Body mass index greater than 35 is associated with severe Clostridium difficile infection.

BACKGROUND: Obesity has been implicated in the acquisition of Clostridium difficile infections (CDI), however, no study has investigated whether there is a correlation between body mass index (BMI) and CDI severity. AIM: To determine whether obesity, as measured by BMI correlates with severe hospital-onset or community-onset CDI. METHODS: Patients admitted with CDI at a tertiary-care center from January 2013 to June 2015 were identified. The cohort was stratified by onset of disease using the National Healthcare Safety Network criteria, and by severity using the 2013 American College of Gastroenterology guidelines. Multivariate logistic regression was used to determine independent predictors of severe CDI. RESULTS: A total of 196 met the inclusion criteria, of which 57.1% (112) met criteria for severe disease. Overall, BMI >35 kg/m2 was 1.7-fold more likely to be associated with severe CDI compared to a BMI 20-35 kg/m2 (P < 0.005), and was an independent predictor of severe CDI (P = 0.038). In patients with community-onset-CDI and hospital-onset-CDI, a BMI >35 kg/m2 was associated with a 1.96-fold and 1.48 greater rate of severe CDI compared to a BMI 20-35 kg/m2 (P = 0.004 and 0.048), and was an independent predictor of severe CDI in these cohorts (P = 0.039 and 0.027) respectively. CONCLUSION: This study has identified an association between body mass index and Clostridium difficile infection severity. A BMI>35 kg/m2 is an independent risk factor for severe community-onset and hospital-onset Clostridium difficile infections.

Anticoagulation-related nephropathy.

Anticoagulation-related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin-induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short-term and long-term all-cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all-cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment.

Direct interaction between NHERF1 and Frizzled regulates ß-catenin signaling.

Although Wnt-Frizzled (Fzd) signaling is critical in the pathophysiology of carcinomas, its role in human breast cancer has been difficult to establish. We show here that the adaptor protein Na(+)/H(+) exchange regulatory factor1 (NHERF1), a protein abundantly expressed in normal mammary epithelium, regulates Wnt signaling, maintaining low levels of ß-catenin activation. NHERF1's effects are mediated by direct interactions between one of its PSD-95/drosophila discs large/ZO-1 (PDZ) domains and the C-terminus of a subset of Fzd receptors. Loss of NHERF1 in breast cancer cell lines enhances canonical Wnt signaling and Wnt-dependent cell proliferation. Furthermore, the mammary glands of NHERF1-knockout mice exhibit increased mammary duct density accompanied by increased proliferation and ß-catenin activity. Finally, we demonstrate a negative correlation between NHERF1 expression and nuclear ß-catenin in human breast carcinomas. Taken together, these results provide a novel insight into the regulation of Wnt signaling in normal and neoplastic breast tissues, and identify NHERF1 as an important regulator of the pathogenesis of breast tumors.

Extracellular heat shock protein 60 (Hsp60) levels in children with septic shock.

OBJECTIVE AND DESIGN: Recent data suggest that extracellular Hsp60 modulates the host innate immune response. We analyzed plasma Hsp60 levels in children admitted to a level III tertiary care PICU with septic shock. MATERIALS AND SUBJECTS: Blood samples were obtained from children meeting criteria for septic shock (n = 63), critically ill children without septic shock (n = 10), and healthy controls (n = 24). TREATMENT: Not applicable. METHODS: Hsp60 levels were measured in the plasma using a commercially available ELISA. Differences between groups were analyzed with a Kruskal-Wallis one way ANOVA due to the non-parametric nature of the data. A p value < or = 0.05 was considered significant. RESULTS: Extracellular Hsp60 levels were significantly higher in children with septic shock (median, 16.7 ng/mL) compared to both critically ill children without septic shock (median, 0 ng/mL) and healthy controls (median, 0 ng/mL, p <0.001). CONCLUSIONS: Extracellular Hsp60 levels are significantly elevated in children with septic shock compared with both healthy controls and critically ill children without sepsis. Extracellular Hsp60 may play a role in the pathogenesis of sepsis in children.

Pentalogy of Cantrell associated with hypoplastic left heart syndrome.

Pentalogy of Cantrell is a rare anomaly characterized by midline closure defects, including a defect in the lower sternum, supraumbilical abdominal wall defect, deficiency of the anterior portion of the diaphragm, deficiency in the diaphragmatic portion of the pericardium with free communication between the pericardial and peritoneal cavities, and congenital heart defects. The long-term prognosis for children with this anomaly depends to a great extent on the complexity of the associated congenital heart defect. We describe the previously unreported association of pentalogy of Cantrell with hypoplastic left heart syndrome.

