Comparative efficacy and safety of multimodality treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: patient-level network meta-analysis.

Background: Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT. Methods: A comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan-Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores. Results: We identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity (I 2 < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 µg/L subgroups. Conclusion: HAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.

Cost-effectiveness and drug wastage of bevacizumab biosimilar with or without chemotherapy for platinum-resistant recurrent ovarian cancer.

INTRODUCTION: The cost-effectiveness of adding bevacizumab biosimilar with or without chemotherapy (CT) and drug wastage in treating platinum-resistant recurrent ovarian cancer (PRrOC) was assessed. METHODS: A three-state partitioned-survival model to compare the clinical and economic outcomes in the treatment of patients with PRrOC from a Taiwan healthcare prospective, extrapolated to two years based on data obtained from the JGOG3023 clinical trial. The primary outcomes of the model were incremental cost-effectiveness ratios (ICERs). RESULTS: In the base-case scenario, using vials of bevacizumab biosimilar (Bevbiol) plus chemotherapy, the ICER was (new Taiwan dollar) NT$ 4,555,878 per QALY gained. The incremental cost savings of an incremental 2.02 QALYs were NT$ 1,605,828 if weight-based Bevbiol plus chemotherapy were used, but the ICER remained high at the willingness-to-pay (WTP) threshold. If the cost of Bevbiol were reduced to 50% per vial, adding it to CT would be cost-effective at an acceptable WTP threshold of NTD 2,994,200, with an ICER of NT$ 2,975,484. CONCLUSIONS: Bevacizumab biosimilars in mg/kg dosage form with chemotherapy are still not cost-effective in Taiwan, but using weight-based dosing will reduce drug waste and save treatment costs.

The use of fractional radiofrequency in Asian patients to improve skin texture.

BACKGROUND AND OBJECTIVES: Fractional radiofrequency devices have been demonstrated to improve skin texture, such as smoothness, rhytides, brightness, and atrophic acne scars, by increasing dermal thickness, dermal collagen content, and dermal fibrillin content. The objective of the study is to assess the efficacy and adverse effects of this device on Asian patients of skin type III and IV with skin textural changes. MATERIALS AND METHODS: The study was designed as a prospective, open-labeled single-arm study, which was conducted with 20 Chinese patients aged 21-60 years and having irregularities in their skin texture, rhytides, and acne scars. The patients received six treatments at intervals of 4 weeks. Treatment was initiated with the maximum energy tolerated, which was then adjusted during the course of treatment if the patients felt excessive discomfort. A total of two passes were delivered in each session. Physician assessment results and standardized photographs were collected at the baseline, after all treatment visits, and at 1, 2, and 6 months after the final treatment visit. RESULTS: A total of 17 patients completed the study according to the established protocol. At the 6-month follow-up, 71% of patients were satisfied and 24% of patients were very satisfied with the received treatments, and the treatment physician reported varying degrees of improvement based on the global assessment scale in 60% of the subjects. While the anticipated side effects, such as erythema, edema, pinpoint bleeding, scab formation, and flare of acne, were noted in the patients, no serious adverse effects occurred. CONCLUSION: The use of fractional radiofrequency improves skin texture and is safe for use in Asian patients of skin type III and IV. No long-term serious adverse effects were noted.

Hypothyroidism and hyperthyroidism related to gynecologic cancers: a nationwide population-based cohort study.

