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In pregnant women, antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein cross the placenta and can be detected in cord-blood at the time of delivery. We measured SARS-CoV-2 full-length antispike IgG in blood samples collected from women living with HIV (WLWHIV) and without HIV when presenting for labour, and from paired cord-blood samples. Antispike IgG was measured in maternal blood at delivery on the Luminex platform. Cord-blood samples from newborns of women in with detectable antispike IgG were analysed. The IgG geometric mean concentrations (GMCs) and the percentage of cord-blood samples with detectable antispike IgG were compared between WLWHIV and without HIV. A total of 184 maternal and cord-blood pairs were analysed, including 47 WLWHIV and 137 without HIV. There was no difference in antispike GMCs between WLWHIV and without HIV [157 binding antibody units (BAU)/ml vs. 187 BAU/ml; P = 0.17)]. Cord-blood samples from newborns of WLWHIV had lower GMCs compared with those without HIV (143 vs. 205 BAU/ml; P = 0.033). Cord-to-maternal blood antibody ratio was 1.0 and similar between the two HIV groups. In WLWHIV, those who were 30 years old or less had lower cord-to-maternal blood antibody ratio (0.75 vs. 1.10; P = 0.037) and their newborns had lower cord-blood GMCs (94 vs. 194 BAU/ml; P = 0.04) compared with the older women. Independently of maternal HIV infection status, there was efficient transplacental transfer of antispike antibodies. The GMCs in cord-blood from newborns of WLWHIV were lower than those in HIV-unexposed newborns.

SARS-CoV-2 infection in pregnant women has been associated with severe illness in the women and higher rates of premature delivery. There is, however, paucity of data on the impact of the timing of SARS-CoV-2 infection and on symptomatic or asymptomatic infections on birth outcomes. Data from low-middle income settings is also lacking.We conducted a longitudinal study from April 2020 to March 2021, in South Africa, where symptomatic or asymptomatic pregnant women were investigated for SARS-CoV-2 infection during the antepartum period. We aimed to evaluate if there was an association between antepartum SARS-CoV-2 infection on birth outcomes. SARS-CoV-2 infection was investigated by nucleic acid amplification test (NAAT), histological examination was performed in a sub-set of placentas.Overall, 793 women were tested for SARS-CoV-2 antenatally, including 275 (35%) who were symptomatic. SARS-CoV-2 infection was identified in 138 (17%) women, of whom 119 had symptoms (COVID-19 group) and 19 were asymptomatic. The 493 women who were asymptomatic and had a negative SARS-CoV-2 NAAT were used as the referent comparator group for outcomes evaluation. Women with COVID-19 compared with the referent group were 1.66-times (95% confidence interval (CI) = 1.02-2.71) more likely to have a low-birthweight newborn (30% vs 21%) and 3.25-times more likely to deliver a very low-birthweight newborn (5% vs 2%). Similar results for low-birthweight were obtained comparing women with SARS-CoV-2 confirmed infection (30%) with those who had a negative NAAT result (22%) independent of symptoms presentation. The placentas from women with antenatal SARS-CoV-2 infection had higher percentage of chorangiosis (odds ratio (OR) = 3.40, 95% CI = 1.18-.84), while maternal vascular malperfusion was more frequently identified in women who tested negative for SARS-CoV-2 (aOR = 0.28, 95% CI = 0.09-0.89).Our study demonstrates that in a setting with high HIV infection prevalence and other comorbidities antenatal SARS-CoV-2 infection was associated with low-birthweight delivery.

Background Younger age of antiretroviral therapy (ART) initiation is associated with smaller viral reservoirs in perinatally acquired HIV-1 infection, but there is wide variability among early-treated infants. Predictors of this variability are not fully described. Methods Sixty-three neonates diagnosed with HIV-1 Results Thirty-one (49.2%) infants initiated ART 14 days of birth. Three-quarters were infected despite maternal antenatal ART (however, only 9.5% of women had undetectable viral load closest to delivery) and 86% were breastfed. Higher infant CD4+ T-cell percentage and viral load 14 days. Conclusions Among very early treated infants, higher CD4+ T-cell percentage and viral load Clinical Trials Registration. clinicaltrials.gov (NCT02431975).

