Evaluating Child Passenger Restraint Use Education.

BACKGROUND: Despite recommendations and laws for child restraint use in motor vehicles, evidence of low restraint use remains, and there is a lack of evidence addressing the effectiveness of restraint use education. OBJECTIVE: This project aims to measure the impact of an education initiative on child passenger restraint use. METHODS: This pre- and postintervention study was conducted in six elementary schools in a Southwestern U.S. metropolitan area over 5 months from October 2022 to March 2023. Motor vehicle restraint use was collected from occupants arriving at elementary schools during the morning drop-off times. Participants were provided one-on-one education regarding child passenger safety guidelines and state laws. Comparison data were collected 1-3 weeks later at the same schools to evaluate the education provided. RESULTS: A total of 1,671 occupants in 612 vehicles were observed across six schools, with 343 adults and 553 children preintervention and 306 adults and 469 children postintervention. Overall restraint adherence in children improved postintervention from 42.3% to 56.1%, a 32.6% increase (p = < .001). In the primary age group of 4-8 years, restraint adherence improved postintervention from 34.8% to 54.2%, a 55.8% increase (p = <.001). CONCLUSIONS: The study results demonstrate that one-on-one education increases child passenger restraint use.

Fibrosing Colonopathy Presenting in a Patient with Cystinosis.

Fibrosing colonopathy is a unique pathology characterized by long segment stricture, usually of the ileocecal region. Historically, it is most commonly described in patients with cystic fibrosis (CF). Fibrosing colonopathy is felt to be secondary to excessive doses of exogenous lipase medication. This condition is rarely seen in the last decade. In this case presentation, fibrosing colonopathy was identified in a patient with the lysosomal storage disorder of cystinosis. Fibrosing colonopathy has not previously been described in patients with cystinosis. The patient was found to have fibrosing colonopathy after perforation of the colon during a colonoscopy for bloody diarrhea. This case report aims to draw attention to a noteworthy case of fibrosing colonopathy in a patient who does not have cystic fibrosis, but rather cystinosis.

Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model.

Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury composed of neurons, microglia, and astrocytes and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration. Pharmacological studies presented here suggest that fragmented mitochondria released by microglia are a key contributor to secondary neuronal damage progression after contusion injury, a pathway that requires astrocyte-microglia crosstalk. Controlling mitochondrial dysfunction thus offers an exciting option for developing therapies for TBI patients.

3D biocomposite culture enhances differentiation of dopamine-like neurons from SH-SY5Y cells: A model for studying Parkinson's disease phenotypes.

Studies of underlying neurodegenerative processes in Parkinson's Disease (PD) have traditionally utilized cell cultures grown on two-dimensional (2D) surfaces. Biomimetic three-dimensional (3D) cell culture platforms have been developed to better emulate features of the brain's natural microenvironment. We here use our bioengineered brain-like tissue model, composed of a silk-hydrogel composite, to study the 3D microenvironment's contributions on the development and performance of dopaminergic-like neurons (DLNs). Compared with 2D culture, SH-SY5Y cells differentiated in 3D microenvironments were enriched for DLNs concomitant with a reduction in proliferative capacity during the neurodevelopmental process. Additionally, the 3D DLN cultures were more sensitive to oxidative stresses elicited by the PD-related neurotoxin 1-methyl-4-phenylpyridinium (MPP). MPP induced transcriptomic profile changes specific to 3D-differentiated DLN cultures, replicating the dysfunction of neuronal signaling pathways and mitochondrial dynamics implicated in PD. Overall, this physiologically-relevant 3D platform resembles a useful tool for studying dopamine neuron biology and interrogating molecular mechanisms underlying neurodegeneration in PD.

Bioengineered models of Parkinson's disease using patient-derived dopaminergic neurons exhibit distinct biological profiles in a 3D microenvironment.

Three-dimensional (3D) in vitro culture systems using human induced pluripotent stem cells (hiPSCs) are useful tools to model neurodegenerative disease biology in physiologically relevant microenvironments. Though many successful biomaterials-based 3D model systems have been established for other neurogenerative diseases, such as Alzheimer's disease, relatively few exist for Parkinson's disease (PD) research. We employed tissue engineering approaches to construct a 3D silk scaffold-based platform for the culture of hiPSC-dopaminergic (DA) neurons derived from healthy individuals and PD patients harboring LRRK2 G2019S or GBA N370S mutations. We then compared results from protein, gene expression, and metabolic analyses obtained from two-dimensional (2D) and 3D culture systems. The 3D platform enabled the formation of dense dopamine neuronal network architectures and developed biological profiles both similar and distinct from 2D culture systems in healthy and PD disease lines. PD cultures developed in 3D platforms showed elevated levels of α-synuclein and alterations in purine metabolite profiles. Furthermore, computational network analysis of transcriptomic networks nominated several novel molecular interactions occurring in neurons from patients with mutations in LRRK2 and GBA. We conclude that the brain-like 3D system presented here is a realistic platform to interrogate molecular mechanisms underlying PD biology.

