Placental accelerated aging in antenatal depression.

BACKGROUND: Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging. OBJECTIVE: This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery. STUDY DESIGN: The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009-2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental "epigenetic clock") that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment. RESULTS: There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (ß=0.21 weeks [95% confidence interval, -0.17 to 0.58; P=.28] during the first trimester of pregnancy; ß=0.41 weeks [95% confidence interval, 0.10-0.71; P=.009] during the second trimester of pregnancy; ß=0.17 weeks [95% confidence interval, -0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29-1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (ß=0.53 weeks; 95% confidence interval, 0.06-1.08; P=.03) but was not significant in pregnancies with female fetuses. CONCLUSION: Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction.

Prophylactic Use Of Levofloxacin During Induction Of Acute Lymphoblastic Leukaemia In Children-Experience From Pakistan.

To assess whether prophylactic use of Levofloxacin would reduce the number of febrile neutropenia episodes during the induction phase, a single-centre, case-control study was carried out. Data was collected prospectively of patients who received Levofloxacin prophylaxis during the induction chemotherapy from September 2019 till October 2020. The cases were compared with historical controls who did not receive antibiotics prophylaxis. A total of 121 patients were enrolled, among which 61 patients were cases, whereas 60 patients were controls. The patients who received Levofloxacin prophylaxis had lower rate of febrile neutropenia episodes than patients who did not receive any prophylaxis (p≤0.01) (odds ratio [OR]:0.23, CI 95%). No significant difference in induction mortality was seen between the two groups (p≤0.14). Levofloxacin prophylaxis reduced the rate of febrile neutropenia episodes among patients, but it did not affect the infection related mortality.

An Externally Validated Model to Predict Prolonged Induction of Labor with an Unfavorable Cervix.

OBJECTIVE: To develop and externally validate a prediction model to calculate the likelihood of prolonged induction of labor (induction start to delivery time > 36 hours). STUDY DESIGN: This was a retrospective cohort study of all nulliparous women with singleton pregnancies and vertex presentation at term who underwent induction of labor and had a vaginal delivery at a single academic center. Women with contraindications for vaginal delivery were excluded. Analyses were limited to women with unfavorable cervix (both simplified Bishop score [dilation, station, and effacement: range 0-9] <6 and cervical dilation <3 cm). Prolonged induction of labor was defined as the duration of induction (induction start time to delivery) longer than 36 hours. A backward stepwise logistic regression analysis was used to identify the factors associated with prolonged induction of labor by considering maternal characteristics and comorbidities as well as fetal conditions. The final model was validated using an external dataset of the Consortium on Safe Labor after applying the same inclusion and exclusion criteria. We developed a receiver observer characteristic curve with area under the curve (AUC) in validation cohorts. RESULTS: Of 2,118 women, 364 (17%) had prolonged induction of labor. Factors associated with prolonged induction of labor included body mass index at admission, hypertension, fetal conditions, and epidural. Factors including younger maternal age, prelabor rupture of membranes, and a more favorable simplified Bishop score were associated with a decreased likelihood of prolonged induction of labor. In the external validation cohort, 4,418 women were analyzed, of whom 188 (4%) had prolonged induction of labor. The AUC of the final model was 0.76 (95% confidence interval: 0.73-0.80) for the external validation cohort. The online calculator was created and is available at: https://medstarapps.org/obstetricriskcalculator. CONCLUSION: Our externally validated model was efficient in predicting prolonged induction of labor with an unfavorable cervix. KEY POINTS: · The number of inductions of labor at 39 weeks' gestation and beyond has been increasing.. · Our model had a good prediction of prolonged induction of labor.. · An online calculator has been created and available..

Influence of maternal psychological distress during COVID-19 pandemic on placental morphometry and texture.

The Coronavirus Disease 2019 (COVID-19) pandemic has been accompanied by increased prenatal maternal distress (PMD). PMD is associated with adverse pregnancy outcomes which may be mediated by the placenta. However, the potential impact of the pandemic on in vivo placental development remains unknown. To examine the impact of the pandemic and PMD on in vivo structural placental development using advanced magnetic resonance imaging (MRI), acquired anatomic images of the placenta from 63 pregnant women without known COVID-19 exposure during the pandemic and 165 pre-pandemic controls. Measures of placental morphometry and texture were extracted. PMD was determined from validated questionnaires. Generalized estimating equations were utilized to compare differences in PMD placental features between COVID-era and pre-pandemic cohorts. Maternal stress and depression scores were significantly higher in the pandemic cohort. Placental volume, thickness, gray level kurtosis, skewness and run length non-uniformity were increased in the pandemic cohort, while placental elongation, mean gray level and long run emphasis were decreased. PMD was a mediator of the association between pandemic status and placental features. Altered in vivo placental structure during the pandemic suggests an underappreciated link between disturbances in maternal environment and perturbed placental development. The long-term impact on offspring is currently under investigation.