BACKGROUND With expansion of antiretroviral therapy (ART) programs, transmission rates are low but new infant infections still occur. We investigated predictors of pre-ART viral load (VL) and CD4+ T-cell counts and percentages in infants diagnosed with HIV at birth in a setting with high coverage of maternal ART and infant prophylaxis. METHODS As part of an early treatment study, 97 infants with confirmed HIV-infection were identified at a hospital in Johannesburg, South Africa. Infant VL and CD4+ T-cell parameters were measured before ART initiation. Data were collected on maternal characteristics, including VL, CD4+ T-cell counts and ART, and infant characteristics, including sex, birth weight, and mode of delivery. RESULTS Pre-ART, median infant VL was 28,405 copies/mL [interquartile range (IQR): 2515-218,150], CD4+ T-cell count 1914 cells/mm (IQR: 1474-2639) and percentage 40.8% (IQR: 32.2-51.2). Most (80.4%) infants were born to mothers who received ART during pregnancy and 97.9% of infants received daily nevirapine prophylaxis until ART initiation at median of 2 days of age (IQR: 1-7). Infant pre-ART VL was more likely to be ≥1000 copies/mL when their mothers had VL ≥1000 copies/mL [Odds Ratio (OR): 6.88, 95% confidence interval (CI): 2.32-20.41] and was higher in boys than girls (OR: 3.29, 95% CI: 1.07-9.95). Lower maternal CD4+ T-cell count (

OBJECTIVES Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority. METHODS This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens. RESULTS The mean age of the 219 uninfected children (45% girls) and the 219 CHIV (48% girls) was 7.0 and 6.4 years, respectively. CHIV had lower adjusted total body fat (P = 0.005) and lower percentage fat at the trunk (P = 0.020), arms (P = 0.001), and legs (P

BACKGROUND Reduced bone mineral mass by dual x-ray absorptiometry is reported in children living with HIV (CLWH), but few studies of bone microarchitecture, particularly in sub-Saharan Africa, have been conducted. Here, we compare bone architecture and strength in black South African CLWH and uninfected control children by peripheral quantitative computed tomography (pQCT). SETTING AND METHODS One hundred seventy-two CLWH on antiretroviral therapy (ART) and 98 controls in the CHANGES Bone Study in Johannesburg, South Africa received pQCT scans of the radius and tibia. Measurements included trabecular and cortical volumetric bone mineral density (vBMD) and bone strength, estimated by the polar strength strain index (SSI), a validated measure of fracture risk. RESULTS CLWH (51% boys) and controls (63% boys) were an average of age 10.4 years. Mean ART duration for CLWH was 9.5 years, with 70.9% on an efavirenz-based, 28.5% on a lopinavir/ritonavir-based, and 1 child on an atazanavir/ritonavir-based regimen. Male CLWH had lower trabecular vBMD at the radius than controls after adjustment for age, radial length, and Tanner stage (β = -17.3, standard error = 7.2, P = 0.018). Bone strength by polar SSI was lower in CLWH than controls (778 vs. 972 mm, P < 0.01). CLWH on an LPV/r-based regimen had lower trabecular vBMD (199 vs. 222 mg/cm, P < 0.001) and cortical vBMD (1074 vs. 1093 mg/cm, P = 0.004) than those on an efavirenz-based regimen. No difference in bone strength by polar SSI was observed between treatment groups. CONCLUSION CLWH initiated on ART early in life with well-controlled HIV have deficits in bone architecture and reductions in bone strength as detected by pQCT.

Introduction: Successful strategies preventing mother-to-child HIV transmission have resulted in increasing numbers of uninfected children exposed to maternal HIV and ART in-utero, and while breast...

