Primary Septic Arthritis in Children Demonstrates Presumed and Confirmed Varieties Which Require Age-specific Evaluation and Treatment Strategies.

BACKGROUND: There is uncertainty involved in the evaluation and treatment of children suspected to have septic arthritis particularly when no causative pathogen is confirmed. This study evaluates children with primary septic arthritis to refine the processes of evaluation and treatment and improve the rate of pathogen confirmation. METHODS: Children suspected to have septic arthritis from 2009 to 2019 were retrospectively studied. Diagnosis of primary septic arthritis, defined as hematogenous joint infection without associated osteomyelitis, was established by clinical evaluation, radiology and laboratory results, including joint fluid analysis. Excluded cases were categorized by etiology. Children with primary septic arthritis were divided into confirmed and presumed cohorts for statistical comparison. RESULTS: A total of 355 children (average age 4.4 y, range 0.05 to 18 y) were initially treated as septic arthritis. Eighty-seven (24.5%) were excluded due to other conditions, including 34 (9.6%) with noninfectious conditions. Among 268 children with primary septic arthritis, 134 were confirmed and 134 were presumed. A higher rate of 16S polymerase chain reaction (PCR) acquisition (71.6% vs. 45.5%) occurred in the confirmed cohort. Overall yield for various methods of pathogen identification were 27 of 239 (11.3%) by blood culture, 83 of 268 (31.0%) by joint fluid culture and 85 of 157 (54.1%) by PCR. PCR identified a pathogen in 87.5% of children with confirmed septic arthritis. Antibiotic pretreatment was associated with a lower rate of joint fluid culture positivity. Pathogens aggregated within specific age groups. The 4 to 9-year-old age group displayed the widest spectrum of pathogens with limited predictability. CONCLUSIONS: This study emphasizes the need for systematic processes of evaluation and treatment for children suspected to have primary septic arthritis, including minimization of antibiotic pretreatment, age-based empiric antibiotic selection, and sufficient follow-up to ensure noninfectious conditions are distinguished in culture-negative cases. Extended observation, before intervention, may be appropriate for some children. LEVEL OF EVIDENCE: Level III-retrospective control study.

Primary Septic Arthritis Among Children 6 to 48 Months of Age: Implications for PCR Acquisition and Empiric Antimicrobial Selection.

INTRODUCTION: Primary septic arthritis requires unique evaluation and treatment considerations for children in the 6- to 48-month age range because of the spectrum of identified pathogens and high rate of negative cultures. The purpose of this study is to evaluate primary septic arthritis in this age group in order to differentiate children with infection caused by Kingella kingae from those with other confirmed pathogens and those with no identified pathogen. METHODS: Preschool children who underwent multidisciplinary evaluation and treatment for septic arthritis between 2009 and 2019 were retrospectively studied. Three cohorts were established for comparison of clinical and laboratory features of primary septic arthritis: (1) confirmed K. kingae, (2) confirmed other pathogen, and (3) presumed (without identified pathogen). RESULTS: Among 139 children with septic arthritis, 40 (29%) were confirmed K. kingae, 29 (21%) other pathogen, and 70 (50%) presumed. Children with Kingella and those with presumed septic arthritis had significantly lower initial C-reactive protein (4.8 and 4.5 vs. 9.3 mg/dL) and fewer febrile hospital days (0.2 and 0.4 vs. 1.3 d) than children with other confirmed pathogens. Children with other pathogens had higher rates of bacteremia (38% vs. 0%) and positive joint fluid cultures (86% vs. 15%) than that of children with Kingella. The rate of polymerase chain reaction (PCR) acquisition was 38 of 40 (95.0%) Kingella cases, 18 of 29 (62.1%) other pathogen cases, and 33 of 70 (47.1%) presumed cases. CONCLUSIONS: K. kingae was the most commonly identified pathogen among 6-month to 4-year-old children. The Kingella and other identified pathogens in this study serve to guide empiric antimicrobial recommendations for this age range. Because of similarities between children with septic arthritis because of K. kingae and those with no identified pathogen, it is likely that an unrecognized burden of Kingella resides in culture negative cases, particularly if no PCR is sent. Systematic evaluation, including PCR acquisition, and a high index of suspicion for K. kingae are recommended to thoroughly evaluate septic arthritis in preschool children. LEVEL OF EVIDENCE: Level III-Retrospective cohort comparison.

