Corrigendum to "The Healthy Kids & Families study: Outcomes of a 24-month childhood obesity prevention intervention" [Prev. Med. Rep. 31 (2023) 102086].

[This corrects the article DOI: 10.1016/j.pmedr.2022.102086.].

Does the Type of Failure and the Choice of the Second Biologic Influence Response and Persistence on Medication in Rheumatoid Arthritis?

BACKGROUND: The type of failure may predict response to a second biologic. We evaluated the response to a second tumor necrosis factor inhibitor (TNFi) or non-TNFi in patients failing their initial TNFi, either primarily or secondarily. METHODS: Patients with rheumatoid arthritis who were biologic-naive and had a Clinical Disease Activity Index (CDAI) >10, who started their first TNFi for ≥3 months and then switched to a second biologic, were included in the study. Secondary failure was defined as 2 consecutive low-CDAI visits and then switching to a second biologic while they had moderate/severe CDAI. Primary failure was defined if it did not meet the definition of secondary failure, or if they had at least 1 moderate/severe CDAI after 3 months on treatment. We used multivariable logistic regression comparing primary versus secondary failure for achievement of CDAI ≤10 (primary outcome) and minimal clinically important differences (secondary outcome) at 6 months after switch. RESULTS: Of the 462 patients included, 64.3% and 35.7% stopped the first TNFi because of a primary and secondary failure, respectively. Patients with primary failure had a more severe disease (CDAI mean, 26.39 vs. 21.61; p < 0.001). The likelihood of achieving CDAI ≤10 (odds ratio, 4.367; 95% confidence interval, 2.428-7.856) and minimal clinically important difference (odds ratio, 2.851; 95% confidence interval, 1.619-5.020) was significantly higher for secondary than primary failure regardless of choice of a second agent. CONCLUSION: Patients with rheumatoid arthritis with secondary failure to a first TNFi responded better to a second biologic agent, regardless of the choice of biologic.

The Healthy Kids & Families study: Outcomes of a 24-month childhood obesity prevention intervention.

Socioeconomically disadvantaged children experience a high burden of obesity but few interventions address obesity prevention in this population subgroup. The Healthy Kids & Families study tested the effect of a parent-focused community health worker (CHW)-delivered lifestyle intervention to prevent childhood obesity. Participants were child-parent/guardian (Kindergarten to 6th grade at baseline) dyads (n = 247) recruited through schools located in socioeconomically disadvantaged neighborhoods in Worcester, MA, USA. Using a quasi-experimental design, the study tested the impact of Healthy Kids & Families, a theory-based, low-intensity, parent-focused, CHW-delivered intervention to improve children's weight, healthy eating and physical activity. The attention-control comparison condition was a positive parenting intervention. The primary outcome was change in child body mass index (BMI) z-score at 24 months. Secondary outcomes included number of positive child and parent changes in selected diet and physical activity behaviors targeted by the intervention and change in parent BMI. Outcomes were assessed following the intent-to-treat principle and using multivariable generalized linear mixed models. Compared to the attention-control comparison condition, the Healthy Kids & Families intervention led to a greater reduction in children's BMI z-score (ß = -0.17, 95 %CI: -1.92 to -0.36; p = 0.057) and a greater number of positive behavior changes among children (ß = 0.57, 95 %CI: 0.08-1.06; p = 0.02) at 24 months. There was no significant change in parent outcomes. The Healthy Kids & Families intervention shows promise for obesity prevention among children in socioeconomically disadvantaged communities.

Longitudinal trends in glycated hemoglobin during and after tuberculosis treatment.

