Long-term outcomes for children and adolescents with Kaposi sarcoma.

OBJECTIVES: Kaposi sarcoma (KS) is one of the most common childhood cancers in eastern and central Africa. It has become a treatable disease with increasing availability of antiretroviral therapy (ART) and chemotherapy. We aimed to fill the data gap in establishing whether long-term survival is achievable for children in low-income countries. METHODS: We retrospectively analysed data for children and adolescents aged ≤ 18.9 years diagnosed with HIV-related or endemic KS from 2006 to 2015 who received standardized institutional treatment regimens utilizing chemotherapy plus ART (if HIV-positive) at a tertiary care public hospital in Lilongwe, Malawi. Long-term survival was analysed and mortality was associated with KS for those with refractory/progressive disease at the time of death. RESULTS: There were 207 children/adolescents with KS (90.8% HIV-related); 36.7% were alive, 54.6% had died, and 8.7% had been lost to follow-up. The median follow-up time for survivors was 6.9 years (range 4.2-13.9 years). Death occurred at a median of 5.3 months after KS diagnosis (range 0.1-123 months). KS progression was associated with mortality for most (61%) early deaths (survival time of < 6 months); conversely, KS was associated with a minority (31%) of late-onset deaths (after 24 months). The 7-year overall survival was 37% [95% confidence interval (CI) 30-44%] and was higher for those diagnosed between 2011 and 2015 compared to 2006-2010: 42% (95% CI 33-51%) versus 29% (95% CI 20-39%), respectively (P = 0.01). Among the 66 HIV-positive survivors, 58% were still on first-line ART. CONCLUSIONS: Long-term survival is possible for pediatric KS in low-resource settings. Despite better survival in more recent years, there remains room for improvement.

Inappropriate Transfer of Burn Patients: A 5-Year Retrospective at a Single Center.

OBJECTIVE: Burn injuries have an annual incidence exceeding 40,000. The Burn Center Referral Criteria published by the American Burn Association (ABA) serve to guide health centers in determining appropriateness of patient transfer to a specialized center. With inappropriate transfer rates reaching up to 77%, reliance on the ABA criteria is critical as the decision to transfer a patient can impose significant costs to both the patient and healthcare system. The aim of this study is to evaluate the appropriateness of all burn patient transfers to a single burn center over a 5-year period and assess the potential role of telemedicine to optimize the assessment and care of this patient population. METHODS: A 5-year retrospective review was conducted to all burn patients transferred or consulted for transfer to our burn center between January 2013 and January 2017. After application of inclusion and exclusion criteria, 767 cases were analyzed, with 612 ultimately being transferred. Outcome measures included basic clinical and demographic information, as well as logistical burn and transfer data such as percent total body surface area and transfer distance. After data collection, 5-year descriptive trends were analyzed, and the ABA criteria were applied to each patient case to evaluate appropriateness of transfer. Patients transferred despite not meeting at least one of the ABA criteria were classified as inappropriately transferred. RESULTS: A total of 25 patients (3.2%) were found to be inappropriate transfers. Statistical analysis compared appropriately transferred patients (n = 587) with those inappropriately transferred. Overall, inappropriately transferred patients were more likely to have superficial partial thickness burns (76% vs 46%, P = 0.05), were less likely to need surgery (4% vs 22%, P < 0.05), and had a higher incidence of upper extremity burns (32% vs 4%, P < 0.01). CONCLUSIONS: Our study increases awareness of the most commonly seen presentation of inappropriately transferred burn patients over a 5-year period at our center. Given the advent of telemedicine, the ability of institutions to pinpoint a subset of patients most vulnerable to inappropriate transfer will allow for a streamlining of resources that will serve to benefit both patients and the health system.

Phone-based psychosocial counseling for people living with HIV: Feasibility, acceptability and impact on uptake of psychosocial counseling services in Malawi.

