Power Has Pitfalls: (In)accuracy of Administrative Data for Nonoperative Management of Appendicitis.

INTRODUCTION: Nonoperative management (NOM) of uncomplicated appendicitis is increasingly common. Effectiveness of NOM has been studied by identifying patients via International Classification of Diseases (ICD) 9/ICD-10 codes for uncomplicated appendicitis and no code for appendectomy. We sought to assess the accuracy of such administrative definitions. METHODS: We retrospectively identified patients with ICD-9/ICD-10 codes for appendicitis at five sites across the United States. Initial management plan and clinical severity were recorded by trained abstractors. We identified a gold standard cohort of patients with surgeon-diagnosed uncomplicated appendicitis and planned NOM. We defined two administrative cohorts with ICD-9/ICD-10 codes for uncomplicated appendicitis and either no surgery during initial admission (definition #1) or no surgery on day 0-1 of admission (definition #2). We compared each definition to the gold standard. RESULTS: Among 1224 patients with uncomplicated appendicitis, 72 (5.9%) underwent planned NOM. NOM patients were older (median [Q1-Q3] of 37 [27-56] versus 32 [25-44] y) and less frequently male (51.4% versus 54.9%), White (54.1% versus 67.6%), and privately insured (38.9% versus 50.2%) than patients managed operatively. Definition #1 had sensitivity of 0.81 and positive predictive value of 0.87 for NOM of uncomplicated appendicitis. Definition #2 had sensitivity of 0.83 and positive predictive value of 0.72. The gold standard cohort had a true failure/recurrence rate of 23.6%, compared with apparent rates of 25.4% and 39.8%, respectively. CONCLUSIONS: Administrative definitions are prone to misclassification in identifying planned NOM of uncomplicated appendicitis. This likely impacts outcomes in studies using administrative databases. Investigators should disclose how misclassification may affect results and select an administrative definition that optimally balances sensitivity and specificity for their research question.

Development and Feasibility Testing of a Decision Aid for Acute Appendicitis.

INTRODUCTION: Patients with acute uncomplicated appendicitis will be increasingly asked to choose between surgery and antibiotic management. We developed a novel decision aid for patients in the emergency department (ED) with acute appendicitis who are facing this choice. We describe the development of the decision aid and an initial feasibility study of its implementation in a busy tertiary care ED. MATERIALS AND METHODS: We conducted a prepost survey analysis comparing patients before and after standardized implementation of the decision aid. Patients were surveyed about their experience making treatment decisions after discharge from the hospital. The primary outcome measure was the total score on the decisional conflict scale (; 0-100; lower scores better). RESULTS: The study included 24 participants (12 in the predecision aid period; 12 in the post period). Only 33% of participants in each group knew antibiotics were a treatment option prior to arriving at the ED. Prior to implementing the use of decision aid, only 75% of patients reported being told antibiotics were a treatment option, while this increased to 100% after implementation of the decision aid. The mean total decisional conflict scalescores were similar in the pre and post periods (mean difference = 0.13, 95% CI: -13 - 13, P > 0.9). CONCLUSIONS: This novel appendicitis decision aid was effectively integrated into clinical practice and helped toinform patients about multiple treatment options. These data support further large-scale testing of the decision aid as part of standardized pathways for the management of patients with acute appendicitis.

The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis.

The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/ß-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further supports the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis.

Outpatient and Ambulatory Extended Recovery Robotic Hepatectomy: Multinational Study of 307 Cases.