AIMS: To investigate the impact of pulmonary TB on glycemic status during and after TB treatment, and associations of glycemic trends with antidiabetic therapy and TB outcomes. METHODS: Data from two prospective cohort studies of adults in Chennai, India, with pulmonary TB were combined for this analysis. Participants were classified by baseline hemoglobin A1c (A1C) as having normoglycemia (NG; n = 74), prediabetes (pre-DM; n = 110), or diabetes (DM; n = 244). Repeat A1C measurements were performed at TB treatment months 3 and 6, and then 6 and 12 months after TB treatment completion. RESULTS: Median A1C at baseline declined after TB treatment initiation in all groups. No baseline NG or pre-DM participants progressed to DM by end of study, while 16.7% of baseline DM participants shifted to pre-DM or NG levels of A1C. In the baseline DM group, rising A1C after the intensive phase of TB treatment was significantly associated with adverse TB outcomes. CONCLUSIONS: Incident TB promotes transient glucose elevation but was not conclusively shown to promote chronic dysglycemia. Rising A1C during and after TB treatment may predict unfavorable treatment response in persons presenting with A1C ≥ 6.5 % at the time of TB diagnosis.

Prospective RandOmised Trial of Emergency Cardiac Computerised Tomography (PROTECCT).

OBJECTIVE: Many patients presenting with suspected acute coronary syndrome (ACS) have high-sensitivity cardiac troponin (hs-cTn) concentrations between rule-in and rule-out thresholds and hence need serial testing, which is time consuming. The Prospective RandOmised Trial of Emergency Cardiac Computerised Tomography (PROTECCT) assessed the utility of coronary CT angiography (CCTA) in patients with suspected ACS, non-ischaemic ECG and intermediate initial hs-cTn concentration. METHODS: Patients were randomised to CCTA-guided management versus standard of care (SOC). The primary outcome was hospital length of stay (LOS). Secondary outcomes included cost of in-hospital stay and major adverse cardiac events (MACE) at 12 months of follow-up. Data are mean (SD); for LOS harmonic means, IQRs are shown. RESULTS: 250 (aged 55 (14) years, 25% women) patients were randomised. Harmonic mean (IQR) LOS was 7.53 (6.0-9.6) hours in the CCTA arm and 8.14 (6.3-9.8) hours in the SOC arm (p=0.13). Inpatient cost was £1285 (£2216) and £1108 (£3573), respectively, p=0.68. LOS was shorter in the CCTA group in patients with <25% stenosis, compared with SOC; 6.6 (5.6-7.8) hours vs 7.5 (6.1-9.4) hours, respectively; p=0.021. More referrals for cardiology outpatient clinic review and cardiac CT-related outpatient referrals occurred in the SOC arm (p=0.01). 12-month MACE rates were similar between the two arms (7 (5.6%) in the CCTA arm and 8 (6.5%) in the SOC arm-log-rank p=0.78). CONCLUSIONS: CCTA did not lead to reduced hospital LOS or cost, largely because these outcomes were influenced by the detection of ≥25% grade stenosis in a proportion of patients. TRIAL REGISTRATION NUMBER: NCT03583320.

"A Tale of 2 Demons"-Concomitant Presence of Hepatocellular Carcinoma and Primary Neuroendocrine Tumor of Liver: A Case Report and Review of Literatures.

Neuroendocrine tumors usually originate from the neuroendocrine cells of gastrointestinal tract and their presence in the liver is mostly in the form of metastases. A primary neuroendocrine tumor in the liver concomitantly with hepatocellular carcinoma is an infrequent phenomenon. We present a 66-year-old woman with a remote history of breast cancer coming with postprandial fullness, later found to have multiple liver masses. After a thorough investigation, she was found to have a combined type of hepatocellular and primary neuroendocrine tumor of liver with pulmonary metastases. She was not a surgical candidate due to distant metastases. She was treated with chemotherapy, immunotherapy, and targeted therapies but continued to deteriorate clinically, and finally succumbed to her illness. The presence of this combined type of tumor in our patient is unique in many different ways: It is extremely rare, she did not have any risk factors for liver cancer, no genetic mutation till date could tie all these cancers (breast cancer, neuroendocrine tumor, and hepatocellular carcinoma) together, and not a lot of literatures/studies performed on this illness.

The Clinical Disease Activity Index and the Routine Assessment of Patient Index Data 3 for Achievement of Treatment Strategies.