People living with HIV experience psychosocial needs that often are not addressed. We designed an innovative low-resource model of phone-based psychosocial counseling (P-PSC). We describe cohort characteristics, acceptability, feasibility and utilization of P-PSC at health facilities supported by Baylor Foundation Malawi. Staff were virtually oriented at 120 sites concurrently. From facility-based phones, people with new HIV diagnosis, high viral load, treatment interruption or mental health concerns were referred without identifiable personal information to 13 psychosocial counselors via a WhatsApp group. Routine program data were retrospectively analyzed using univariate approaches and regressions with interrupted time series analyses. Clients utilizing P-PSC were 63% female, 25% youth (10-24 y) and 9% children (<10 y). They were referred from all 120 supported health facilities. Main referral reasons included new HIV diagnosis (32%), ART adherence support (32%) and treatment interruption (21%). Counseling was completed for 99% of referrals. Counseling sessions per month per psychosocial counselor increased from 77 before P-PSC to 216 in month 1 (95% CI = 82, 350, p = 0.003). Total encounters increased significantly to 31,642 in year 1 from ~6,000 during the 12 prior months, an over fivefold increase. P-PSC implementation at 120 remote facilities was acceptable and feasible with immediate, increased utilization despite few psychosocial counselors in Malawi.

Cultured Skin in the Modern Era and the Impact of Infrastructure Volatility on Learning Curves: A 33-Year Institutional Review.

Finding a perfect epidermal transplant remains a holy grail of burn surgery. The epidermis is a site of stem cells that allows for the epithelial regeneration. The use of CEA for the treatment of major burns was first reported in 1981. CEA requires specialized skills; thus, reports from different burn-centers have shown mixed results. Comparing our modern data with past data shows how this field has advanced while maintaining institutional control. We performed a retrospective analysis of all patients admitted between 01/01/1988-12/31/2021 for massive burns that were managed with CEA. Patients were divided into pre-defined groups: G1(early-era)=1988-1999, G2(pre-modern-era)=2000-2010, and G3(modern-era)=2011-2021. We compared demographics, %TBSA, presence of inhalation-injury, LOS, complications, and mortality. We treated 52 patients with CEA during the study period. In the modern-era, we found 11 patients; in the pre-modern-era, 10; and in the early-era, 31. Injury characteristics, including %TBSA and the presence of inhalation-injury, were not significantly different between the groups. We observed lower mortality rates in G1 and G3 (G1:20% vs. G2:42% vs. G3:27%, p<0.05), although the predicted mortality was not significantly different between the groups (G1:50% vs. G2:47% vs. G3:49%, NS). Patients in G1 also had a shorter hospital LOS, in days, (G1:90 vs. G2:127 vs. G3:205, p<0.05). Finally, the surface-area grafted per patient was the highest in G2 (G1:2,000cm2 vs. G2:4,187cm2 vs. G3:4,090cm2, p<0.01). CEA has not gained popularity despite proven positive outcomes. Our retrospective analysis showed that CEA should be considered as a treatment option for patients with large burns, given proper training and infrastructure.

Clinical characteristics and outcomes of HIV-infected children diagnosed with Kaposi sarcoma in Malawi and Botswana.

