Assessing Loss to Follow-up After Newborn Hearing Screening in the Neonatal Intensive Care Unit: Sociodemographic Factors That Affect Completion of Initial Audiological Evaluation.

OBJECTIVES: Neonatal intensive care unit (NICU) patients are at high risk for congenital hearing loss. Previous studies have found sociodemographic factors associated with loss to follow-up for newborn hearing screening, but none have specifically studied the NICU population. Our objective is to determine if demographics and socioeconomic status is associated with loss to follow-up in a newborn population with extended NICU stay. DESIGN: A retrospective cohort study was conducted on 443 NICU infants with extended NICU stay utilizing data extracted from infant and maternal medical records at an urban safety-net hospital. RESULTS: Younger maternal age (adjusted odds ratio [OR] 0.95, confidence interval [CI] 0.91 to 0.99), higher gravidity (adjusted OR 1.39, CI 1.12 to 1.72), and former smoking status (adjusted OR 2.57, CI 1.07-6.18) were identified as independent predictors of loss to follow-up for NHS after conducting a multivariable logistic regression. Demographic and socioeconomic variables, such as sex, parity, birth weight, mode of birth, highest level of maternal education, maternal race/ethnicity, zip code metrics, and maternal language were not found to be associated with loss to follow-up. CONCLUSIONS: Maternal age, gravidity, and smoking status are risk factors for loss to follow-up for NHS in newborns with extended NICU stay, a group at high risk for hearing loss. Our findings demonstrate that socioeconomic and demographic factors for loss to follow-up in the extended-stay NICU population are distinct from the well-baby population. Further investigation of these patients will allow prioritization of limited resources to subgroups within the extended-stay NICU population at risk for loss to follow-up for newborn hearing screening.

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration.

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations. In parallel, we describe a large population of stem-like alveolar tuft cells that express the endodermal stem cell markers Sox9 and Lgr5 and a receptor profile making them uniquely sensitive to cues produced by pleural Mesothelium. We hypothesized that crosstalk from mesothelial cells to alveolar tuft cells might be central to the regulation of post-penumonectomy lung regeneration. Following pneumonectomy, we find that mesothelial cells display radically altered phenotype and ligand expression, in a pattern that closely tracks with parenchymal epithelial proliferation and alveolar tissue growth. During an initial pro-inflammatory stage of tissue regeneration, Mesothelium promotes epithelial proliferation via WNT ligand secretion, orchestrates an increase in microvascular permeability, and encourages immune extravasation via chemokine secretion. This stage is followed first by a tissue remodeling period, characterized by angiogenesis and BMP pathway sensitization, and then a stable return to homeostasis. Coupled with key changes in parenchymal structure and matrix production, the cumulative effect is a now larger organ including newly-grown, fully-functional tissue parenchyma. This study paints Mesothelial cells as a key orchestrating cell type that defines the boundary of the lung and exerts critical influence over the tissue-level signaling state regulating resident stem cell populations. The cellular circuits unearthed here suggest that human lung regeneration might be inducible through well-engineered approaches targeting the induction of tissue regeneration and safe return to homeostasis.

Case report of congenital intestinal malrotation in an adult discovered three months status-post appendectomy.

INTRODUCTION AND IMPORTANCE: Intestinal malrotation is a congenital anomaly primarily diagnosed in children, with limited cases reported in adults. Prompt recognition is necessary to prevent life-threatening complications including bowel ischemia and death. We present a rare case of adult intestinal malrotation highlighting difficulty in diagnosis and surgical management. CASE PRESENTATION: A 37-year-old Caucasian woman presented with a 3-day history of worsening diffuse abdominal pain, three months status-post laparoscopic appendectomy. CT scan with contrast of the abdomen and pelvis demonstrated small bowel mesenteric swirling and descending duodenal transition point. Differential diagnosis included intestinal malrotation versus small bowel obstruction. Pre-operatively, the patient expressed frustration with years of abdominal pain and lack of improvement. Treatment with open surgical small bowel detorsion and ligation of the Ladd's bands was performed, after initial laparoscopic intervention was complicated by enterotomy. The patient recovered well post-operatively with final diagnosis of intestinal malrotation with midgut volvulus. Discharge home was delayed due to polysubstance withdrawal. Post-operatively, the patient reported immediate relief of symptoms which persisted at 2-week and 2-month follow-ups. CLINICAL DISCUSSION: Few reports of congenital malrotation diagnosed in adulthood are reported. This highlights the importance of evaluating all patients for malrotation when the appendix is found outside of the normal positioning in the RLQ, as surgical correction of malrotation is of utmost importance in such patients. CONCLUSION: Clinicians should consider intestinal malrotation in adults with recurrent vague abdominal symptoms. To our knowledge, this is the first report of congenital malrotation discovered in an adult after prior appendectomy.

Long-term social dysfunction after trauma: What is the prevalence, risk factors, and associated outcomes?

