Novel Oppositional Defiant Disorder or Conduct Disorder 24 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI). METHODS: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury. RESULTS: Of the children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified who were recruited in this study, 165 were included in this sample; 95 of these children returned for the 24-month assessment. Multiple imputation was used to address attrition. The prevalence of novel oppositional defiant disorder or conduct disorder was 23.7 out of 165 (14%). In univariable analyses, novel oppositional defiant disorder or conduct disorder was significantly associated with psychosocial adversity (p=0.049) and frontal white matter lesions (p=0.016) and was marginally but not significantly associated with SES. In the final multipredictor model, frontal white matter lesions were significantly associated with novel oppositional defiant disorder or conduct disorder (p=0.021), and psychosocial adversity score was marginally but not significantly associated with the outcome. The odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel depressive disorder was significantly higher for girls than boys (p=0.025), and the odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel attention-deficit hyperactivity disorder (ADHD) was significantly higher for boys than girls (p=0.006). CONCLUSION: Approximately 14% of children with TBI developed oppositional defiant disorder or conduct disorder. The risk for novel oppositional defiant disorder or conduct disorder can be understood from a biopsychosocial perspective. Sex differences were evident for comorbid novel depressive disorder and comorbid novel ADHD.

Supporting the Art: Medication Adherence Patterns in Persons Prescribed Ingestible Sensor-enabled Oral Pre-Exposure Prophylaxis to Prevent Human Immunodeficiency Virus Infection.

BACKGROUND: Timely, accurate adherence data may support oral pre-exposure prophylaxis (PrEP) success and inform prophylaxis choice. We evaluated a Food and Drug Administration (FDA)-approved digital health feedback system (DHFS) with ingestible-sensor-enabled (IS) tenofovir-disoproxil-fumarate plus emtricitabine (Truvada®) in persons starting oral PrEP. METHODS: Human immunodeficiency virus (HIV)-negative adults were prescribed IS-Truvada® with DHFS for 12 weeks to observe medication taking behavior. Baseline demographics, urine toxicology, and self-report questionnaires were obtained. Positive detection accuracy and adverse events were computed as percentages, with Kaplan Meier Estimate for persistence-of-use. In participants persisting ≥28 days, adherence patterns (taking and timing) were analyzed, and mixed-effects logistic regression modeled characteristics associated with treatment adherence. RESULTS: Seventy-one participants were enrolled, mean age 37.6 years (range 18-69), 90.1% male, 77.5% White, 33.8% Hispanic, 95.8% housed, and 74.6% employed. Sixty-three participants (88.7%) persisted ≥28 days, generating 4987 observation days, average 79.2 (29-105). Total confirmed doses were 86.2% (95% confidence interval [CI] 82.5, 89.4), decreasing over time, odds ratio (OR) 0.899 (95% CI .876, .923) per week, P < .001; 79.4% (95% CI 66.7%, 87.3%) of participants had ≥80% adherence. Pattern analysis showed days without confirmed doses clustered (P = .003); regular dose timing was higher among participants with ≥80% confirmed doses (0.828, 95% CI .796 to .859) than among those with <80% (0.542, 95% CI95 .405 to .679) P < .001. In multi-predictor models, better adherence was associated with older age, OR 1.060 (95% CI 1.033, 1.091) per year, P < .001; negative vs positive methamphetamine screen, OR 5.051 (95% CI 2.252, 11.494), P < .001. CONCLUSIONS: DHFS with IS-Truvada® distinguished adherent persons from those potentially at risk of prophylactic failure. Ongoing methamphetamine substance use may impact oral PrEP success.

Lung function tracking in children with perinatally acquired HIV following early antiretroviral therapy initiation.