Mitochondrial impairment is reported in HIV-infected children receiving antiretroviral therapy (ART), as well as those naive to ART. Whether mitochondrial function recovers with early initiation of ART and sustained viral suppression on long-term ART is unclear. In this study, we evaluate mitochondrial markers in well-suppressed perinatally HIV-infected children initiated on ART early in life. We selected a cross-sectional sample of 120 HIV-infected children with viral load

Little is known about how growing up with HIV impacts educational outcomes in sub-Saharan African children. We evaluated if South African children living with HIV (CLWH) were in the appropriate school grade-for-age compared to uninfected control children. We observed higher rates of not being in the correct grade-for-age in CLWH compared with controls (OR 3.32, 95% CI: 2.07-5.34), adjusted for study site, sex, whether the child's biological father was alive, and caregiver education. Initiation of ART before 6 months of age reduced but did not eliminate this association. Whether these associations are due to biological factors or other social and environmental determinants, and how best to support CLWH to achieve educational goals, warrants further investigation.

BACKGROUND: HIV-1 viral load (VL) has been found to be an independent predictor for disease progression among untreated HIV-infected children. However, qualitative polymerase chain reaction (PCR) assays are routinely used for early infant diagnosis (EID). OBJECTIVES: To predict HIV-1 VL at birth using qualitative EID real-time PCR cycle-threshold (Ct) values. STUDY DESIGN: This study was a secondary analysis of results from a cohort of intrauterine HIV-1 infected neonates. Neonates were enrolled at Rahima Moosa Mother & Child Hospital in Johannesburg, South Africa between June 2014 and November 2017. Laboratory EID HIV-1 PCR testing was performed at birth using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test v2.0 (EID CAP/CTM). Some infants had simultaneous EID point-of-care (POC) testing using Xpert HIV-1 Qualitative assay (EID Xpert). Neonates with a confirmed HIV-1 detected EID result and plasma HIV-1 RNA VL test were included in this analysis. Bland-Altman analysis was used to determine extent of agreement between Ct values of both EID assays. Multivariable linear regression models adjusting for time between EID and VL testing were used to describe the association between EID Ct values and VL and to predict VL at given EID Ct values. RESULTS: Among 107 HIV-1 infected neonates included in the study, 59 had POC EID testing. Median VL was 28400 copies per millilitre (cps/ml) (IQR: 1918 – 218358) - two neonates had VL 5.0 log(10)cps/ml in 82.2% (95% CI: 73.9 – 88.3) and 84.7% (95% CI: 73.7 – 91.8) of cases, respectively. CONCLUSION: EID Ct values at birth predict VL and accurately identify infants with VL >5.0 log(10) cps/ml.

Background In the EU funded MARIO project, specific technological tools are adopted for the people living with dementia (PLWD). In the final stage of the project, a validation of the MARIO companion robot was performed from August to October 2017. Objective The aims of the present study are: 1) to illustrate the key results and evidence obtained in the final evaluation phase of the project across the three different pilot sites; 2) to assess the engagement dimensions of the PLWD who interacted with the MARIO robot; and 3) to assess the acceptability and efficacy of the MARIO companion robot on clinical, cognitive, neuropsychiatric, affective and social aspects, resilience, quality of life in PLWD, and burden level of the caregivers. Methods 38 people (M = 14; F = 24) with Alzheimer's disease were screened for eligibility and all were included. The following tests were administered Pre and Post interactions with MARIO: Observational Measurement of Engagement (OME), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Frontal Assessment Battery (FAB), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD), Multidimensional Scale of Perceived Social Support (MSPSS), 14-item Resilience Scale (RS-14), Quality of Life in Alzheimer's Disease (QOL-AD), Caregiver Burden Inventory (CBI), Tinetti Balance Assessment (TBA), and Comprehensive Geriatric Assessment (CGA) was carried out. Results In Post-MARIO interactions, significant improvements were observed in RS-14 (p = 0.020).Considering the age of the people, PLWD with 68-76 years perceived that they had major social support (MSPSS Total: p = 0.016) and friends to support them (MSPSS Fri: p = 0.014). Indeed, the younger people (55-67 years) were less depressed (CSDD: p = 0.033), and more resilient (RS-14: p = 0.003). The people aged 77-85 years perceived they had major family support (MSPSS Fam: p = 0.018). The participants were gender and education matched without any statistically significant difference. Conclusion MARIO may be a useful tool in mitigating depression and loneliness, while enhancing social connectedness, resilience, and overall quality of life for people with dementia.