OBJECTIVE: To compare the Clinical Disease Activity Index (CDAI) with the Routine Assessment of Patient Index Data 3 (RAPID3) from 2 large United States registries. METHODS: Using a cross section of clinic visits within 2 registries, we determined whether the outcome of each metric would place the patient in remission (REM), low (LDA), moderate (MDA), or high disease activity (HDA) using the CDAI, with the assumption that a patient in MDA or HDA would be a candidate for acceleration of treatment. RESULTS: We identified significant disparities between the 2 indices in final disease categorization using each index system. For patients identified in LDA by CDAI, RAPID3 identified 20.4% and 28.3% as LDA in Corrona and the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS), respectively. For patients identified as MDA by CDAI, RAPID3 identified 36.2% and 31.1% as MDA in Corrona and BRASS, respectively, with the greatest disparities within each system identified for LDA and MDA activity by the CDAI (20.4% and 36.2% agreement of RAPID3 with CDAI, respectively, in Corrona and 28.3% and 31.1% agreement in BRASS). Overall comparison between CDAI and RAPID3 in the 4 disease categories resulted in estimated κ = 0.285 in both. The RAPID3 scores indicated the potential for treat-to-target acceleration in 34.4% of patients in REM or LDA based on CDAI in Corrona and 27.7% in BRASS, respectively. CONCLUSION: The RAPID3, based on patient-reported outcomes, shows differences with CDAI categories of disease activity. The components of CDAI are not highly correlated with RAPID3, except for patient global assessment. These differences could significantly affect the decision to advance treatment when using a treat-to-target regimen.

Hydroxychloroquine and the risk of respiratory infections among RA patients.

OBJECTIVES: To determine the effect of hydroxychloroquine on the incidence of new respiratory infections in a large registry of rheumatoid arthritis (RA) patients compared with a matched cohort receiving other conventional disease-modifying antirheumatic drugs (csDMARDs). METHODS: We reviewed physician-reported infections including upper respiratory infections (URI), bronchitis and pneumonia in the Corrona RA registry from June 2008 to February 2020 with the goal of comparing infections in biologic/targeted synthetic (b/ts) DMARDs naive HCQ starts compared with starts of other csDMARDs and no HCQ. Patients on different interventions were compared using time-varying adjusted Cox models adjusting for age, sex, duration of RA, BMI, disease activity, smoking status, concurrent medications, season of the year, year of onset and history of serious infections, diabetes or cardiovascular disease (CVD). A secondary analysis in a set of propensity-matched starts were also compared adjusting for time-varying covariates. The analysis was repeated including URI and bronchitis only and also for serious respiratory infections only. RESULTS: No evidence of differences was found in the incidence of any respiratory infection (URI, bronchitis, pneumonia) in patients receiving HCQ compared with other csDMARDs: HR=0.87 (0.70 to1.07) in adjusted analyses and HR=0.90 (0.70 to 1.17) in adjusted matched analysis. Similar results were found in the analysis of URI and bronchitis only and for serious respiratory infections only. CONCLUSIONS: In patients with RA, the risk for respiratory infections was similar among patients using HCQ as compared to other non-biologic DMARDs.

Impact of Diabetes and Low Body Mass Index on Tuberculosis Treatment Outcomes.

BACKGROUND: Diabetes was identified as a tuberculosis (TB) risk factor mostly in retrospective studies with limited assessments of metabolic variables. The prospective Effects of Diabetes on Tuberculosis Severity study compared adults with pulmonary TB in Chennai, India, who were classified as having either diabetes or a normal glucose tolerance at enrollment. METHODS: Baseline TB severity, sputum conversion, and treatment outcomes (cure, failure, death, or loss to follow-up) were compared between groups with respect to glycemic status and body mass index (BMI). RESULTS: The cohort of 389 participants included 256 with diabetes and 133 with a normal glucose tolerance. Low BMIs (<18.5 kg/m2) were present in 99 (74.4%) of nondiabetic participants and 85 (33.2%) of those with diabetes. Among participants with normal or high BMIs, rates of cure, treatment failure, or death did not vary by glycemic status. Participants with low BMIs had the highest radiographic severity of disease, the longest time to sputum culture conversion, and the highest rates of treatment failure and death. Among participants with low BMIs, poorly controlled diabetes (glycohemoglobin [HbA1c] ≥8.0%) was unexpectedly associated with better TB treatment outcomes. A high visceral adiposity index was associated with adverse outcomes and, despite an overall correlation with HbA1c, was elevated in some low-BMI individuals with normal glucose tolerance. CONCLUSIONS: In this South Indian cohort, a low BMI was significantly associated with an increased risk for adverse TB treatment outcomes, while comorbid, poorly controlled diabetes lessened that risk. A high visceral adiposity index, either with or without dysglycemia, might reflect a novel TB susceptibility mechanism linked to adipose tissue dysfunction.