INTRODUCTION: Lung disease remains a frequent complication in children with perinatal HIV infection (CHIV) and exposure without infection (CHEU), resulting in diminished lung function. In CHIV, early antiretroviral therapy (ART) initiation improves survival and extrapulmonary outcomes. However, it is unknown if there is benefit to lung function. METHODS: Cohorts of CHIV (ART initiated at median 4.0 months), CHEU and HIV-unexposed children (CHU) prospectively performed pulmonary function testing (PFT) consisting of spirometry, plethysmography and diffusing capacity from 2013 to 2020. We determined lung function trajectories for PFT outcomes comparing CHIV to CHU and CHEU to CHU, using linear mixed effects models with multiple imputation. Potential confounders included sex, age, height, weight, body mass index z-score, urine cotinine and Tanner stage. RESULTS: 328 participants (122 CHIV, 126 CHEU, 80 CHU) performed PFT (ages 6.6-15.6 years). Spirometry (forced expiratory volume in 1 s, FEV1, forced vital capacity (FVC), FEV1/FVC) outcomes were similar between groups. In plethysmography, the mean residual volume (RV) z-score was 17% greater in CHIV than CHU (95% CI 1% to 33%, p=0.042). There was no difference in total lung capacity (TLC) or RV/TLC z-scores between groups. Diffusing capacity for carbon monoxide was similar in all groups, while alveolar volume (VA) differed between HIV groups by sex. CONCLUSION: Our study indicates that early ART initiation can mitigate the loss of lung function in CHIV with lasting benefit through childhood; however, there remains concern of small airway disease. CHEU does not appear to disrupt childhood lung function trajectory.

Cerebrospinal fluid CD14++CD16+ monocytes in HIV-1 subtype C compared with subtype B.

CD14++CD16+ monocytes are susceptible to HIV-1 infection, and cross the blood-brain barrier. HIV-1 subtype C (HIV-1C) shows reduced Tat protein chemoattractant activity compared to HIV-1B, which might influence monocyte trafficking into the CNS. We hypothesized that the proportion of monocytes in CSF in HIV-1C is lower than HIV-1B group. We sought to assess differences in monocyte proportions in cerebrospinal fluid (CSF) and peripheral blood (PB) between people with HIV (PWH) and without HIV (PWoH), and by HIV-1B and -C subtypes. Immunophenotyping was performed by flow cytometry, monocytes were analyzed within CD45 + and CD64 + gated regions and classified in classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14lowCD16+). Among PWH, the median [IQR] CD4 nadir was 219 [32-531] cell/mm3; plasma HIV RNA (log10) was 1.60 [1.60-3.21], and 68% were on antiretroviral therapy (ART). Participants with HIV-1C and -B were comparable in terms of age, duration of infection, CD4 nadir, plasma HIV RNA, and ART. The proportion of CSF CD14++CD16+ monocytes was higher in participants with HIV-1C than those with HIV-1B [2.00(0.00-2.80) vs. 0.00(0.00-0.60) respectively, p = 0.03 after BH correction p = 0.10]. Despite viral suppression, the proportion of total monocytes in PB increased in PWH, due to the increase in CD14++CD16+ and CD14lowCD16+ monocytes. The HIV-1C Tat substitution (C30S31) did not interfere with the migration of CD14++CD16+ monocytes to the CNS. This is the first study to evaluate these monocytes in the CSF and PB and compare their proportions according to HIV subtype.

Comparison of two donor-derived cell-free DNA tests and a blood gene-expression profile test in heart transplantation.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd-cfDNA and gene-expression profiling (GEP) testing in heart transplant (HTx) recipients. METHODS: This is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd-cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR. RESULTS: A total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay (p < .001). Both standard and expanded SNP tests showed low sensitivity (39%, p = 1.0) but high specificity (82% and 84%, p = 1.0) for AR. GEP did not improve sensitivity and showed worse specificity (p < .001) compared to standard dd-cfDNA. CONCLUSION: We found no significant difference between standard and expanded SNP assays in detecting AR. We show improved specificity without change in sensitivity using dd-cfDNA in place of GEP testing. Prospective controlled studies to address how to best implement dd-cfDNA testing into clinical practice are needed.

