Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology.

OBJECTIVES: Sjögren disease (SjD) diagnosis often requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of patients with SjD lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD. METHODS: IgG binding to a high-density whole human peptidome array was quantified using sera from SSA- SjD cases and matched non-autoimmune controls. We identified the highest bound peptides using empirical Bayesian statistical filters, which we confirmed in an independent cohort comprising SSA- SjD (n=76), sicca-controls without autoimmunity (n=75) and autoimmune-feature controls (SjD features but not meeting SjD criteria; n=41). In this external validation, we used non-parametric methods for binding abundance and controlled false discovery rate in group comparisons. For predictive modelling, we used logistic regression, model selection methods and cross-validation to identify clinical and peptide variables that predict SSA- SjD and FS positivity. RESULTS: IgG against a peptide from D-aminoacyl-tRNA deacylase (DTD2) bound more in SSA- SjD than sicca-controls (p=0.004) and combined controls (sicca-controls and autoimmune-feature controls combined; p=0.003). IgG against peptides from retroelement silencing factor-1 and DTD2 were bound more in FS-positive than FS-negative participants (p=0.010; p=0.012). A predictive model incorporating clinical variables showed good discrimination between SjD versus control (area under the curve (AUC) 74%) and between FS-positive versus FS-negative (AUC 72%). CONCLUSION: We present novel autoantibodies in SSA- SjD that have good predictive value for SSA- SjD and FS positivity.

Cervical Cancer and a History of Incarceration: Examining a Social Determinant of Health.

Females who are incarcerated are disproportionately burdened by cancer, particularly cervical cancer. We measured the odds of cervical cancer compared with nonscreenable cancers for females who were incarcerated before diagnosis. By comparing a cancer for which screening and vaccination are available with cancers for which neither are available, we aimed to assess the relationship of incarceration with diseases for which preventive care mitigates risk. We created a novel data set combining cancer data from a large cancer center with incarceration data from the state department of corrections. We then estimated the odds of cervical cancer relative to nonscreenable cancers for those with and without a history of incarceration. Females with a history of incarceration had greater odds of being diagnosed with cervical cancer compared with nonscreenable cancers (odds ratio = 7.04; 95% confidence interval [CI]: 4.4-11.0) relative to those who had not been incarcerated. Adjusting for race and age, the odds of cervical cancer remained significantly greater for those with a history of incarceration (adjusted odds ratio = 3.86; 95% CI: 2.3-6.3). Our findings support the need for expanded cervical cancer screening and vaccination opportunities for incarcerated females and increased access to preventive health care after release.

Decreased Intraoperative Renal Tissue Oxygenation after Cardiopulmonary Bypass Predicts Cardiac Surgery-Associated Acute Kidney Injury in Neonates.

(1) Background: Near-infrared spectroscopy (NIRS) is a noninvasive tool frequently used during cardiac surgery and postoperatively in the cardiac intensive care unit to monitor regional tissue oxygen saturation. A relationship between trends of intraoperative renal oxygenation and the risk of developing cardiac surgery-associated acute kidney injury (AKI) post-operatively has not yet been established in the neonatal population. The objective of this study is to evaluate the relationship of cerebral and renal oxygenation during cardiopulmonary bypass with cardiac surgery-associated AKI in the first 72 h post-operation in neonates < 30 days of age. (2) Methods: A prospective cohort study at a tertiary care children's hospital was performed. Renal and cerebral oxygenation measured were collected intraoperatively from neonates < 30 days of age who underwent cardiopulmonary bypass for the correction of congenital heart disease. AKI was defined accordance with the Kidney Disease: Improving Global Outcomes criteria modified for neonates. Variables were compared between groups. (3) Results: 32 neonates with 35 cardiopulmonary bypass cases were included. AKI was diagnosed in 60% of cases. Intra-operative renal oxygenation, both on- and off-bypass, did not differ among the three AKI groups (p > 0.19). Renal oxygenation after coming off, but not during, cardiopulmonary bypass steadily decreased with increasing levels of AKI (Jonckheere's test, one-sided p = 0.024). (4) Conclusions: Renal oxygenation decreased in proportion to AKI severity after coming off, but not during, cardiopulmonary bypass.