BACKGROUND: Social functioning-the ability to participate in organized or informal family, friend, or peer groups and communal activities-is intertwined with physical and emotional health. Although trauma can have a lasting effect on both the physical and emotional well-being of patients, little is known about the long-term impact of injury on social functioning. We sought to determine the prevalence of, risk factors for, and outcomes associated with long-term social dysfunction after trauma. METHODS: Adults with moderate-to-severe injuries managed at three Level I trauma centers were contacted at 6 to 12 months after injury to inquire about social dysfunction. Demographics, socioeconomic parameters, and injury-related and hospital course information were also obtained. A stepwise backward logistic regression model was fitted to determine independent risk factors of social dysfunction, and multiple logistic regression models were used to determine associations between social dysfunction and post-traumatic stress disorder, functional limitations, and return to work. RESULTS: Of the 805 screened patients, 45.2% reported social dysfunction. Patients with social dysfunction were more likely to be African American, be Medicaid beneficiaries, be of lower education, require mechanical ventilation, be discharged less often to home, have a lower mean age and had longer hospital stays. In multivariable analysis, low education, longer hospital stay, past psychiatric illness, and African-American race independently increased the risk for social dysfunction. Furthermore, patients with social dysfunction were more likely to screen positive for post-traumatic stress disorder (odds ratio: 16.25 [95% confidence interval: 9.49-27.85]), be experiencing functional limitations (odds ratio: 2.80 [95% confidence interval: 1.76-4.44]), and to not have returned to work (odds ratio: 5.65 [95% confidence interval: 3.92-8.14]). CONCLUSION: Lower educational attainment, long hospital stay, past pyschiatric illness, and African-American race appear to predispose to social dysfunction after trauma, which in turn is associated with a positive post-traumatic stress disorder screen, functional limitations, and delayed return to work.

Lower education and income predict worse long-term outcomes after injury.

BACKGROUND: Lower socioeconomic status (SES) is known to be associated with higher morbidity and mortality following injury. However, the impact of individual SES on long-term outcomes after trauma is unknown. The objective of this study was to determine the impact of educational level and income on long-term outcomes after injury. METHODS: Trauma patients with moderate to severe injuries admitted to three Level-I trauma centers were contacted 6 months to 12 months after injury to evaluate functional status, return to work/school, chronic pain, and posttraumatic stress disorder (PTSD). Lower SES status was determined by educational level and income. Adjusted logistic regression models were built to determine the association between educational level and income (lowest vs. highest quartile determined by census-tract area) on each of the long-term outcomes. A sensitivity analysis was performed using the national median household income ($57,617) as threshold for defining low versus high income. RESULTS: A total of 1,516 patients were followed during a 36-month period. Forty-nine percent had a low educational level, and 26% were categorized in the low-income group. Mean (SD) age and injury severity score were 60 (21.5) and 14.3 (7.3), respectively, with most patients (94%) having blunt injuries. After adjusting for confounders, low educational level was associated with poor long-term outcomes: functional limitation [odds ratio (OR), 1.78 (95% confidence interval (CI), 1.41-2.26)], has not yet returned to work/school [OR, 2.48 (95% CI, 1.70-3.62)], chronic pain [OR, 1.63 (95% CI, 1.27-2.10)], and PTSD [OR, 2.23 (95% CI, 1.60-3.11)]. Similarly, low-income level was associated with not yet return to work/school [OR, 1.97 (95% CI, 1.09-3.56)], chronic pain [OR,1.70 (95% CI, 1.14-2.53)], and PTSD [OR, 2.20 (95% CI, 1.21-3.98)]. In sensitivity analyses, there were no significant differences in long-term outcomes between income levels. CONCLUSION: Low educational level is strongly associated with worse long-term outcomes after injury. However, although household income is associated with long-term outcomes, it matters where the threshold is. The impact of different socioeconomic measures on long-term outcomes after trauma cannot be assumed to be interchangeable. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

The Drosophila Werner exonuclease participates in an exonuclease-independent response to replication stress.

Members of the RecQ family of helicases are known for their roles in DNA repair, replication, and recombination. Mutations in the human RecQ helicases, WRN and BLM, cause Werner and Bloom syndromes, which are diseases characterized by genome instability and an increased risk of cancer. While WRN contains both a helicase and an exonuclease domain, the Drosophila melanogaster homolog, WRNexo, contains only the exonuclease domain. Therefore the Drosophila model system provides a unique opportunity to study the exonuclease functions of WRN separate from the helicase. We created a null allele of WRNexo via imprecise P-element excision. The null WRNexo mutants are not sensitive to double-strand break-inducing reagents, suggesting that the exonuclease does not play a key role in homologous recombination-mediated repair of DSBs. However, WRNexo mutant embryos have a reduced hatching frequency and larvae are sensitive to the replication fork-stalling reagent, hydroxyurea (HU), suggesting that WRNexo is important in responding to replication stress. The role of WRNexo in the HU-induced stress response is independent of Rad51. Interestingly, the hatching defect and HU sensitivity of WRNexo mutants do not occur in flies containing an exonuclease-dead copy of WRNexo, suggesting that the role of WRNexo in replication is independent of exonuclease activity. Additionally, WRNexo and Blm mutants exhibit similar sensitivity to HU and synthetic lethality in combination with mutations in structure-selective endonucleases. We propose that WRNexo and BLM interact to promote fork reversal following replication fork stalling and in their absence regressed forks are restarted through a Rad51-mediated process.