Novel Psychiatric Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: To investigate the factors predictive of novel psychiatric disorders in the interval 0-6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years consecutively hospitalized for mild to severe TBI at five hospitals were recruited. Participants were evaluated at baseline (soon after injury) for pre-injury characteristics including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, family function, family psychiatric history, and adaptive function. In addition to the psychosocial variables, injury severity and lesion location detected with acquisition of a research MRI were measured to develop a biopsychosocial predictive model for development of novel psychiatric disorders. Psychiatric outcome, including occurrence of a novel psychiatric disorder, was assessed 6 months after the injury. RESULTS: The recruited sample numbered 177 children, and 141 children (80%) returned for the six-month assessment. Of the 141 children, 58 (41%) developed a novel psychiatric disorder. In univariable analyses, novel psychiatric disorder was significantly associated with lower SES, higher psychosocial adversity, and lesions in frontal lobe locations, such as frontal white matter, superior frontal gyrus, inferior frontal gyrus, and orbital gyrus. Multivariable analyses found that novel psychiatric disorder was independently and significantly associated with frontal-lobe white matter, superior frontal gyrus, and orbital gyrus lesions. CONCLUSION: The results demonstrate that occurrence of novel psychiatric disorders following pediatric TBI requiring hospitalization is common and has identifiable psychosocial and specific biological predictors. However, only the lesion predictors were independently related to this adverse psychiatric outcome.

Assessment of the American Academy of Dermatology diagnostic criteria for pediatric atopic dermatitis and modification into a checkbox form: A cross-sectional study.

BACKGROUND/OBJECTIVES: Diagnostic criteria for atopic dermatitis (AD) are limited in their performance and/or usability. The American Academy of Dermatology (AAD) consensus criteria include hierarchical categories of disease features to improve these metrics but have not been validated. Our objective was to create and validate a checkbox form of the AAD consensus criteria in the pediatric population. METHODS: We performed a cross-sectional study of 100 pediatric patients with AD (n = 58) and diseases in the differential diagnosis of AD (n = 42). RESULTS: Having three or more "Essential," ≥2 "Important," ≥1 "Associated" features of the AAD criteria was optimal for the diagnosis of AD in children. This combination was 91.4% (95% CI, 84.2%-98.6%) sensitive and 95.2% (88.8%-100%) specific. The UK working party criteria and the Hanifin-Rajka criteria had sensitivities of 96.6% (95% CI 91.9%-100%) and 98.3% (95% CI 94.9%-100%) and specificities of 83.3% (95% CI 72.1%-94.6%) and 71.4% (95% CI 57.8%-85.1%), respectively. The AAD criteria had significantly greater specificity than the Hanifin-Rajka criteria (p = .002). CONCLUSIONS: This study represents an important step in validating the AAD consensus criteria and formulating a useable checkbox form for diagnosing AD in the pediatric population.

Early vs Interval Postpartum Intrauterine Device Placement: A Randomized Clinical Trial.

Importance: The early postpartum period, 2 to 4 weeks after birth, may be a convenient time for intrauterine device (IUD) placement; the placement could then coincide with early postpartum or well-baby visits. Objective: To determine expulsion rates for IUDs placed early postpartum compared with those placed at the standard interval 6-week visit. Design, Setting, and Participants: In this randomized noninferiority trial, people who had a vaginal or cesarean birth were randomly assigned to undergo early (14-28 days) or interval (42-56 days) postpartum IUD placement. Clinicians blinded to participant study group used transvaginal ultrasonography to confirm IUD presence and position at the 6-month postpartum follow-up. The study assessed 642 postpartum people from 4 US medical centers, enrolled a consecutive sample of 404 participants from March 2018 to July 2021, and followed up each participant for 6 months postpartum. Interventions: Early postpartum IUD placement, at 2 to 4 weeks postpartum, vs standard interval placement 6 to 8 weeks postpartum. Main Outcomes and Measures: The primary outcome was complete IUD expulsion by 6 months postpartum; the prespecified noninferiority margin was 6%. Secondary outcomes were partial IUD expulsion, IUD removal, pelvic infection, patient satisfaction, uterine perforation, pregnancy, and IUD use at 6 months postpartum. IUD malposition was an exploratory outcome. Results: Among 404 enrolled participants, 203 participants were randomly assigned to undergo early IUD placement and 201 to undergo interval IUD placement (mean [SD] age, 29.9 [5.4] years; 46 [11.4%] were Black, 228 [56.4%] were White, and 175 [43.3%] were Hispanic). By 6 months postpartum, 53 participants (13%) never had an IUD placed and 57 (14%) were lost to follow-up. Among the 294 participants (73%) who received an IUD and completed 6-month follow-up, complete expulsion rates were 3 of 149 (2.0% [95% CI, 0.4%-5.8%]) in the early placement group and 0 of 145 (0% [95% CI, 0.0%-2.5%]) in the interval placement group (between-group difference, 2.0 [95% CI, -0.5 to 5.7] percentage points). Partial expulsion occurred in 14 (9.4% [95% CI, 5.2%-15.3%]) participants in the early placement group and 11 (7.6% [95% CI, 3.9%-13.2%]) participants in the interval placement group (between-group difference, 1.8 [95% CI, -4.8 to 8.6] percentage points). IUD use at 6 months was similar between the groups: 141 (69.5% [95% CI, 62.6%-75.7%]) participants in the early group vs 139 (67.2% [95% CI, 60.2%-73.6%]) in the interval group. Conclusions and Relevance: Early IUD placement at 2 to 4 weeks postpartum compared with 6 to 8 weeks postpartum was noninferior for complete expulsion, but not partial expulsion. Understanding the risk of expulsion at these time points may help patients and clinicians make informed choices about the timing of IUD placement. Trial Registration: ClinicalTrials.gov Identifier: NCT03462758.

