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Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor

Front Immunol. 2023 May 3;14:1164724. doi: 10.3389/fimmu.2023.1164724. eCollection 2023.

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown.

METHODS: We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).

RESULTS: The genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.

DISCUSSION: Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.

PMID:37207204 | PMC:PMC10189048 | DOI:10.3389/fimmu.2023.1164724

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Comparison of Urinary Incontinence in Older White and Black Women: A Pilot Study

Int J Nurs Health Care Res (Lisle). 2022;5(7):1324. doi: 10.29011/2688-9501.101324. Epub 2022 Aug 17.

ABSTRACT

This pilot-cross sectional study compared Urinary Incontinence symptom type and severity, and impact of UI on Quality of Life among older White and Black women. Outcome measures included a three-day bladder diary (3dbd), Incontinence Impact Questionnaire Short Form (IIQ-7), Urinary Distress Inventory Short Form (UDI-6), Medical Epidemiological Social Aspects of Ageing (MESA) questionnaire, and Patient Global Impact of Severity Scale (PGI-S). Participants’ characteristics and UI outcomes were analysed with descriptive statistics, Fisher’s Exact and Mann-Whitney U tests. Twenty women (10 White, and 10 Black) with mean age of 76.5 (± 4.9 years) participated in the study. There were no significant differences in most UI symptoms based on 3dbd, MESA, PGI-S, UDI-6, and IIQ-7. However, older Black women reported moderate and/or severe impact of UI on their emotional health more frequently (n=7, 70%) compared to White women (n=1, 10%, p=0.02) based on the IIQ-7.

PMID:37207183 | PMC:PMC10195058 | DOI:10.29011/2688-9501.101324

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Preoperative diagnosis of solitary pulmonary nodules with a novel hematological index model based on circulating tumor cells

Front Oncol. 2023 May 3;13:1150539. doi: 10.3389/fonc.2023.1150539. eCollection 2023.

ABSTRACT

OBJECTIVE: Preoperative noninvasive diagnosis of the benign or malignant solitary pulmonary nodule (SPN) is still important and difficult for clinical decisions and treatment. This study aimed to assist in the preoperative diagnosis of benign or malignant SPN using blood biomarkers.

METHODS: A total of 286 patients were recruited for this study. The serum FR+CTC, TK1, TP, TPS, ALB, Pre-ALB, ProGRP, CYFRA21-1, NSE, CA50, CA199, and CA242 were detected and analyzed.

RESULTS: In the univariate analysis, age, FR+CTC, TK1, CA50, CA19.9, CA242, ProGRP, NSE, CYFRA21-1, and TPS showed the statistical significance of a correlation with malignant SPNs (P <0.05). The highest performing biomarker is FR+CTC (odd ratio [OR], 4.47; 95% CI: 2.57-7.89; P <0.001). The multivariate analysis identified that age (OR, 2.69; 95% CI: 1.34-5.59, P = 0.006), FR+CTC (OR, 6.26; 95% CI: 3.09-13.37, P <0.001), TK1 (OR, 4.82; 95% CI: 2.4-10.27, P <0.001), and NSE (OR, 2.06; 95% CI: 1.07-4.06, P = 0.033) are independent predictors. A prediction model based on age, FR+CTC, TK1, CA50, CA242, ProGRP, NSE, and TPS was developed and presented as a nomogram, with a sensitivity of 71.1% and a specificity of 81.3%, and the AUC was 0.826 (95% CI: 0.768-0.884).

CONCLUSIONS: The novel prediction model based on FR+CTC showed much stronger performance than any single biomarker, and it can assist in predicting benign or malignant SPNs.

PMID:37207165 | PMC:PMC10189144 | DOI:10.3389/fonc.2023.1150539

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Mendelian randomization to explore the direct or mediating associations between socioeconomic status and lung cancer

Front Oncol. 2023 May 3;13:1143059. doi: 10.3389/fonc.2023.1143059. eCollection 2023.

ABSTRACT

OBJECTIVE: The purpose of this study was to verify whether there are direct or mediated causal associations between socioeconomic status and lung cancer.

METHODS: Pooled statistics were obtained from corresponding genome-wide association studies. The inverse-variance weighted, weighted median, MR-Egger, MR-PRESSO and contamination-mixture methods were used as supplements to Mendelian randomization (MR) statistical analysis. Cochrane’s Q value and the MR-Egger intercept were used for sensitivity analysis.

RESULTS: In the univariate MR analysis, household income and education had protective effects on overall lung cancer (income: P = 5.46×10-4; education: P = 4.79×10-7) and squamous cell lung cancer (income: P = 2.67×10-3; education: P = 1.42×10-10). Smoking and BMI had adverse effects on overall lung cancer (smoking: P = 2.10×10-7; BMI: P = 5.67×10-4) and squamous cell lung cancer (smoking: P = 5.02×10-6; BMI: P = 2.03×10-7). Multivariate MR analysis found that smoking and education were independent risk factors for overall lung cancer (smoking: P = 1.96×10-7; education: P = 3.11×10-3), while smoking was an independent risk factor for squamous cell lung cancer (P = 2.35×10-6). Smoking, education, and household income mediate the effect of BMI on overall lung cancer (smoking 50.0%, education 49.2%, income 25.3%) and squamous cell lung cancer (smoking 34.8%, education 30.8%, income 21.2%). Smoking, education, and BMI mediate the effect of income on overall lung cancer (smoking 13.9%, education 54.8%, BMI 9.4%) and squamous cell lung cancer (smoking 12.6%, education 63.3%, BMI 11.6%). Smoking, BMI, and income mediate the effect of education on squamous cell lung cancer (smoking 24.0%, BMI 6.2%, income 19.4%).