Prediction of Postoperative Day 1 Hemoglobin Level after Cesarean Delivery.

OBJECTIVE: To create a prediction model for postoperative hemoglobin levels after cesarean delivery, which could reduce routine use of postoperative laboratory test. STUDY DESIGN: This was a secondary analysis of a retrospective cohort study of all women who underwent cesarean delivery (primary or repeat) at or more than 23 weeks' gestation at a single academic center. The cohort was randomly divided into a training cohort to develop a prediction model and a validation cohort to test the model in a 2:1 ratio. Variables with p-value <0.10 were considered for the mixed multivariable linear regression model in a backward stepwise fashion. We obtained the best cut-off point of the predicted hemoglobin level to detect severe anemia (postoperative hemoglobin level less than 7.0 g/dL) in the training cohort. A receiver operating characteristic curve with the area under a curve was created. We calculated the sensitivity and specificity of the model in the validation cohort using the best cut-off point obtained in the training cohort as well as postoperative hemoglobin of 10.0 g/dL. RESULTS: Of 2,930 women, 1,954 (66.6%) and 976 (33.3%) were randomly allocated to training and validation cohorts. The final model included preoperative hemoglobin level, preoperative platelet level, quantitative blood loss, height, weight, magnesium administration, labor, and general anesthesia. The best cut-off to predict severe anemia was predicted hemoglobin level of 8.57 g/dL in the training cohort. Using this cut-off, the sensitivity and specificity in the validation cohort were 77% (95% confidence interval [CI]: 56-91%) and 87% (95% CI: 85-89%), respectively. The use of postpartum hemorrhage yielded the sensitivity of 58% (95% CI: 37-77%) and specificity 79% (95% CI: 76-81%), respectively. CONCLUSION: We developed a validated model to predict the postoperative day 1 hemoglobin levels after cesarean delivery that could assist with identifying women who may not need postoperative laboratory tests. KEY POINTS: · Postoperative laboratory tests are routine.. · A prediction model may allow reduce routine tests.. · We developed an accurate mathematical model..

18F FDG PET-CT Super scan: Paediatric Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma, making 50% of all diagnosed cases. It is a complex disease that has the potential to arise from any tissue of the body except the bones. There are four types of rhabdomyosarcoma; embryonal, botryoidal, alveolar and pleomorphic. [18F]-FDG PET-CT plays a vital role in staging, response evaluation and follow-up of the disease. Due to significant morbidity and mortality with high-risk disease, proper staging is of paramount importance.  Staging of rhabdomyosarcoma depends on tumour localization, infiltration of local structures by the primary tumour, nodal involvement, and presence of visceral metastases. Without timely intervention, rhabdomyosarcoma progresses at an exponential speed.

Maternal psychological distress during the COVID-19 pandemic and structural changes of the human fetal brain.

Background: Elevated maternal psychological distress during pregnancy is linked to adverse outcomes in offspring. The potential effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown. Methods: We prospectively enrolled 202 pregnant women: 65 without known COVID-19 exposures during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5 T MRI Scanner. Volumes of six brain tissue types were calculated. Cortical folding measures, including brain surface area, local gyrification index, and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety, and depression scales. Generalized estimating equations were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts. Results: Stress and depression scores are significantly higher in the pandemic cohort, compared to the pre-pandemic cohort. Fetal white matter, hippocampal, and cerebellar volumes are decreased in the pandemic cohort. Cortical surface area and local gyrification index are also decreased in all four lobes, while sulcal depth is lower in the frontal, parietal, and occipital lobes in the pandemic cohort, indicating delayed brain gyrification. Conclusions: We report impaired fetal brain growth and delayed cerebral cortical gyrification in COVID-19 pandemic era pregnancies, in the setting of heightened maternal psychological distress. The potential long-term neurodevelopmental consequences of altered fetal brain development in COVID-era pregnancies merit further study.