BACKGROUND: For open minor hepatectomy, morbidity and recovery are dominated by the incision. The robotic approach may transform this "incision dominant procedure" into a safe outpatient procedure. STUDY DESIGN: We audited outpatient (less than 2 midnights) robotic hepatectomy at 6 hepatobiliary centers in 2 nations to test the hypothesis that the robotic approach can be a safe and effective short-stay procedure. Establishing early recovery after surgery programs were active at all sites, and home digital monitoring was available at 1 of the institutions. RESULTS: A total of 307 outpatient (26 same-day and 281 next-day discharge) robotic hepatectomies were identified (2013 to 2023). Most were minor hepatectomies (194 single segments, 90 bi-segmentectomies, 14 three segments, and 8 four segments). Thirty-nine (13%) were for benign histology, whereas 268 were for cancer (33 hepatocellular carcinoma, 27 biliary, and 208 metastatic disease). Patient characteristics were a median age of 60 years (18 to 93 years), 55% male, and a median BMI of 26 kg/m 2 (14 to 63 kg/m 2 ). Thirty (10%) patients had cirrhosis. One hundred eighty-seven (61%) had previous abdominal operation. Median operative time was 163 minutes (30 to 433 minutes), with a median blood loss of 50 mL (10 to 900 mL). There were no deaths and 6 complications (2%): 2 wound infections, 1 failure to thrive, and 3 perihepatic abscesses. Readmission was required in 5 (1.6%) patients. Of the 268 malignancy cases, 25 (9%) were R1 resections. Of the 128 with superior segment resections (segments 7, 8, 4A, 2, and 1), there were 12 positive margins (9%) and 2 readmissions for abscess. CONCLUSIONS: Outpatient robotic hepatectomy in well-selected cases is safe (0 mortality, 2% complication, and 1.6% readmission), including resection in the superior or posterior portions of the liver that is challenging with nonarticulating laparoscopic instruments.

Use and Outcomes of Dexamethasone in the Management of Malignant Small Bowel Obstruction.

Objective: To describe rates of dexamethasone use in the nonoperative management of malignant small bowel obstruction (mSBO) and their outcomes. Background: mSBO is common in patients with advanced abdominal-pelvic cancers. Management includes prioritizing quality of life and avoiding surgical intervention when possible. The use of dexamethasone to restore bowel function is recommended in the National Comprehensive Cancer Network guidelines for mSBO. Yet, it is unknown how often dexamethasone is used for mSBO and whether results from nonresearch settings support its use. Methods: This is a multicenter retrospective cohort study including unique admissions for mSBO from January 1, 2019 to December 31, 2021. Dexamethasone use and management outcomes were summarized with descriptive statistics and multiple logistic regression. Results: Among 571 admissions (68% female, mean age 63 years, 85% history of abdominal surgery) that were eligible and initially nonoperative, 26% [95% confidence interval (CI) = 23%-30%] received dexamethasone treatment (69% female, mean age 62 years, 87% history of abdominal surgery). Dexamethasone use by site ranged from 13% to 52%. Among dexamethasone recipients, 13% (95% CI = 9%-20%) subsequently required nonelective surgery during the same admission and 4 dexamethasone-related safety-events were reported. Amongst 421 eligible admissions where dexamethasone was not used, 17% (95% CI = 14%-21%) required nonelective surgery. Overall, the unadjusted odds ratio (OR) for nonelective surgery with dexamethasone use compared to without its use was 0.7 (95% CI = 0.4-1.3). Using multiple logistic regression, OR after adjusting for site, age, sex, history of abdominal surgery, nasogastric tube, and Gastrografin use was 0.6 (95% CI = 0.3-1.1). Conclusion: Dexamethasone was used in about 1 in 4 eligible mSBO admissions with high variability of use between tertiary academic centers. This multicenter retrospective cohort study suggested an association between dexamethasone use and lower rates of nonelective surgery, representing a potential opportunity for quality improvement.

Evaluation of an auditory assessment protocol for Chinese infants with nonsyndromic cleft lip and/or palate.

OBJECTIVE: To objectively investigate the auditory status of mainland Chinese infants with nonsyndromic cleft lip and/or palate and to evaluate an auditory assessment protocol for this group. DESIGN: Prospective cohort case review. PATIENTS OR OTHER PARTICIPANTS: A total of 42 Chinese infants with nonsyndromic cleft lip and/or palate aged 6 to 24 months. INTERVENTION: The hearing profiles of participants were acquired using otoscopy, tympanometry, transient-evoked otoacoustic emissions, and auditory brainstem response estimated hearing threshold. The efficiency of the current audiological test battery was analyzed also. RESULTS: Sixty-four (64.2) percent of infants with nonsyndromic cleft lip and/or palate (55.9% of ears) were suspected to have middle ear disorder, and 85.7% of all subjects (83.3% of ears) were found to have hearing loss. Of those with confirmed loss, the overall mean auditory brainstem response estimated air-conduction hearing threshold was 53.5 ± 13.6 decibel normal hearing level [db nHL]. Using auditory brainstem response thresholds as a reference standard, the diagnostic agreement with the other assessment tools for normal/abnormal results was otoscopy, 69% (κ  =  .57); tympanometry, 66.7% (κ  =  .53); and transient-evoked otoacoustic emissions, 80% (κ  =  .64). CONCLUSION: The high prevalence of middle ear disease and hearing loss in mainland Chinese infants with nonsyndromic cleft lip and/or palate in this study was in contrast to previous studies of older age groups of Chinese children conducted in Hong Kong and Singapore. The audiological assessment protocol used in our study could provide useful information; although, modifications may be necessary to ensure a complete diagnostic overview for children with craniofacial clefts.