The purpose of this study was to assess the risks of hyperthyroidism and hypothyroidism related to gynecological cancers. Population-based retrospective cohort study. We conducted a cohort study using the Taiwan National Health Insurance Research Database to explore hyperthyroidism and hypothyroidism associated with site-specific gynecologic cancers in women from January 1, 2000 to December 31, 2018. The examined gynecologic cancers included endometrial (EC), uterine corpus cancer (UC), and ovarian cancer (OC). The incidence and hazard ratios were quantified using Cox proportional hazards models. The incidence of developing gynecological (Gyn) cancers in the hyperthyroid and hypothyroid women was 0.29 and 0.44 per 1000 person-years, which was 0.86 fold lower and 1.13 fold higher than that in the comparison cohort (p < 0.001). Compared with patients aged 20-40 years, patients in older age groups had a lower and higher risk of developing Gyn cancers (for hyperthyroid, 40-65 years: adjusted hazard ratio (aHR) = 0.82; > 65 years: aHR = 0.94; for hypothyroid, adjusted hazard ratio (aHR) = 1.26; > 65 years: aHR = 1.38). Compared with the non-hypothyroid women and non-hyperthyroid women beyond 6 years of follow-up, hypothyroid and hyperthyroid women showed decreased risk of Gyn cancers. Medication treatment for hyperthyroid and hypothyroid disease did not showed significant association in subgroup analyses (aHR = 0.99 and 0.80, respectively). Our results show that women with hyperthyroidism have a significantly reduced risk of gynecological cancers, whereas women with hypothyroidism have a slightly increased risk of gynecological cancers suggesting an association between thyroid function level and risk of gynecological cancers.

Temporal processing tele-intervention improves language, attention, and memory in children with neurodevelopmental disorders.

Objective: Temporal processing is the brain's ability to process rapid successive stimuli, and children with neurodevelopmental disorders showed temporal processing deficits. Empirical evidence suggests that in-person intervention on temporal processing improves various cognitive functions of these children, and the present study aimed to study the effects of temporal processing tele-intervention (TPT) on the cognitive functions of children with neurodevelopmental disorders. Methods: Ninety-five children with neurodevelopmental disorders were recruited and randomly assigned to remotely receive either TPT or conventional language remediation (CLR) in 20 parallel group-based intervention sessions once per week. Their cognitive functions were assessed before and after the intervention. Results: The TPT group demonstrated a specific and significant improvement in working memory (p < .001). While there was an overall significant improvement in sustained attention in terms of processing speed after both types of intervention (p = .006), the positive effects of TPT might be more prominent than that of CLR given the significant pre-post difference after receiving TPT (p = .012) but not CLR (p = .21). Regarding rapid naming accuracy which had marginally significant improvement after the intervention (p = .03), the trend of improvement in TPT (p = .05) also seemed more apparent than that of CLR (p = .18). Finally, the TPT group had significant improvement in word knowledge (p < .001), rapid naming speed (p < .001), sustained attention in terms of accuracy (p < .001), and verbal learning and memory (p < .01) to an extent similar to that of the CLR group. Conclusions: These findings suggest that TPT can be a potential intervention for improving cognitive functions in children with neurodevelopmental disorders. Clinical trial registration number: NCT05428657 at ClinicalTrials.gov (https://clinicaltrials.gov/).

Increased histological severity and chronicity of interface inflammation in anti-MDA5 dermatomyositis-A comparative dermatopathological analysis.

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis is characterized by serological detection of anti-MDA5 antibody and rapidly progressive interstitial lung disease. In this study, the largest cohort of skin biopsies to date of anti-MDA5 dermatomyositis was reviewed and compared with cases of dermatomyositis with negative serology. Findings contribute to the histological diagnosis and evaluation of the severity of cutaneous inflammation in anti-MDA5 dermatomyositis. Skin biopsies collected over a 7-year period from individuals with clinically and histologically confirmed dermatomyositis with anti-MDA5 serology were reviewed. A total of 46 cases with 17 anti-MDA5 positive cases were retrieved. Patients with positive antibody were younger (53.7 vs. 60.6 years, p = .013). No differences in epidermal changes (p > .05) were observed. Pertaining to interface changes, anti-MDA5 dermatomyositis showed a higher degree of pigmentary incontinence (p = .014), suggesting increased and sustained cutaneous inflammation. Periodic acid-Schiff (PAS) stain demonstrated a greater degree of basement membrane thickening (p = .045). Other parameters, including dermal inflammation, dermal mucin deposition and vasculitic/vasculopathic features did not show statistical difference between anti-MDA5 positive and negative dermatomyositis (p > .05). Findings suggest increased cutaneous inflammation for anti-MDA5 dermatomyositis. In skin biopsies, marked pigmentary incontinence or basement membrane thickening should raise suspicion of anti-MDA5 dermatomyositis.