Comparison of preoperative retrobulbar bupivacaine and postoperative subcutaneous liposome-encapsulated bupivacaine on postoperative analgesia in dogs undergoing enucleation.

OBJECTIVE: To compare the effectiveness of preoperative bupivacaine inferotemporal retrobulbar blocks to postoperative liposome-encapsulated bupivacaine (Nocita) line blocks for analgesia following enucleation. ANIMALS: 39 client-owned dogs (40 eyes) presenting to the Ophthalmology Service for enucleation. METHODS: Dogs were randomly assigned to receive either a preoperative inferotemporal retrobulbar block with 0.5% bupivacaine or a peri-incisional line block with liposome-encapsulated bupivacaine (Nocita) at closure. Patients underwent unilateral enucleation and were hospitalized for 24 hours after surgery. Pain scores were performed by a masked observer with the Glasgow Composite Measure Pain Scale and the University of Wisconsin Ocular Pain Scale at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours following surgery. Intraoperative use of blood pressure and anesthetic support mediations as well as need for rescue pain control were recorded and compared between groups. RESULTS: There was no significant difference in rescue rates between treatment groups. When comparing the use of medical intraoperative heart rate, blood pressure, or anesthetic plane support, there were no significant differences in use between groups. CLINICAL RELEVANCE: Use of preoperative bupivacaine retrobulbar blocks and postoperative Nocita line blocks were equally effective at postoperative pain control with similarly low complication rates.

The Importance of Outcomes Ascertainment for Accurate Assessment of the Mammography Screening Cancer Detection Rate: A Simulation Study.

PURPOSE: Cancer detection rate (CDR), an important metric in the mammography screening audit, is designed to ensure adequate sensitivity. Most practices use biopsy results as the reference standard; however, commonly ascertainment of biopsy results is incomplete. We used simulation to determine the relationship between the cancer ascertainment rate of biopsy (AR-biopsy), CDR estimation, and associated error rates in classifying whether practices and radiologists meet the established ACR benchmark of 2.5 per 1,000. MATERIALS AND METHODS: We simulated screening mammography volume, number of cancers detected, and CDR, using negative binomial and beta-binomial distributions, respectively. Simulations were performed at both the practice and radiologist level. Average CDR was based on linearly rescaling a published CDR by the AR-biopsy. CDR distributions were simulated for AR-biopsy between 5% and 100% in steps of five percentage points and were summarized with boxplots and smoothed histograms over the range of AR-biopsy, to quantify the proportion of practices and radiologists meeting the ACR benchmark at each level of AR-biopsy. RESULTS: Decreasing AR-biopsy led to an increasing probability of categorizing CDR performance as being below the ACR benchmark. Our simulation predicts that at the practice level, an AR-biopsy of 65% categorizes 17.6% below the benchmark (compared to 1.6% at an AR-biopsy of 100%), and at the radiologist level, an AR-biopsy of 65% categorizes 34.7% as being below the benchmark (compared to 11.6% at an AR-biopsy of 100%). CONCLUSIONS: Our simulation demonstrates that decreasing the AR-biopsy (in currently clinically relevant ranges) has the potential to artifactually lower the assessed CDR on both the practice and radiologist levels and may, in turn, increase the chance of erroneous categorization of underperformance per the ACR benchmark.

Risk of Hypovitaminosis and Vitamin C Deficiency in Pediatric Patients Undergoing Cardiopulmonary Bypass.

