Use of Low-Dose Computed Tomography in Children With Nephrolithiasis: An Analysis From 2 Tertiary Pediatric Centers.

INTRODUCTION: Although ultrasound (US) is the preferred first-line imaging for pediatric nephrolithiasis, CT may be necessary in cases of a nondiagnostic US or when US in not available. Utilization of dose reduction strategies in children undergoing CT for nephrolithiasis is not well described. We compared use of low-dose CT (LDCT) in children presenting to 2 pediatric centers. METHODS: We performed a retrospective chart review of children ≤ 17 years of age presenting with suspected nephrolithiasis to 2 tertiary children's hospitals, inclusive of those referred to these centers from nonpediatric facilities between 2013 and 2019. Children were included with an index CT scan from either the pediatric or referring center while those who had prior documented CT for nephrolithiasis within the study period or missing radiation dose assessment were excluded. The primary outcome was LDCT as defined as radiation dose < 3 mGy. The primary comparator was pediatric vs outside referral center. Exploratory analysis evaluated other factors associated with LDCT, including radiation dosage as a continuous variable. RESULTS: A total of 155 individuals met inclusion criteria, with 126 (81.3%) receiving standard dose and 29 (18.7%) receiving LDCT. Pediatric facilities were more likely to utilize LDCT as compared to referral centers (P < .05). Older age and higher BMI were also found to be associated with increased radiation dose exposure. CONCLUSIONS: Pediatric facilities utilized LDCT more frequently, although age and BMI may also influence imaging choices. An understanding of the factors associated with dose reduction in CT will impact future efforts to explore optimum imaging stewardship in pediatric nephrolithiasis.

Addressing drivers of healthcare utilization for neonatal opioid withdrawal syndrome.

OBJECTIVE: Aim to reduce healthcare utilization (HU) for infants at risk of neonatal opioid withdrawal syndrome (NOWS) by 30% in 1 year and sustain for 2 years. STUDY DESIGN: Baseline data from three Level I & II newborn nurseries from January 2016 to June 2018 informed PDSA cycles from August 2018 to December 2021. Shewhart process control charts evaluated length of stay (LOS), pharmacologic treatment (PT) rates, direct cost (DC), process, and balancing measures for special cause variation (SCV). RESULTS: Two hundred and seventeen infants showed downward SCV in LOS (12.6 to 4.4 days), PT (53% to 17%) and DC ($12593.82 to $5219.17). Onset of the COVID-19 pandemic coincided with reversible SCV. DC varied by provider specialty. CONCLUSION: Transition from MFNASS to ESC led to decrease in healthcare utilization for infants at risk of NOWS. QI methodology identified persistent drivers of variability, including the COVID-19 pandemic and provider specialty.

Risk factors for subsequent stone events in pediatric nephrolithiasis: A multi-institutional analysis.

INTRODUCTION: Children with nephrolithiasis have a 50% risk of recurrence 3 years following an index urinary stone event. The American Urological Association guidelines for medical management of nephrolithiasis suggest metabolic evaluations be stratified according to risk of future stone events. However, no such risk stratification exists across the pediatric population with urinary stone disease. We aim to assess the risk factors among pediatric patients for a subsequent stone event (SSE). MATERIALS AND METHODS: A retrospective review for children <17 years of age with a diagnosis of nephrolithiasis and at least one completed follow-up at two tertiary-care children's hospitals within our state between 2012 and 2017 was performed. Children with known monogenic stone disease were excluded as well as those with follow-up less than 1 year. SSEs following initial diagnosis and treatment for nephrolithiasis were defined as follows: subsequent surgical intervention, new stone on imaging, reported stone passage, or ED evaluation for renal colic. Clinical and demographic factors were compared between patients with and without SSEs and analyzed using univariate and multivariate analyses via Cox proportional hazard models. Survival curves for significant associations for SSEs were generated and evaluated using Log-Rank and Wilcoxon comparisons. RESULTS: A total of 200 patients with median clinical follow-up of 2.9 years were analyzed. Median age was 11.5 years (IQR: 6.0-15.5), with 109 (54.5%) males and 91 (45.5%) females, 94 (47%) of whom had a relevant comorbidity. An SSE occurred in 82 patients (41.0%). Age >12 (HR 2.21, 95%CI 1.42-3.45), reported stone event prior to enrollment encounter (i.e. personal history of nephrolithiasis) (HR 1.82, 95%CI 1.14-2.89), and family history of nephrolithiasis (HR 1.62, 95%CI 1.05-2.51) were associated with SSE on univariate analysis while age >12 (HR 2.09, 95%CI 1.33-3.27) and personal history of nephrolithiasis (HR 1.63, 1.02-2.6) retained significance on multivariable analysis. Survival analysis shows increased risk of recurrence with accumulation of risk factors (Summary Figure). Sensitivity analysis accounting for missing family history data retained significance for all three variables. CONCLUSIONS: Adolescent age and a personal history of nephrolithiasis are independent risk factors for SSE in children. Understanding these risk factors and the nature of SSE among the pediatric population can potentially enhance counseling for further metabolic work-up and tailored clinical follow-up.