Machine Learning Quantifies Accelerated White-Matter Aging in Persons With HIV.

BACKGROUND: Persons with HIV (PWH) undergo white matter changes, which can be quantified using the brain-age gap (BAG), the difference between chronological age and neuroimaging-based brain-predicted age. Accumulation of microstructural damage may be accelerated in PWH, especially with detectable viral load (VL). METHODS: In total, 290 PWH (85% with undetectable VL) and 165 HIV-negative controls participated in neuroimaging and cognitive testing. BAG was measured using a Gaussian process regression model trained to predict age from diffusion magnetic resonance imaging in publicly available normative controls. To test for accelerated aging, BAG was modeled as an age × VL interaction. The relationship between BAG and global neuropsychological performance was examined. Other potential predictors of pathological aging were investigated in an exploratory analysis. RESULTS: Age and detectable VL had a significant interactive effect: PWH with detectable VL accumulated +1.5 years BAG/decade versus HIV-negative controls (P = .018). PWH with undetectable VL accumulated +0.86 years BAG/decade, although this did not reach statistical significance (P = .052). BAG was associated with poorer global cognition only in PWH with detectable VL (P < .001). Exploratory analysis identified Framingham cardiovascular risk as an additional predictor of pathological aging (P = .027). CONCLUSIONS: Aging with detectable HIV and cardiovascular disease may lead to white matter pathology and contribute to cognitive impairment.

Main lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in HIV-1 subtypes C and B.

HIV-1 subtype C (HIV-1C) shows reduced Tat protein chemoattractant activity compared with HIV-1B. The impact of HIV-1C Tat on the chemotaxis of the main lymphocyte subpopulations in the cerebrospinal fluid (CSF) and the peripheral blood (PB) is unclear. We hypothesized that there would be a lower frequency of specific lymphocyte subpopulations CD3+ or CD19+ in CSF in HIV-1C than in HIV-1B. The objectives were to detect the differences in the proportions of main lymphocyte subpopulations in CSF and PB, between people with HIV (PWH) and HIV-1-uninfected volunteers (PWoH) and in HIV-1B and HIV-1C. Lymphocyte immunophenotyping was studied in CSF and paired PB samples of PWH (n = 22) and PWoH (n = 14). Lymphocytes were analyzed within the CD45+ gated region. The proportions of CSF CD3+CD4+, CD3+CD8+, and CD3-CD19+ lymphocytes in CSF were comparable in HIV-1B and C. There was an increase in the proportion of CD3+CD8+ cells and a decrease in CD3+CD4+ T cells (ps = 0.016) in the CSF samples of the PWH compared with the PWoH group. In the PWH group, both CD3+CD4+ and CD3+CD8+ lymphocytes were significantly higher in the CSF than in the PB (p = 0.047 and 0.005). The proportion of CD3+CD4+ was lower and that of CD3+CD8+ was higher in the CSF samples of the aviremic group than that of HIV-negative control (p = 0.0008 and < 0.0001, respectively). HIV-1C Tat substitution (C30S) did not interfere with the CNS migration of the main lymphocyte subpopulations. This is the first study to evaluate these lymphocytes in CSF and PB of HIV-1C compared with HIV-1B.