Feasibility and safety of outpatient administration of ifosfamide and etoposide for pediatric patients with Ewing sarcoma in a resource-limited setting amid the COVID-19 pandemic.

BACKGROUND: To assess feasibility and safety of outpatient administration of ifosfamide and etoposide (IE) for pediatric Ewing sarcoma (EWS) patients in a resource-limited setting amid the COVID-19 pandemic. MATERIALS AND METHODS: Retrospective study of patients with EWS who received outpatient IE from January 2020 until January 2021 at our institution. Ifosfamide 1800 mg/m2 was given for 5 days with MESNA (2-mercaptoethane sulfonate sodium) infusion and additional boluses before and after 9 hours of hydration. Patients >10 years of age with the ability to drink orally at home, no pre-existing renal dysfunction or history of hematuria were included. They were monitored for hemorrhagic cystitis with a urine dipstick before, midway, and at end of infusion. A urine analysis was done 24 hours after the last dose of ifosfamide. RESULTS: Forty-seven (100%) cycles were given as outpatient during the study period. Thirty-five (74%) cycles were given on time, two (4%) cycles were delayed due to mucositis, two (4%) due to delayed count recovery, and eight (18%) due to unavailability of outpatient appointments. The median interval between these cycles was 15 days (range 14-44 days). No episode of hemorrhagic cystitis was reported. Urine analysis was not done at 24 hours for 27 (58%) cycles, so microscopic hematuria may have been missed. This outpatient protocol saved 32% (USD 299) per cycle in cost and 282 days of hospitalization. CONCLUSION: Outpatient administration of IE for pediatric patients with EWS is feasible, safe, and cost-effective during the COVID-19 pandemic.

Evaluation of blood transfusion rates by blood loss estimation techniques.

BACKGROUND: Postpartum hemorrhage is a major cause of maternal morbidity and mortality. Though the American College of Obstetricians and Gynecologists and quality improvement initiatives recommend the use of a quantitative measurement of blood loss, it is not known if the quantitative measurement compared to visual estimation of blood loss improves maternal outcomes. OBJECTIVE: To compare rates of red blood cell transfusion between a quantitative measurement and visual estimation of blood loss. STUDY DESIGN: This was a retrospective cohort study of all women who underwent cesarean delivery at a single academic institution from January 2012 to June 2018. Women were excluded if they received a preoperative transfusion or had missing data. Our institution implemented a quantitative measurement of blood loss in September 2015. Our primary outcome was red blood cell transfusion (intraoperative or postoperative). Women who had the quantitative measurement of blood loss (October 2015 to June 2018) were compared with those who had a visual estimation of blood loss (January 2012 to August 2015). Coarsened Exact Matching with a k-to-k solution was performed using predefined variables. RESULTS: In total, 4068 had a visual estimation of blood loss and 3117 had the quantitative measurement of blood loss; 1101 women with the quantitative measurement of blood loss were matched to 1101 women with a visual estimation of blood loss. In the unmatched cohort, women who had the quantitative measurement of blood loss compared to those who had a visual estimation of blood loss were more likely to have an increased amount of blood loss (734 ml vs. 700 ml, p < .001) and red blood cell transfusion (7.2% [223/3117] vs. 5.4% [221/4068]; crude odds ratio 1.34; 95% confidence interval 1.11-1.63). This increase in the amount of blood loss (717 ml vs. 700 ml, p < .05) and the rate of red blood cell transfusion (4.5% [49/1101] vs. 2.7% [30/1101]; crude odds ratio 1.66; 95% confidence interval 1.05-2.64) remained statically significant after matching. CONCLUSION: Women who had the quantitative measurement compared with those who had a visual estimation of blood loss were more likely to have an increased amount of blood loss and red blood cell transfusion.

Impact of COVID-19 Pandemic on Treatment of Pediatric Oncology Patients: Report from Resource-limited Setting.