Quadriceps Muscle Size Following ACL Injury and Reconstruction: A Systematic Review.

Image-based assessments of quadriceps muscle size facilitate examination of structural changes after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). Understanding the effects of ACLR on muscle size measures may aid in clarifying the contribution of quadriceps atrophy toward quadriceps strength. The purpose of this study was to systematically review the literature examining the effects of ACLR on quadriceps muscle volume and cross-sectional area (CSA). An online database search was conducted using Web of Science, SportDISCUS, PubMed (Medline), CINHAL (EBSCO), and Cochrane Library limited to articles published after January 1, 1980. Means and standard deviations were extracted for the ACLR limb and the contralateral limb, and sample characteristics from relevant articles. Magnitude of between limb differences were assessed using pooled effect sizes (Hedge's g) and 95% confidence intervals. Eleven articles (five CSA, six muscle volume) were included in this systematic review. Included studies reported negative effective sizes, indicating that the ACLR limb was smaller in CSA or muscle volume compared with the contralateral limb; however, 36% of the included articles reported meaningful difference between the limbs. Quadriceps atrophy may occur following ACL injury and persist after rehabilitation, however, the magnitude of these reductions may not be clinically meaningful and may only partially explain the persistent quadriceps weakness that is ubiquitous among this patient population. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:598-608, 2020.

Design and methods of the Healthy Kids & Families study: a parent-focused community health worker-delivered childhood obesity prevention intervention.

BACKGROUND: One third of U.S. children and two thirds of adults are overweight or obese. Interventions to prevent obesity and thus avert threats to public health are needed. This paper describes the design and methods of the Healthy Kids & Families study, which tested the effect of a parent-focused community health worker (CHW)-delivered lifestyle intervention to prevent childhood obesity. METHODS: Participants were English or Spanish-speaking parent-child dyads (n = 247) from nine elementary schools (grades K-6) located in racial/ethnically diverse low-income communities in Worcester, Massachusetts. Using a quasi-experimental design with the school as the level of allocation, the study compared the lifestyle intervention vs. an attention-control comparison condition. The lifestyle intervention was guided by social cognitive theory and social ecological principles. It targeted the child's social and physical home environment by intervening with parental weight-related knowledge, beliefs, and skills for managing child obesogenic behaviors; and addressed families' needs for community resources supportive of a healthy lifestyle. The two-year CHW-delivered intervention was structured based on the 5As model (Agenda, Assess, Advise, Assist, Arrange follow up) and included two in person sessions and two telephone follow-ups per year with the parent, with a personalized letter and print materials sent after each contact. Parents also received quarterly newsletters, Facebook messages, and invitations to community events. The attention-control comparison condition used the same format and contact time as the intervention condition, but targeted positive parenting skills. Measurements occurred at baseline, and at 6-, 12-, 18- and 24-month follow-up. Assessments included anthropometrics, accelerometry, global positioning system (GPS), and self-report surveys. The primary outcome was child body mass index (BMI) z score. Secondary outcomes were parent BMI; and parent and child diet, physical activity, sedentariness, and utilization of community resources supportive of a healthy lifestyle. DISCUSSION: A CHW-delivered parent-focused lifestyle intervention may provide a translatable model for targeting the high priority public health problem of childhood obesity among low-income diverse communities. If demonstrated effective, this intervention has potential for high impact. TRIAL REGISTRATION: ClinicalTrials NCT03028233. Registered January 23,2017. The trial was retrospectively registered.