Paying For Value From Costly Medical Technologies: A Framework For Applying Value-Based Payment Reforms.

Innovative medical products offer significant and potentially transformative impacts on health, but they create concerns about rising spending and whether this rise is translating into higher value. The result is increasing pressure to pay for therapies in a way that is tied to their value to stakeholders through improving outcomes, reducing disease complications, and addressing concerns about affordability. Policy responses include the growing application of health technology assessments based on available evidence to determine unit prices, as well as alternatives to volume-based payment that adjust product payments based on predictors or measures of value. Building on existing frameworks for value-based payment for health care providers, we developed an analogous framework for medical products, including drugs, devices, and diagnostic tools. We illustrate each of these types of alternative payment mechanisms and describe the conditions under which each may be useful. We discuss how the use of this framework can help track reforms, improve evidence, and advance policy analysis involving medical product payment.

Are Patients with Perforated Peptic Ulcers Who are Negative for Helicobacter pylori at a Greater Risk?

Background: The link between Helicobacter pylori infection and peptic ulceration is well established. Recent studies have reported a decrease of H. pylori-related peptic ulcer disease; Helicobacter pylori eradication is likely the cause of this decrease. We hypothesized that patients with H. pylori-positive perforated peptic ulcer disease (PPUD) requiring surgical intervention had worse outcomes than patients with H. pylori-negative PPUD. Patients and Methods: A prospectively collected Acute and Critical Care Surgery registry spanning the years 2008 to 2015 was searched for patients with PPUD and tested for H. pylori serum immunoglobulin G (IgG) test. Patients were divided into two cohorts: H. pylori positive (HPP) and H. pylori negative (HPN). Demographics, laboratory values, medication history, social history, and esophagogastroduodenoscopy were collected. Student t-test was used for continuous variables and χ2 test was used for categorical variables. Linear regression was applied as appropriate. Results: We identified 107 patients diagnosed with PPUD, of whom 79 (74%) patients had H. pylori serum IgG testing. Forty-two (53.2%) tested positive and 37 (46.8%) tested negative. Helicobacter pylori-negative PPUD was more frequent in females (70.27%, p = 0.004), whites (83.78%, p = 0.001) and patients with higher body mass index (BMI) 28.81 ± 8.8 (p = 0.033). The HPN group had a lower serum albumin level (2.97 ± 0.96 vs. 3.86 ± 0.91 p = 0.0001), higher American Society of Anesthesiologists (ASA; 3.11 ± 0.85 vs. 2.60 ± 0.73; p = 0.005), and Charlson comorbidity index (4.81 ± 2.74 vs. 2.98 ± 2.71; p = 0.004). On unadjusted analysis the HPN cohort had a longer hospital length of stay (LOS; 20.20 ± 13.82 vs. 8.48 ± 7.24; p = 0.0001), intensive care unit (ICU) LOS (10.97 ± 11.60 vs. 1.95 ± 4.59; p = 0.0001), increased ventilator days (4.54 ± 6.74 vs. 0.98 ± 2.85; p = 0.004), and higher rates of 30-day re-admission (11; 29.73% vs. 5; 11.91%; p = 0.049). Regression models showed that HPN PPUD patients had longer hospital and ICU LOS by 11 days (p = 0.002) and 8 days (p = 0.002), respectively, compared with HPP PPUD. Conclusion: In contrast to our hypothesis, HPN patients had clinically worse outcomes than HPP patients. These findings may represent a difference in the baseline pathophysiology of the peptic ulcer disease process. Further investigation is warranted.

Nonoperative management of giant omphalocele leading to early fascial closure.