BACKGROUND: Kaposi sarcoma (KS) is the most common HIV-associated malignancy in sub-Saharan Africa. The presentation and outcomes of pediatric KS are not well understood. PROCEDURE: We performed a retrospective cohort analysis of 81 HIV-infected children with KS at the Baylor Children's Clinical Centres of Excellence in Malawi and Botswana from March 2003 to October 2009. RESULTS: Eighty-one children with KS were identified whose median age was 8.0 (inter-quartile range 5.1-11.3) years. KS lesions were presented primarily on the skin (83%), lymph nodes (52%), and oral mucosa (41%). Occasionally disease was limited to the lymph nodes only (10%). Severe immunosuppression (70%), anemia (29%), and thrombocytopenia (17%) were common laboratory findings. Highly active antiretroviral therapy (HAART) was administered to 94% of children, including 77% who received HAART plus chemotherapy. KS immune reconstitution inflammatory syndrome (IRIS) occurred in 22%. Disease status 12 months after KS diagnosis was determined for 69 children: 43% were alive and 57% had died. Severe immunosuppression was independently associated with mortality in multivariate analysis (OR = 4.3; 95% CI 1.3-14.6; P = 0.02). CONCLUSION: KS occurs in a significant number of HIV infected children in sub-Saharan Africa. Pediatric KS is distinct from KS in adults. Lymph node involvement was a common manifestation of KS in children, and severe immunosuppression was associated with the highest mortality risk. Though overall mortality was high in children with KS, patients did achieve clinical remission in settings with limited diagnostic and therapeutic resources.

Hidradenitis Suppurativa Reddit Support Group: Finding New Meaning in Social Media During the COVID-19 Pandemic.

Hidradenitis suppurativa (HS) can significantly impact quality of life. Reddit allows users with common interests, like HS, to form a community and share information. This has become increasingly important with pandemic-related social isolation. We administered a survey from May 2021 to July 2021 to characterize patients with HS use of Reddit and social media more broadly before and during the COVID-19 pandemic. An analysis of a popular HS support page on Reddit from January 2019 to August 2021 was also conducted, analyzing subscribers over time. The rate of subscriber increase was higher before the pandemic. Of 42 patients contacted, 20 patients enrolled (90% female, mean age of 32.4 years) and 18 of the 20 fully completed the survey that was administered. Participants were stratified into two groups: online support group users (n = 8) and nonusers (n = 12). There were no differences in sex, age, education level, antidepressant usage, and overall social media usage between these groups. However, there was a difference in Hurley staging, with more than four times as many users reporting a Hurley III staging compared to nonusers (p = .003). Nonusers ranked the following as desired features of a social media group more frequently than current users: bandaging/dressing boils, living with HS, medical advice from professionals, causes of HS, and diet (P = .047, P = .043, P = .043, P = .047, and P = .013, respectively). This study demonstrates that online support group use is associated with HS of higher clinical severity. Based on the needs/expectations identified in this study, recommendations can be made to providers to help fill any lacunae in clinical care.

Invasive Non-Candida Fungal Infections in Acute Burns-A 13-Year Review of a Single Institution and Review of the Literature.

The past decade has demonstrated increased burn wound infections with atypical invasive fungal organisms. The range of previously regiospecific organisms has expanded, and plant pathogens are increasingly represented. Our institution sought to examine changes in severe fungal non-Candida infections in our patients, via retrospective review of patients admitted to our burn center from 2008 to 2021. We identified 37 patients with atypical invasive fungal infections. Non-Candida genera included Aspergillus (23), Fusarium (8), Mucor (6), and 13 cases of 11 different species, including the second-ever human case of Petriella setifera. Three fungi were resistant to at least one antifungal. Concomitant infections included Candida (19), Staphylococcus and Streptococcus (14), Enterococcus and Enterobacter (13), Pseudomonas (9), and 14 additional genera. Complete data was available for 18 patients, who had a median of 3.0 (IQR 8.5, range 0-15) additional bacteria required a median of 1 (IQR 7, range 0-14) systemic antibacterials and 2 (IQR 2.5, range 0-4) systemic antifungals. One case of total-drug-resistant Pseudomonas aeruginosa required bacteriophage treatment. One case of Treponema pallidum was found in infected burn wound tissue. Every patient required Infectious Disease consultation. Eight patients became bacteremic and one developed Candida fermentatifungemia. There were five patient deaths (13.8%), all due to overwhelming polymicrobial infection. Burn patients with atypical invasive fungal infections can have severe concomitant polymicrobial infections and multidrug resistance with fatal results. Early Infectious Disease consultation and aggressive treatment is critical. Further characterization of these patients may provide better understanding of risk factors and ideal treatmentpatterns.

