Response Burden Research Articles

Predicting Response Rates Once Again

We investigate the relation between a survey’s response burden and response rate, differentiating recruitment efforts and incentives paid. The results indicate that the effect of response burden is more negative than previously expected. Recruitment shifts the response curve upwards, while incentives flatten it. Surveys beyond 2,000 points appear overly burdensome, sustaining high response rates only through recruitment coupled with incentives. Without incentives, the level effect of recruitment quickly vanishes. Contrary to previous findings, we can not identify a negative time-trend. The data, functions and workflow underlying this analysis are organized as an R-package to foster a collective effort towards understanding response rates.

Understanding the Experiences of Nurses' Work: Development and Psychometric Evaluation of an End of Shift Survey.

To explore and validate an end of shift survey with a low response burden, practical application and generated evidence of related associations between workload, quality of work and patient care, missed care and job satisfaction. A retrospective cross-sectional survey of the experiences of nursing staff. Data were collected from 265 nurses who responded to a questionnaire at the end of their shift in 2022. Exploratory factor analysis was undertaken using IBM SPSS v.27 and confirmatory factor analysis was undertaken using IBM AMOS v27. Hypotheses testing was undertaken using IBM SPSS v.27 using multiple regression analyses. All of the hypotheses were supported. There was a negative association between workload and quality of work and job satisfaction. Quality of work was negatively associated with workload and missed care and positively associated with job satisfaction. The association between missed care and job satisfaction was negative. The EOSS is a valid and reliable tool with a low response burden. The tool supports previous research which demonstrated there is a negative relationship between level of workload and shift type with satisfaction, quality of work and potentially nurse retention. In the context of a global nursing shortage nursing leaders must ensure that care we provide is of the highest quality. We must take every action to address high workload to reduce the risk that fundamental care is not sacrificed, job satisfaction is improved and nurses remain in the profession. The EOSS gives nurse leaders a reliable, practical, consistent, applied tool that will better enable associations to be observed between resource configuration, workload and critical impacts on nursing and patient care. We have adhered to the relevant EQUATOR guidelines using the STROBE reporting method. No Patient or Public Contribution.

Crafting an ultrashort workplace incivility scale and determining cutoffs for varied risk levels through item response theory

Workplace incivility (WI), characterized by disrespectful or rude behavior in the workplace, is linked to poor mental health and overall well-being. The Workplace Incivility Scale (WIS) is a popular 7-item measure for assessing WI. There is a current need for an ultrashort conceptually clear version of the WIS. In addition, the cutoffs for varied at-risks of WI, requiring intervention, remains unknown. Using data from 426 employees across diverse organizations, we employed item response theory (IRT) to create an ultrashort WIS and establish cutoffs for high, moderate, low, and at-not risk of WI. Confirmatory factor analyses were utilized to validate WIS construct validity. In supporting convergent validity, WIS was correlated with workplace bullying and poor health-related quality of life. All items demonstrated adequate severity threshold parameters with very high discrimination and good reliability parameters except for item WIS7. We successfully developed an ultrashort and valid 3-item WIS, specifically comprising items WIS2–4, and identified cutoffs for varying levels of WI risk. This streamlined measure aims to reduce response burden and foster a healthier organizational culture. In essence, cutoff points streamline the classification process, allowing for quicker and more standardized identification of at-risk employees. This concise, valid, and reliable ultrashort WIS holds potential for use in intervention studies conducted by organizational and occupational health psychologists, ultimately promoting employee well-being and cultivating a positive workplace environment. The current study further advances the existing theoretical framework rooted in the social interactionist perspective by delineating WI as a distinct and independent construct.