Children with Primary Septic Arthritis Have a Markedly Lower Risk of Adverse Outcomes Than Those with Contiguous Osteomyelitis.

BACKGROUND: It is widely believed that septic arthritis poses a risk of joint destruction and long-term adverse outcomes for children if not treated emergently. In the present study, children who had primary confirmed septic arthritis were compared with those who had septic arthritis and adjacent osteomyelitis to evaluate differences that affect the relative risk of adverse outcomes. METHODS: Children who underwent multidisciplinary treatment for septic arthritis with or without contiguous osteomyelitis between 2009 and 2019 were retrospectively studied. Clinical, laboratory, treatment, and outcome data were compared between cohorts of children with primary confirmed septic arthritis and children with septic arthritis and contiguous osteomyelitis. RESULTS: One hundred and thirty-four children had primary confirmed septic arthritis, and 105 children had septic arthritis with contiguous osteomyelitis. Children with osteomyelitis were older (median, 7.4 versus 2.4 years), had higher initial C-reactive protein (median, 15.7 versus 6.4 mg/dL), and had a higher rate of thrombocytopenia (21.0% versus 1.5%). They also had a higher rate of bacteremia (69.5% versus 20.2%) for a longer duration (median, 2.0 versus 1.0 days). Detected pathogens in children with osteomyelitis as compared with those with primary septic arthritis were more likely to be Staphylococcus aureus (77.1% versus 32.1%) and less likely to be Kingella kingae (2.9% versus 32.1%). Children with contiguous osteomyelitis had longer hospitalizations (median, 8.0 versus 4.0 days), a higher rate of intensive care (21.0% versus 1.5%), a higher readmission rate (17.1% versus 5.2%), and a higher complication rate (38.1% versus 0.7%). CONCLUSIONS: Primary septic arthritis in children is dissimilar to septic arthritis associated with osteomyelitis. The present study demonstrates that long-term adverse outcomes in children with septic arthritis are likely due to the contiguous osteomyelitis. Children with primary septic arthritis are sufficiently distinguishable from those who have contiguous osteomyelitis to guide decisions for magnetic resonance imaging acquisition, duration of antibiotic therapy, and length of outpatient follow-up in order to recognize and address adverse outcomes. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Stimulation of 5-HT(1B) receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior.

Paradoxically, stimulation of 5-HT(1B) receptors (5-HT(1B)Rs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT(1B)R agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT(1B)Rs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT(1B)Rs may be a novel target for developing medications for cocaine dependence.

Routine upper gastrointestinal Gastrografin swallow after laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Upper gastrointestinal (UGI) swallow radiographs following laparoscopic Roux-en-Y gastric bypass (LRYGBP) may detect an obstruction or an anastomotic leak. The aim of our study was to determine the efficacy of routine imaging following LRYGBP. METHODS: Radiograph reports were reviewed for 201 consecutive LRYGBP operations between April 1999 and June 2001. UGI swallow used Gastrografin, static films, fluoroscopic video, and a delayed image at 10 minutes. Mean values with one standard deviation were tested for significance (P < 0.05) using the Mann-Whitney U test statistic. RESULTS: Of 198 available reports, UGI detected jejunal efferent (Roux) limb narrowing (n = 17), partial obstruction (n = 12), anastomotic leak (n = 3), complete bowel obstruction (n = 3), diverticulum (n = 1), hiatal hernia (n = 1), and proximal Roux limb narrowing (n = 1). A normal study was reported in 160 cases (81%). Partial obstruction resolved without intervention. Complete obstruction required re-operation. Compared to 6 patients who developed delayed leaks, early identification of a leak by routine UGI swallow resulted in a shorter hospital stay (mean 7.7 +/- 1.5 days vs 40.2 +/- 12.3 days, P < 0.03). CONCLUSIONS: Early intervention after UGI swallow may lessen morbidity. Routine UGI swallow following LRYGBP does not obviate the importance of close clinical follow-up.

Effect of sleep deprivation on the performance of simulated laparoscopic surgical skill.