Correlating Scores but Contrasting Outcomes for Eat Sleep Console Versus Modified Finnegan.

OBJECTIVES: The Modified Finnegan Neonatal Abstinence Scoring System (M-FNASS) and the newer Eat, Sleep, and Console (ESC) model guide the clinical management of neonatal opioid withdrawal syndrome (NOWS). In this study, we evaluate how the M-FNASS and ESC model directly compare in inpatient practice. We hypothesized that ESC scores would correlate with M-FNASS scores, whereas ESC management would reduce health care use for infants with NOWS. METHODS: In this retrospective cohort study, we compared management of infants with NOWS admitted to nursery settings. Epoch 1 was managed by using an M-FNASS algorithm. Epoch 2 was scored simultaneously with the M-FNASS and ESC model and managed by using the ESC approach. In the statistical analysis, we compared M-FNASS and ESC scores and outcomes between epochs. RESULTS: A total of 158 infants provided 2101 scoring instances for analysis. Demographic characteristics were similar between epochs. ESC scores significantly correlated with overall M-FNASS scores and specific M-FNASS domains. Receiver operating characteristic (ROC) curve analysis revealed that an ESC score containing at least 1 "no" was best predicted by an M-FNASS cutoff value of 7.5 (sensitivity 0.84; specificity 0.70; area under the curve = 0.842). Length of stay (median 9.5 vs 5 days; P = .0002) and initiation (53% vs. 33%; P = .018) and duration of pharmacologic treatment (median 11 vs 7 days; P = .0042), as well as length of stay for infants who were pharmacologically treated (median 15 vs 10 days; P = .0002), were significantly reduced with ESC-based management after adjustment for covariates. CONCLUSIONS: The ESC approach meaningfully correlates with the M-FNASS to detect NOWS. Management with the ESC approach continues to be associated with reduced health care use when compared with an M-FNASS approach, implying that the ESC approach may facilitate higher-value inpatient care.

Is Opioid-free Post-Vasectomy Analgesia a Pain? A Single Surgeon Experience.

OBJECTIVE: To determine the impact of transitioning from opioid to non-opioid analgesia post-vasectomy on unplanned opioid prescriptions and health encounters. METHODS: A retrospective review for patients who underwent vasectomy from October 2018 through December 2019 was performed. Beginning February 1st, 2019, patients were counseled to take scheduled acetaminophen and ibuprofen in lieu of acetaminophen with codeine, with an opioid prescription only provided upon request. Analysis was performed comparing 200 consecutive patients before and after this transition. Baseline patient characteristics, unplanned postoperative encounters for pain within 30 days of vasectomy, and associated narcotic prescriptions were compared between groups. RESULTS: 400 patients were included, consisting of 200 patients pre and 200 patients postintervention. There were no differences in socioeconomic characteristics between groups. No differences between the pre- and postintervention groups were observed in terms of generating telephone calls to clinic (9% vs 11%, P = .5), clinic visits (2.5% vs 2.5%, P = 1), or ED visits (0% vs 1%), P = .5) for the pre and postintervention cohorts, respectively. CONCLUSIONS: Patients that are not prescribed opioids after vasectomy do not generate additional phone calls, clinic, or ED visits compared to those that were routinely prescribed prior to our institutional change. We have permanently discontinued the routine use of opioids for post-vasectomy analgesia. Other physicians performing vasectomy should consider making this change as well.

Bacterial endophthalmitis: therapeutic challenges and host-pathogen interactions.