The aim of this study was to determine how the COVID-19 pandemic impacted on the effective management; and the outcome of pediatric oncology patients in Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore. Data was retrospectively reviewed from 15 March to 15 June 2020 after the approval of Institutional Review Board Committee. A total of 258 patients on active oncology treatment between the study period were included. The total number of patients whose treatment was affected were 118 (45.7%), while 140 (54.3%) patients received treatment in time. There was total 34 (13.2%) patients relapsed, 23 (67.6%) patients in which treatment delayed, and 11 (32.4%) patients in which their treatment not delayed; while, n=218 (84.5%) were in remission, and 6 (2.3%) patients absconded. COVID-19 pandemic caused a sudden impediment in the treatment of pediatric oncology patients, and is likely to affect the long-term survival outcome of pediatric oncology patients. Key Words: Chemotherapy, Radiotherapy, Surgery, Long term outcome.

Acute Morbidity and Mortality Analysis of COVID-19 in Children Receiving Cancer Treatment.

The aim of this study was to determine overall morbidity and mortality of COVID-19 infection in children on cancer treatment. It was an observational study, carried at Shaukat Khanum Cancer Hospital from 1st April 2020 to 31st July 2020. A total of 165 children on active cancer treatment were tested for COVID-19 with PCR; out of these, 17 were detected positive. Twelve children were symptomatic having fever with or without cough, sore throat, body aches, rash or diarrhea. Two children had concurrent gram negative bacteremia. Ten children (58.8%) required hospitalisation, 23.5% required oxygen and two had intensive care unit admission. One death was reported in this study. Chemotherapy was modified in five children, while elective surgery, chemotherapy and radiotherapy schedule were affected in eight children. Overall, the spread of Covid-19 was limited, the course of disease was mild, and anticancer treatment was provided and continued as per standard protocols. Key Words: Covid -19, Cancer, Anticancer chemotherapy, Immunosuppression, Children.

Educational Video on Pain Management and Subsequent Opioid Use After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether viewing an educational video on pain management reduces opioid use after cesarean delivery. METHODS: We conducted a randomized, controlled trial of women aged 18 years or older who underwent cesarean delivery at a tertiary care center. Eligible women were randomized in a 1:1 ratio to usual discharge pain medication instructions plus an educational video on pain management or to usual discharge pain medication instructions alone. All women received the same opioid prescription at discharge: Twenty 5-mg oxycodone tablets. Participants were contacted at 7 days and at 14 days after delivery to assess the number of oxycodone tablets used, adjunct medication (acetaminophen and ibuprofen) use, pain scores, and overall satisfaction of pain control. The primary outcome was the number of oxycodone tablets used from discharge through postpartum day 14. A sample size of 23 per group (n=46) was planned to detect a 25% difference in mean number of oxycodone tablets used between groups, as from 20 to 15. RESULTS: From July 2019 through December 2019, 61 women were screened and 48 were enrolled-24 in each group. Women who viewed the educational video used significantly fewer opioid tablets from discharge through postpartum day 14 compared with women who received usual pain medication instructions (median 1.5, range 0-20 vs median 10, range 0-24, P<.001). Adjunct medication use, pain scores, and satisfaction with pain control did not differ significantly between groups. CONCLUSION: Among women who underwent cesarean delivery, viewing an educational video on pain management reduced postdischarge opioid use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03959969.

Indeterminate Pulmonary Nodules in Osteosarcoma Are Associated With Increased Risk of Pulmonary Metastasis.

Osteosarcoma is the most common primary malignant bone tumor in children. In addition to pulmonary metastasis, computed tomography frequently detects indeterminate pulmonary nodules (IPN). We conducted this study to determine the clinical significance of IPN in terms of progression to pulmonary metastasis and its impact on survival. It was a retrospective cohort study of pediatric nonmetastatic osteosarcoma patients treated from January 2005 to December 2018. Baseline computed tomography scans were reviewed for the presence of IPN (defined as a single nodule of <10 mm or ≥3 nodules of <5 mm). Subsequent scans were reviewed for the development of pulmonary metastasis. Of 155 patients, 31.6% (n=49) had IPN at baseline. A total of 43% (n=21) of those with IPN subsequently progressed to pulmonary metastasis compared with only 26% (n=28) of those without IPN (P<0.001) with a relative risk of 1.6 (1.03 to 2.5) in the IPN group. Patients with ≥3 IPN at baseline were at significantly greater risk of pulmonary metastasis as compared with <3 IPN (P=0.013). Overall and event-free survival in patients with and without IPN was 58% and 35%, and 72% and 46%, respectively. Our results suggest that patients with IPN may be at greater risk for progressing to pulmonary metastasis.