A randomized, blinded comparison of chloral hydrate and midazolam sedation in children undergoing echocardiography.

The objective of this prospective, randomized, and blinded study was to compare the use of chloral hydrate versus oral midazolam sedation in children undergoing echocardiography. No adverse effects (nausea, vomiting, paradoxical agitation, or significant deviations from baseline vital signs) were noted with either medication. No differences were noted in onset of sedation between the 2 groups, however, the time to complete recovery was significantly shorter with midazolam than with chloral hydrate. The children in the chloral hydrate group had a significantly deeper level of sedation and were more likely to receive a more nearly comprehensive echocardiographic evalation.

The suppressive effects of intraperitoneal cocaine are augmented when evaluated in nondeprived rats.

Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with all drugs of abuse tested including morphine, cocaine, heroin, amphetamine, and ethanol. Although most of these drugs suppress intake when administered via a range of routes, the efficacy of cocaine is an exception. Specifically, cocaine-induced suppression of saccharin intake is much greater when administered subcutaneously than when administered intraperitoneally. The subcutaneous route of administration of cocaine, however, is somewhat problematic because, unless diluted, can cause stark necrosis. The present study, then, reexamined the effectiveness of intraperitoneal cocaine using less restrictive deprivation regimens that are known to facilitate the expression of the phenomenon. The results showed that, while only a 10- and 20-mg/kg dose of cocaine suppressed intake of the saccharin CS when evaluated in moderately water-deprived rats, all doses tested (i.e., 5, 10, and 20 mg/kg) significantly reduced CS intake when saccharin-cocaine pairings were evaluated in rats maintained on food and water ad libitum. Taken together, these data show that rats will readily avoid intake of a saccharin cue when paired with the intraperitoneal administration of cocaine and that the magnitude of the effect is augmented when examined in a need-free state.

Chronic morphine treatment exaggerates the suppressive effects of sucrose and cocaine, but not lithium chloride, on saccharin intake in Sprague-Dawley rats.

Three experiments examined the effect of chronic morphine treatment on cocaine-, sucrose-, and lithium chloride (LiCl)-induced suppression of saccharin intake in Sprague-Dawley rats. All rats were either water- or food-deprived and then implanted subcutaneously with 1 morphine (75 mg) or vehicle pellet for 5 days. They were then given brief access to 0.15% saccharin and soon thereafter injected with either cocaine (10 mg/kg s.c.), LiCl (0.009 M, 1.33 ml/100 g body weight i.p.), or saline, or, in Experiment 2, given a 2nd access period to either a preferred 1.0 M sucrose solution or the same 0.15% saccharin solution. There was 1 taste-drug or taste-taste pairing per day for a number of days. The results showed that a history of chronic morphine treatment exaggerated the suppressive effects of a rewarding sucrose solution and cocaine but not those of the aversive agent, LiCl. These data provide further support for the reward comparison hypothesis.

The impact of molecular biology on the practice of pediatric critical care medicine.

Molecular biology is increasingly affecting all areas of clinical medicine, including pediatric critical care medicine. Recent advances in genomics will allow for a more in-depth understanding of disease processes that are relevant to the pediatric intensivist, such as sepsis, the acute respiratory distress syndrome, and multiple organ dysfunction syndrome. In turn, understanding critical illness at the genomic level may allow for more effective stratification of patient subclasses and targeted, patient-specific therapy. The related fields of pharmacogenomics and pharmacogenetics hold the promise of improved drug development and the tailoring of drug therapy based on the individual's drug metabolism profile. Therapeutic strategies aimed at modulating host inflammatory responses remain viable but will need to take into account the inherent redundancy of the host inflammatory response and the heterogenous responses between individual patients. Thus, "immuno-phenotyping" of critically ill patients will allow for more rational immune-modulating therapies, either in the form of inhibiting or enhancing specific immune/inflammatory responses. The host also contains powerful, broad cytoprotective mechanisms that could potentially be harnessed as a strategy for organ and tissue protection in many forms of critical illness. Finally, prospects for gene therapy, although quite challenging at present, may be applicable to the intensive care unit in the near future. With these rapid advancements in molecular biology, it is imperative that all pediatric critical care practitioners become, at least, familiar with the field and its related technology. Hopefully, clinician-scientists involved in pediatric critical care will also shape the direction of these future prospects.

Resident training in pediatric critical care transport medicine: a survey of pediatric residency programs.

OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME) Program Requirement for Pediatrics includes specific objectives that pediatric residents participate in both the pre-hospital care of acutely ill or injured patients and the stabilization and transport of patients to critical care areas. Previously, residents were often included as the physician component for many pediatric critical care transport teams. Subsequent regionalization of transport services and development of nurse-only transport teams prompted us to determine the current level of resident participation in pediatric critical care transport as well as how individual residency programs were meeting the educational objectives. METHODS: A questionnaire was mailed to each pediatric residency program listed in the 1996-1997 GME Directory. Information was obtained regarding the size of the hospital and the residency program, the presence of a pediatric critical care transport team, the number of annual transports, and transport team leader. In addition, the use of pediatric residents for transports was ascertained, as well as their specific role, training requirements, and method of evaluation. RESULTS: Data were received from 138 programs for a return rate of 65%. Eighty percent of programs offered a pediatric critical care transport service. Nurse-led teams were used for 51% of NICU and 44% of PICU transports. Of the 82 NICU and 84 PICU teams that used residents, the majority used them as team leaders (60% and 70%; respectively) with only the minority requiring that they be at the PL-3 year or greater. The training and/or certification required for resident participation in transports varied among programs, with 85% requiring completion of a NICU or PICU rotation, and 94% requiring NRP or PALS certification. Programs that did not allow resident participation provided exposure to Transport Medicine by various mechanisms, including lectures and emergency department (ED) rotations. CONCLUSION: Pediatric resident participation in critical care transport varies widely among pediatric critical care transport teams. The degree to which residents participate in the transport team would appear to have diminished in comparison to previous studies. Transport teams often use other resources, such as nurses, fellows, or attendings, to lead their transport teams. Pediatric resident exposure to and participation in Transport Medicine varies among programs, as do the methods used to prepare residents for their experience.

Pediatric emergency preparedness in the office.

Pediatric office emergencies occur more commonly than is usually perceived by family physicians, and most offices are not optimally prepared to deal with these situations. Obtaining specific training in pediatric emergencies and performing mock "codes" to check office readiness can improve the proper handling of pediatric emergencies. Common airway emergencies include foreign-body aspiration and croup. Cool mist, racemic epinephrine nebulization and dexamethasone are typical treatment measures for croup. Asthma and bronchiolitis are common causes of respiratory distress. Hypovolemic shock is the most common cause of circulatory failure in children. Intraosseous access is a simple and underutilized route for vascular access in a critically ill child. Status epilepticus is the most common neurologic emergency. Avoidance of iatrogenic respiratory depression and hypotension can be optimized by taking an algorithmic approach to the use of anticonvulsant medications. Transport of patients after initial stabilization of an emergency should always be done in a manner that provides adequate safety and monitoring.

The pediatric critical care experience at Naval Hospital Guam: suggestions for critical care training during residency.

OBJECTIVES: To determine the critical care experience encountered by three recently graduated military pediatricians at an overseas military hospital and present one model of maximizing allowable critical care training time during residency. METHOD: Retrospective reviews of all admissions to the special care nursery and intensive care unit at U.S. Naval Hospital Guam were performed for a 3-year and a 2-year period, respectively. Age, diagnosis, birth weight (if applicable), level of nursery care, invasive procedures performed in the nursery (endotracheal tube, umbilical artery, and umbilical venous catheter placement), patient outcome, and the need for medical transport were recorded. RESULTS: During a 3-year period, there were 122 admissions to the special care nursery (7.1% of all deliveries). In addition, pediatricians performed a total of 53 invasive procedures on these patients, and 29 infants required medical transport to an off-island neonatal intensive care unit for additional care. During a 2-year period, 70 pediatric patients were admitted to the adult intensive care unit, representing 10.2% of all intensive care unit admissions during this period. Fourteen of these patients required medical transport to an off-island referral hospital. CONCLUSION: Graduating military pediatric residents may be faced with caring for a wide range of critically ill neonatal and pediatric patients depending on their assignment. Residency training programs, with the recent increased emphasis on primary pediatric care, will need to streamline instruction in pediatric critical care to provide maximal benefit to the resident while maintaining compliance with Residency Review Committee guidelines.

Use of gabapentin in the treatment of childhood reflex sympathetic dystrophy.

Reflex sympathetic dystrophy, a painful syndrome involving an extremity after trauma or injury, is increasingly reported in the pediatric population. Although no clear pathophysiologic mechanism for this disorder has been identified, the role of central serotonin activity seems important. Gabapentin, a new antiepileptic medication, has been demonstrated to be effective in adults with reflex sympathetic dystrophy. The first reported case of a child with a diagnosis of reflex sympathetic dystrophy who was treated successfully with gabapentin is presented.

Isoflurane therapy for status asthmaticus in children: A case series and protocol.