Role of inflammatory burden and treatment on joint space width in psoriatic arthritis-a high-resolution peripheral quantitative computed tomography study.

BACKGROUND: To investigate the relationship between disease-related parameters and joint space width (JSW) on high-resolution peripheral quantitative computed tomography (HR-pQCT) in psoriatic arthritis (PsA) patients. METHODS: PsA patients who underwent HR-pQCT examination of the second to fourth metacarpophalangeal joint (MCPJ 2-4) were recruited in this cross-sectional study. The joint space metrics included joint space volume (JSV), mean, minimum, and maximum JSW, JSW asymmetry, and distribution. Correlation analysis and multivariable linear regression models were used to determine the association between disease-related variables and JSW. RESULTS: Sixty-seven patients [37 (55.2%) males; median (IQR) age: 57.0 (53.0, 63.0); median disease duration: 21 (16, 28) years] were included in this analysis. Multivariable linear regression analysis demonstrated that males had larger JSV (MCPJ 2-4), mean (MCPJ 4), and maximum JSW (MCPJ 3). Longer disease duration (MCPJ 2-3) and higher ESR values (MCPJ 3) were negatively associated with mean and maximum JSW, while higher damage joint count was negatively associated with mean and minimum JSW (MCPJ 2). Use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was negatively associated with minimum JSW (MCPJ 3) while use of biologic DMARDs (bDMARDs) was positively associated with minimum JSW (MCPJ 2). CONCLUSION: Higher inflammatory burden as reflected by longer disease duration, higher ESR levels, and damage joint count was negatively associated with mean, maximum, and minimum JSW, while suppression of inflammation using bDMARDs seems to limit the decline in JSW.

Photobiomodulation may enhance cognitive efficiency in older adults: a functional near-infrared spectroscopy study.

Introduction: The relative oxygenated hemoglobin (HbO) measured using functional near-infrared spectroscopy (fNIRS) has been considered as an index for cognitive loading, with the more difficult the task, the higher the level. A previous study reported that young adults who received transcranial photobiomodulation (tPBM) showed a reduced HbO of a difficult task, suggesting that tPBM may enhance cognitive efficiency. The present study further investigated the effect of tPBM on cognitive efficiency in older adults. Methods: Thirty participants received a single tPBM on the forehead for 350 s. Before and after tPBM, their HbO in the visual span task with various difficulties was measured with fNIRS. Results: After tPBM, participants exhibited significantly lower HbO in a harder (span 7) but not an easier level (span 2) of the task, but their behavioral performance remained unchanged. In addition, factors affecting the reduction of HbO were examined, and the results showed that individuals with better memory (as measured by a 30-min delayed recall test) showed more reduction of HbO. Discussion: The results suggest that tPBM may enhance cognitive efficiency, with individuals with better memory tend to benefit more.

Borrelia PeptideAtlas: A proteome resource of common Borrelia burgdorferi isolates for Lyme research.

Lyme disease, caused by an infection with the spirochete Borrelia burgdorferi, is the most common vector-borne disease in North America. B. burgdorferi strains harbor extensive genomic and proteomic variability and further comparison is key to understanding the spirochetes infectivity and biological impacts of identified sequence variants. To achieve this goal, both transcript and mass spectrometry (MS)-based proteomics was applied to assemble peptide datasets of laboratory strains B31, MM1, B31-ML23, infective isolates B31-5A4, B31-A3, and 297, and other public datasets, to provide a publicly available Borrelia PeptideAtlas http://www.peptideatlas.org/builds/borrelia/. Included is information on total proteome, secretome, and membrane proteome of these B. burgdorferi strains. Proteomic data collected from 35 different experiment datasets, with a total of 855 mass spectrometry runs, identified 76,936 distinct peptides at a 0.1% peptide false-discovery-rate, which map to 1,221 canonical proteins (924 core canonical and 297 noncore canonical) and covers 86% of the total base B31 proteome. The diverse proteomic information from multiple isolates with credible data presented by the Borrelia PeptideAtlas can be useful to pinpoint potential protein targets which are common to infective isolates and may be key in the infection process.