Impact of socioeconomic status on cardiac arrest outcomes during COVID-19 pandemic

IntroductionThe coronavirus disease 19 (COVID-19) pandemic has affected healthcare services, potentially leading to inequitable outcomes based on patients’ socioeconomic status (SES). This study aimed to evaluate the impact of COVID-19 on out-of-hospital cardiac arrest (OHCA) outcomes by examining disparities across SES levels. MethodsThe study analyzed non-traumatic OHCA cases registered in the Korean Out-of-Hospital Cardiac Arrest Registry from 2010 to 2021, encompassing 238,668 patients aged 18 years and older. SES was assessed at both the individual (Medicaid vs non-Medicaid) and area levels using a deprivation index. Outcomes included any return of spontaneous circulation, survival to admission, survival to discharge, and favorable neurological recovery. Logistic regression and generalized additive models (GAMs) were used for analysis. ResultsOHCA outcomes—including survival to admission, survival to discharge, and favorable neurological recovery—improved over the years, peaking in 2019 before subsequently declining. Logistic regression showed that the lowest SES area was associated with lower rates of ROSC (adjusted odds rations [aOR] 0.82, 95 % confidence interval [CI] 0.75–0.88) and survival to admission (aOR 0.56, 95%CI 0.49–0.64) and discharge (aOR 0.78, 95%CI 0.61–0.98) during the pandemic. GAM analysis revealed that lower SES groups (deprivation index levels 4 and 5) experienced higher-than-expected survival to admission and discharge rates, as well as favorable neurological recovery. Although outcomes in the deprivation index level 1 group (5.5 % in 2021) remained superior, indicating poor outcomes for the lowest SES area group (3.43 % in 2021), the disparity decreased following the pandemic. ConclusionLower levels of SES are a significant risk factor for unfavorable neurological recovery in OHCA, independent of the COVID-19 pandemic. However, SES-related disparities in the outcomes decreased post-pandemic. Despite the overall negative impact of COVID-19, certain lower SES groups showed improved survival rates, likely due to differences in the EMS response and healthcare burden across regions.

Extrachromosomal circular DNAs in prostate adenocarcinoma: global characterizations and a novel prediction model.

The role of focal amplifications and extrachromosomal circular DNA (eccDNA) is still uncertain in prostate adenocarcinoma (PRAD). Here, we first mapped the global characterizations of eccDNA and then investigate the characterization of eccDNA-amplified key differentially expressed encoded genes (eKDEGs) in the progression, immune response and immunotherapy of PRAD. Circular_seq was used in conjunction with the TCGA-PRAD transcriptome dataset to sequence, annotate, and filter for eccDNA-amplified differentially expressed coding genes (eDEGs) in PRAD and para-cancerous normal prostate tissues. Afterwards, risk models were created and eKDEGs linked to the PRAD prognosis were identified using Cox and Lasso regression analysis. The immune microenvironment of the risk model was quantified using a variety of immunological algorithms, which also identified its characteristics with regard to immunotherapy, immune response, and immune infiltration. In this research, there was no significant difference in the size, type, and chromosomal distribution of eccDNA in PRAD and para-cancerous normal prostate tissues. However, 4,290 differentially expressed eccDNAs were identified and 1,981 coding genes were amplified. Following that, 499 eDEGs were tested in conjunction with the transcriptome dataset from TCGA-PRAD. By using Cox and Lasso regression techniques, ZNF330 and PITPNM3 were identified as eKDEGs of PRAD, and a new PRAD risk model was conducted based on this. Survival analysis showed that the high-risk group of this model was associated with poor prognosis and validated in external data. Immune infiltration analysis showed that the model risks affected immune cell infiltration in PRAD, not only mediating changes in immune cell function, but also correlating with immunophenotyping. Furthermore, the high-risk group was negatively associated with anti-CTLA-4/anti-PD-1 response and mutational burden. In addition, Tumor Immune Dysfunction and Exclusion analyses showed that high-risk group was more prone to immune escape. Drug sensitivity analyses identified 10 drugs, which were instructive for PRAD treatment. ZNF330 and PITPNM are the eKDEGs for PRAD, which can be used as potential new prognostic markers. The two-factor combined risk model can effectively assess the survival and prognosis of PRAD patients, but also can predict the different responses of immunotherapy to PRAD patients, which may provide new ideas for PRAD immunotherapy.