Public perception of household risks for pediatric burn injuries and assessment of management readiness.

INTRODUCTION: Children are uniquely vulnerable to injury because of near-complete dependence on caregivers. Unintentional injury is leading cause of death in children under the age of 14. Burns are one of the leading causes of accidental and preventable household injuries, with scald burns most common in younger children and flame burns in older ones. Education is a key tool to address burn prevention, but unfortunately these injuries persist. Critically, there is a paucity of literature investigating adult comprehension with respect to potential risks of household burns. To date, no study has been performed to assess management readiness for these types of injuries without seeking medical care. METHODS: Qualtrics™ surveys were distributed to laypersons via Amazon Mechanical Turk. Demographics were self-reported. The survey was divided into two parts, management knowledge, and risk identification. The management part involved a photograph of a first-degree pediatric burn injury and required identification of the degree of injury and three potential initial managements. The risk-identification section required correctly identifying the most common mechanisms of burn injury for different age groups followed by general identification of 20 household burn risks. Survey responses were analyzed using two-tailed Student's t-tests and chi-square analyses, univariate and multivariate analysis, and linear regression. RESULTS: Of the 467 respondents, the mean age was 36.57 years, and was 59.7% (279) male. Only 3.2% of respondents were able to correctly identify all 20 potential risks listed in our survey. Additionally, only 4.5% of respondents correctly identified all three appropriate initial management options (cool water, sterile gauze, and over-the-counter analgesics) without misidentifying incorrect options. However, 56.1% of respondents were able to select at least one correct management option. For image-based injury classification, the most common response was incorrectly second-degree with 216 responses (42.2%) and the second-most common response was correctly first-degree with 146 responses (31.3%). Most respondents claimed they would not seek medical attention for the injury presented in the photograph (77.7%). When comparing the responses of individuals with children to those without, there were no statistically significant differences in ability to assess household risks for pediatric burns. For the entire population of respondents, the mean score for correctly identifying risks was 38%. CONCLUSION: This study revealed a significant gap in public awareness of household risks for pediatric burns. Furthermore, while most individuals would not seek medical care for a first-degree pediatric burn injury, they were readily available to identify proper initial management methods. This gap in knowledge and understanding of household pediatric burn injuries should be addressed with increased burn injury prevention education initiatives and more parental counseling opportunities.

Virological Findings and Treatment Outcomes of Cases That Developed Dolutegravir Resistance in Malawi's National HIV Treatment Program.

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.

Carry That Weight! The Challenge of Managing Weight Changes During Inpatient Admission for Patients With Burn Injuries ≥20% TBSA.

The hypermetabolic state of patients with ≥20% total body surface area (TBSA) causes loss of muscle mass and compromised immune function with delayed wound healing. Weight loss is most severe in patients with ≥20% TBSA with initial weight gain due to fluid resuscitation. The American Burn Association (ABA) proposed quality measures for burn injury admissions, including weight loss from admission to discharge. We assessed how our outcomes adhere to these measures and if they correlate with previously described results. We retrospectively reviewed adult admissions with ≥20% TBSA burn injuries from 2016 to 2021. Four groups were established based on %TBSA: 20% to 29% (Group 1), 30% to 39% (Group 2), 40% to 59% (Group 3), and ≥60% (Group 4). We assessed weight changes from admission to discharge and performed multivariate analyses to account for age, sex, total surgeries, and length of stay. Data from 123 patients revealed 40 with 20% to 29% TBSA, 29 with 30% to 39% TBSA, 33 with 40% to 59% TBSA, 21 with ≥60% TBSA. A significant difference in weight loss was observed when comparing Groups 1 and 2 and Groups 3 and 4 (Group 1: -3.63%, Group 2: -2%, Group 3: -9.28%, Group 4: -13.85%; P-value ≤ .05). Groups 3 and 4 had significantly longer lengths of stay compared to Groups 1 and 2 (Group 1: 32.16, Group 2: 37.5, Group 3: 71.13, Group 4: 87.18; P-value ≤ .01). Most patients that experienced weight loss during their admission had <15% weight loss. We found no significant difference in outcomes for patients receiving oxandrolone vs not. The mean weight change was -11% for patients with an overall weight loss and +5% for patients with an overall weight gain. The significant difference between the two groups was admission body mass index (BMI; loss: 30.4 kg/m2, gain: 26.0 kg/m2; P-value ≤ .05). Patients with ≥20% TBSA suffer weight changes, likely due to metabolic disturbances. Increased length of stay and higher %TBSA may be associated with greater weight loss. Patients experiencing weight gain had lower admission BMI suggesting that patients with higher BMI are more prone to weight loss. Our findings support that patients with %TBSA ≥40 are unique, requiring specialized nutritional protocols and metabolic analysis.