The current study focuses on the short-term effect of MARIO, a social robot, on quality of life, depression, and perceived social support in persons with dementia (PWD) and evaluates their acceptability of MARIO. Ten PWD in one nursing home took part in a 4-week pilot study, where each participant had up to 12 sessions with MARIO. Sessions comprised engagement in music, news, reminiscence, games, and calendar applications. Standardized questionnaires were administered before and after the 4-week period. Participants had a sustained interest in MARIO during their interactions and an acceptance of MARIO's appearance, sound, and applications. Consequently, participants spent more time socially engaged. No statistically significant differences were found in quality of life, depression, and perceived social support. PWD can engage with a social robot in a real-world nursing home. Future research should incorporate a larger sample and longer intervention period. Funding received from European Union Horizons 2020—The Framework Programme for Research and Innovation (2014–2020) (grant agreement 643808). The authors acknowledge all members of the MARIO Project Advisory Board and the Irish Research Council Government of Ireland Postdoctoral Fellowship scheme (project ID: GOIPD/2017/1301). peer-reviewed 2020-06-25

BACKGROUND Younger age at antiretroviral therapy (ART) initiation has been associated with smaller HIV reservoirs. We investigated whether younger age of ART initiation is associated with testing negative and weaker signal on a standard HIV diagnostic test in treated children. METHODS At exit from a longitudinal study at 2 sites in Johannesburg, South Africa, 316 school-aged, HIV-infected children on continuous ART started at a median age of 6.3 months, were tested with standard total nucleic acid PCR used for infant diagnosis. All negative results were repeated. Simultaneous viral load (VL) and CD4 T-cell counts/percentages, along with data collected over the prior 4 years, were used in multivariable regression to predict negative PCR results and higher cycle threshold (Ct) values (weaker signal). RESULTS Seven children (2.2%, 95% confidence interval: 0.6 to 3.8) in the full cohort had negative PCR results; all 7 were in a subset of 102 (6.9%, 95% confidence interval: 2.0 to 11.8) who had initiated ART at age 0-4 months and had VL

BACKGROUND Continuous digital cryotherapy experimentally prevents development and reduces severity of sepsis-associated laminitis. A sleeve style ice boot where ice is in direct contact with the skin, and water drains from the boot is being used clinically for distal limb cryotherapy. The degree of cooling achieved by this boot is unknown. OBJECTIVES Evaluate skin and lamellar cooling after application of the ice sleeve in healthy horses, and the same horses during an endotoxaemia model. STUDY DESIGN Prospective study, crossover design. METHODS In eight healthy horses thermocouples were inserted into dorsal lamellae of both front feet, and under skin on both metacarpi. One forelimb received cryotherapy using sleeve style ice boot, with contralateral limb as control. Temperature was recorded on data logging devices at 5 min intervals during each cryotherapy session. Day 1: temperature data was collected for healthy horses. Day 2: data was collected for the same horses during i.v. administration of endotoxin. RESULTS In healthy and endotoxaemic horses, the sleeve style ice boot significantly decreased mean skin (7.2°C and 5.8°C respectively) and lamellar (10.8°C and 9.6°C respectively) temperatures compared with control limbs (P

We evaluated bone quality among South African children with HIV (HIV) over a 2-year period by qualitative ultrasound (QUS). Children with HIV have persistently lower bone quality compared with controls reflecting increased porosity, reduced strength and possibly an increased short and long-term risk of fracture.

