Silmitasertib plus gemcitabine and cisplatin first-line therapy in locally advanced/metastatic cholangiocarcinoma: A Phase 1b/2 study.

BACKGROUND AND AIMS: This study aimed to investigate safety and efficacy of silmitasertib, an oral small molecule casein kinase 2 inhibitor, plus gemcitabine and cisplatin (G+C) versus G+C in locally advanced/metastatic cholangiocarcinoma. APPROACH AND RESULTS: This work is a Phase 1b/2 study (S4-13-001). In Phase 2, patients received silmitasertib 1000 mg twice daily for 10 days with G+C on Days 1 and 8 of a 21-day cycle. Primary efficacy endpoint was progression-free survival (PFS) in the modified intent-to-treat population (defined as patients who completed at least one cycle of silmitasertib without dose interruption/reduction) from both phases (silmitasertib/G+C n = 55, G+C n = 29). The response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. The median PFS was 11.2 months (95% confidence interval [CI], 7.6, 14.7) versus 5.8 months (95% CI, 3.1, not evaluable [NE]) ( p  = 0.0496); 10-month PFS was 56.1% (95% CI, 38.8%, 70.2%) versus 22.2% (95% CI, 1.8%, 56.7%); and median overall survival was 17.4 months (95% CI, 13.4, 25.7) versus 14.9 months (95% CI, 9.9, NE) with silmitasertib/G+C versus G+C. Overall response rate was 34.0% versus 30.8%; the disease control rate was 86.0% versus 88.5% with silmitasertib/G+C versus G+C. Almost all silmitasertib/G+C (99%) and G+C (93%) patients reported at least one treatment emergent adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib/G+C versus G+C were diarrhea (70% versus 13%), nausea (59% vs. 30%), fatigue (47% vs. 47%), vomiting (39% vs. 7%), and anemia (39% vs. 30%). Twelve patients (10%) discontinued treatment because of TEAEs during the study. CONCLUSIONS: Silmitasertib/G+C demonstrated promising preliminary evidence of efficacy for the first-line treatment of patients with locally advanced/metastatic cholangiocarcinoma.

Synthesis and characterization of Ag-ion-exchanged zeolite/TiO2 nanocomposites for antibacterial applications and photocatalytic degradation of antibiotics.

This paper investigates the synthesis, antibacterial, and photocatalytic properties of silver ion-exchanged natural zeolite/TiO2 photocatalyst nanocomposite. Zeolite is known to have a porous surface structure, making it an ideal substrate and framework in different nanocomposites. Moreover, natural zeolite has a superior thermal and chemical stability, with hardly any reactivity with chemicals. Finding an effective and low-cost method to remove both antibiotics and bacteria from water resources has become a vital global issue due to the worldwide excessive use of chemicals and antibiotics. This research aims to propose a facile method to synthesize Ag-ion-exchanged zeolite/TiO2 catalyst for anti-bacterial purposes and photocatalytic removal of atibiotics from wastewaters. TiO2 particles were deposited on the surface of natural zeolite. Ag ion exchanging was performed via a liquid ion-exchange method using 0.1 M AgNO3 solution. X-ray diffractometry (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Fourier-transform infrared spectroscopy (FTIR) were used to evaluate the structure of synthesized powders. Antibacterial activities of samples were assessed, using Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 by disc diffusion method. It was shown that Ag-containing nanocomposite samples have an improved antibacterial performance in both cases. Results showed that the synthesized catalyst has promising potentials in wastewater treatment.

Serological diagnosis of pulmonary Mycobacterium tuberculosis infection by LIPS using a multiple antigen mixture.