Vitamin C levels are known rapidly decrease in adult critical illness. Vitamin C scavenges free radicals, provides critical protection of the endothelial barrier, and improves endothelial responsiveness to catecholamines. Children with congenital heart disease and undergoing cardiac surgery might be at increased risk for low circulating vitamin C levels. A prospective single-center observational study investigated perioperative changes in vitamin C levels in critically ill Children who underwent congenital heart surgery using CPB. Vitamin C serum levels were collected preoperatively and postoperatively (upon admission to the ICU, 24 and 72 h). Linear mixed-effect model was used to estimate mean circulating concentration of vitamin C and to estimate changes in concentration over time. Primary outcome was change in circulating levels of vitamin C before and after CPB. Secondary outcomes were hospital length of stay (LOS), acute kidney injury (AKI), and illness severity. Forty-one patients with a median age of 4.5 [interquartile range (IQR) 2.6-65.6] months at the time of surgery were consented and enrolled. Median CPB duration was 130 [90-175] minutes, and hospital LOS was 9.1 [5.2-19] days. Mean vitamin C levels (µmol/L) before CPB, at PICU admission, 24 h, and 72 h were 82.0 (95% CI 73.4-90.7), 53.4 (95% CI 44.6,62.0), 55.1 (95% CI 46.3,63.8), and 59.2 (95% CI 50.3,68.1), respectively. Upon postoperative admission to the PICU, vitamin C levels decreased by 28.7 (95% CI 20.6-36.8; p < 0.001) µmol/L, whereas levels at 24 and 72 h recovered and did not differ substantially from concentrations reported upon PICU admission (p > 0.15). Changes in vitamin C concentration were not associated with CPB time, STAT mortality category, age, or PIM3. Three patients had post-CPB hypovitaminosis C or vitamin C deficiency. Reduction in vitamin C levels was not associated with hospital LOS (p = 0.673). A 25 µmol/L decrease in vitamin C levels upon PICU admission was associated with developing AKI (aOR = 3.65; 95% CI 1.01-18.0, p = 0.049). Pediatric patients undergoing cardiac surgery with CPB showed decreased vitamin C levels during the immediate postoperative period. Effects of hypovitaminosis C and vitamin C deficiency in this population remain unclear.

Exploring knowledge gaps in the understanding of peripheral and deep en face margin assessment.

In 2022, National Comprehensive Cancer Network updated the phrase of "complete circumferential peripheral and deep margin assessment (CCPDMA)" to "peripheral and deep en face margin assessment (PDEMA)," which was meant to create more consistency across all treatment modalities and provide clarity to the meaning of total margin evaluation. The aim of this project was to investigate the interpretation of PDEMA across pertinent specialties and to identify any existing knowledge gaps in hopes of improving clinical performance of institutional practice. An electronic survey was administered to medical professionals within the divisions of dermatology and otolaryngology retrieving demographic data and assessing respondents' knowledge on tissue processing techniques and PDEMA. Of the four knowledge-based assessment questions administered, dermatology respondents answered three questions with > 80% accuracy and one question with < 65% accuracy. Otolaryngology respondents answered one question with > 80% accuracy and three with < 65% accuracy. Both groups answered the knowledge-based question evaluating the concept of "what must be true for Mohs or PDEMA to have value" with under 65% accuracy. When comparing dermatology and otolaryngology respondents, only one question which evaluated the proper methods to "achieve processing of the epidermal edge and the base of the tumor along a single plane in the lab" significantly differed between groups, with a percentage correct of 96% for dermatologists compared to 54% for otolaryngologists (p < 0.001). Results were found to be similar when resident physicians were removed from analysis. The overall percent correct for knowledge-based questions was shifted higher for dermatologists compared to otolaryngologists (p = 0.014). This trend was also redemonstrated when analyzing the data excluding residents (p = 0.053).

Review of Tobramycin Dosing in Pediatric Patients With Cystic Fibrosis.