Protease-Activated Receptor 2 Agonist as Adjuvant: Augmenting Development of Protective Memory CD8 T Cell Responses Induced by Influenza Virosomes.

Protease-activated receptor 2 (PAR-2) is expressed in various tissues, including lung, and when activated, promotes inflammation, differentiation, and migration of dendritic cells. We found that combining influenza virosomes containing hemagglutinin and neuraminidase with a PAR-2 agonist peptide (PAR-2AP) in an intranasal prime boost approach increased survival of mice challenged weeks later with lethal influenza virus over that by virosome or PAR-2AP prime boost alone. No weight loss occurred from influenza challenge after virosome-plus-PAR-2AP prime boost compared with either virosomes or PAR-2AP alone. Thus, virosomes plus PAR-2AP prevented morbidity as well as mortality. Through adoptive transfer, CD8+ lung T cells but not CD4+ T cells from virosomes plus PAR-2AP-primed mice protected from lethal influenza virus challenge and enhanced survival with less weight loss and faster recovery. Virosome-plus-PAR-2AP prime boost resulted in greater percentages of T effector memory phenotype cells (Tem) in lung, and higher frequencies of CD8 Tem and T central memory cells displayed effector functions in response to virus challenge in vivo. Virosome-plus-PAR-2AP prime boost also resulted in greater percentages of Ag-specific CD8+ T cells, both Tem and T central memory cells, in lungs of animals subsequently challenged with live influenza virus. Our findings indicate that PAR-2AP, a short peptide, may be a new and useful mucosal adjuvant.

Listeria monocytogenes infection enhances the interaction between rat non-classical MHC-Ib molecule and Ly49 receptors.

Murine NK cell Ly49 receptors, functionally analogous to KIRs in humans recognize MHC class I molecules and play a key role in controlling NK cell function. We have previously shown that the paired activating Ly49s4 and inhibitory Ly49i4 receptors recognize undefined non-classical MHC-Ib ligands from the RT1-CE region in rats. Here, the RT1-CE16 gene of the RT1d haplotype was stably transfected into the mouse RAW macrophage cell line, termed RAW-CE16d cells. Combining RAW-CE16d cells with Ly49 expressing reporter cells demonstrated Ly49i4 and Ly49s4 specificity for CE16d. The Ly49s4/i4:CE16d interaction was confirmed by specific MHC-I blocking monoclonal Abs. Further, we used our in vitro model to study the effect of Listeria monocytogenes (LM) on CE16d after infection. LM infection and IFN-γ stimulation both led to enhanced CE16d expression on the surface of transfected RAW-CE16d cells. Interestingly, the reporter cells displayed increased response to LM-infected RAW-CE16d cells compared with IFN-γ-treated RAW-CE16d cells, suggesting a fundamental difference between these stimuli in supporting enhanced Ly49 recognition of CE16d. Collectively, our data show that Ly49s4 and Ly49i4 recognize the non-classical RT1-CE16d molecule, which in turn is up-regulated during LM infection and thereby may contribute to NK-mediated responses against infected cells.

Dual-Positive CD4/CD8 Primary Cutaneous Peripheral T-Cell Lymphoma Previously Classified as Mycosis Fungoides a Tumor D'Emblée.

Cutaneous peripheral T-cell lymphoma, not otherwise specified represents a "waste basket" of all cases that cannot be put into another of the categories of mature cutaneous T-cell lymphoma. Previously, the sudden multifocal development of cutaneous CD4 tumors without preceding a patch or plaque stage was classified as d'emblée form of mycosis fungoides (MF). Currently, the term "MF" reserved only for the classic Alibert-Bazin type characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. The authors describe a 75-year-old white woman who presented with a solitary skin tumor in the right supraclavicular region, with no lymph node or systemic involvement. Local external beam radiation treatment resulted in a complete response. The patient relapsed after 5 months with new tumors in the left neck and left upper chest. Biopsy of the lesions showed a dermal infiltrate of atypical small- to medium-sized T-lymphocytes, and immunohistochemical staining showed coexpression of CD4/CD8 in a subset of these cells, which was confirmed with flow cytometry of the tumor. Although the patient had no preceding patch or plaque stage, the authors herein report this extremely rare case of CD4/CD8 dual-positive peripheral T-cell lymphoma, not otherwise specified presented as MF d'emblée and discuss the seldom similar cases published previously.