This study examined behavioral functioning and quality of life in South African children living with perinatally acquired HIV. Compared with controls, children living with perinatally acquired HIV had a higher mean total difficulties score assessed by the Strengths and Difficulties Questionnaire and lower mean quality of life scores assessed by the Pediatric Quality of Life Inventory.

Summary Background Initiation of antiretroviral therapy (ART) following diagnosis of HIV infection at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Methods From September, 2013 (era 1), only high-risk HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June, 2014 (era 2), all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October, 2014 (era 3), point of care (POC) diagnostic PCR tests were also done if staff availability allowed. We describe time to ART initiation, mortality, retention in care, and viral suppression among the HIV-infected infants identified across these eras. Findings We tested 5449 HIV-exposed infants who were born between Sept 1, 2013, and June 30, 2016. 88 neonates with confirmed HIV infection were identified and included in the study, of which 86 (98%) started ART. Median age at ART initiation decreased from 9 days (IQR 6–25) in eras 1 and 2 to 2 days (1–8) in era 3. In era 3, more neonates who were co-tested with POC testing started ART within 48 h of birth (29 [83%] of 35; median 1 day [IQR 1–2]) than infants who were not co-tested (one [4%] of 29; median 6 days [5–10]). The probability of mortality by 12 months across the eras was 14% (95% CI 8–24) and did not differ by era. Of the 72 infants who survived and initiated ART at the site, 56 (78%) were retained at 12 months. Of the 56 infants retained in care, 40 (71%) had a viral load less than 400 copies per mL at 12 months, with no differences between eras (p=0·23). Interpretation HIV-infected infants can be identified at birth and ART can be initiated within hours to days. Although most infants in our cohort started ART, mortality remained unacceptably high with suboptimal retention and viral suppression. Reducing mortality and improving retention and viral suppression remain urgent priorities. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Allergy and Infectious Disease, National Institutes of Health, USAID/PEPfAR, and the South African National HIV Programme.

BACKGROUND: Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin meglumine. OBJECTIVES: We hypothesised that treatment of post-surgical SISO horses with firocoxib (COX-2 selective) would reduce the signs of endotoxaemia to a greater extent than flunixin meglumine (nonselective COX inhibitor) while continuing to provide similar levels of pain control. STUDY DESIGN: Blinded randomised clinical trial. METHODS: In addition to clinical monitoring, preoperative and 12-, 24- and 48-h post-operative plasma samples were assessed for prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), TNFα and soluble CD14 (sCD14). RESULTS: In 56 recruited SISO horses, either flunixin meglumine (1.1 mg/kg, i.v., q12h) or firocoxib (0.3 mg/kg, i.v. loading dose; 0.1 mg/kg, i.v., q24h) was given in the post-operative period in three university hospitals from 2015 to 2017. COX-2 selectivity was confirmed by a relative lack of inhibition of the COX-1 prostanoid TXB(2) by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX-2 prostanoid PGE(2). There were no significant differences in pain scores between groups (P = 0.2). However, there was a 3.23-fold increased risk (P = 0.04) of increased plasma sCD14 in horses treated with flunixin meglumine, a validated biomarker of equine endotoxaemia. MAIN LIMITATIONS: Horses were all treated with flunixin meglumine prior to referral. In addition, many horses were treated with lidocaine, which has been shown to mitigate the deleterious effects of flunixin meglumine. CONCLUSIONS: In SISO cases, firocoxib reduced a biomarker of endotoxaemia as compared with flunixin meglumine while continuing to provide similar levels of pain control.

