Combination of vaniprevir with peginterferon and ribavirin significantly increases the rate of SVR in treatment-experienced patients with chronic HCV genotype 1 infection and cirrhosis.

BACKGROUND & AIMS: The combination of vaniprevir (a NS3/4A protease inhibitor) with peginterferon and ribavirin was shown to increase rates of sustained virologic response (SVR) significantly, compared with peginterferon and ribavirin alone, in treatment-experienced patients with chronic hepatitis C virus (HCV) genotype 1 infection without cirrhosis. We performed a blinded, randomized, controlled trial of the effects of vaniprevir with peginterferon and ribavirin in patients with cirrhosis who did not respond to prior therapy with peginterferon and ribavirin. METHODS: Treatment-experienced patients (88% white and 35% prior null responders) with HCV genotype 1 infection and compensated cirrhosis were assigned randomly to groups given vaniprevir (600 mg twice daily) with peginterferon and ribavirin for 24 weeks (n = 16), vaniprevir (600 mg twice daily) for 24 weeks with peginterferon and ribavirin for 48 weeks (n = 14), vaniprevir (300 mg twice daily) with peginterferon and ribavirin for 48 weeks (n = 15), vaniprevir (600 mg twice daily) with peginterferon and ribavirin for 48 weeks (n = 15), or placebo with peginterferon and ribavirin for 48 weeks (n = 14, control). Cirrhosis was documented by liver biopsy (84%) or noninvasive methods (16%). Before randomization, participants were stratified based on their historical response to peginterferon and ribavirin. RESULTS: In the primary analysis, SVR rates among patients in the respective vaniprevir groups were 9 of 15 (60.0%), 9 of 13 (69.2%), 8 of 15 (53.3%), and 10 of 13 (76.9%), compared with 2 of 14 (14.3%) in the control group (pairwise P values ≤ .016). Cirrhotic patients with null or partial responses to prior therapy achieved SVR less often than patients with prior breakthrough or relapse, although 42.1% of prior null responders in the vaniprevir groups achieved SVRs. Patients in the vaniprevir groups more frequently experienced mild-moderate nausea, vomiting, and diarrhea than controls; 5% developed grade 2 anemia compared with none in the control group (no patient developed grade 3 or 4 anemia). Among patients in the vaniprevir groups who experienced virologic failure, resistance-associated variants were detected predominantly at positions 155, 156, and 168 in the HCV protease gene. CONCLUSIONS: In a controlled phase 2B trial, vaniprevir with peginterferon and ribavirin significantly increased rates of SVR among treatment-experienced patients with chronic HCV genotype 1 infection, compared with re-treatment with peginterferon and ribavirin alone. Vaniprevir generally was well tolerated for up to 48 weeks in patients with compensated cirrhosis. ClinicalTrials.gov number, NCT00704405.

Utilizing a critical airway response team expedites esophageal button battery removal.

BACKGROUND: Esophageal button battery ingestion is a significant problem that can lead to significant complications such as tracheoesophageal fistula, esophageal perforation, and aortoesophageal fistula. Due to this, prompt recognition and treatment is integral in the care of these patients. METHODS: Patients who presented to a single institution from August 2015 to April 2022 with esophageal button battery ingestion were included in this study. All esophageal button battery ingestion patients were included in a clinical algorithm for Critical Airway Response Team (CART) activation in October 2019. Time from diagnosis to treatment was compared for pre-CART clinical algorithm implementation to post-CART. RESULTS: Data on pre-CART patients (n = 6) and post-CART patients (n = 7) was collected. Including esophageal button battery ingestions to CART activations shortened the time from chest x-ray to button battery removal from 73 ± 32 min to 35 ± 11 min (p < 0.05). CONCLUSION: These data highlight the importance of implementation of a clinical care algorithm to shorten the time from diagnosis to treatment in patients with esophageal button battery ingestion. LEVEL OF EVIDENCE: III.

Caspofungin use in patients with invasive candidiasis caused by common non-albicans Candida species: review of the caspofungin database.