Response rates, long term outcomes and toxicity profile of gemcitabine and vinorelbine based outpatient chemotherapy regimen in primary progressive and relapsed childhood Hodgkin lymphoma.

This study aimed to determine response rates, overall survival (OS), event-free survival (EFS) and toxicity profile of an outpatient chemotherapy regimen based on gemcitabine and vinorelbine (GV) for relapsed childhood Hodgkin lymphoma (HL). This was a retrospective study that included 41 patients up to the age of 18 years with relapsed HL. Twelve patients (29%) had primary progressive disease (PPD), 6 (15%) had early relapse (ER) and 23 (56%) had late relapse (LR). The overall initial response rate was 83% (LR: 87%, ER: 83%, PPD: 75%. p-value: .2). Three-year combined OS was 80% (LR: 89%, ER: 80%, PPD: 65%. p-value: .07) and EFS 71% (LR: 86%, ER: 62%, PPD: 47%. p-value: .01). There were no toxic deaths. Febrile neutropenia was observed in four patients (9.6%) and lung toxicity in 1 patient (2.4%). This study suggests that outpatient GV is an effective and low toxicity salvage regimen for relapsed childhood HL.

Ovarian torsion in utero diagnosed at 37 weeks of pregnancy: A case report.

BACKGROUND: Fetal ovarian masses are common abdominal anomalies in female fetuses, often diagnosed in the third trimester. Most masses are benign and tend to resolve spontaneously within a few months after birth, but larger masses may present complications such as torsion. CASE: A 21-year-old primagravid woman was noted to have a complex avascular solid mass in the fetal left pelvis, which was consistent with complex fetal left ovarian torsion. The patient underwent induction of labor at 39 weeks for possible intervention. The infant underwent surgery at 5 weeks of age and a torsed, necrotic ovary was discovered. CONCLUSION: The diagnosis of ovarian torsion in utero is rare, and prenatal and postnatal guidelines are needed on frequency of monitoring, timing of delivery, and postnatal follow-up.

Aberrant epigenetic silencing of neuronatin is a frequent event in human osteosarcoma.

The paternally imprinted neuronatin (NNAT) gene has been identified as a target of aberrant epigenetic silencing in diverse cancers, but no association with pediatric bone cancers has been reported to date. In screening childhood cancers, we identified aberrant CpG island hypermethylation in a majority of osteosarcoma (OS) samples and in 5 of 6 human OS cell lines studied but not in normal bone-derived tissue samples. CpG island hypermethylation was associated with transcriptional silencing in human OS cells, and silencing was reversible upon treatment with 5-aza-2'-deoxycytidine. Expression of NNAT was detectable in osteoblasts and chondrocytes of human bone, supporting a potential role in bone homeostasis. Enforced expression of NNAT in human OS cells lacking endogenous expression resulted in significant reduction in colony formation and in vitro migration compared to nonexpressor control cells. We next analyzed the effect of NNAT expression on intracellular calcium homeostasis and found that was associated with an attenuated decay of calcium levels to baseline following ATP-induced release of calcium from endoplasmic reticulum (ER) stores. Furthermore, NNAT expression was associated with increased cytotoxicity in OS cells from thapsigargin, an inhibitor of calcium reuptake into ER and an inducer of the ER stress response. These results suggest a possible tumor suppressor role for NNAT in human osteosarcoma. Additional study is needed ascertain sensitization to ER stress-associated apoptosis as a mechanism of NNAT-dependent cytotoxicity. In that case, epigenetic modification therapy to effect NNAT transcriptional derepression may represent a therapeutic strategy potentially of benefit to a majority of osteosarcoma patients.

Feasibility of Compressed Chemotherapy Pediatric Ewing Sarcoma Regimen In Pakistan.