Traumatic Brain Injury in Children and Adolescents: Psychiatric Disorders 24 Years Later.

OBJECTIVE: The investigators aimed to extend findings regarding predictive factors of psychiatric outcomes among children and adolescents with traumatic brain injury (TBI) from 2 to 24 years postinjury. METHODS: Youths aged 6-14 years who were hospitalized following TBI from 1992 to 1994 were assessed at baseline for TBI severity and for preinjury psychiatric, adaptive, and behavioral functioning; family functioning; family psychiatric history; socioeconomic status; and intelligence within weeks of injury. Predictors of psychiatric outcomes following pediatric TBI at 3, 6, 12, and 24 months postinjury have previously been reported. In this study, repeat psychiatric assessments were completed at 24 years postinjury with the same cohort, now adults aged 29-39 years, with the outcome measure being presence of a psychiatric disorder not present before the TBI ("novel psychiatric disorder"). RESULTS: Fifty participants with pediatric TBI were initially enrolled, and the long-term outcome analyses focused on data from 45 individuals. Novel psychiatric disorder was present in 24 out of 45 (53%) participants. Presence of a current novel psychiatric disorder was independently predicted by the presence of a preinjury lifetime psychiatric disorder and by severity of TBI. CONCLUSIONS: Long-term psychiatric outcome (mean=23.92 years [SD=2.17]) in children and adolescents hospitalized for TBI can be predicted at the point of the initial hospitalization encounter by the presence of a preinjury psychiatric disorder and by greater injury severity.

Novel Oppositional Defiant Disorder 12 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators examined the factors predictive of novel oppositional defiant disorder in the 6-12 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years old who experienced a TBI were recruited from consecutive admissions to five hospitals. Participants were evaluated soon after injury (baseline) for preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, and injury severity, to develop a biopsychosocial predictive model for development of novel oppositional defiant disorder. MRI analyses were conducted to examine potential brain lesions. Psychiatric outcome, including that of novel oppositional defiant disorder, was assessed 12 months after injury. RESULTS: Although 177 children were recruited for the study, 120 children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 12-month assessment. Of these 120 children, seven (5.8%) exhibited novel oppositional defiant disorder, and none developed conduct disorder or DBD NOS in the 6-12 months postinjury. Novel oppositional defiant disorder was significantly associated with lower socioeconomic status, higher psychosocial adversity, and lower preinjury adaptive functioning. CONCLUSIONS: These results demonstrate that novel oppositional defiant disorder following TBI selectively and negatively affects an identifiable group of children. Both proximal (preinjury adaptive function) and distal (socioeconomic status and psychosocial adversity) psychosocial variables significantly increase risk for this outcome.

Novel Oppositional Defiant Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators aimed to assess predictive factors of novel oppositional defiant disorder (ODD) among children and adolescents in the first 6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years who experienced a TBI were recruited from consecutive admissions to five hospitals. Testing of a biopsychosocial model that may elucidate the development of novel ODD included assessment soon after injury (baseline) of preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, injury severity, and postinjury processing speed (which may be a proxy for brain injury). MRI analyses were also conducted to examine potential brain lesions. Psychiatric outcome, including that of novel ODD, was assessed 6 months after the injury. RESULTS: A total of 177 children and adolescents were recruited for the study, and 134 who were without preinjury ODD, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 6-month assessment. Of those who returned 6 months postinjury, 11 (8.2%) developed novel ODD, and none developed novel conduct disorder or DBD NOS. Novel ODD was significantly associated with socioeconomic status, preinjury family functioning, psychosocial adversity, and processing speed. CONCLUSIONS: These findings show that an important minority of children with TBI developed ODD. Psychosocial and injury-related variables, including socioeconomic status, lower family function, psychosocial adversity, and processing speed, significantly increase risk for this outcome.