The validation of short eating disorder, body dysmorphia, and Weight Bias Internalisation Scales among UK adults

BackgroundWhen collecting data from human participants, it is often important to minimise the length of questionnaire-based measures. This makes it possible to ensure that the data collection is as engaging as possible, while it also reduces response burden, which may protect data quality. Brevity is especially important when assessing eating disorders and related phenomena, as minimising questions pertaining to shame-ridden, unpleasant experiences may in turn minimise any negative affect experienced whilst responding.MethodsWe relied on item response theory to shorten three eating disorder and body dysmorphia measures, while aiming to ensure that the information assessed by the scales remained as close to that assessed by the original scales as possible. We further tested measurement invariance, correlations among different versions of the same scales as well as different measures, and explored additional properties of each scale, including their internal consistency. Additionally, we explored the performance of the 3-item version of the modified Weight Bias Internalisation Scale and compared it to that of the 11-item version of the scale.ResultsWe introduce a 5-item version of the Eating Disorder Examination Questionnaire, a 3-item version of the SCOFF questionnaire, and a 3-item version of the Dysmorphic Concern Questionnaire. The results revealed that, across a sample of UK adults (N = 987, ages 18–86, M = 45.21), the short scales had a reasonably good fit. Significant positive correlations between the longer and shorter versions of the scales and their significant positive, albeit somewhat weaker correlations to other, related measures support their convergent and discriminant validity. The results followed a similar pattern across the young adult subsample (N = 375, ages 18–39, M = 28.56).ConclusionsThese results indicate that the short forms of the tested scales may perform similarly to the full versions.

Selective editing for asymmetry analysis in intra-EU trade Micro-Data Exchange (MDE)

Since January 2022, the Regulation on European Business Statistics (EU 2019/2152) requires EU Member States to compulsorily share microdata on intra-EU exports. Establishing intra-EU export Micro-Data Exchange (MDE) provides National Statistical Institutes with a new data source to compile intra-EU import statistics. The availability of MDE tackles two key challenges: diminishing the overall response burden on data providers and meeting user expectations regarding the quality of the produced statistics. However, transitioning to a data production system based on MDE data requires the assessment of the coherence and comparability between MDE and National import data. To identify asymmetries between the two data sources, Istat developed an innovative application designed to foster cooperation among Member States. The tool was developed using the Shiny package in R. The implemented solution allows users to perform exploratory analysis, systematic error detection, and selective editing. The most relevant asymmetries are identified through relative contribution and the asymmetry suspicion indices assessed by user-defined thresholds. Sharing the open tool within the European Statistical System enhances interoperability, promotes method harmonization, and encourages the adoption of official statistical standards.

Item reduction of the “Support Intensity Scale” for people with intellectual disabilities, using machine learning

AbstractBackgroundThe study focuses on the need to optimise assessment scales for support needs in individuals with intellectual and developmental disabilities. Current scales are often lengthy and redundant, leading to exhaustion and response burden. The goal is to use machine learning techniques, specifically item‐reduction methods and selection algorithms, to develop shorter and more efficient scales.MethodsA data set of 93 participants was analysed using the Supports Needs Scale. Five feature‐selection algorithms were evaluated to create a shortened questionnaire. For each algorithm, a Random Forest model was trained, and performance was assessed using metrics like accuracy, precision, recall and F1‐score to measure how well each model predicted support needs.FindingsThe "Select from Model" algorithm successfully identified key items that could predict the level of Support Needs using the Random Forest model. Only 51 variables, out of the original 147, were needed to maintain predictive accuracy. The reduced questionnaire maintained good reliability and internal consistency compared to the original instrument, with a strong F1 score indicating excellent predictive performance.ConclusionsThe study demonstrates that machine learning techniques are effective in reducing the length of support needs questionnaires while preserving their psychometric properties. These methods can help institutions provide more efficient access to information about support needs without compromising validity or reliability, potentially leading to better resource allocation and improved care for individuals with intellectual disabilities.

Interpretable Causal System Optimization Framework for the Advancement of Biological Effect Prediction and Redesign of Nanoparticles.