Prefrontal hemodynamic features of older adults with preserved visuospatial working memory function.

Memory decline has been observed in the aging population and is a risk factor for the later development of dementia. Understanding how memory is preserved in older adults has been an important topic. The present study examines the hemodynamic features of older adults whose memory is comparable with that of young adults. In the present study, 45 younger and 45 older adults performed the visual memory task with various difficulty levels (i.e., the items to be remembered), and their cerebral hemodynamics at each level were measured by functional near-infrared spectroscopy (fNIRS). The results showed that older adults exhibited higher activation than younger adults under more difficult but not easier levels. In addition, older adults whose performance is comparable with that of young adults (i.e., being able to remember six items) showed more right-lateralized activation. However, those unable to do so showed more left-lateralized activation. The results suggested that high-performing older adults possess successful compensatory mechanisms by recruiting cognitive resources in a specialized brain region.

Association of markers of inflammation on attention and neurobehavioral outcomes in survivors of childhood acute lymphoblastic leukemia.

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at-risk of developing cognitive impairment and neurobehavioral symptoms. Inflammation induced by a compromised health status during cancer survivorship is proposed as a pathophysiological mechanism underlying cognitive impairment in cancer survivors. Objectives: To evaluate the associations of biomarkers of inflammation with attention and neurobehavioral outcomes in survivors of childhood ALL, and to identify clinical factors associated with biomarkers of inflammation in this cohort. Methods: We recruited patients who were diagnosed with ALL at ≤ 18 years old and were currently ≥5 years post-cancer diagnosis. The study outcomes were attention (Conners Continuous Performance Test) and self-reported behavioral symptoms (Adult Self-Report [ASR] checklist). Using a commercial screening kit, survivors' plasma (5ml) was assayed for 17 cytokines/chemokine cell-signaling molecules that are associated with neurodegenerative diseases. The final panel of the targeted markers included interleukin (IL)-8, IL-13, interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1ß, and tumor necrosis factor-α. Biomarker levels were rank-ordered into tertiles based on the sample distribution. Multivariable general linear modeling was used to test for associations between biomarkers and study outcomes in the overall cohort and stratified by gender. Results: This study included 102 survivors (55.9% males, mean[SD] age 26.2[5.9] years; 19.3[7.1] years post-diagnosis). Survivors within top tertiles of IFN-γ (Estimate =6.74, SE=2.26; P=0.0037) and IL-13 (Estimate =5.10, SE=2.27; P=0.027) demonstrated more inattentiveness. Adjusting for age, gender and treatment, more self-reported thought (Estimate=3.53, SE=1.78; P=0.050) and internalizing problems (Estimate =6.52, SE=2.91; P=0.027) correlated with higher IL-8. Higher levels of IL-13 (RR = 4.58, 95% CI: 1.01-11.10) and TNF-α (RR = 1.44, 95% CI: 1.03-4.07) were observed in survivors had developed chronic health conditions (n=26, 25.5%). The stratified analysis showed that association of IFN-γ with attention was stronger in male survivors than in female survivors. Conclusion: Inflammation due to cancer-related late effects may potentially be mechanistic mediators of neurobehavioral problems in pediatric ALL survivors. Markers of inflammation can potentially be applied to assess or monitor the effectiveness of interventions, particularly behavioral interventions, in improving cognitive outcomes in survivors. Future work includes understanding the underlying gender-specific pathophysiology behind functional outcomes in the population.

A CRISPR-enhanced metagenomic NGS test to improve pandemic preparedness.

The lack of preparedness for detecting and responding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen (i.e., COVID-19) has caused enormous harm to public health and the economy. Testing strategies deployed on a population scale at day zero, i.e., the time of the first reported case, would be of significant value. Next-generation sequencing (NGS) has such capabilities; however, it has limited detection sensitivity for low-copy-number pathogens. Here, we leverage the CRISPR-Cas9 system to effectively remove abundant sequences not contributing to pathogen detection and show that NGS detection sensitivity of SARS-CoV-2 approaches that of RT-qPCR. The resulting sequence data can also be used for variant strain typing, co-infection detection, and individual human host response assessment, all in a single molecular and analysis workflow. This NGS work flow is pathogen agnostic and, therefore, has the potential to transform how large-scale pandemic response and focused clinical infectious disease testing are pursued in the future.