Increasing rates of invasive candidiasis caused by non-albicans Candida species have been reported worldwide. Particular concerns have been raised for C. parapsilosis because of reduced in vitro susceptibility to echinocandins. We identified 212 patients with invasive candidiasis due to non-albicans Candida species (>or=5 cases per species) in 5 clinical trials of caspofungin monotherapy from the pharmaceutical sponsor's (Merck and Co., Inc.) database: 71 cases were caused by C. parapsilosis, 65 by C. tropicalis, 54 by C. glabrata, 10 by C. krusei, 9 by C. guilliermondii, and 5 by C. lusitaniae. One hundred sixty-seven cases caused by C. albicans were also identified. Efficacy was assessed at the end of caspofungin therapy. Success (favorable overall response) required favorable clinical and microbiological responses. The mean APACHE II scores were 16.5 in the non-albicans group and 15.7 in the C. albicans group. Neutropenia at study entry was more common in the non-albicans group (12%) than in the C. albicans group (5%). The median duration of caspofungin therapy was 14 days in both groups. The success rates were 77% in both groups and at least 70% for each non-albicans species: 74% for C. parapsilosis, 71% for C. tropicalis, 85% for C. glabrata, 70% for C. krusei, 89% for C. guilliermondii, and 100% for C. lusitaniae. The times to negative blood culture were similar for the various species. The overall mortality rates were 26% in the non-albicans group and 29% in the C. albicans group. Drug-related serious adverse events and discontinuations due to caspofungin toxicity were uncommon. Although the sample sizes were limited, caspofungin demonstrated favorable efficacy and safety profiles in the treatment of invasive candidiasis caused by the following non-albicans Candida species: C. parapsilosis, C. tropicalis, C. glabrata, C. krusei, C. guilliermondii, and C. lusitaniae.

Scrotal abcess mimicking testicular torsion in a premature infant.

The differential diagnosis between testicular torsion and scrotal abscess in the neonate can be extremely difficult. Early surgical exploration in all cases is the intervention of choice in the postnatal acute scrotum.

Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.

BACKGROUND: Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B. METHODS: In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point. RESULTS: Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events. CONCLUSIONS: Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.

Efficacy of Analgesic Treatments to Manage Children's Postoperative Pain After Laparoscopic Appendectomy: Retrospective Medical Record Review.

Knowledge of the effectiveness of multimodal analgesic treatments to manage children's postoperative pain during hospital stays is limited. Our retrospective chart review of a convenience sample of 200 pediatric surgical patients' pain experiences during the first 24 hours after laparoscopic appendectomy demonstrates the benefits of a multimodal analgesic approach. We found that pediatric patients who received perioperative IV ketorolac in addition to opioids reported statistically significantly lower mean pain intensity (n = 134, mean [M] = 2.9, standard deviation [SD] = 1.7) during the first 24 hours after surgery when compared with the pain intensity of patients who did not receive perioperative IV ketorolac (n = 66, M = 3.7, SD = 1.7, t = 3.14, P = .002). Patients who received perioperative IV ketorolac (M = 0.94, SD = 0.71) also received significantly fewer morphine equivalents of postoperative opioids during the first 24 hours after surgery than those who did not (M = 1.21, SD = 0.78, t = 2.41, P = .02). We will use data from these patients to introduce the potential for a personalized medicine approach to postoperative pain.

Presentation and Surgical Management of Duodenal Duplication in Adults.

Duodenal duplications in adults are exceedingly rare and their diagnosis remains difficult as symptoms are largely nonspecific. Clinical presentations include pancreatitis, biliary obstruction, gastrointestinal bleeding from ectopic gastric mucosa, and malignancy. A case of duodenal duplication in a 59-year-old female is presented, and her treatment course is reviewed with description of combined surgical and endoscopic approach to repair, along with a review of historic and current recommendations for management. Traditionally, gastrointestinal duplications have been treated with surgical resection; however, for duodenal duplications, the anatomic proximity to the biliopancreatic ampulla makes surgical management challenging. Recently, advances in endoscopy have improved the clinical success of cystic intraluminal duodenal duplications. Despite these advances, surgical resection is still recommended for extraluminal tubular duplications although combined techniques may be necessary for long tubular duplications. For duodenal duplications, a combined approach of partial excision combined with mucosal stripping may offer advantage.

Overview of safety experience with caspofungin in clinical trials conducted over the first 15 years: a brief report.

Safety experience is available from 32 completed clinical studies (17 Phase I and 15 Phase II-III) of caspofungin (CAS) conducted between 1995 and 2010 in adult and paediatric patients. Clinical and laboratory adverse events (AEs) were collected from all enrolled subjects and patients. Investigators identified the seriousness, causality and result of all AEs noted during study therapy and for up to 28 days post therapy. Up to 31 December 2010, full safety data are available from 1951 individuals who have received at least one dose of CAS in Phase I-III clinical studies, including 171 paediatric patients, 394 volunteer adult subjects and 1386 adult patients (276 with oropharyngeal/oesophageal candidiasis, 366 with invasive candidiasis, 180 with invasive aspergillosis and 564 with persistent fever and neutropenia). CAS was administered for up to 196 days at daily doses ranging from 5mg to 210 mg. Overall, 41.8% of CAS recipients had an AE that was classified as drug-related. The most frequently reported drug-related AEs were fever (9.3%), chills (5.2%), increased alanine aminotransferase (6.5%), increased aspartate aminotransferase (6.0%) and increased alkaline phosphatase (5.2%). Serious AEs were reported in 27.3% of CAS recipients overall but were attributed to CAS in only 0.8%, and discontinuation of CAS due to a drug-related AE was infrequent (2.7%). Dose-related CAS toxicity was not observed. In conclusion, CAS has demonstrated a favourable safety profile in 1951 adult and paediatric patients enrolled in clinical trials.