Accelerated Brain Aging and Cerebral Blood Flow Reduction in Persons With Human Immunodeficiency Virus.

BACKGROUND: Persons with human immunodeficiency virus (PWH) are characterized by altered brain structure and function. As they attain normal lifespans, it has become crucial to understand potential interactions between human immunodeficiency virus (HIV) and aging. However, it remains unclear how brain aging varies with viral load (VL). METHODS: In this study, we compare magnetic resonance imaging (MRI) biomarkers among PWH with undetectable VL (UVL; ≤50 genomic copies/mL; n = 230), PWH with detectable VL (DVL; >50 copies/mL; n = 93), and HIV-uninfected (HIV-) controls (n = 206). To quantify gray matter cerebral blood flow (CBF), we utilized arterial spin labeling. To measure structural aging, we used a publicly available deep learning algorithm to estimate brain age from T1-weighted MRI. Cognitive performance was measured using a neuropsychological battery covering 5 domains. RESULTS: Associations between age and CBF varied with VL. Older PWH with DVL had reduced CBF vs PWH with UVL (P = .02). Structurally predicted brain aging was accelerated in PWH vs HIV- controls regardless of VL (P < .001). Overall, PWH had impaired learning, executive function, psychomotor speed, and language compared to HIV- controls. Structural brain aging was associated with reduced psychomotor speed (P < .001). CONCLUSIONS: Brain aging in HIV is multifaceted. CBF depends on age and current VL and is improved by medication adherence. By contrast, structural aging is an indicator of cognitive function and reflects serostatus rather than current VL.

Predictors and significance of histologic response to neoadjuvant therapy for gastric cancer.

BACKGROUND: Perioperative therapy is the standard-of-care for locally-advanced gastric cancer but many patients do not respond. There are currently no known factors that predict response to therapy. METHODS: This was a retrospective study aimed to evaluate treatment effect grade (TEG) in patients with locally advanced gastric cancer treated with neoadjuvant therapy and surgery at a single center. Ordinal logistic regression was performed to identify predictors of TEG, scaled from 0 to 3. RESULTS: Fifty patients were identified. The majority were male (n = 33) and 50% were Hispanic. The most common regimens given were: 5-fluorouracil/leucovorin, oxaliplatin, and docetaxel (n = 23, 46%), epirubicin, cis- or oxaliplatin, and 5-fluorouracil/leucovorin or Xeloda (n = 8, 16%), and 5-fluorouracil/leucovorin and oxaliplatin (n = 9, 18%). Twenty-seven patients (55%) had complete or partial response to therapy (TEG 0-2), and 23 patients (46%) had no response (TEG 3). Of numerous variables analyzed, only race and SRC histology were associated with TEG. TEG was associated with disease free, but not disease specific survival. CONCLUSIONS: In this cohort, 46% of patients had no histologic response to therapy. SRC histology, and possibly race, should be considered in determination of optimal multidisciplinary regimens and in amount of therapy to be given upfront, as patients with SRC histology and those of non-Asian race are less likely to respond to standard regimens.

Paresthesia Predicts Increased Risk of Distal Neuropathic Pain in Older People with HIV-Associated Sensory Polyneuropathy.

OBJECTIVE: Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized. METHODS: This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates. RESULTS: Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]). CONCLUSIONS: Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.

Blood amyloid-ß protein isoforms are affected by HIV-1 in a subtype-dependent pattern.