OBJECTIVE: To describe the use of inhaled isoflurane by using a standardized protocol in the treatment of respiratory failure secondary to status asthmaticus in a series of pediatric patients. DESIGN: Case series. SETTING: Pediatric intensive care unit of a tertiary care military medical facility. PATIENTS: Six pediatric patients ranging in age from 14 months to 15 yrs who were treated with isoflurane in our pediatric intensive care unit for status asthmaticus from 1995 to 1998. INTERVENTION: Inhaled isoflurane therapy was initiated by using the treatment protocol after the patients had failed conventional medical management in the treatment of their asthma. MEASUREMENTS AND MAIN RESULTS: All patients tolerated isoflurane therapy well by using our standardized protocol in conjunction with careful hemodynamic monitoring and support. The administration of inhaled isoflurane resulted in measurable improvements in the subject patients, as evidenced by statistically significant decreases in Paco2 and peak inspiratory pressures, as well as a significant increase in pH. All six patients were successfully extubated and were discharged from the hospital without apparent sequelae. CONCLUSIONS: We conclude isoflurane may be a safe, effective treatment modality in the management of status asthmaticus refractory to aggressive medical therapy, although further study is warranted. We emphasize this mode of therapy should be instituted only after traditional treatment modalities have failed and appropriate intensive care support is available.

Emergency medical services for children: a general pediatrician's perspective.

The EMSC movement is still in its infancy, and there is much that remains to be done. The primary care pediatrician plays a major role in the EMSC system and should continue to advocate for efficient, high-quality pediatric emergency care. In summary, there are several ways that the office-based pediatrician can and should become involved with EMSC: 1. Pediatricians should emphasize safe and injury prevention at each health maintenance visit throughout a child's life. 2. Pediatricians should encourage all parents to become certified in BLS/CPR. Ideally, training in CPR should be provided during prenatal and childbirth classes. 3. Pediatricians should advocate for injury prevention and safety campaigns in their communities. They can also become involved with efforts to develop legislation dealing with issues in injury prevention and safety. 4. Pediatricians should ensure that all children receive the appropriate immunizations. 5. Pediatricians need to maintain office emergency preparedness. All office personnel should maintain certification in BLS as a minimum and ideally, PALS. Equipment used for pediatric resuscitation should be available and functional. Monthly mock codes should be scheduled to ensure that all personnel clearly know their roles and responsibilities in the event of an emergency. 6. Pediatricians should maintain their skills in emergency pediatrics. In addition, they should maintain certification in PALS. Continuing medical education (CME) workshops and conferences in emergency pediatrics are available throughout the year. Also, pediatricians can maintain their airway management skills by practicing endotracheal intubation in the operating room setting. 7. Pediatricians must become familiar with the prehospital care providers, EDs, and transport services in their communities. Association with a pediatric intensive care unit at a tertiary care center would also be beneficial. 8. Pediatricians must be available for consultation to local EDs. They must realize that, in many instances, they may represent the physician who is most experienced with caring for the critically ill or injured child. 9. Pediatricians can serve as medical advisors to the EMS systems in their communities. 10. Pediatricians should stay well informed on issues pertaining to EMSC.

Development of a pediatric critical care transport team: experience at a military medical center.

INTRODUCTION: A pediatric critical care transport program was initiated and organized at Naval Medical Center San Diego in January 1994. The primary goal of the program was to formally train military pediatric residents in the early stabilization and transport of the critically ill neonatal and pediatric patient. It was also felt that such a program would generate significant cost savings to the Department of Defense. We present the statistics, training protocol, and the cost savings. In addition, we surveyed previous residents who had been involved with this program to determine its perceived benefit. METHODS: In the first phase of this project, the pediatric critical care transport program database from January 1994 to December 1997 was reviewed. The number and types of transports were recorded. Next, we determined cost savings for the transport program for fiscal year 1996-1998 (the period for which fiscal data were available). In the second phase of this project, we sent surveys to the 23 graduating residents who had participated in the pediatric critical care transport program. The survey sought to determine the perceived value of the transport training experience and the degree to which that training is now being used. All investigators were blinded to the responses. Statistical analysis consisted of determining the percentage of each response. RESULTS: During the 4-year period reviewed, 404 transports were performed (198 neonatal and 206 pediatric). During fiscal year 1996-1998, there was a cost avoidance of $1,962 per transport. In the second phase, 91% of the surveys were returned and analyzed. The majority of residents were practicing in overseas or isolated communities. All respondents rated their experience in the pediatric critical care transport program as worthwhile and educational, and they complemented their training in the neonatal and pediatric intensive care units. Seventy-one percent of the respondents had transported a critically ill neonate or child to another facility within the last year. CONCLUSIONS: In summary, we report our experience with the development of a pediatric critical care transport program. The program was developed to provide military pediatric residents instruction and experience in the stabilization and transport of critically ill children. In addition, we were able to demonstrate a significant cost avoidance.