Nanomedicine has promising applications in disease treatment, given the remarkable safety concerns (e.g., nanotoxicity and inflammation) of nanomaterials, and realizing the trade-off between the immune response and organ burden of NPs and deeply understanding the interactions of the organism-nano systems are crucial to facilitate the biological applications of NPs. Here, we propose an interpretable causal system optimization (ICSO) framework and construct the upstream and downstream tasks of accurate prediction and intelligent NP optimization. ICSO framework screens the key drivers (recovery duration, specific surface area, and nanomaterial size) and potential causal information for immune responses and organ burden, revealing the hidden priming/constraint effects in bionano interactions. ICSO can be used to quantify the thresholds of biological responses to multiple properties (e.g., the specific surface area, diameter, and zeta potential). ICSO provides quantitative information and constraint conditions for the design of highly biocompatible and targeted organ delivery nanomaterials. For example, negative inflammation is reduced by 36.19%, and positive lung accumulation is promoted by 40.14% by optimizing the specific surface areas and shape and increasing the diameter-to-length ratio. ICSO overcomes the limitations of experience-dependent approaches and provides powerful and automated solutions for decision-makers during nanomaterial design.

Does the addition of Patient-Reported Outcome Measure Information System (PROMIS) pain instruments improve the sensitivity of PROMIS upper extremity scores after arthroscopic rotator cuff repair?

Although Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity (P-UE) has been validated in upper extremity orthopedics, its ability to capture a patient's functional recovery after arthroscopic rotator cuff repair (aRCR), as measured by its responsiveness, is minimal in the early postoperative period. The primary purpose of this study is to determine if the addition of PROMIS Pain Intensity (P-Intensity) or Pain Interference (P-Interference) scores to PROMIS UE improves the responsiveness throughout the 1-year postoperative period after aRCR. This prospective, longitudinal study included 100 patients who underwent aRCR. Patients completed P-UE, P-Interference, P-Intensity, American Shoulder and Elbow Surgeons, and Western Ontario Rotator Cuff Index scores preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after surgery. Responsiveness at each time point relative to preoperative baseline and 1-way analysis of variance with post hoc analysis was conducted for each PROM. The responsiveness of the outcome score was determined using the effect size, graded as small (0.2), medium (0.5), or large (0.8). The Pearson correlation coefficient (r) was determined between these instruments at each time point. In isolation, P-UE, P-Interference, and P-Intensity showed a medium-large ability to detect change (positive and negative) throughout the 1-year postoperative period. The addition of PROMIS pain scores to P-UE improved the responsiveness of the instrument (from medium to a large effect size) starting at 3 months and continued throughout the 12-month follow-up period. Although the addition of pain scores increases the response burden for PROMIS, this was still lower than the response burden for the legacy outcome scores (P<.05). The addition of PROMIS pain instruments improves the responsiveness of the P-UE function score in patients undergoing aRCR.

The "Double Victim Phenomenon"-Results From a National Pilot Survey on Second Victims in German Family Caregivers (SeViD-VI Study).

Second-victim phenomena may lead to severe reactions like depression or posttraumatic disorder, as well as dysfunction and absenteeism. Medical error as a cause for second victims is not limited to professionals, as family caregivers care for millions of patients at home. It remains unclear whether these are first, second, or double victims in case of error. This explorative study investigated whether second victim effects and signs of moral injury are detectable in family caregivers and whether existing instruments are applicable in lay persons. In an open convenience sampling online survey, we recruited 66 German family caregivers. Propensity score matching was conducted to obtain a balanced sample of family caregivers and qualified nurses who took part in the previous study by adjusting for age and sex. The groups were compared regarding the German Version of the Second Victim Experience and Support Tool-Revised and the German version of the Moral Injury Symptom and Support Scale for Health Professionals. Sixty-six caregivers participated, of whom 31 completed the survey. Of all, 58% experienced a second victim-like effect, 35% experienced a prolonged effect, and 45% reported to still suffer from it. In a matched sample (22 family caregivers and 22 nurses), no significant differences were observed between the groups. Regarding the limitations of this pilot study, demanding for resampling in larger populations, we could show that second victim effects and moral injury are detectable in family caregivers by validated instruments and are not inferior to professionals' experiences. Concerning the demand for further studies, we confirmed the applicability of the testing instruments but with need for item reduction to lower response burden.