BACKGROUND: There is an urgent need for a simple and accurate test for the diagnosis of human Mycobacterium tuberculosis, the infectious agent causing tuberculosis (TB). Here we describe a serological test based on light emitting recombinant proteins for the diagnosis of pulmonary Mycobacterium tuberculosis infection. METHODS: Luciferase Immunoprecipitation Systems (LIPS), a fluid-phase immunoassay, was used to examine antibody responses against a panel of 24 different M. tuberculosis proteins. Three different strategies were used for generating the constructs expressing the recombinant fusion M. tuberculosis proteins with luciferase: synthetic gene synthesis, Gateway recombination cloning, and custom PCR synthesis. A pilot cohort of African pulmonary TB patients was used for initial antibody screening and confirmatory studies with selected antigens were performed with a cohort from Thailand and healthy US blood donors. In addition to testing M. tuberculosis antigens separately, a mixture that tested seven antigens simultaneously was evaluated for diagnostic performance. RESULTS: LIPS testing of a pilot set of serum samples from African pulmonary TB patients identified a potential subset of diagnostically useful M. tuberculosis antigens. Evaluation of a second independent cohort from Thailand validated highly significant antibody responses against seven antigens (PstS1, Rv0831c, FbpA, EspB, bfrB, HspX and ssb), which often showed robust antibody levels up to 50- to 1000-fold higher than local community controls. Marked heterogeneity of antibody responses was observed in the patients and the combined results demonstrated 73.5% sensitivity and 100% specificity for detection of pulmonary TB. A LIPS test simultaneously employing the seven M. tuberculosis antigen as a mixture matched the combined diagnostic performance of the separate tests, but showed an even higher diagnostic sensitivity (90%) when a cut-off based on healthy US blood donors was used. CONCLUSION: A LIPS immunoassay employing multiple M. tuberculosis antigens shows promise for the rapid and quantitative serological detection of pulmonary TB.

Anti-cytokine autoantibodies in postherpetic neuralgia.

BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN.

No Evidence of Antibodies against GAD65 and Other Specific Antigens in Children with Autism.

BACKGROUND: The presence of autoantibodies has been proposed as evidence for a role of autoimmunity in autism. This report investigates the prevalence of autoantibodies in children with autism using the luciferase immunoprecipitation systems (LIPS) immunoassay technology. A panel of autoantibody targets against several known and candidate neurological autoantigens, autoimmune-associated autoantigens and viruses was employed. METHODS: Serological analysis was performed on typically developing children (n = 55), developmentally delayed children without autism (n = 24) and children diagnosed with autism (n=104). Autoantibodies were measured against glutamic acid decarboxylase-65 (GAD65), a CNS autoantigen proposed to be associated with autism and against Ro52, glial fibrillary acidic protein, tyrosine hydroxylase, aquaporin-4, and gamma-enolase, the mouse mammary tumor virus and the xenotropic murine leukemia virus. Antibody levels and seropositivity prevalence were analyzed for statistically significant differences between the three groups. RESULTS: The majority of the children (98%) were seronegative for all targets in the antigen panel. No GAD65 seropositive children were detected in the cohort. Several low level seropositive sera against several of the protein targets were identified in isolated children in each of the three groups, but there was no difference in prevalence. CONCLUSION: Using this panel of antigens and a sensitive, robust assay, no evidence of unusual immunoreactivity was detected in children with autism, providing evidence against a role of autoimmunity against several previously implicated proteins in autism spectrum disorder pathogenesis. GENERAL SIGNIFICANCE: The idea that autoantibodies represent an underlying cause or are biomarkers for autism pathophysiology is not supported by this report.

PI3K/AKT and Mdm2 activation are associated with inhibitory effect of cAMP increasing agents on DNA damage-induced cell death in human pre-B NALM-6 cells.

DNA damage response (DDR) consists of both proapoptotic and prosurvival signaling branches. Superiority of each signaling branch determines the outcome of DNA damage: death or allowing the repair. The present authors have previously shown that an increased intracellular level of cAMP disrupts p53-mediated apoptosis in human pre-B NALM-6 cells and inhibition of NF-κB prevents prosurvival effect of cAMP during DNA damage. AKT/PKB (protein kinase B) is a general mediator of survival signaling. AKT signaling inhibits p53-mediated transcription and apoptosis. The results of present study showed that cAMP disrupted DNA damage/p53-mediated apoptosis through AKT and subsequent NF-κB activation. These results suggested that AKT may be found as part of a complex with scaffolding proteins, beta-arrestins and PDE4D. cAMP disarticulated the complex through binding to PDE4D compartment. It seems that release of AKT protein potentiated DDR activated pro-survival AKT in NALM-6 cells. Taken together, the present data indicated that regulation of AKT signaling may determine the fate of cells exposed to genotoxic stress.