Effects of prefrontal transcranial direct current stimulation on social functioning in autism spectrum disorder: A randomized clinical trial.

LAY ABSTRACT: Currently available pharmacological and behavioral interventions for adolescents and young adults with autism spectrum disorder (ASD) yield only modest effect in alleviating their core behavioral and cognitive symptoms, and some of these treatment options are associated with undesirable side effects. Hence, developing effective treatment protocols is urgently needed. Given emerging evidence shows that the abnormal connections of the frontal brain regions contribute to the manifestations of ASD behavioral and cognitive impairments, noninvasive treatment modalities that are capable in modulating brain connections, such as transcranial direct current stimulation (tDCS), have been postulated to be potentially promising for alleviating core symptoms in ASD. However, whether tDCS can reduce behavioral symptoms and enhance cognitive performance in ASD remains unclear. This randomized controlled trial involving 105 adolescents and young adults with ASD showed that multiple sessions of a tDCS protocol, which was paired up with computerized cognitive training, was effective in improving social functioning in adolescents and young adults with ASD. No prolonged and serious side effects were observed. With more future studies conducted in different clinical settings that recruit participants from a wider age range, this tDCS protocol may be potentially beneficial to a broad spectrum of individuals with autism.

Temporal processing deficit in children and adolescents with autism spectrum disorder: An online assessment.

Objective: The sensory deficit has been considered as one of the core features in children and adolescents with autism spectrum disorder (ASD). The present study aimed to examine the temporal processing of simple and more complex auditory inputs in ASD children and adolescents with an online assessment that can be conducted remotely. Methods: One hundred fifty-eight children and adolescents aged 5-17 years participated in this study, including 79 ASD participants and 79 typically developing (TD) participants. The online assessment consisted of two temporal-order judgment tasks that required repeating the sequence of two pure tones or consonant-vowel (CV) syllabic pairs at varying interstimulus intervals (ISIs). Results: Significantly lower accuracy rates were found in ASD than TD participants in the pure tone and the CV conditions with both short and long ISI. In addition, ASD participants (M = 245.97 ms) showed a significantly higher passing threshold than TD participants (M = 178.84 ms) in the CV task. Receiver operating characteristic analysis found that the age × ISI passing threshold composite yielded a sensitivity of 74.7% and a specificity of 50.6% at the cutoff point of -0.307 in differentiating ASD participants from TD participants. Conclusion: In sum, children and adolescents with ASD showed impaired temporal processing of both simple and more complex auditory stimuli, and the online assessment seems to be sensitive in differentiating individuals with ASD from those with TD.

First uterine transplant case at the Royal Prince Alfred Hospital.

Uterine transplantation (UT) is an emerging medical treatment for women affected by absolute uterine factor infertility (AUFI). To date there have been over 90 documented cases of UT performed worldwide, with over 50 live births. UT allows women affected by AUFI the opportunity to carry and deliver a childd. The Royal Prince Alfred Hospital (RPAH) introduced a UT study in 2019; however, due to the impacts of the COVID pandemic the study was placed on hold for two years. In February 2023, RPAH performed the centre's first UT from a living unrelated donor to a 25-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome. The donor and recipient surgeries were uncomplicated and both are recovering well in the early post-operative period.

Effectiveness of lifestyle medicine on cognitive functions in mild cognitive impairments and dementia: A systematic review on randomized controlled trials.