Orthopedic injuries constitute the majority of wounds sustained by U.S. soldiers in recent conflicts. The risk of infection is considerable with fracture fixation devices. In this pilot study, we examined the use of unique bactericidal micron-thin sol-gel films on fracture fixation devices and their ability to prevent and eradicate infections. External fixation was studied with micron-thin sol-gel coated percutaneous pins releasing triclosan and inserted medially into rabbit tibiae. A total of 11 rabbits received percutaneous pins that were either uncoated or sol-gel/triclosan coated. Internal fracture fixation was also studied using sol-gel coated intramedullary (IM) nails releasing vancomycin in the intramedullary tibiae. Six sheep received IM nails that were coated with a sol-gel film that either contained vancomycin or did not contain vancomycin. All animals were challenged with Staphylococcus aureus around the implant. Animals were euthanized at 1 month postoperative. Rabbits receiving triclosan/sol-gel coated percutaneous pins did not show signs of infection. Uncoated percutaneous pins had a significantly higher infection rate. In the sheep study, there were no radiographic signs of osteomyelitis with vancomycin/sol-gel coated IM nails, in contrast to the observations in the control cohort. Hence, the nanostructured sol-gel controlled release technology offers the promise of a reliable and continuous delivery system of bactericidals from orthopedic devices to prevent and treat infection.

Objective—To document causes of colic in equine neonates, evaluate clinical features of neonates managed medically versus surgically, determine short- and long-term survival rates for neonates with specific medical and surgical lesions, and assess ability of patients to achieve intended use. Design—Retrospective case series. Animals—137 client-owned equine neonates (< 30 days old) with a history of colic or signs of colic within 1 hour after hospital admission examined between 2000 and 2010. Procedures—Signalment, history, results of physical examination, laboratory data, ancillary diagnostic tests, details of treatment, primary diagnosis, concurrent diseases and short-term survival rate were obtained from the medical records. Long-term follow-up information was obtained through phone survey. Results—137 neonates with colic were included. The majority (122 [89%]) of neonates were managed medically. The 3 most common diagnoses associated with colic were enterocolitis (37 [27%]), meconium-associated colic (27 [20%]), and transient medical colic (26 [19%]). The most common reason for surgery was small intestinal strangulating obstruction, and these neonates were more likely to have severe, continuous pain and were less responsive to analgesics. Concurrent diseases were common (87 [64%]) but did not significantly impact survival rate. Short-term survival rate was not significantly different between medically (75%) and surgically (73%) managed neonates. Long-term survival rate was excellent (66/71 [93%]) for horses that survived to hospital discharge. Most neonates surviving to maturity were used as intended (49/59 [83%]). Conclusions and Clinical Relevance—Most neonates examined for signs of colic can be managed medically. Short-term survival rate in medically and surgically treated neonates was good. Long-term survival rate of foals discharged from the hospital was excellent, with most achieving intended use.

Fetal alcohol spectrum disorder (FASD) is the leading cause of preventable intellectual disabilities in the United States and a significant public health issue.The purpose of this study is to evaluate the knowledge and screening practices of pre-clinical medical students and clinical providers on FAS, FASD, and alcohol consumption.A short survey sent to medical students and residents on the campus of a large medical school and university hospital.On the survey of clinical providers, 38% of respondents stated they always survey pregnant women about their alcohol consumption, 34% stated they always screen patients planning to get pregnant, and 9% screen women of childbearing age. There were a significant percentage of providers who never screen women. When questioned regarding safe amounts of alcohol consumption during pregnancy, 69% of pre-clinical medical students and 67% of clinical providers stated there is no safe amount of alcohol consumption. Clinical providers were much more likely to correctly select the facial features necessary for the diagnosis (p-value0.01).Significant differences exist in the knowledge and screening practices of these different healthcare providers and trainees. Future interventions should seek to improve knowledge on FAS, FASD, and alcohol consumption, in order for practitioners to be more consistent with national guidelines and the Surgeon General recommendations.

Purpose Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS. Patients and Methods We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response. Results Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS. Conclusion In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.