OBJECTIVE: An institution's tobramycin pharmacokinetics (PK) database was reviewed to evaluate the efficacy and safety of empiric tobramycin dosing and monitoring strategies used in pediatric patients with cystic fibrosis (CF). The relationship between patient age and tobramycin dosing needed to achieve the area under the curve (AUC) goal was investigated. METHODS: Retrospective chart review was performed for patients who received tobramycin during a CF exacerbation from 2009 to 2019 who received PK monitoring by pediatric pharmacists. Tobramycin dosing needed to achieve an AUC of 100 mg·hr/L was calculated for each patient. Serum creatinine and concomitant nephrotoxin use were collected as surrogate nephrotoxicity endpoints to evaluate safety. RESULTS: Goal AUC (100 ± 15 mg·hr/L) was achieved based on initial or repeat PK calculations in 43.5% (95% CI, 37.7-49.3) of 85 unique patients across 326 encounters. Patients with calculated recommended doses of 9.5 to 11.9 mg/kg every 24 hours empirically achieved goal AUC in 77% (78/101) of encounters. The odds of achieving goal AUC were 56% higher for children aged 10 vs 5 years (OR = 1.56; 95% CI, 1.04-2.34; p = 0.033) and 32% higher for children aged 15 vs 10 years (OR = 1.32; 95% CI, 1.07-1.61; p = 0.008). Overall rates of acute kidney injury and concomitant nephrotoxin use were 10.8% (95% CI, 6.2-15.5) and 80.7% (95% CI, 74.3-87.1), respectively. CONCLUSIONS: Desired AUC was achieved by 43.5% of pediatric patients with CF using tobramycin 10 mg/kg every 24 hours. Older patient age was associated with higher initial AUC attainment and fewer dose modifications. Younger children may require higher weight-based dosing to meet AUC goals.

Retrospective investigation of perioperative risk factors for immediate postoperative corneal erosions in dogs undergoing phacoemulsification.

OBJECTIVE: To characterize the incidence, contributing risk factors, and healing characteristics of immediate postoperative corneal erosions (IPCE) in dogs undergoing routine phacoemulsification. ANIMALS STUDIED: Medical records of 313 canine eyes (159 dogs) undergoing routine phacoemulsification surgery. PROCEDURES: Medical records of dogs undergoing planned cataract surgery at UW Veterinary Care were retrospectively reviewed. Patient-related variables including age, skull conformation, diabetes status, and cataract stage at the time of surgery were recorded. Intraoperative variables per eye were also recorded including surgical technique, surgeon expertise level, average phacoemulsification power, and phacoemulsification time. Diagnosis of IPCE ≤ 24 h after completion of surgery and time to IPCE healing were recorded where follow-up data were available. RESULTS: Immediate postoperative corneal erosions were observed in 48/313 (15.3%) operated eyes. The presence of diabetes mellitus or brachycephalic skull conformation, preoperative Schirmer tear test (STT) value, surgical technique and surgeon experience level, phacoemulsification time, and absolute phacoemulsification time were not statistically significant risk factors for IPCE. Average phacoemulsification power was associated with IPCE (RR 1.52, p = .001). Time to IPCE healing was similar in diabetic and non-diabetic dogs (median [IQR] 8 [6-11] days and 8 [6-15] days, respectively). Diabetes mellitus, brachycephaly, and phacoemulsification parameters were not associated with IPCE healing at 7 or 14 days postoperatively. CONCLUSIONS: Higher average phacoemulsification power may be associated with the development of IPCE in canine eyes. The presence of diabetes mellitus or brachycephaly are not risk factors for the development of IPCE, nor are they factors that influence IPCE healing.

In vivo fluorescence lifetime imaging of macrophage intracellular metabolism during wound responses in zebrafish.

The function of macrophages in vitro is linked to their metabolic rewiring. However, macrophage metabolism remains poorly characterized in situ. Here, we used two-photon intensity and lifetime imaging of autofluorescent metabolic coenzymes, nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), to assess the metabolism of macrophages in the wound microenvironment. Inhibiting glycolysis reduced NAD(P)H mean lifetime and made the intracellular redox state of macrophages more oxidized, as indicated by reduced optical redox ratio. We found that TNFα+ macrophages had lower NAD(P)H mean lifetime and were more oxidized compared to TNFα- macrophages. Both infection and thermal injury induced a macrophage population with a more oxidized redox state in wounded tissues. Kinetic analysis detected temporal changes in the optical redox ratio during tissue repair, revealing a shift toward a more reduced redox state over time. Metformin reduced TNFα+ wound macrophages, made intracellular redox state more reduced and improved tissue repair. By contrast, depletion of STAT6 increased TNFα+ wound macrophages, made redox state more oxidized and impaired regeneration. Our findings suggest that autofluorescence of NAD(P)H and FAD is sensitive to dynamic changes in intracellular metabolism in tissues and can be used to probe the temporal and spatial regulation of macrophage metabolism during tissue damage and repair.