Mild cognitive impairment (MCI) and dementia are associated with lifestyle risk factors, making lifestyle medicine a potentially viable intervention for people with MCI and dementia. The present study aims to examine the effectiveness of lifestyle medicine on cognitive functions among people with MCI and dementia, by performing a systematic review and meta-analysis on randomized controlled trials (RCT). A systematic literature search was conducted to extract RCTs adopting lifestyle interventions of diet, exercise, and stress management or emotional well-being. Results showed that 65 studies were eligible. Exercise was the most promising lifestyle intervention that improved various cognitive functions among people with MCI and dementia, and was more effective in MCI than in dementia. Interventions on stress management or emotional well-being did not show a significant effect on people with MCI, and the evidence for people with dementia was insufficient to conclude. Similarly, due to the lack of RCTs on a healthy dietary pattern, the effectiveness of diet interventions was not examined. In conclusion, the exercise component of lifestyle medicine can be an effective and clinically significant intervention for protecting people with MCI and dementia against cognitive declines, especially when served as an early intervention at the stage of MCI.

WT1 as a myoepithelial marker: a comparative study of breast, cutaneous, and salivary gland lesions.

WT1 immunostain is expressed in various benign and malignant neoplasms, as well as normal myoepithelial cells. WT1 shows differential expression in non-neoplastic, benign, and malignant neoplastic myoepithelial cells of the salivary gland. In this study, WT1 immunostain and other myoepithelial markers were compared to investigate the value of WT1 as a myoepithelial marker, and to delineate the expression profile of WT1 in nonsalivary gland myoepithelial cells. WT1, p63, and calponin immunostains were performed on normal and lesional tissues from the breast (adenosis, sclerosing adenosis, lactating adenoma, nipple adenoma, tubular adenoma, adenomyoepithelioma, and adenoid cystic carcinoma [ACC]), skin (cutaneous mixed tumor, hidradenoma, spiradenoma, and ACC), and salivary gland (pleomorphic adenoma and ACC). The stained slides were digitized and orientated with H&E images and assessed simultaneously using QuPath. A total of 129, 58, and 56 breast, cutaneous, and salivary gland lesions, respectively, were included. There was poor agreement between WT1-p63 and WT1-calponin (κ < 0.1) in all organs, with absence of WT1 expression in normal salivary gland myoepithelium and most ACCs. There were no significant differences in WT1 expression in myoepithelial cells in normal breast tissue and benign breast neoplasms. Compared to pleomorphic adenomas, cutaneous mixed tumors showed lower WT1 expression (P < .001). WT1 is a less sensitive myoepithelial marker than calponin and p63. However, its unique pattern of expression in salivary gland primary for pleomorphic adenomas/cutaneous mixed tumor can favor a diagnosis of benign salivary gland tumors, particularly in small biopsy specimens.

Associations between Lifestyle Factors and Neurocognitive Impairment among Chinese Adolescent and Young Adult (AYA) Survivors of Sarcoma.

BACKGROUND: The effect of lifestyle on neurocognitive impairment among cancer survivors remain an understudied area. This study explored the association between lifestyle factors and neurocognitive outcomes (specifically, attention, memory, processing speed and cognitive flexibility) in AYA survivors (aged 15-39 years) of sarcoma. METHODS: This study recruited 116 AYA survivors (age 28.2 (SD = 8.2) years), who were diagnosed with osteosarcoma (49%) or soft-tissue sarcoma (51%) at age 13.3 (SD = 7.2) years. The neurocognitive battery included measures of attention, memory, motor-processing speed, and cognitive flexibility. Survivors reported health-damaging practices, which included: physical inactivity, smoking, alcohol intake, inadequate sleep (<7 h of actual sleep/day), sleep-related fatigue (Multidimensional Fatigue Scale) and long working hours (>9 h/day). General linear modeling was conducted to examine the association between lifestyle factors and neurocognitive outcomes, adjusting for age at diagnosis, sex, education attainment and clinical/treatment variables. RESULTS: At 14.9 (SD = 7.6) years post-diagnosis, survivors demonstrated impairment in attentiveness (4.3-13.0%), processing speed (34.5%) and cognitive flexibility (18.1%). Nearly half (45.7%) had developed a chronic health condition (CHC). Low physical activity (estimate = -0.97, p = 0.003) and sleep-related fatigue (estimate = -0.08, p = 0.005) were associated with inattention. Survivors who worked >9 h/day (n = 15) demonstrated worse attention (estimate = 5.42, p = 0.023) and cognitive flexibility (estimate = 5.22, p = 0.005) than survivors who worked ≤9 h/day (n = 66). Interaction analysis (CHCs*physical activity) showed that survivors who developed CHCs and reported low physical activity had worse attention (p = 0.032) and cognitive-flexibility (p = 0.019) scores than other subgroups. CONCLUSION: Treatment-related CHCs, coupled with continued physical inactivity, may exacerbate inattention and executive dysfunction among survivors. Long working hours and sleep-related fatigue are associated with worse functioning; this finding should be validated with prospective assessment of work-related stressors and objective sleep measures.