National trends in the surgical management of Meckel's diverticulum.

BACKGROUND: Treatment recommendations for Meckel's diverticulum (MD) come mostly from single-institution case series. The objective of this study was to review the surgical management and outcomes of children undergoing Meckel's diverticulectomy using contemporary data from a national database. METHODS: We queried 2007 to 2008 data from the Pediatric Health Information System database and analyzed demographic and outcome variables for patients undergoing surgical resection of MD. Cases were classified as primary (symptomatic MD) or secondary (incidental MD). Outcomes in primary cases were compared between open and laparoscopic approaches. Statistical analyses were performed using SPSS (Chicago, IL). RESULTS: Eight hundred fifteen children underwent Meckel's diverticulectomy. Meckel's diverticulectomy was more common in boys (boy-girl, 2.3:1), and half (53%) of the children required surgery before their fourth birthday. More cases (n = 485; 60%) were classified as primary, and most children were approached by laparotomy (75%). The most common presentations for primary cases were obstruction (30%), bleeding (27%), and intussusception (19%). In the primary group, patients treated with the laparoscopic approach had a shorter length of stay (open approach, 5.7 ± 5.2 days; laparoscopic approach, 4.3 ± 2.7 days; P < .02). CONCLUSION: These data describe current trends in the surgical treatment of MD in the United States. Laparoscopic Meckel's diverticulectomy appears to shorten length of stay but is used much less frequently than the traditional open approach.

All-terrain vehicle riding among youth: how do they fair?

PURPOSE: Pediatric all-terrain vehicle (ATV) injuries have been increasing annually for more than a decade. The objective of this study was to describe the riding behaviors, helmet use, and crash history of young ATV riders. METHODS: A 38 question self-administered survey was distributed to a convenience sample of children at 4 agricultural fairs during 2007. A total of 228 surveys were reviewed. Collected data included demographic information, ATV characteristics, helmet use, driving habits, and crash history. RESULTS: Survey respondents were predominantly male (71%) with an average age of 13.6 +/- 2.0 years. Riding began at a young age (9.2 +/- 3.2 years). Few children reported using age-appropriate sized engines (3% < 90 cm(3)), and 22% of children rode ATVs with engines more than 300 cm(3). Respondents rode primarily for recreation (94%), and more than a third reported riding without a helmet (40%). More than 70% of children reported riding with passengers, 60% without adult supervision, and nearly half (46%) rode after dark. Less than 5% of riders received any formal ATV riding/safety instruction. Of the respondents, 45% reported being involved in an ATV crash. Those children who reported a crash also rode more powerful ATVs, were more often self-taught, and overall reported higher rates of riding with passengers and without supervision, and riding after dark (P < .05). CONCLUSION: Dangerous driving behavior among children who ride ATVs is widespread, and current safety recommendations are largely ignored. Renewed efforts are needed to improve safety programs and create policy measures that prevent pediatric ATV crash-related injuries.

A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia.

BACKGROUND: Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients. METHODS: Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or L-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee. RESULTS: Eighty-two patients received study therapy (caspofungin 56, L-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; L-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95% confidence interval] were similar between the caspofungin and L-AmB groups (clinical 48.2% [34.7-62.0] versus 46.2% [26.6-66.6]; laboratory 10.7% [4.0-21.9] versus 19.2% [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8%) of caspofungin-treated patients and 3 (11.5%) of L-AmB-treated patients. Overall success rates [95% CI] were 46.4% [33.4-59.5] for caspofungin and 32.0% [13.7-50.3] for L-AmB. CONCLUSIONS: Caspofungin and L-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.

Safety experience with caspofungin in pediatric patients.

We analyzed the caspofungin safety experience in 5 clinical registration studies in 171 pediatric patients, 1 week to 17 years of age. Caspofungin was administered for 1 to 87 (mean 12.1) days. The most common drug-related adverse events were fever, increased AST, increased ALT, and rash; few events were serious or required treatment discontinuation. Caspofungin was well tolerated in this pediatric population.

Clostridium septicum infections in children: a case report and review of the literature.