A retrospective chart review was conducted to determine the feasibility of interval-compressed chemotherapy regimen in pediatric Ewing sarcoma (ES) patients treated at Department of Pediatric Oncology, Shaukat Khanum Memorial Trust Cancer Hospital, Lahore, Pakistan, from June 2017 to December 2018. Data was collected regarding demographics, treatment duration and timing, complications and outcome. Completion of treatment within 8 months as considered on time. There were 24 patients (male: female ratio = 1.4:1, average age = 10.2 ±5.3 years. Involved sites were extremity in 13 (54%), pelvis in 4 (16.6%), and spine in 3 (12.5%) patients. Twenty patients (83.3%) completed chemotherapy on time. The mean duration of treatment was 7.2 ±1.2 months. Only three patients (12%) exceeded 8 months of duration of treatment. There was an average of 2.5 febrile neutropenia events per patient. Seventeen (70.8%) patients are alive at the time of review. Two patients died of sepsis, one developed cardiac failure, and one died of progressive disease. This single-institution review showed that patients can tolerate interval-compressed chemotherapy protocol regimen for ES with adequate supportive care. Key Words: Ewing sarcoma, chemotherapy, Compressed regimen, feasibility, Pediatrics.

Outcomes of Refractory and Relapsed Hodgkin Lymphoma With Autologous Stem-Cell Transplantation: A Single Institution Experience.

PURPOSE: Hodgkin lymphoma is the most common cancer in children, adolescents, and young adults. Overall survival is approximately 80% to 90%. A subset of these patients has refractory disease or experience disease relapse. Conventional salvage therapies and autologous stem-cell transplantation is usually considered the standard of care for these patients. Our analysis reports outcomes in these patients. PATIENTS AND METHODS: After institutional review board approval, a retrospective analysis of patients with Hodgkin lymphoma who were up to 18 years of age and who had refractory or relapsed disease at Shaukat Khanum Memorial Cancer Hospital and Research Centre from September 2009 to December 2013 was performed. Patients who underwent high-dose chemotherapy followed by stem-cell rescue were included in this analysis. RESULTS: A total of 567 patients with Hodgkin lymphoma registered at the hospital. Sixty of the patients (10.6%) had either primary progressive or refractory disease or relapse after finishing with first-line chemotherapy. High-dose chemotherapy followed by stem cell was administered to 25 of these patients (42%). Thirteen patients (40%) had progressive disease (PD), five (22%) had early relapse, and seven (38%) had late relapse. A number of salvage regimens were used, including etoposide, prednisolone, ifosfamide, and cisplatin; dexamethasone, cytarabine, and carboplatin; and gemcitabine plus vinorelbine. Re-evaluation was performed before taking patients to a high dose, and it showed complete response in 17 patients (68%), partial response in six patients (24%), and PD in two patients (8%). Twenty-one patients (84%) are in remission after transplantation, with two patients (8%) having died as a result of disease progression and two patients (2%) having relapsed after treatment. Overall survival is 92% at 4 years, with event-free survival of 80% at 4 years. CONCLUSION: Our retrospective analysis shows good outcomes in patients who had PD or refractory disease. Disease response before transplantation is important in predicting outcomes.

Malnutrition, Sepsis, and Tumor Lysis Syndrome Are Associated with Increased Rate of Acute Mortality in Mature B Cell Non-Hodgkin Lymphoma in a Pediatric Population-Study from Tertiary Care Hospital in Pakistan.

BACKGROUND: Outcomes of pediatric mature B cell non-Hodgkin's lymphoma in resource-challenged countries are negatively affected by an increased rate of early and toxic deaths. Aim of this study is to assess the rate of acute mortality and define significant risk factors present in children with mature B cell non-Hodgkin's lymphoma. METHODS: A retrospective analysis was done of patients with B cell non-Hodgkin's lymphoma from January 2012 till December 2016. Risk factors studied for acute mortality were malnutrition, stage, prior surgery with open laparotomy, lactate dehydrogenase levels, tumor lysis syndrome, sepsis, and fungal infection. RESULTS: A total of 233 patients were enrolled in the study. Eighty-five (36.4%) were below 15th percentile weight for age. Treatment was started in 226 patients. Eighty-eight percent of children showed a 20% response after COP pre-phase. Tumor lysis syndrome was developed in 20.6% (n = 48) children and 42.9% (n = 100) patients had sepsis, 71/100 patients had culture-proven sepsis. 19.7% (n = 46) patients developed fungal infection. There was 19.7% (n = 46) acute mortality. The most common cause of death was sepsis (n = 22, 47.8%) followed by acute renal failure secondary to tumor lysis syndrome. On multivariate analysis, three independent variables found significant for early death are malnutrition, sepsis, and tumor lysis syndrome. CONCLUSION: Rate of acute mortality in mature B cell NHL is high in our set up and significant risk factors are tumor lysis syndrome, sepsis, and malnourishment at the time of presentation.