Clinical utility and real-world application of molecular genetic sequencing in the management of patients with acute myeloid leukemia and myelodysplastic syndromes.

Recurrently mutated genes in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have proven useful in risk stratification and clinical decision-making. Sequencing technologies that detect these genetic mutations are now widely available, though there is variability in the use of such data among hematologists. Molecular genetic sequencing trends were assessed in 470 patients presenting to a single institution with AML or MDS to determine how molecular data impacts clinical management of patients with myeloid malignancies. Patients with AML were more likely to have molecular genetic sequencing performed compared to patients with MDS, and clinicians were more likely to reference molecular data in decision-making for patients with AML. Furthermore, the presence of molecular data was associated with an increased odd of bone marrow transplantation (BMT). This study demonstrates the real-world application of molecular data in the management of myeloid malignancies and also highlights disparities in the use of such data based on diagnosis.

Risk factors for enterococcal bacteriuria in dogs: A retrospective study.

BACKGROUND: In humans, Enterococcus spp. urinary tract infections (UTI) are commonly associated with urinary catheter-induced urothelial inflammation but this is not the case in dogs. HYPOTHESIS/OBJECTIVES: To identify risk factors predisposing dogs to enterococcal bacteriuria. ANIMALS: Seventy dogs with Enterococcus spp. bacteriuria (case) and 70 dogs with Enterococcus coli bacteriuria (control). METHODS: A single center retrospective case-control study with subjects and controls identified by a medical records search for Enterococcus spp. (subject) or E coli (control) bacteriuria from January 1, 2014 to December 31, 2017. Cases and controls were balanced with respect to average age and weight. Binary logistic regression was used to estimate and test whether the odds of having Enterococcus spp. bacteriuria (instead of E coli) were associated with the presence of any given characteristic. RESULTS: A history of recurrent bacteriuria was significantly more common in Enterococcus spp. cases than in E coli controls (odds ratio [OR]: 2.07; 95% confidence interval [CI]: 1.04-4.16, P = .04). Comorbidities associated with the presence of Enterococcus spp. bacteriuria included lower urinary tract (LUT) anatomic abnormalities (OR: 2.94; 95% CI: 1.17-8.10, P = .02), urolithiasis (P = .01), and the presence of LUT neoplasia (P = .04). Small frequencies (n = 12 and n = 6, respectively) compromise our ability to precisely estimate the genuine OR for the latter 2 characteristics. CONCLUSIONS AND CLINICAL IMPORTANCE: If the identified risk factors promote Enterococcus spp. colonization in dogs via induced LUT inflammation similar to people then Enterococcus spp. bacteriuria could be a sentinel for underlying LUT inflammation.

Retrospective analysis of complications associated with retrobulbar bupivacaine in dogs undergoing enucleation surgery.

OBJECTIVE: To investigate complications associated with, and without, bupivacaine retrobulbar local anesthesia in dogs undergoing unilateral enucleation surgery. STUDY DESIGN: Retrospective, observational study. ANIMALS: A total of 167 dogs underwent unilateral enucleation surgery via a transpalpebral approach. METHODS: Records from 167 dogs that underwent unilateral enucleation surgery that did (RB) or did not (NB) include retrobulbar bupivacaine anesthesia were reviewed, including anesthetic record, daily physical examination records, surgery report, patient discharge report and patient notes within 14 days of the surgery. Specific complications and severity were compared between RB and NB using the Wilcoxon rank-sum test. A 'complication burden' (0-5) comprising five prespecified complications was assigned and tested using rank-sum procedures. Statistical significance was set to 0.05. RESULTS: Group RB included 97 dogs and group NB 70 dogs. Dogs in NB had a 17.0 percentage points (points) greater risk for a postoperative recovery complication (38.6% versus 21.6%; 95% confidence interval: 3.0-30.6 points; p = 0.017). There was inconclusive evidence that dogs in group RB had a lower risk of requiring perioperative anticholinergic administration (12.4% versus 22.9%; 10.5 points; p = 0.073). Other complications were similar between groups RB and NB with risks that differed by <10 points. The risk of hemorrhage was similar between groups RB (22.7%) and NB (20.0%) with no significant difference in the level of severity (p = 0.664). CONCLUSIONS AND CLINICAL RELEVANCE: In this retrospective study, the use of retrobulbar bupivacaine for enucleation surgery in dogs was not associated with an increased risk of major or minor complications.