This study aimed to compare serum amyloid processing biomarkers among HIV subtype B (n = 25), HIV subtype C (n = 26), healthy HIV-negative controls (n = 18), and patients with Alzheimer's disease (AD; n = 24). Immunoassays were used to measure main soluble Aß isoforms Aß38, Aß40, Aß42, and Aß-total in serum and cerebrospinal fluid (CSF). People living with HIV (PLWH) and HIV(-) samples, including AD samples, were compared for gender and age, while HIV subtypes were compared for nadir CD4 and plasma viral load suppression. CSF/serum ratios of Aß40, Aß42, and Aß-total were lower in HIV-1C group than in HIV-1B group (p = 0.020, 0.025, and 0.050, respectively). In serum, these biomarkers were comparable. Serum Aß isoforms were significantly lower in PLWH than in AD. Serum Aß42 levels in PLWH were decreased compared to those in control group, thus similar to Aß42 alterations in CSF; these results were different from those observed in AD. Impaired cellular immunity, low CD4 cell count (nadir or current) influences serum Aß metabolism in HIV-1B but not HIV-1C. However, in PLWH overall, but not in individual HIV subtype groups, greater CD4 recovery, calculated as the difference between current and nadir CD4, correlated with Aß42/Aß40 ratio in serum (rs 0.246; p = 0.0479). No significant correlation was found with global deficit score (GDS), an index of neurocognitive performance, age, or duration of infection. These findings are consistent with those of subtype-dependent amyloid processing in blood in chronic HIV disease.

Evidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.

We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.

Patterns of malformation associated with esophageal atresia/tracheoesophageal fistula: A retrospective single center study.

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is one of the most common gastrointestinal birth defects. It can occur in isolation or in association with other birth defects or genetic syndromes. We retrospectively reviewed the EA/TEF cases evaluated at Rady Children's Hospital San Diego (San Diego, CA) between 2007 and 2016. Data were collected for 157 patients. The majority of patients (105, 66.8%) had an associated major malformation present, and 52 patients (33.1%) had isolated EA/TEF. The patients with associated malformations were distributed as follows: 16 patients (10.2%) had a known genetic syndrome (the most common being Trisomy 21 in 11 patients); six patients (3.8%) had a suspected genetic syndrome; one patient had a suspected teratogenic syndrome (diabetic embryopathy); 30 patients had VACTERL association (19.1%); 32 patients had a "partial VACTERL" association (only two VACTERL-type defects without other malformation); nine patients (5.7%) had one additional non-VACTERL-type birth defect, two patients had VACTERL-type defects plus auricular malformations; and nine patients (5.7%) were classified as "unknown syndrome." A classification of the patterns of malformation of patients with congenital EA/TEF is proposed based on reviewing the data of this relatively large and phenotypically diverse patient group.

Rapid dissemination of practice-changing information: A longitudinal analysis of real-world rates of minimally invasive radical hysterectomy before and after presentation of the LACC trial.

OBJECTIVE: Characterize change in rates of minimally invasive (MIS) radical hysterectomy after presentation of the LACC trial. METHODS: Longitudinal analysis of data from Vizient® database for surgically treated patients with invasive cervical cancer from April 2017-March 2019. Covariates studied included patient demographic and obesity categories, dates of LACC trial presentation and publication, and hospital characteristics. RESULTS: 2102 cervical cancer patients had surgery at 201 hospitals. Most were age 31-50 (51.2%), White (64.8%), and had public (49.2%) health insurance. Annual rates of MIS fell from 51.9% to 27.1% after the LACC trial presentation (RR 0.52, 95% CI 0.47, 0.58; p < 0.0001). Adjusting for within hospital correlation, the odds of MIS dropped by 13% per month (OR = 0.872 per month, 95% CI 0.852, 0.891; p < 0.001), without further change in rates of MIS after the peer-review publication (OR = 1.033 per month, 95% CI 0.897, 1.189; p = 0.65). Rates of MIS declined across all demographics (RR = 0.32-0.65; p < 0.01), except in morbidly obese women (RR = 0.90; p = 0.60). Applying mixed effects model, rates of MIS fell by 3% per month in morbidly obese women versus 18% per month if body mass index<40 kg/m2. NCCN member hospitals and hospitals with gynecologic oncology fellowship training programs significantly reduced rates of MIS radical hysterectomy faster, but not earlier, than other hospitals. CONCLUSIONS: Rates of MIS radical hysterectomy fell dramatically and pervasively after the LACC trial presentation, despite ongoing substantive controversy. Practice pattern changes were not significant in morbidly obese women.