Sodium Houttuyfonate Ameliorates DSS-induced Colitis Aggravated by Candida albicans through Dectin-1/NF-κB/miR-32-5p/NFKBIZ Axis Based on Intestinal microRNA Profiling.

Our previous research indicated that Sodium houttuyfonate (SH) can effectively ameliorate dextran sulfate sodium (DSS)-induced colitis exacerbated by Candida albicans. However, the underlying protective mechanism of SH remains unclear. Therefore, in this study, a mice colitis model was infected with C. albicans, and the total colonic miRNAs were assessed. Furthermore, the differentially expressed miRNAs were enriched, clustered, and analyzed. Moreover, based on the dual luciferase analysis of NFKBIZ modulation by miR-32-5p, the in vitro and in vivo therapeutic effects of SH on inflammatory response, fungal burden, oxidative stress, and apoptosis were assessed at transcriptional and translational levels in the presence of agonist and antagonist. A total of 1157 miRNAs were identified, 84 of which were differentially expressed. Furthermore, qRT-PCR validated that SH treatment improved 17 differentially expressed miRNAs with > fourfold upregulation or > sixfold downregulation. Similar to most differentially altered miRNA, C. albicans significantly increased Dectin-1, NF-κB, TNF-α, IL-1β, IL-17A, and decreased miR-32-5p which negatively targeted NFKBIZ. In addition, SH treatment reduced inflammatory response and fungal burden in a colitis model with C. albicans infection. Further analyses indicated that in C. albicans infected Caco2 cells, SH inhibited fungal growth, oxidative stress, and apoptosis by increasing Dectin-1, NF-κB, NFKBIZ, TNF-α, IL-1β, IL-17A, and decreasing miR-32-5p. Therefore, SH can ameliorate the severity of colitis aggravated by C. albicans via the Dectin-1/NF-κB/miR-32-5p/NFKBIZ axis.

Prevalence of Acute on Chronic Liver Failure in Autoimmune Hepatitis, Treatment Response and Mortality Burden Assessment: A Region-Predominant Systematic Review and Meta-Analysis.

Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and mortality outcomes have also been reported differently. The study was conducted to estimate the overall prevalence of ACLF among patients with autoimmune hepatitis (AIH) and determine the associated treatment response and mortality. We scrutinized wide literature in Scopus, PubMed, Embase, Web of Science, and Cochrane, and assessed published articles completely, studies performed and reported from around the globe, until December 07, 2023, according to the PROSPERO registered protocol (CRD42023412176). Studies (retrospective and prospective cohort study type) that stated the ACLF development among established AIH cases were considered. Features of the study, duration of follow-up, and numeric patient information were retrieved from the studies included. The research paper quality was checked for risk of bias. Random effect meta-analysis with metaregression and subsection scrutinies were performed with R. The main outcome was the collective prevalence of ACLF in the AIH patients, whereas treatment response and mortality in AIH-associated ACLF were secondary outcomes. Six studies were involved with confirmed diagnoses in 985 AIH patients for the data synthesis. The pooled prevalence of ACLF in the explored patients was 12% (95% CI: 8-17) ( P =0.01). Heterogeneity was found to be high in the present meta-analysis ( I2 =72%; P < 0.01). For the secondary endpoint analysis, the pooled prevalence of complete remission at 1-year follow-up was 71% (0.52; 0.85), and mortality from the ACLF-AIH patient population was 32% (95% CI: 18-50). Sensitivity analysis showed no influence on the overall estimations of the pooled prevalence of ACLF by omitting studies one by one. One in 10 AIH patients likely present with ACLF. The response to treatment is seen in two-thirds of patients, and mortality is high.