Clostridium myonecrosis is a rare and deadly infection that progresses very rapidly; thus, prompt diagnosis and treatment is vital. In adults, clostridial myonecrosis used to be a well-known complication of war wounds. Today, it is usually seen in settings of trauma, surgery, malignancy, skin infections/burns, and septic abortions. More recently, cases of nontraumatic or spontaneous clostridial myonecrosis have been reported in both adults and children. Clostridium perfringens and Clostridium septicum are responsible for the majority of the clinically relevant infections. Higher mortality rates are seen when C septicum is the causative agent. Here we present a child who survived a severe case of C septicum myonecrosis involving both abdominal and thoracic cavities. This rare infection has a high mortality rate and might be easily misdiagnosed in children, even by experienced clinicians, because of its nonspecific presentation. We also review all reported pediatric cases of C septicum infection and myonecrosis and discuss the surgical and medical interventions associated with improved survival. We identified a total of 47 cases of C septicum infection; of these, 22 (47%) were cases of C septicum associated with myonecrosis. Several factors, if available, were analyzed for each case: age, gender, infection location, previous diagnoses, presenting signs and symptoms, neutropenia, gross pathology of the colon, antibiotic use, surgical intervention, and final outcome. We found that conditions related with C septicum infection in children can be grouped into 3 major categories: patients with neutrophil dysfunction; patients with associated bowel ischemia; and patients with a history of trauma. Malignancies were found in 49% of the cases, cyclic or congenital neutropenia in 21%, hemolytic-uremic syndrome in 11%, structural bowel ischemia in 4%, and local extremity trauma in 6%. In addition, 6% of the cases had no known underlying disorder. Abdominal symptoms including vomiting, diarrhea, blood per rectum, abdominal pain, anorexia, and/or acute abdomen, were reported in 85% of the children. Fever was also a common finding. The mainstay of treatment for C septicum infection was parenteral antibiotics and/or surgical intervention. The mortality rate for children with C septicum infection and myonecrosis was 57% and 59%, respectively. Although 82% of all cases received antibiotics, only 43% underwent therapeutic surgical intervention. Several clinical factors were found to be associated with improved survival. Only 35% of the children with gastrointestinal tract involvement survived, compared with 86% of the children without gastrointestinal tract involvement. The survival rates for other conditions ranged from 0% to 50%. One hundred percent survival was reported in patients with no previously diagnosed conditions and those with infections resulting from trauma to the extremities. All survivors received antibiotic treatment, compared with only 68% of the nonsurvivors. Most survivors (84%) underwent therapeutic surgical intervention, compared with only 12% of nonsurvivors. Other treatments were used adjunctively, including hyperbaric oxygen, granulocyte colony-stimulating factor, granulocyte transfusions, and intravenous immunoglobulin. C septicum infections in children are often fatal; thus, one needs to have a high index of suspicion in at-risk patients. This review describes who these patients are, their clinical presentation, and the therapeutic strategies associated with improved survival.

Inguinal hernia in preterm infants (< or = 32-week gestation).

The current incidence of inguinal hernia (IH) in premature infants is not well-established. It is also unclear whether common co-morbidities in this population, i.e., chronic lung disease (CLD) or nutritional status or both contribute to the development of IH. The purpose of this study was to establish the epidemiologic profile of preterm infants of 32 weeks gestational age (GA) or less at birth with IH and determine whether the severity of CLD or poor nutritional status predisposes to the development of IH. Perioperative profiles of infants undergoing surgery were also reviewed. A retrospective study of 1,057 infants born at 23-32 weeks GA from January 1990 to December 1995 was done. Specific risk and demographic factors were identified. Factors used to determine severity of CLD were: days on intermittent mandatory ventilation (IMV); days on positive pressure (IMV + continuous positive airway pressure); and total number of days on supplemental oxygen. Overall nutritional status was determined by weight gain in g/kg per day. The incidence of IH in preterm infants of 32 weeks GA or less who were admitted for 28 days or more was 9.34% (65/696) prior to discharge. The incidence in infants weighing 1,500 g or less was 11.11% (63/567) and in infants 1,000 g or less 17.39% (48/276). All parameters that determined the severity of CLD were statistically significant in infants with IH by univariate analysis. In a multivariate regression model, male gender was the most important variable that was significantly associated with IH (odds ratio OR=9.6; 95% confidence interval CI=3.90-23.59), followed by total days on supplemental oxygen (adjusted OR=1.00; 95% CI= 1.01-1.02). Weight gain (g/kg per day) was not significantly different between the two groups. Surgical correction before discharge was well tolerated. We conclude that the incidence of IH is GA-dependent. Factors related to severity of CLD play a more important role than weight gain in predisposing to IH.