Circadian Behavioral Responses to Light and Optic Chiasm-Evoked Glutamatergic EPSCs in the Suprachiasmatic Nucleus of ipRGC Conditional vGlut2 Knock-Out Mice.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN. vGlut2 has been conditionally deleted in ipRGCs in mice [conditional knock-outs (cKOs)] and their aberrant photoentrainment and residual attenuated light responses have been ascribed to ipRGC PACAP release. However, there is no direct evidence that all ipRGC glutamatergic neurotransmission is eliminated in vGlut2 cKOs. Here, we examined two lines of ipRGC vGlut2 cKO mice for SCN-mediated behavioral responses under several lighting conditions and for ipRGC glutamatergic neurotransmission in the SCN. Circadian behavioral responses varied from a very limited response to light to near normal photoentrainment. After collecting behavioral data, hypothalamic slices were prepared and evoked EPSCs (eEPSCs) were recorded from SCN neurons by stimulating the optic chiasm. In cKOs, glutamatergic eEPSCs were recorded and all eEPSC parameters examined (stimulus threshold, amplitude, rise time or time-to-peak and stimulus strength to evoke a maximal response) were similar to controls. We conclude that a variable number but functionally significant percentage of ipRGCs in two vGlut2 cKO mouse lines continue to release glutamate. Thus, the residual SCN-mediated light responses in these cKO mouse lines cannot be attributed solely to ipRGC PACAP release.

Effect of a hospital-associated urinary tract infection reduction policy on general surgery patients.

BACKGROUND: Hospital-associated UTI rates in surgery patients have not improved despite recommendations for reducing indwelling catheter days. METHODS: We performed a retrospective review of institutional NSQIP general surgery patient data, 2006-2015. During this time, a UTI-reduction policy was implemented. Demographics, HA-UTI incidence, CA-UTI incidence, indwelling catheter days, straight catheterization rates, and mortality were examined. RESULTS: Females had significantly higher risk of HA-UTI. There was no significant change in HA-UTI (X12 = 0.02, p = .878) or indwelling catheter days (5.18 ±â€¯1.12 days v 3.73 ±â€¯0.39 days, p = .23). Straight catheterizations among those with HA-UTI increased (0.04 ±â€¯0.04 v 0.32 ±â€¯0.12, p = .029). There was no change in CA-UTI (1.38 v 1.11 CAUTI/1000 patient hospital-days P = .555) or in initial indwelling catheter days of patients with CA-UTI (7.2 SD 8.89 v 47.0 SD 7.04 days P = .961) after policy implementation. CONCLUSIONS: The reduction policy increased the number of straight catheterizations for patients developing HA-UTI, but did not reduce the number of initial indwelling catheter days, HA-UTI rates, or CA-UTI rates.

NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice.