PURPOSE: We describe our series of giant omphalocele patients treated with a serial taping method for gradual reduction of the abdominal contents and early fascial closure. METHODS: Between 2010 and 2017 we cared for ten newborns with giant omphaloceles. The average gestational age was 35.5 weeks (range 29-38) and average birthweight was 2.84 kg. Seven infants had other major anomalies, including one with a variant of Pentology of Cantrell. Four had abnormal chromosomes. None had any attempt to primarily close the defect. Omphalocele defects were serially taped at bedside in the NICU with the child awake until the viscera were completely reduced, and the defect could be closed. RESULTS: Mean time to closure was 13.7 days (median 14 days). Six were closed primarily without a patch. The remaining four infants required Gore-Tex patch (covered by skin) which was later removed and fascia closed in three infants (at 70 days, 75 days, and 11 months of age). Total length of stay was a mean 71.8 days (median 71). CONCLUSIONS: Serial taping achieves early fascial closure and avoids complications of a staged surgical approach, such as multiple anesthetics, loss of fascial margin integrity, silo dehiscence, and fistula formation. Compression of the viscera is slow enough to avoid abdominal compartment syndrome and the fascia and amnion are left intact leaving the option available to use escharotic agents if required. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Pre-Operative Anti-Fungal Therapy Does Not Improve Outcomes in Perforated Peptic Ulcers.

BACKGROUND: With the advent of anti-Helicobacter pylori therapy, hospital admissions for peptic ulcer disease (PUD) have declined significantly since the 1990s. Despite this, operative treatment of PUD still is common. Although previous papers suggest that Candida in peritoneal fluid cultures may be associated with worse outcomes in patients with perforated peptic ulcers (PPUs), post-operative anti-fungal therapy has not been effective. We hypothesized that pre-operative anti-fungal drugs improve outcomes in patients with PPUs undergoing operative management. PATIENTS AND METHODS: A prospectively maintained Acute and Critical Care Surgery (ACCS) database spanning 2008-2015 and including more than 7,000 patients was queried for patients with PPUs. Demographics and clinical outcomes were abstracted. Pre-operative anti-fungal use, intra-operative peritoneal fluid cultures, and infectious outcomes were abstracted manually. We compared outcomes and the presence of fungal infections in patients receiving peri-operative anti-fungal drugs in the entire cohort and in patients with intra-operative peritoneal fluid cultures. Frequencies were compared by the Fisher exact or χ2 test as appropriate. The Student's t-test was used for continuous variables. RESULTS: There were 107 patients with PPUs who received operative management; 27 (25.2%) received pre-operative anti-fungal therapy; 33 (30.8%) received peritoneal fluid culture, and 17 cultures (51.5%) were positive for fungus. The presence of fungus in the cultures did not affect the outcomes. There were no differences in length of stay (LOS), intensive care unit (ICU) LOS, ventilator days, 30-day re-admission rates, or rates of intra-abdominal abscess formation or fungemia in patients who received pre-operative anti-fungal drugs regardless of the presence of fungi in the peritoneal fluid. CONCLUSION: Candida has been recovered in 29%-57% of peritoneal fluid cultures in patients with PPUs. However, no studies have evaluated pre-operative anti-fungal therapy in PPUs. Our data suggest that pre-operative anti-fungal drugs are unnecessary in patients undergoing operative management for PPU.

Fungal Infections Increase the Mortality Rate Three-Fold in Necrotizing Soft-Tissue Infections.

BACKGROUND: Necrotizing soft-tissue infections (NSTIs) result in significant morbidity and mortality rates, with as many as 76% of patients dying during their index admission. Published data suggest NSTIs rarely involve fungal infections in immunocompetent patients. However, because of the recent recognition of fungal infections in our population, we hypothesized that such infections frequently complicate NSTIs and are associated with higher morbidity and mortality rates. METHODS: A prospectively maintained Acute and Critical Care Surgery (ACCS) database spanning 2008-2015 and including more than 7,000 patients was queried for patients with NSTIs. Microbiologic data, demographics, and clinical outcomes were abstracted. Risk factors and outcomes associated with NSTI with positive intra-operative fungal cultures were determined. Frequencies were compared by χ2 and continuous variables by the Student t-test using SPSS. Because the study included only archived data, no patient permission was needed. RESULTS: A total of 230 patients were found to have NSTIs; 197 had intra-operative cultures, and 21 (10.7%) of these were positive for fungi. Fungal infection was more common in women, patients with higher body mass index (BMI), and patients who had had prior abdominal procedures. There were no significant differences in demographics, co-morbidities, or site of infection. The majority of patients (85.7%) had mixed bacterial and fungal infections; in the remaining patients, fungi were the only species isolated. Most fungal cultures were collected within 48 h of hospital admission, suggesting that the infections were not hospital acquired. Patients with positive fungal cultures required two more surgical interventions and had a three-fold greater mortality rate than patients without fungal infections. CONCLUSIONS: This is the largest series to date describing the impact of fungal infection in NSTIs. Our data demonstrate a three-fold increase in the mortality rate and the need for two additional operations. Consideration should be given to starting patients on empiric anti-fungal therapy in certain circumstances.