Endophthalmitis is an infection of the posterior segment of the eye that frequently results in loss of vision. This devastating result occurs despite prompt and often aggressive therapeutic and surgical intervention. Over the past decade, research has centered on determining the bacterial and host factors involved in this potentially blinding disease. The initial focus on the bacterial factors responsible for intraocular virulence has recently expanded into analysis the inflammatory response to infection, including the molecular and cellular interactions between the pathogen and host. This review discusses the epidemiology and therapeutic challenges posed by endophthalmitis, as well as recent findings from the analysis of interactions between the host and pathogen. Based on these findings, a model for the pathogenesis of endophthalmitis is presented. A more comprehensive understanding of the molecular and cellular interactions taking place between pathogen and host during endophthalmitis will expose possible therapeutic targets designed to arrest the infection and prevent vision loss.

Abnormal Electroretinogram after Kir7.1 Channel Suppression Suggests Role in Retinal Electrophysiology.

The KCNJ13 gene encodes the inwardly rectifying potassium channel, Kir7.1. Mutations in this gene cause childhood blindness, in which the a- and b-wave responses of electroretinogram (ERG) are abolished. The ERG a-wave is the light-induced hyperpolarization of retinal photoreceptors, and the b-wave is the depolarization of ON-bipolar cells. The Kir7.1 channel is localized to the apical aspects of retinal pigment epithelium (RPE) cells and contributes to a delayed c-wave response. We sought to understand why a defect in an RPE ion-channel result in abnormal electrophysiology at the level of the retinal neurons. We have established the expression of Kir7.1 channels in the mouse RPE. ERGs recorded after mice Kir7.1 suppression by shRNA, or by blocking with VU590, showed reduced a-, b- and c-wave amplitudes. In contrast, the Kir7.1 blocker had no effect on the ex-vivo isolated mouse retina ERG where the RPE is not attached to the isolated retina preparation. Finally, we confirmed the specificity of VU590 action by inhibition of native mouse RPE Kir7.1 current in patch-clamp experiment. We propose that mutant RPE Kir7.1 channels contribute directly to the abnormal ERG associated with blindness via alterations in sub-retinal space K+ homeostasis in the vicinity of the photoreceptor outer segment.

Bacillus cereus-induced permeability of the blood-ocular barrier during experimental endophthalmitis.

PURPOSE: The purpose of this study was to determine to what extent blood-retinal barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability. METHODS: Mice were intravitreally injected with 100 colony-forming units of B. cereus, and eyes were analyzed at specific times after infection for permeability to fibrin and albumin, quantitation of intraocular plasma constituent leakage, production of inflammatory cytokines, and alterations in tight junction protein localization and expression at the level of the retinal pigment epithelium. RESULTS: B. cereus induced the leakage of albumin and fibrin into the aqueous and vitreous humor by 8 hours after infection. BRB permeability occurred as early as 4 hours and increased 13.30-fold compared with uninfected controls by 8 hours. Production of proinflammatory cytokines IL-6, MIP-1alpha, IL-1beta, and KC increased over the course of infection. In the retina, ZO-1 disruption began by 4 hours and was followed by decreasing occludin and ZO-1 expression at 4 and 8 hours, respectively. Tubulin condensation and RPE65 degradation occurred by 12 hours. A quorum-sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Wild-type and mutant B. cereus sterile supernatants induced blood-ocular barrier permeability similarly to that of wild-type infection. CONCLUSIONS: These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 hours after infection. Disruption of tight junctions at the level of the retinal pigment epithelium may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability.

Rate of bacterial eradication by ophthalmic solutions of fourth-generation fluoroquinolones.

INTRODUCTION: Antibacterial activity of ophthalmic fourth-generation fluoroquinolones has traditionally been evaluated by comparing only their active ingredients, gatifloxacin and moxifloxacin. However, ophthalmic formulations of fourth-generation fluoroquinolones differ in terms of the inclusion of preservatives. While gatifloxacin ophthalmic solution 0.3% (Zymar; Allergan, Inc., Irvine, CA, USA) contains 0.005% benzalkonium chloride (BAK), moxifloxacin ophthalmic solution 0.5% (Vigamox; Alcon Laboratories, Inc., Fort Worth, TX, USA) is preservative-free. Recent studies have demonstrated that the presence of BAK dramatically affects the antibacterial activity of the ophthalmic formulation of gatifloxacin. This study was designed to compare the kill rates of ophthalmic solutions of fourth-generation fluoroquinolones against isolates of common ocular bacterial pathogens. METHODS: Approximately 5.6 log(10) colony-forming units (CFU)/mL of Haemophilus influenzae (n=1), Streptococcus pneumoniae (n=1), Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillinresistant Staphylococcus epidermidis (MRSE) (n=4), and fluoroquinolone-resistant S. epidermidis (n=1) were incubated with ophthalmic solutions of either gatifloxacin or moxifloxacin. Viable bacteria were quantified at specific time points up to 60 minutes. RESULTS: Gatifloxacin 0.3% completely eradicated H. influenzae and Strep. pneumoniae in 5 minutes, one of two S. aureus isolates in 15 minutes, and the other S. aureus isolate in 60 minutes. Gatifloxacin 0.3% completely killed all MRSA, MRSE, and fluoroquinolone-resistant S. epidermidis isolates in 15 minutes. Moxifloxacin 0.5% completely eradicated Strep. pneumoniae and one of four MRSA isolates in 60 minutes. All other isolates incubated with moxifloxacin 0.5% retained viable bacteria ranging from 1.8 to 4.4 log(10) CFU/mL. CONCLUSIONS: The ophthalmic solution of gatifloxacin 0.3% eradicated bacteria that frequently cause postoperative ocular infections substantially faster than did the ophthalmic solution of moxifloxacin 0.5%.