Changes in Burn Surgery Operative Volume and Metrics due to COVID-19.

Due to COVID-19, hospitals underwent drastic changes to operating room policy to mitigate the spread of the disease. Given these unprecedented measures, we aimed to look at the changes in operative volume and metrics of the burn surgery service at our institution. A retrospective review was conducted for operative cases and metrics for the months of March to May for 2019, 2020, and 2021, which correspond with pre-COVID, early COVID (period without elective cases), and late COVID (period with resumed elective cases). Inclusion criteria were cases related to burns. Case types and operative metrics were compared amongst the three time-periods. Compared to the hospital, the burn service had a smaller decrease in volume during early COVID (28.7% vs 50.1%) and exceeded prepandemic volumes during late COVID (+21.8% vs -4.6%). There was a significant increase in excision and grafting cases in early and late COVID periods (P < .0001 and P < .002). There was a significant decrease in laser scar procedures that persisted even during late COVID (P < .0001). The projected and actual lengths of cases significantly increased and persisted into late COVID (P < .01). COVID-19 related operating room closures led to an expected decrease in the number of operative cases. However, there was no significant decline in the number of burn specific cases. The elective cases were largely replaced with excision and grafting cases and this shift has persisted even after elective cases have resumed. This change is also reflected in increased operative times.

Outcomes of Patients with Burns Associated with Home Oxygen Therapy: An Institutional Retrospective Review.

Home oxygen therapy (HOT) burns carry high morbidity and mortality. Many patients are active smokers, which is the most frequent cause of oxygen ignition. We conducted a retrospective review at our institution to characterize demographics and outcomes in this patient population. An IRB-approved single-institution retrospective review was conducted for home oxygen therapy burn patients between July 2016 and January 2021. Demographic and clinical outcome data were compared between groups. We identified 100 patients with oxygen therapy burns. Mean age was 66.6 years with a male to female ratio of 1.3:1 and median burn surface area of 1%. In these patients, 97% were on oxygen for COPD and smoking caused 83% of burns. Thirteen were discharged from the emergency department, 35 observed for less than 24 hours, and 52 admitted. For admitted patients, 69.2% were admitted to the ICU, 37% required intubation, and 11.5% required debridement and grafting. Inhalational injury was found in 26.9% of patients, 3.9% underwent tracheostomy, and 17.3% experienced hospital complications. In-hospital mortality was 9.6% and 7.7% were discharged to hospice. 13.5% required readmission within 30 days. Admitted patients had significantly higher rates of admission to the ICU, intubation, and inhalational injury compared to those that were not admitted (P < .01). Most HOT-related burns are caused by smoking and can result in significant morbidity and mortality. Efforts to educate and encourage smoking cessation with more judicious HOT allocation would assist in preventing these unnecessary highly morbid injuries.

Dolutegravir Resistance in Malawi's National HIV Treatment Program.