Detection of antibodies to varicella-zoster virus in recipients of the varicella vaccine by using a luciferase immunoprecipitation system assay.

A high-throughput test to detect varicella-zoster virus (VZV) antibodies in varicella vaccine recipients is not currently available. One of the most sensitive tests for detecting VZV antibodies after vaccination is the fluorescent antibody to membrane antigen (FAMA) test. Unfortunately, this test is labor-intensive, somewhat subjective to read, and not commercially available. Therefore, we developed a highly quantitative and high-throughput luciferase immunoprecipitation system (LIPS) assay to detect antibody to VZV glycoprotein E (gE). Tests of children who received the varicella vaccine showed that the gE LIPS assay had 90% sensitivity and 70% specificity, a viral capsid antigen enzyme-linked immunosorbent assay (ELISA) had 67% and 87% specificity, and a glycoprotein ELISA (not commercially available in the United States) had 94% sensitivity and 74% specificity compared with the FAMA test. The rates of antibody detection by the gE LIPS and glycoprotein ELISA were not statistically different. Therefore, the gE LIPS assay may be useful for detecting VZV antibodies in varicella vaccine recipients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00921999.).

HIV antibody characterization as a method to quantify reservoir size during curative interventions.

Quantitative humoral profiling of recent samples from a human immunodeficiency virus (HIV)-infected adult who was cured following a delta32/delta32 CCR5 stem cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid, integrase, protease, and gp120, but low levels of antibodies against reverse transcriptase, tat, and gp41. Antibody levels to these HIV proteins persisted at high and stable levels in most noncontrollers, elite controllers, and antiretroviral-treated subjects, but a rare subset of controllers had low levels of antibodies against matrix, reverse transcriptase, integrase, and/or protease. Comprehensive HIV antibody profiles may prove useful for monitoring curative interventions.

Altered antibody profiles against common infectious agents in chronic disease.

Despite the important diagnostic value of evaluating antibody responses to individual human pathogens, antibody profiles against multiple infectious agents have not been used to explore health and disease mainly for technical reasons.  We hypothesized that the interplay between infection and chronic disease might be revealed by profiling antibodies against multiple agents. Here, the levels of antibodies against a panel of 13 common infectious agents were evaluated with the quantitative Luciferase Immunoprecipitation Systems (LIPS) in patients from three disease cohorts including those with pathogenic anti-interferon-γ autoantibodies (IFN-γ AAB), HIV and Sjögren's syndrome (SjS) to determine if their antibody profiles differed from control subjects.  The IFN-γ AAB patients compared to controls demonstrated statistically higher levels of antibodies against VZV (p=0.0003), EBV (p=0.002), CMV (p=0.003), and C. albicans (p=0.03), but lower antibody levels against poliovirus (p=0.04). Comparison of HIV patients with blood donor controls revealed that the patients had higher levels of antibodies against CMV (p=0.0008), HSV-2 (p=0.0008), EBV (p=0.001), and C. albicans (p=0.01), but showed decreased levels of antibodies against coxsackievirus B4 (p=0.0008), poliovirus (p=0.0005),   and HHV-6B (p=0.002). Lastly, SjS patients had higher levels of anti-EBV antibodies (p=0.03), but lower antibody levels against several enteroviruses including a newly identified picornavirus, HCoSV-A (p=0.004), coxsackievirus B4 (p=0.04), and poliovirus (p=0.02). For the IFN-γ AAB and HIV cohorts, principal component analysis revealed unique antibody clusters that showed the potential to discriminate patients from controls.  The results suggest that antibody profiles against these and likely other common infectious agents may yield insight into the interplay between exposure to infectious agents, dysbiosis, adaptive immunity and disease activity.