Long-Term Outcomes following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Origin.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major treatment of colorectal peritoneal carcinomatosis (CPC). The aim was to determine the disease-free survival (DFS) and overall survival (OS) of patients undergoing CRS-HIPEC for CPC and factors associated with long-term survival (LTS). consecutive CPC patients who underwent CRS-HIPEC at a HIPEC center between 2007 and 2021 were included. Actual survival was calculated, and Cox proportional hazards models were used to identify factors associated with OS, DFS and LTS. there were 125 patients with CPC who underwent primary CRS-HIPEC, with mean age of 54.5 years. Median follow-up was 31 months. Average intraoperative PCI was 11, and complete cytoreduction (CC-0) was achieved in 96.8%. Median OS was 41.6 months (6-196). The 2-year and 5-year OS were 68% and 24.8%, respectively, and the 2-year DFS was 28.8%. Factors associated with worse OS included pre-HIPEC systemic therapy, synchronous extraperitoneal metastasis, and PCI ≥ 20 (p < 0.05). Progression prior to CRS-HIPEC was associated with worse DFS (p < 0.05). Lower PCI, fewer complications, lower recurrence and longer DFS were associated with LTS (p < 0.05). CRS and HIPEC improve OS in CPC patients but they have high disease recurrence. Outcomes depend on preoperative therapy response, extraperitoneal metastasis, and peritoneal disease burden.

Enhanced antibacterial properties of enteric glial cells attenuate intestinal inflammation through the GABABR-mediated autophagy pathway

Enterotoxigenic Escherichia coli (ETEC) infection is a severe threat to global public health because of its high morbidity and mortality among children and infants. Enteric glial cells (EGCs) are involved in host–bacteria communication. However, the mechanisms through which EGCs interact with ETEC remain unclear. We attempted to assess whether γ-aminobutyric acid type B receptor (GABABR) activation participated in EGC autophagy during Escherichia coli K88 (ETECK88) infection. Alterations in autophagy and EGC activity were observed in the intestines of the ETECK88-infected mice, and similar results were obtained from experiments in which the EGCs were directly infected with ETECK88. EGC pretreatment with specific autophagy agonists significantly decreased the inflammatory response and bacterial burden, whereas pretreatment with inhibitors had the opposite effect. Interestingly, in EGCs, GABABR activation notably increased Beclin 1 and LC3 levels and autophagosome and autolysosome numbers, thus promoting autophagy activation and enhancing antimicrobial responses against ETECK88 infection. Furthermore, GABABR defense was mediated via myeloid differentiation factor 88 (MyD88) signaling in EGCs, which was proven to be based on the inhibition or overexpression of MyD88. Notably, comparable results of GABABR activation in vivo were observed in response to ETECK88, implicating this as a defense mechanism that reinforced antibacterial activity to alleviate intestinal inflammation in mice. Our study revealed previously unappreciated roles for GABABR in linking EGC antibacterial autophagy to strengthen host defense against ETECK88 infection, thus identifying GABABR as an important target for the treatment of infective enteritis.

MiR-181d targets BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to Cryptosporidium parvum infection via the intrinsic apoptosis pathway

Cryptosporidium parvum is an important zoonotic pathogen that is studied worldwide. MicroRNAs (miRNAs) act as post-transcriptional regulators and may play a key role in modulating host epithelial responses following Cryptosporidium infection. Our previous study has shown that C. parvum downregulates the expression of miR-181d through the p50-dependent TLRs/NF-κB pathway. However, the mechanism by which miR-181d regulates host cells in response to C. parvum infection remains unclear. The present study found that miR-181d downregulation inhibited cell apoptosis and increased parasite burden in HCT-8 cells after C. parvum infection. Bioinformatics analysis and luciferase reporter assays have shown that BCL2 was a target gene for miR-181d. Moreover, BCL2 overexpression and miR-181d downregulation had similar results. To further investigate the mechanism by which miR-181d regulated HCT-8 cell apoptosis during C. parvum infection, the expression of molecules involved in the intrinsic apoptosis pathway was detected. Bax, caspase-9, and caspase-3 expression was decreased at 4, 8, 12, and 24 hpi and upregulated at 36 and 48 hpi. Interfering with the expression of miR-181d or BCL2 significantly affected the expression of molecules in the intrinsic apoptosis pathway. These data indicated that miR-181d targeted BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to C. parvum infection via the intrinsic apoptosis pathway. These results allowed us to further understand the regulatory mechanisms of host miRNAs during Cryptosporidium infection, and provided a theoretical foundation for the design and development of anti-cryptosporidiosis drugs.