Global distribution of hepatocellular carcinomas (HCCs) is dominated by its incidence in developing countries, accounting for >700,000 estimated deaths per year, with dietary exposures to aflatoxin (AFB1) and subsequent DNA adduct formation being a significant driver. Genetic variants that increase individual susceptibility to AFB1-induced HCCs are poorly understood. Herein, it is shown that the DNA base excision repair (BER) enzyme, DNA glycosylase NEIL1, efficiently recognizes and excises the highly mutagenic imidazole ring-opened AFB1-deoxyguanosine adduct (AFB1-Fapy-dG). Consistent with this in vitro result, newborn mice injected with AFB1 show significant increases in the levels of AFB1-Fapy-dG in Neil1-/- vs. wild-type liver DNA. Further, Neil1-/- mice are highly susceptible to AFB1-induced HCCs relative to WT controls, with both the frequency and average size of hepatocellular carcinomas being elevated in Neil1-/- The magnitude of this effect in Neil1-/- mice is greater than that previously measured in Xeroderma pigmentosum complementation group A (XPA) mice that are deficient in nucleotide excision repair (NER). Given that several human polymorphic variants of NEIL1 are catalytically inactive for their DNA glycosylase activity, these deficiencies may increase susceptibility to AFB1-associated HCCs.

Surgical Quality Predicts Length of Stay in Patients with Congenital Heart Disease.

Historically, the primary marker of quality for congenital cardiac surgery has been postoperative mortality. The purpose of this study was to determine whether additional markers (10 surgical metrics) independently predict length of stay (LOS), thereby providing specific targets for quality improvement. Ten metrics (unplanned ECMO, unplanned cardiac catheterization, revision of primary repair, delayed closure, mediastinitis, reexploration for bleeding, complete heart block, vocal cord paralysis, diaphragm paralysis, and change in preoperative diagnosis) were defined in 2008 and subsequently collected from 1024 consecutive index congenital cardiac cases, yielding 990 cases. Four patient characteristics and 22 case characteristics were used for risk adjustment. Univariate and multivariable analyses were used to determine independent associations between each metric and postoperative LOS. Increased LOS was independently associated with revision of the primary repair (p = 0.014), postoperative complete heart block requiring a permanent pacemaker (p = 0.001), diaphragm paralysis requiring plication (p < 0.001), and unplanned postoperative cardiac catheterization (p < 0.001). Compared with patients without each metric, LOS was 1.6 (95 % CI 1.1-2.2, p = 0.014), 1.7 (95 % CI 1.2-2.3, p = 0.001), 1.8 (95 % CI 1.4-2.3, p < 0.001), and 2.0 (95 % CI 1.7-2.4, p < 0.001) times as long, respectively. These effects equated to an additional 4.5-7.8 days in hospital, depending on the metric. The other 6 metrics were not independently associated with increased LOS. The quality of surgery during repair of congenital heart disease affects outcomes. Reducing the incidence of these 4 specific surgical metrics may significantly decrease LOS in this population.

Expanding the net: The re-evaluation of the multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) in the setting of secondary hyperparathyroidism and the development of the MultIdimensional Predictive hyperparaTHyroid model (Mi-PTH).

BACKGROUND: The multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) model identifies a personalized upper limit of normal parathyroid hormone (PTH) and successfully predicts classical primary hyperparathyroidism (PHP). We aimed to assess whether maxPTH can distinguish normocalcemic PHP (NCPHP) from secondary hyperparathyroidism (SHP), including subjects who underwent bariatric surgery (BrS). METHODS: A total of 172 subjects with 359 complete datasets of serum calcium (Ca), 25-OH vitamin D, and intact PTH from Oregon were analyzed: 123 subjects (212 datasets) with PHP and 47 (143) with SHP, including 28 (100) with previous BrS. An improved prediction model, MultIdimensional evaluation for Primary hyperparaTHyroidism (Mi-PTH), was created with the same variables as maxPTH by the use of a combined cohort (995 subjects) including participants from previous studies. RESULTS: In the Oregon cohort, maxPTH's sensitivity was 100% for classical PHP and 89% for NCPHP, but only 50% for normohormonal PHP (NHPHP) and 40% specific for SHP. In comparison, although sensitivity for NCPHP was similar (89%), Mi-PTH vastly improved SHP specificity (85%). In the combined cohort, Mi-PTH had better sensitivity of 98.5% (vs 95%) and specificity 97% (vs 85%). CONCLUSION: MaxPTH was sensitive in detecting PHP; however, there was low specificity for SHP, especially in patients who underwent BrS. The creation of Mi-PTH provided improved performance measures but requires further prospective evaluation.