Lack of serum antibodies against Borrelia burgdorferi in children with autism.

It has been proposed that Borrelia burgdorferi infection is present in ∼25% of children with autism spectrum disorders. In this study, antibodies against Borrelia burgdorferi were assessed in autistic (n = 104), developmentally delayed (n = 24), and healthy control (n = 55) children. No seropositivity against Borrelia burgdorferi was detected in the children with and without autism. There was no evidence of an association between Lyme disease and autism.

Quantitative determinations of anti-Kaposi sarcoma-associated herpesvirus antibody levels in men who have sex with men.

Infection with Kaposi sarcoma-associated herpesvirus (KSHV; also called human herpesvirus-8) is common among men who have sex with men (MSM). Here, quantitative anti-KSHV antibody levels were measured using luciferase immunoprecipitation systems (LIPS) in an MSM cohort with and without HIV from the NIH Clinical Center. Antibodies were detected using a mixture of 4 KSHV antigens in the MSM cohort and in Kaposi sarcoma (KS) patients. Along with HIV status, these results were compared with K8.1 and ORF73 ELISA, PCR virus detection, and additional LIPS testing. LIPS revealed that 25% (76/307) of the MSM cohort were KSHV seropositive, including 59 HIV+ and 17 HIV- subjects. The anti-KSHV antibody levels detected by LIPS were not statistically different between the KSHV+/HIV+ and KSHV+/HIV- subgroups but were lower than the KS patients (P < 0.0001). ELISA analysis of the MSM cohort detected a 35.5% frequency of KSHV infection and showed agreement with 81% of the samples evaluated by LIPS. Further LIPS testing with v-cyclin, a second ORF73 fragment and ORF38 reconciled some of the differences observed between LIPS and the ELISA immunoassays, and the revised LIPS seroprevalence in the MSM cohort was increased to 31%. Additional quantitative antibody analysis demonstrated statistically lower KSHV antibody levels in MSM compared to KS patients, but no difference was found between KSHV infected with and without HIV coinfection. These findings also suggest that antibodies against v-cyclin and ORF38 are useful for identifying patients with asymptomatic KSHV infection.

Early hemodynamic changes after mitral valve replacement in patients with severe and mild pulmonary artery hypertension.

PURPOSE: to assess the early hemodynamic changes after elective mitral valve replacement (MVR) in patients with severe and mild pulmonary arterial hypertension (PAH). METHODS: a total of 45 consecutive patients, who were candidate for elective MVR, were enrolled in this prospective observational study. Patients were divided into two groups based on the absence (group A, 20 patients) or presence (group B, 25 patients) of severe pulmonary artery hypertension (PAH) defined as systolic pulmonary artery pressure ≥50 mmHg measuring by catheterization. MVR was performed using standard cardiopulmonary bypass (CBD) technique. The hemodynamic and arterial blood gas assessments were carried out at baseline before the induction of general anesthesia, in the operating room immediately after MVR, and then continued after stabilization of hemodynamic status with 2 hr interval up to 24 hours. RESULTS: The mean CPB and aortic cross-clamp times were similar in two groups (95.3 ± 49.5 and 61.8 ± 36.3 minutes in group A and 103.1 ± 34.7and 61.9 ± 20.0 minutes in group B). In group A, the mean PAP showed an increase immediately after the operation (from 40.4 ± 7.3 to 43.10 ± 6.2 mmHg) and then decreased significantly to 32.5 ± 3.9 mmHg (P <0.05). In group B, the mean PAP showed no significant reduction immediately after MVR, but it decreased significantly below the range of severe PAP over the first 24 hours. CONCLUSION: MVR is safe and effective even in patients with severe PAH. The anesthetic technique and postoperative cares can be useful in improving the outcome in such patients.

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.

Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases. Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101). Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors. Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region. In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity. To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibodies. While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B. However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients. These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV-6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.

Extrapancreatic autoantibody profiles in type I diabetes.

Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing ß-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-ß. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-ß (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together, these results suggest that autoantibody portraits derived from islet and organ-specific targets will likely be useful for enhancing the clinical management of T1D.

The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma.

Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP), Kaposi's sarcoma (KS), or non-Hodgkin lymphoma (NHL). Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84%) showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94%) in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.

Psychological evaluation in hemodialysis patients.

INTRODUCTION: End stage renal disease has a high burden of disease affecting patient's quality of life and this may dramatically shorten their life expectancy. These patients may be faced with serious stressors which are related to the disease and its treatment. Considering psychosocial problems in hemodialysis patients, we designed this study to evaluate depression, anxiety, social support and to determine temperament, character and correlation between these factors in hemodialysis patients. METHODS: This was a multicenter cross-sectional study which was done on 218 hemodialysis patients in Isfahan during April-July 2011. Depression, anxiety, social support, temperament and character were evaluated in patients using Hospital Anxiety and Depression Scale (HADS), Persian version of Multidimensional Scale of Perceived Social Support (MSPSS-P) and Temperament and Character Inventory (TCI) questionnaires. RESULTS: 138 (63.3%) subjects were male. Mean age was 58.18 +/- 14.3 years. 95 (43.6%) participants had depression and 94 (43.1%) had anxiety. Family support had the highest score between social support subscales. Family support was significantly correlated with self-directedness (p = 0.012), cooperativeness (p = 0.03), self-transcendence (p = 0.018), reward dependence and friends support (p = 0.036) and cooperativeness and others support (p = 0.049). CONCLUSION: Physicians should be aware of depression and anxiety in hemodialysis patients. Our results showed that patients had a supportive relation with their family and it could be because of Iranian culture and religious believes. In terms of temperament and character, patients were tolerant, supportive, humble and sociable.

Ionic liquid based on α-amino acid anion and N7,N9-dimethylguaninium cation ([dMG][AA]): theoretical study on the structure and electronic properties.

The interactions between five amino acid based anions ([AA](-) (AA = Gly, Phe, His, Try, and Tyr)) and N7,N9-dimethylguaninium cation ([dMG](+)) have been investigated by the hybrid density functional theory method B3LYP together with the basis set 6-311++G(d,p). The calculated interaction energy was found to decrease in magnitude with increasing side-chain length in the amino acid anion. The interaction between the [dMG](+) cation and [AA](-) anion in the most stable configurations of ion pairs is a hydrogen bonding interaction. These hydrogen bonds (H bonds) were analyzed by the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. Finally, several correlations between electron densities in bond critical points of hydrogen bonds and interaction energy as well as vibrational frequencies in the most stable configurations of ion pairs have been checked.

Analgesia and sedation for children undergoing burn wound care.

Standard care of burn wounds consists of cleaning and debridement (removing devitalized tissue), followed by daily dressing changes. Children with burns undergo multiple, painful and anxiety-provoking procedures during wound care and rehabilitation. The goal of procedural sedation is safe and efficacious management of pain and emotional distress, requiring a careful and systematic approach. Achieving the best results needs understanding of the mechanisms of pain and the physiologic changes in burn patients, frequent evaluation and assessment of pain and anxiety, and administration of suitable pharmacological and nonpharmacological therapies. Pharmacological therapies provide the backbone of analgesia and sedation for procedural pain management. Opioids provide excellent pain control, but they must be administered judiciously due to their side effects. Sedative drugs, such as benzodiazepines and propofol, provide excellent sedation, but they must not be used as a substitute for analgesic drugs. Ketamine is increasingly used for analgesia and sedation in children as a single agent or an adjuvant. Nonpharmacological therapies such as virtual reality, relaxation, cartoon viewing, music, massage and hypnosis are necessary components of procedural sedation and analgesia for children. These can be combined with pharmacological techniques and are used to limit the use of drugs (and hence side effects), as well as to improve patient participation and satisfaction. In this article, we review the pathophysiologic changes associated with major thermal injury in children, the options available for sedation and analgesia for wound care procedures in these children and our institutional guidelines for procedural sedation.