Comparison of the efficacy of taxanes with carboplatin and anthracyclines with taxanes in neoadjuvant chemotherapy for stage II–III triple negative breast cancer: a retrospective analysis

PurposeThe neoadjuvant chemotherapy (NACT) regimen for triple negative breast cancer (TNBC) primarily consists of anthracyclines and taxanes, and the addition of platinum-based drugs can further enhance the efficacy. However, it is also accompanied by more adverse events, and considering the potential severe and irreversible toxicity of anthracyclines, an increasing number of studies are exploring nonanthracycline regimens that combine taxanes and platinum-based drugs.MethodsThe retrospective study included 273 stage II–III TNBC patients who received NACT. The AT group, consisting of 195 (71.4%) patients, received a combination of anthracyclines and taxanes, while the TCb group, consisting of 78 (28.6%) patients, received a combination of taxanes and carboplatin. Logistic regression analysis was performed to evaluate the factors influencing pathological complete response (pCR) and residual cancer burden (RCB). The log-rank test was used to assess the differences in event-free survival (EFS) and overall survival (OS) among the different treatment groups. Cox regression analysis was conducted to evaluate the factors influencing EFS and OS.ResultsAfter NACT and surgery, the TCb group had a higher rate of pCR at 44.9%, as compared to the AT group at 31.3%. The difference between the two groups was 13.6% (OR = 0.559, 95% CI 0.326–0.959, P = 0.035). The TCb group had a 57.7% rate of RCB 0–1, which was higher than the AT group's rate of 42.6%. The difference between the two groups was 15.1% (OR = 0.543, 95% CI 0.319–0.925, P = 0.024), With a median follow-up time of 40 months, the TCb group had better EFS (log-rank, P = 0.014) and OS (log-rank, P = 0.040) as compared to the AT group. Clinical TNM stage and RCB grade were identified as independent factors influencing EFS and OS, while treatment group was identified as an independent factor influencing EFS, with a close-to-significant impact on OS.ConclusionIn stage II–III triple TNBC patients, the NACT regimen combining taxanes and carboplatin yields higher rates of pCR and significant improvements in EFS and OS as compared to the regimen combining anthracyclines and taxanes.

Infection dynamics following experimental challenge of pigs orally dosed with different stages of two archetypal genotypes of Toxoplasma gondii

Toxoplasma gondii is a food-borne zoonotic parasite widespread in a variety of hosts, including humans. With a majority of infections in Europe estimated to be meat-borne, pork, as one of the most consumed meats worldwide, represents a potential risk for consumers. Therefore, we aimed to investigate the progress of T. gondii infection and tissue tropism in experimentally infected pigs, using different T. gondii isolates and infectious stages, i.e. tissue cysts or oocysts. Twenty-four pigs were allocated to treatment in four groups of six, with each group inoculated orally with an estimated low dose of either 400 oocysts or 10 tissue cysts of two European T. gondii isolates, a type II and a type III isolate. The majority of pigs seroconverted two weeks post-inoculation. Pigs infected with the type III isolate had significantly higher levels of anti-T. gondii antibodies compared to those infected with the type II isolate. Histopathological exams revealed reactive hyperplasia of the lymphatic tissue of all pigs. Additionally, a selected set of nine tissues was collected during necropsy at 50 dpi from each of the remaining 22 pigs for T. gondii DNA detection by quantitative real-time PCR. A positive result was obtained in 29.8 % (59/139) of tested tissues. The brain was identified as the most frequently positive tissue in 63.6 % (14/22) of the animals. In contrast, liver samples tested negative in all animals. The highest mean parasite load, calculated by interpolating the average Cq values on the standard curve made of ten-fold serial dilutions of the genomic DNA, corresponding to 100 to 104 tachyzoites/µL, was observed in shoulder musculature with an estimated concentration of 84.4 [0.0–442.5] parasites per gram of tissue. The study highlights the variability in clinical signs and tissue distribution of T. gondii in pigs based on the combination of parasite stages and strains, with type III isolates, particularly oocysts, causing a stronger antibody response and higher tissue parasite burden. These findings suggest the need for further investigation of type III isolates to better understand their potential risks to humans.