Structural abnormalities of the central auditory pathway in infants with nonsyndromic cleft lip and/or palate.

OBJECTIVE: To investigate possible structural abnormalities of the central auditory pathway in infants with nonsyndromic cleft lip and/or palate (NSCL/P). PARTICIPANTS: Twenty-seven Chinese infants with NSCL/P, aged from 6 to 24 months. INTERVENTION: Morphological magnetic resonance imaging (MRI) measurements of the central auditory nervous system (CANS) in infants with NSCL/P were analyzed and compared with those of age- and sex-matched normal controls. RESULTS: No significant group differences were found in general brain measurements, including volumes of the brain stem and right hemisphere. However, infants with NSCL/P had statistically significantly smaller volumes of the left thalamus and left auditory cortex and notably decreased thickness of the left auditory cortex. CONCLUSION: Cortical abnormalities were more marked compared with other MRI measurements. Structural CANS abnormalities in infants with NSCL/P may be located mainly in the left cerebral hemisphere. The development and maturation of the auditory cortex in infants with NSCL/P may be abnormal when compared with those of normal children.

Fracture healing in osteoporotic bone.

As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing. Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor (ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments to elucidate. In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis. Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that differences exist between diaphyseal and metaphyseal fractures. An animal model that satisfies three main criteria (metaphyseal region, plate fixation, osteoporosis) is suggested for future research for more comprehensive understanding of the impairment in osteoporotic fractures. Therefore, a metaphyseal fracture or osteotomy that achieves complete discontinuity fixed with metal implants is suggested on ovariectomized aged rodent models.

The pathological role and prognostic impact of miR-181 in acute myeloid leukemia.

In addition to genetic abnormalities, such as chromosomal translocations and somatic mutations that have been widely acknowledged in the leukemogenesis of acute myeloid leukemia (AML), epigenetic modifications also play a vital role in this process. MicroRNA (miRNA) regulation is emerging as a new layer of epigenetic regulation besides DNA methylation and histone modifications. Among the miRNAs first identified to be specifically expressed in hematopoietic cells, the miR-181 family has been implicated in regulating the differentiation of B cells, T cells, and natural killer cells during normal hematopoiesis, and has been linked tightly to the pathogenesis and prognosis of AML. Accumulating evidence indicates that miR-181 acts as a tumor suppressor in the pathogenesis of AML and exhibits a significant impact on the survival of patients with AML. Herein, we review the role of miR-181 as a diagnostic marker and prognostic predictor in AML, and discuss the potential use of miR-181 as a therapeutic target for AML.

Central auditory nervous system dysfunction in infants with non-syndromic cleft lip and/or palate.

OBJECTIVE: Peripheral hearing loss has been commonly reported in children with non-syndromic cleft lip and/or palate (NSCLP) but few studies have provided information about central auditory nervous system (CANS) functioning for this group. The main objective of this study was to explore CANS functioning in infants with NSCLP through analysis of auditory evoked potentials (AEPs). METHODS: AEPs including auditory brainstem response (ABR), middle latency response (MLR), and mismatch negativity (MMN) recordings were conducted in 34 infants of Chinese ethnicity with NSCLP and an equivalent number of normal controls. RESULTS: There was no significant difference in ABR (all measurements, including wave I, III, V latencies, I-V inter-wave latency, and wave V amplitude), or MLR (recordable components, Na, Pa latencies, and Na-Pa amplitude) findings between the two groups. However, infants with NSCLP had a significantly smaller MMN response than their normal controls, using MMN strength as the measurement. CONCLUSIONS: Significant abnormal auditory evoked potential findings at the cortical level suggest that infants with NSCLP may be at risk of central auditory discrimination dysfunction. Further effort is needed to determine auditory processing abilities in infants with NSCLP.