Dolutegravir HIV drug resistance (HIVDR) data from Africa remain sparse. We reviewed HIVDR results of Malawians on dolutegravir-based antiretroviral therapy (November 2020-September 2021). Of 6462 eligible clients, 33 samples were submitted to South Africa, 27 were sequenced successfully, and 8 (30%) had dolutegravir HIVDR. Malawi urgently requires adequate HIVDR testing capacity.

Using Pressure Mapping to Optimize Hospital-Acquired Pressure Injury Prevention Strategies in the Burn Intensive Care Unit.

Although prior studies have demonstrated the utility of real-time pressure mapping devices in preventing pressure ulcers, there has been little investigation of their efficacy in burn intensive care unit (BICU) patients, who are at especially high risk for these hospital-acquired injuries. This study retrospectively reviewed clinical records of BICU patients to investigate the utility of pressure mapping data in determining the incidence, predictors, and associated costs of hospital-acquired pressure injuries (HAPIs). Of 122 patients, 57 (47%) were studied prior to implementation of pressure mapping and 65 (53%) were studied after implementation. The HAPI rate was 18% prior to implementation of pressure monitoring, which declined to 8% postimplementation (chi square: P = .10). HAPIs were less likely to be stage 3 or worse in the postimplementation cohort (P < .0001). On multivariable-adjusted regression accounting for known predictors of HAPIs in burn patients, having had at least 12 hours of sustained pressure loading in one area significantly increased odds of developing a pressure injury in that area (odds ratio 1.3, 95% CI 1.0-1.5, P = .04). Patients who developed HAPIs were significantly more likely to have had unsuccessful repositioning efforts in comparison to those who did not (P = .02). Finally, implementation of pressure mapping resulted in significant cost savings-$6750 (standard deviation: $1008) for HAPI-related care prior to implementation, vs $3800 (standard deviation: $923) after implementation, P = .008. In conclusion, the use of real-time pressure mapping decreased the morbidity and costs associated with HAPIs in BICU patients.

Kaposi's sarcoma in the pediatric population: the critical need for a tissue diagnosis.

Kaposi's sarcoma (KS) is a low-grade vascular neoplasm mediated by the human herpesvirus-8. Only 1 clinical subtype, the endemic/African subtype, commonly affects the pediatric population. Although adults with KS often present with cutaneous findings and generalized lymphadenopathy, African children are more likely to present without classic skin findings. Definitive diagnosis requires histologic examination from tissue biopsy; however, as pathology resources are scarce in many developing African countries where KS is prominent, appropriate diagnosis and treatment of the condition are challenging. We report the case of a Malawian child who presented with generalized lymphadenopathy and was presumptively treated for lymphoma, with clinical worsening of his lesions. A diagnosis of KS was made after excisional biopsy of a superficial lymph node, with the initiation of appropriate therapy. The literature regarding pediatric KS is reviewed and recommendations are offered to allow accurate and timely diagnosis of the condition.

Examining the Rates of Anxiety, Depression, and Burnout Among Providers at a Regional Burn Center.

Burnout, defined by feelings of inefficacy, cynicism, and emotional exhaustion, affects the performance and well-being of health care providers. Burn care exposes providers to factors known to cause or worsen burnout, but no research has presented prevalence rates of burnout in this population. We estimate the rates of anxiety, depression, and burnout among nonphysician providers in a regional burn center and compare those rates to a reference population of critical care nurses. In our sample of 22 providers, 64% screened positive for anxiety; 32% for depression; 82% for emotional exhaustion; 18% for personal achievement burnout; and 54% for depersonalization. When compared with a national sample of critical care nurses, burn center providers demonstrated a significantly higher rate of anxiety (risk difference [RD]: 0.453, 95% confidence interval [CI] [0.244, 0.622]), a significantly higher rate of emotional exhaustion (RD: 0.207, 95% CI [0.001, 0.323]), and a significantly lower rate of personal achievement burnout (RD: -0.325, 95% CI [-0.442, -0.119]). These findings constitute the first evidence that many burn care providers meet criteria for burnout and that burnout in burn care providers may qualitatively differ from burnout in other critical care providers. Future research should identify burn care-specific predictors of burnout and determine the feasibility and efficacy of interventions to prevent and reduce burnout in burn care providers.