Evaluation and comparison of four quantitative SARS-CoV-2 serological assays in COVID-19 patients and immunized healthy individuals, cancer patients, and patients with immunosuppressive therapy.

BACKGROUND: Semi-quantitative and quantitative immunoassays are the most commonly used methodology to evaluate immunity post immunization. OBJECTIVES: To compare four quantitative SARS-CoV-2 serological assays in COVID-19 patients and immunized healthy individuals, cancer patients, and patients with immunosuppressive therapy. STUDY DESIGN: 210 serological samples from COVID-19 infection and vaccination cohorts were used to create a serological sample repository. Serological methods from four manufacturers, namely Euroimmun, Roche, Abbott, and DiaSorin, were evaluated for quantitative, semi-quantitative, and qualitative antibody measurements. All four methods measure IgG antibodies against the SARS-CoV-2 spike receptor-binding domain and report the results in Binding Antibody Unit/mL (BAU/mL). A Total Error Allowable (TEa) of ±25% was chosen as the criteria to determine whether two methods are clinically equivalent quantitatively. Semi-quantitative results (titers) were derived using numeric antibody concentration divided by the cut-off value for each method. RESULTS: All paired quantitative comparisons demonstrated unacceptable performance. With ±25% as TEa, the best agreement was 74 (35.2% out of 210 samples) between Euroimmun and DiaSorin, whereas the lowest agreement was 11 (5.2% out of 210 samples) between Euroimmun and Roche. Antibody titers amongst all four methods were significantly different (p < 0.001). The highest titer difference from the same sample is between Roche and DiaSorin with a 1392-fold difference. On qualitative comparison, none of the paired comparison showed acceptable comparison (p < 0.001). CONCLUSIONS: Poor correlation exists between four evaluated assays, quantitatively, semi-quantitatively, and qualitatively. Further harmonization of assays is required to achieve comparable measurements.

Comparative Efficacy and safety of new targeted therapies and immunotherapies for metastatic triple negative breast cancer: a network meta-analysis.

BACKGROUND: Several therapies directed at novel targets and also immunotherapies have recently shown promising results in advanced or metastatic TNBC. We aimed to compare the efficacy and safety of these new regimens for advanced or metastatic TNBC (mTNBC). METHODS: The PubMed, Embase, and Cochrane Library electronic databases were searched for phase III randomized trials. We conducted a network meta-analysis to compare the efficacy and safety of new targeted and immunotherapy regimens. Trial quality was assessed using the GRADE method. The comparative outcomes were progression-free survival, overall survival, and G3-4 adverse drug events (ADEs). RESULTS: Thirteen phase III randomized controlled trials were identified in the network meta-analysis. Olaparib significantly improved PFS in comparison with the pembrolizumab plus chemotherapy 1, atezolizumab plus nab-paclitaxel and pembrolizumab regimens. Sacituzumab yielded a significant improvement in OS over immunotherapies, veliparib, and chemotherapy alone, but no significantly superiority over pembrolizumab, olaparib, and talazoparib. The risk of ≥grade 3 ADEs associated with olaparib was significantly lower than the risks associated with the other regimens. CONCLUSION: For mTNBC, sacituzumab had a better effect on overall survival, with comparatively high risk of SAE, whereas olaparib improved progression-free survival with a lower risk of SAE, particularly in those patients with BRCA mutations.