[The effects of interleukin-11 and epidermal growth factor on residual small intestine after experimental extensive small bowel resection]. / Az interleukin-11 és az epidermális növekedési faktor trophicus hatásának vizsgálata kisérletes kiterjesztett vékonybél-reszekció után.

BACKGROUND/PURPOSE: Interleukin 11 (IL-11) is a multifunctional cytokine derived from bone marrow, which has a trophic effect on small bowel epithelium. This study compares the effects of IL-11 with epidermal growth factor (EGF), a growth factor known to enhance small bowel adaptation. METHODS: Forty Sprague-Dawley rats (90-100 g) underwent an 85% mid-small bowel resection with primary anastomosis on day 0. Rats were divided into four treatment groups: controls (group I) received bovine serum albumin (BSA), group II received IL-11, 125 mg/kg subcutaneously (SC) twice daily, group III received EGF, 0.10 mg/g SC bid, and group IV received EGF and IL-11 in the above doses. Half of the animals (five per group) were killed on day 4 of therapy, and the rest on day 8. Animals were evaluated for weight, mucosal length, and bowel wall muscle thickness on days 4 and 8, and expression of proliferating cell nuclear antigen (PCNA) in intestinal crypt and smooth muscle cells on day 8. RESULTS: Body weight was similar at day 4 and 8. Mucosal thickness in groups II (IL-11) and IV (IL-11 and EGF) was significantly increased at days 4 and 8 compared with controls (group I) and EGF (group III, P < 0.001). Muscle thickness was significantly increased in the EGF and combined group IV compared with the BSA controls and IL-11 groups (P < 0.001). Thirty-two percent of the mucosal crypt cells in group I stained positive for PCNA, whereas 51%, 53%, and 60% stained positive in groups II (IL-11), III (EGF), and IV (IL-11 and EGF), respectively. In groups I and II, 2% and 1.7% of the myocytes stained positive for PCNA, whereas 11.2% and 5.2% in group III and IV. CONCLUSIONS: These data suggest that IL-11 has a trophic effect on small intestinal enterocytes, causing cell proliferation and increased mucosal thickness. EGF has a more generalized effect causing proliferation of both enterocytes and myocytes. IL-11, with or without EGF may be a useful adjunct in treatment of short bowel syndrome.

[Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN)]. / A pancreas intraepithelialis neoplasiája (PanIN) és intraductalis papillaris mucinosus neoplasiái (IPMN).

Pancreatic Intraepithelial Neoplasia (PanIN1-3) and Intraductal Papillary Mucinous Neoplasms (IPMNs) putative precursors of and associated to pancreatic cancer represent a distinct, however pathologically heterogenous entity. Recently a new classification and nomenclature was established. We analysed the clinicopathologic and cytogenetic characteristics of six patients with PanIN and two with IPMN undergoing curative surgical resection. The most valuable tool in the diagnosis of these preinvasive neoplasms is ERCP combined with brush cytology. Conventional laboratory blood tests, tumor markers (CEA, CA19-9) were within normal values and imaging modalities were informative in only one third of the cases, however, not pathognostic. Based on our hypothesis that tumor ploidy pattern correlates with biological behaviour, malignant potential and prognosis, we measured the nuclear DNA content, ploidy, synthetic (S) phase or proliferative fractions of each neoplasm by flow cytometry. Each neoplasm demonstrated diploid stemline, with a low mean S-phase or proliferative fraction (3,77%) and mean DNA index (DI) of 0.96. The diploid DNA pattern and the low proliferative activity are consistent with the nonaggressive biological behavior of intraepithelial and intraductal neoplasms and, in part, explain their favorable prognosis.

Splenic injury presenting with isolated scrotal findings in a stable newborn.

Splenic injury in a newborn is a rare occurrence. It typically presents as an acute abdomen in an unstable patient. The authors present a case of splenic injury in a stable newborn infant with isolated scrotal findings. Workup included a testicular ultrasound scan with colorflow Doppler as well as abdominal and pelvic computerized tomography. The patient was treated nonoperatively with serial hematocrits and examinations and was discharged home after a brief hospital course.