Clinical Factors Associated with Long-Term Complete Remission versus Poor Response to Chemotherapy in HIV-Infected Children and Adolescents with Kaposi Sarcoma Receiving Bleomycin and Vincristine: A Retrospective Observational Study.

Kaposi sarcoma (KS) is the most common HIV-associated malignancy in children and adolescents in Africa. Pediatric KS is distinct from adult disease. We evaluated the clinical characteristics associated with long-term outcomes. We performed a retrospective observational analysis of 70 HIV-infected children and adolescents with KS less than 18 years of age diagnosed between 8/2010 and 6/2013 in Lilongwe, Malawi. Local first-line treatment included bleomycin and vincristine plus nevirapine-based highly active anti-retroviral therapy (HAART). Median age was 8.6 years (range 1.7-17.9); there were 35 females (50%). Most common sites of presentation were: lymph node (74%), skin (59%), subcutaneous nodules (33%), oral (27%), woody edema (24%), and visceral (16%). Eighteen (26%) presented with lymphadenopathy only. Severe CD4 suppression occurred in 28%. At time of KS diagnosis, 49% were already on HAART. Overall, 28% presented with a platelet count < 100 x 109/L and 37% with hemoglobin < 8 g/dL. The 2-year event-free (EFS) and overall survival (OS) were 46% and 58% respectively (median follow-up 29 months, range 15-50). Multivariable analysis of risk of death and failure to achieve EFS demonstrated that visceral disease (odds ratios [OR] 19.08 and 11.61, 95% CI 2.22-163.90 and 1.60-83.95 respectively) and presenting with more than 20 skin/oral lesions (OR 9.57 and 22.90, 95% CI 1.01-90.99 and 1.00-524.13 respectively) were independent risk factors for both. Woody edema was associated with failure to achieve EFS (OR 7.80, 95% CI 1.84-33.08) but not death. Univariable analysis revealed that lymph node involvement was favorable for EFS (OR 0.28, 95% CI 0.08-0.99), while T1 TIS staging criteria, presence of cytopenias, and severe immune suppression were not associated with increased mortality. Long-term complete remission is achievable in pediatric KS, however outcomes vary according to clinical presentation. Based on clinical heterogeneity, treatment according to risk-stratification is necessary to improve overall outcomes.

Regulation of the gadd45beta promoter by NF-kappaB.

In addition to coordinating immune and inflammatory responses, NF-kappaB/Rel transcription factors control cell survival. The NF-kappaB antiapoptotic function is crucial to oncogenesis, cancer chemoresistance, and to antagonize tumor necrosis factor (TNF) receptor-induced killing. Recently, we have shown that the suppression of the c-Jun-N-terminal kinase (JNK) cascade is a pivotal protective mechanism by NF-kappaB, and that this suppression involves the upregulation of gadd45beta/myd118. Induction of gadd45beta by stress and cytokines requires NF-kappaB; however, the regulatory mechanisms underlying this induction are not known. Here, we report that, in HeLa cells, the NF-kappaB subunit RelA is sufficient to activate gadd45beta expression, whereas Rel and p50 are not. Activation of gadd45beta by RelA depends on three kappaB elements at positions -447/-438 (kappaB-1), -426/-417 (kappaB-2), and -377/-368 (kappaB-3) of the gadd45beta promoter. Each of these sites binds to NF-kappaB complexes in vitro, and is required for optimal promoter transactivation. The data establish the direct participation of NF-kappaB in the regulation of Gadd45beta, thereby providing important mechanistic insights into the control of apoptosis by the transcription factor.