Listeria monocytogenes infection differentially affects expression of ligands for NK cells and NK cell responses, depending on the cell type infected.

The pivotal role of NK cells in viral infection is extensively studied, whereas the role of NK cells in bacterial infection has been poorly investigated. Here, we have examined how Listeria monocytogenes (LM) affects expression of ligands for NK cell receptors and subsequent NK cell responses, depending on the type of cell infected. LM infected rat cell lines derived from different tissues were coincubated with splenic NK cells, and NK cell proliferation and IFN-γ production were measured. In addition, expression of ligands for the NK cell receptors Ly49 and NK cell receptor protein 1 (NKR-P1), MHC class I and C-type lectin-related molecules, respectively, was assessed. Infected pleural R2 cells, but not epithelium-derived colon carcinoma cell line CC531 cells, induced proliferation of NK cells. Reporter cells expressing the inhibitory NKR-P1G receptor or the activating NKR-P1F receptor were less stimulated under incubation with infected CC531 cells versus uninfected CC531 controls, suggesting that the ligand(s) in question were down-regulated by infection. Conversely, LM infection of R2 cells did not affect reporter cell stimulation compared with uninfected R2 controls. We characterized a rat monocyte cell line, termed RmW cells. In contrast to LM infected R2 cells that up-regulate MHC class I molecules, RmW cells displayed unchanged MHC class I expression following infection. In line with MHC class I expression, more NK cells produced a higher amount of IFN-γ against infected R2 cells compared with RmW cells. Together, L. monocytogenes infection may variously regulate cellular ligands for NK cells, depending on the cell type infected, affecting the outcome of NK cell responses.

Youth access to indoor tanning salons in urban versus rural/suburban communities.

BACKGROUND/PURPOSE: Research suggests that youth proximity to tanning salons may promote use; however, little is known about tanning salon proximity to schools. We assessed the proximity of tanning salons to schools in urban versus rural/suburban communities across Worcester County, Massachusetts (population > 800K). To put findings in context, we compared school proximity to tanning salons to school proximity to McDonald's restaurants, a large franchise that also caters to young people. MATERIALS & METHODS: Accessibility was measured by ArcGIS 10.2 Network Analyzer (ESRI, Redlands, CA, USA) and the most current road network data layer from Massachusetts Department of Transportation (MassDOT). RESULTS: A total of 145 schools were observed in the study area, of which about 39% of schools were within 1 mile from a tanning salon. Urban schools (53.41%) had a higher proportion within 1 mile of a tanning salon than rural/suburban schools (17.54%; P < .001). More schools (39.31%) were within 1 mile of a tanning salon than schools within 1 mile of a McDonald's (22.70%; P < .001). CONCLUSIONS: Schools may be particularly impactful for implementing skin cancer prevention programing.

Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice.

Dedifferentiation of acini to duct-like cells occurs during the physiologic damage response in the pancreas, but this process can be co-opted by oncogenic Kras to drive carcinogenesis. Myeloid cells infiltrate the pancreas during the onset of pancreatic cancer, and promote carcinogenesis. Here, we show that the function of infiltrating myeloid cells is regulated by oncogenic Kras expressed in epithelial cells. In the presence of oncogenic Kras, myeloid cells promote acinar dedifferentiation and carcinogenesis. Upon inactivation of oncogenic Kras, myeloid cells promote re-differentiation of acinar cells, remodeling of the fibrotic stroma and tissue repair. Intriguingly, both aspects of myeloid cell activity depend, at least in part, on activation of EGFR/MAPK signaling, with different subsets of ligands and receptors in different target cells promoting carcinogenesis or repair, respectively. Thus, the cross-talk between epithelial cells and infiltrating myeloid cells determines the balance between tissue repair and carcinogenesis in the pancreas.