Probiotic bacteria can modulate immune responses to paratuberculosis vaccination.

Mycobacterium avium subsp. paratuberculosis (Map) is the etiological agent of paratuberculosis (PTB), a chronic intestinal inflammatory disease that causes high economical losses in dairy livestock worldwide. Due to the absence of widely available preventive or therapeutical treatments, new alternative therapies are needed. In this study, the effect of a probiotic alone or in combination with a commercial vaccine has been evaluated in a rabbit model. Vaccination enhanced the humoral response, exerted a training effect of peripheral polymorphonuclear neutrophils (PMNs) against homologous and heterologous stimuli, stimulated the release of pro-inflammatory cytokines by gut-associated lymphoid tissue (GALT) macrophages, and reduced the bacterial burden in GALT as well. However, the administration of the probiotic after vaccination did not affect the PMN activity, increased metabolic demand, and supressed pro-inflammatory cytokines, although humoral response and bacterial burden decrease in GALT was maintained similar to vaccination alone. The administration of the probiotic alone did not enhance the humoral response or PMN activity, and the bacterial burden in GALT was further increased compared to the only challenged group. In conclusion, the probiotic was able to modulate the immune response hampering the clearance of the infection and was also able to affect the response of innate immune cells after vaccination. This study shows that the administration of a probiotic can modulate the immune response pathways triggered by vaccination and/or infection and even exacerbate the outcome of the disease, bringing forward the importance of verifying treatment combinations in the context of each particular infectious agent.

Objective response after immune checkpoint inhibitors in a chemotherapy-refractory pMMR/MSS metastatic rectal cancer patient primed with experimental AlloStim® immunotherapy

BackgroundImmune Checkpoint Inhibitor (ICI) immunotherapy is most effective in immune effector cell infiltrated ‘hot’ tumor lesions, such as occurs in deficient mismatch repair, microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). However, most all metastatic CRC tumors are mismatch repair proficient/microsatellite stable (pMMR/MSS) ‘cold’ lesions, without significant immune cell infiltration, and are unresponsive to ICI. AlloStim®, is an experimental, allogeneic immunomodulatory cell therapy designed to convert ‘cold’ metastatic tumor lesions to ‘hot’ inflamed lesions. After AlloStim® immunotherapy, this cold to hot inflammatory mechanism can make it difficult to distinguish between pseudoprogression and actual progression on restaging CT scans, as inflamed metastatic lesions can appear larger and occult disease can appear as new small lesions.MethodsTo explore whether radiological progression after AlloStim® immunotherapy is due to immune-flare or disease progression, we administered a short course of a combination ICI therapy to a pMMR/MSS chemotherapy-refractory metastatic colorectal cancer patient enrolled in the StimVax Phase IIb clinical study that presented with radiological progression after AlloStim® immunotherapy. Our rationale was that an accelerated response to ICI should occur if the lesions were inflamed, while if the enlarged lesions were due to disease progression there would not be a response.ResultsHere we report a rapid, significant reduction in tumor burden in response to ICI administration in an AlloStim® primed pMMR/MSS mCRC patient with retroperitoneal and lung metastases.ConclusionThis rare objective response to ICIs in a pMMR/MSS mCRC patient supports further evaluation of the combination of AlloStim® with ICI immunotherapy in MSS mCRC and other cold or ICI refractory tumors.Trial registrationNational Library of Medicine (NLM) at the National Institutes of Health (NIH). Registered 22 June 2020, https://clinicaltrials.gov/study/NCT04444622.