a common and deadly hospital-acquired infection. However, inconsistent surveillance methods and unclear estimates of attributable ...mortality challenge prevention.
To estimate the incidence, variability, outcomes, and population attributable mortality of NV-HAP.
This cohort study retrospectively applied clinical surveillance criteria for NV-HAP to electronic health record data from 284 US hospitals. Adult patients admitted to the Veterans Health Administration hospital from 2015 to 2020 and HCA Healthcare hospitals from 2018 to 2020 were included. The medical records of 250 patients who met the surveillance criteria were reviewed for accuracy.
NV-HAP, defined as sustained deterioration in oxygenation for 2 or more days in a patient who was not ventilated concurrent with abnormal temperature or white blood cell count, performance of chest imaging, and 3 or more days of new antibiotics.
NV-HAP incidence, length-of-stay, and crude inpatient mortality. Attributable inpatient mortality by 60 days follow-up was estimated using inverse probability weighting, accounting for both baseline and time-varying confounding.
Among 6 022 185 hospitalizations (median IQR age, 66 54-75 years; 1 829 475 26.1% female), there were 32 797 NV-HAP events (0.55 per 100 admissions 95% CI, 0.54-0.55 per 100 admissions and 0.96 per 1000 patient-days 95% CI, 0.95-0.97 per 1000 patient-days). Patients with NV-HAP had multiple comorbidities (median IQR, 6 4-7), including congestive heart failure (9680 29.5%), neurologic conditions (8255 25.2%), chronic lung disease (6439 19.6%), and cancer (5,467 16.7%); 24 568 cases (74.9%) occurred outside intensive care units. Crude inpatient mortality was 22.4% (7361 of 32 797) for NV-HAP vs 1.9% (115 530 of 6 022 185) for all hospitalizations; 12 449 (8.0%) were discharged to hospice. Median IQR length-of-stay was 16 (11-26) days vs 4 (3-6) days. On medical record review, pneumonia was confirmed by reviewers or bedside clinicians in 202 of 250 patients (81%). It was estimated that NV-HAP accounted for 7.3% (95% CI, 7.1%-7.5%) of all hospital deaths (total hospital population inpatient death risk of 1.87% with NV-HAP events included vs 1.73% with NV-HAP events excluded; risk ratio, 0.927; 95% CI, 0.925-0.929).
In this cohort study, NV-HAP, which was defined using electronic surveillance criteria, was present in approximately 1 in 200 hospitalizations, of whom 1 in 5 died in the hospital. NV-HAP may account for up to 7% of all hospital deaths. These findings underscore the need to systematically monitor NV-HAP, define best practices for prevention, and track their impact.
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