BACKGROUND: Resident work hours may impact patient care. We hypothesized that "call-associated" acute sleep deprivation has no effect on technical dexterity as measured on a minimally invasive surgery trainer, virtual reality (MIST VR) surgical simulator. METHODS: Thirty-five surgical residents were prospectively evaluated pre-call (rested), on-call (rested), and post-call (acutely sleep deprived). Participants completed questionnaires regarding sleep hours and level of fatigue. Technical skill was assessed using the MIST VR. Speed, errors, and economy of motion were automatically recorded by the MIST VR computer simulator. Data were analyzed by paired Student t test and analysis of variance. RESULTS: Estimated hours of sleep and subjective indicators of fatigue were different between rested and sleep-deprived residents. The number of errors and time to complete all tasks increased at the post-call assessment. CONCLUSIONS: Resident work schedules lead to sleep deprivation and fatigue. Call-associated sleep deprivation and fatigue are associated with increased technical errors in the performance of simulated laparoscopic surgical skills.

Stimulation of medial prefrontal cortex serotonin 2C (5-HT(2C)) receptors attenuates cocaine-seeking behavior.

Serotonin 2C receptor (5-HT(2C)R) agonists administered systemically attenuate both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior. To further elucidate the function of these receptors in addiction-like processes, this study examined the effects of microinfusing the 5-HT(2C)R agonist MK212 (0, 10, 30, 100 ng/side/0.2 microl) into the medial prefrontal cortex (mPFC) on cocaine self-administration and reinstatement of extinguished cocaine-seeking behavior. Male Sprague-Dawley rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. Once responding stabilized, rats received MK212 microinfusions before tests for maintenance of cocaine self-administration. Next, extinction training to reduce cocaine-seeking behavior, defined as responses performed without cocaine reinforcement available, occurred until low extinction baselines were achieved. Rats then received MK212 microinfusions before tests for reinstatement of extinguished cocaine-seeking behavior elicited by cocaine-priming injections (10 mg/kg, i.p.) or response-contingent presentations of the cocaine-associated cues; operant responses during cocaine-primed reinstatement tests produced no consequences. MK212 microinfusions into the prelimbic and infralimbic, but not anterior cingulate, regions of the mPFC dose-dependently attenuated both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior, but did not reliably affect cocaine self-administration. A subsequent experiment showed that the effects of MK212 (100 ng/side/0.2 microl) on reinstatement of extinguished cocaine-seeking behavior were blocked by co-administration of the 5-HT(2C)R antagonist SB242084 (200 ng/side/0.2 microl). MK212 administered alone into the mPFC as a drug prime produced no discernable effects on cocaine-seeking behavior. These findings suggest that stimulation of 5-HT(2C)Rs in the mPFC attenuates the incentive motivational effects produced by sampling cocaine or exposure to drug-paired cues.

Cancer risk in endoscopically unresectable colon polyps.

BACKGROUND: The purpose of the current study was to define the rate of underlying malignancy in endoscopically unresectable polyps. METHODS: An institutional review board-approved review identified all patients undergoing colectomy for radiologically identified or endoscopically unresectable polyps between 1997 and 2006. Patients were included if the endoscopic impression and biopsy findings suggested an adenomatous polyp without invasive cancer. Patient information was abstracted. RESULTS: Eighty procedures in 79 patients were identified. Median patient age was 66 (range 38 to 85) years, and patients were predominately male (98%) and Caucasian (73%). The median endoscopic size of polyps was 3.0 cm (range 0.8 to 10 cm). Polyps were most frequently proximal to the splenic flexure (72%). Biopsy histology included 36 (51%) tubulovillous and villous adenomas. Invasive cancer was identified in 13 of 80 (16%) subsequent surgical specimens, but only 3 of 71 (4%) were lymph node-positive. Surgical morbidity was 37% and in-hospital mortality 3%. Size of polyp (P = .81) and histologic type (P = .34) were not significantly associated with invasive cancer. Compared with polyps proximal to the splenic flexure, polyps located distally were more likely to harbor malignancy (rate; P < .02), by both univariate and multivariate analysis (odds ratio [OR] 1.38 [95% confidence interval 1.07 to 1.8]). CONCLUSION: The cancer risk in polyps deemed inappropriate for endoscopic resection was lower than previously reported. Neither polyp size nor histologic type appeared to be significantly associated with invasive cancer. Location of an endoscopically unresectable polyp distal to the splenic flexure confers an increased risk for occult malignancy.