A role for tumor necrosis factor-alpha in experimental Bacillus cereus endophthalmitis pathogenesis.

PURPOSE: To determine the contribution of tumor necrosis factor-alpha (TNFalpha) in the pathogenesis of experimental Bacillus cereus endophthalmitis. METHODS: Experimental B. cereus endophthalmitis was induced in wild-type control (B6.129F1) and age-matched homozygous TNFalpha knockout mice (TNFalpha(-/-), B6.129S6-Tnf(tm1Gk1)/J). At various times after infection, eyes were analyzed by electroretinography and were harvested for quantitation of bacteria, myeloperoxidase, proinflammatory cytokines and chemokines, and histologic analysis. RESULTS: B. cereus replicated more rapidly in the eyes of TNFalpha(-/-) mice than in the eyes of B6.129F1 mice. Retinal function decreased more rapidly in TNFalpha(-/-) mice than in B6.129F1 mice. Retinal layers were not as structurally intact at 6 and 12 hours after infection in TNFalpha(-/-) eyes as in B6.129F1 eyes. Histologic analysis suggested less polymorphonuclear leukocyte (PMN) infiltration into the vitreous of TNFalpha(-/-) mice than of B6.129F1 mice. B6.129F1 eyes also had greater myeloperoxidase concentrations than did eyes of TNFalpha(-/-) mice. In general, concentrations of proinflammatory cytokines and chemokines (IL-1beta, KC, IL-6, and MIP-1alpha) were greater in eyes of TNFalpha(-/-) mice than of B6.129F1 mice. CONCLUSIONS: TNFalpha is important to intraocular pathogen containment by PMNs during experimental B. cereus endophthalmitis. In the absence of TNFalpha, fewer PMNs migrated into the eye, facilitating faster bacterial replication and retinal function loss. Although greater concentrations of proinflammatory cytokines were synthesized in the absence of TNFalpha, the resultant inflammation was diminished, and an equally devastating course of infection occurred.

Fallacy of thoracic side-branch steal from the internal mammary artery: analysis of left internal mammary artery coronary flow during thoracic side-branch occlusion with pharmacologic and exercise-induced hyperemia.

In some patients, myocardial ischemia after coronary artery bypass graft surgery has been attributed to a coronary steal phenomenon through a thoracic side branch originating from the left internal mammary artery (LIMA), even in the absence of subclavian or LIMA stenosis. To demonstrate that coronary flow through the LIMA is unchanged by occlusion of a LIMA side branch, we examined LIMA coronary flow velocity measurements (0.014" Doppler flow wire) in three patients at rest, during adenosine hyperemia, and again during hyperemia induced by left arm exercise before and again after the balloon occlusion of the thoracic side branch. For the three patients, no significant changes in resting or hyperemic flow were noted due to side-branch occlusion. Before side-branch occlusion, pharmacologic intra-arterial (adenosine) coronary flow reserve (hyperemic-to-basal flow velocity ratio) was 2.6, 1.5, and 3.2 and exercise flow reserve was 2.1, 1.3, and 1.2, respectively. After side-branch occlusion, pharmacologic coronary flow reserve was 2.5, 1.8, and 2.7 with exercise flow reserve of 1.8, 1.1, and 1.3, respectively. Under most ordinary circumstances, thoracic side-branch steal does not exist and that side-branch occlusion does not alter LIMA flow at rest or during pharmacologic or exercise-induced hyperemia. These data further suggest that a demonstration of the physiologic value of side-branch occlusion should precede surgical or percutaneous interruption of the thoracic artery in such patients.