CONCLUSION: Income, education, BMI, and smoking are causally associated with both overall lung cancer and squamous cell lung cancer. Smoking and education are independent association factors for overall lung cancer, while smoking is an independent association factor for squamous cell lung cancer. Smoking and education also play important mediating roles in overall lung cancer and squamous cell lung cancer. No causal relationship was found between multiple risk factors associated with socioeconomic status and lung adenocarcinoma.

PMID:37207156 | PMC:PMC10189779 | DOI:10.3389/fonc.2023.1143059

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Physical Versus Virtual Reality-Based Calm Rooms for Psychiatric Inpatients: Quasi-Randomized Trial

J Med Internet Res. 2023 May 19;25:e42365. doi: 10.2196/42365.

ABSTRACT

BACKGROUND: Interest in sensory rooms or so-called “calm rooms” in psychiatric inpatient care has increased significantly. In a hospital setting, their purpose is to introduce a relaxing environment to increase well-being as well as to decrease anxiety and aggressive behaviors. Calm rooms can also be used as a tool to provide self-help through a convenient environment for the patients and, at the same time, strengthen the therapeutic relationship between the patient and the professional. Recent developments in virtual reality (VR) have made virtual calm rooms possible, but these have not yet been evaluated in psychiatric inpatient care.

OBJECTIVE: This study aimed to compare the effects of VR and physical calm rooms on self-reported well-being and physiological markers of arousal.

METHODS: The study was conducted in 2 inpatient psychiatric wards specializing in bipolar disorder from March 2019 to February 2021. Patients who were already admitted were asked if they were interested in using a calm room and willing to provide ratings. This study relied on the quasi-randomized allocation of patients to the wards, which either had a physical or VR calm room. Self-assessment scales (Montgomery-Åsberg Depression Rating Scale-Self Assessment [MADRS-S], Beck Anxiety Scale, and Clinical Global Impression) were used to determine the participants’ baseline level of depressive and anxiety symptoms before their use of the physical or VR calm room. The study determined the state of well-being measured using an 11-point visual analog scale (VAS) as well as arousal measured by blood pressure (systolic and diastolic) and heart rate before and after the use of the calm rooms. The primary end point was self-reported well-being using the VAS.

RESULTS: A total of 60 participants were included-40 used the VR calm room and 20 used the physical calm room. The mean age of participants was 39 years and the majority were women (35/60, 58%). Analysis of VAS measurement showed improved well-being at the group level from before to after the intervention (P<.05), with no statistically significant difference in effects between the 2 different interventions. Effects were not moderated by baseline depression levels (dichotomized as MADRS-S >20 or ≤20) despite an overall difference in reported well-being between subgroups.

CONCLUSIONS: Although the power in this study was low, the findings of this first study indicate comparable effects with respect to well-being and arousal of a VR calm room and a physical calm room. This suggests that a VR calm room can be a viable alternative when the use of a physical calm room is not an option for logistic or other reasons.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03918954; https://clinicaltrials.gov/ct2/show/NCT03918954.

PMID:37204858 | DOI:10.2196/42365

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TSH level as a risk factor of thyroid malignancy for nodules in euthyroid patients

Acta Otorhinolaryngol Ital. 2023 Jun;43(3):183-188. doi: 10.14639/0392-100X-N2288.

ABSTRACT

OBJECTIVE: With the increased prevalence of incidental thyroid cancer, determining the predictors of thyroid malignancy has become a source of debate. This study aimed to determine the impact of thyroid stimulating hormone (TSH) levels on rates of thyroid cancer in euthyroid patients.

METHODS: A retrospective study included 421 patients who underwent thyroidectomy at a tertiary hospital between 2016 and 2020. Patients’ demographics, history of cancer, pre-operative workup and final histology reports were obtained. The study sample was divided into two groups based on the final histopathology (benign vs malignant). The two groups were compared using the appropriate statistical tests to determine the predictors of thyroid cancer in euthyroid patients.

RESULTS: TSH levels were significantly higher in patients with malignant nodules compared to those with benign nodules (1.94 vs 1.62, p = 0.002). It was 1.54 times more likely for thyroid nodules to be malignant when TSH levels were higher (p = 0.038). Meanwhile, larger nodules (> 4 cm) were significantly more prevalent in benign nodules (43.1%) than in malignant nodules (21.1%). Larger nodules decreased the possibility of thyroid cancer by 24% (OR = 0.760, p-value = 0.004).

CONCLUSIONS: High TSH levels in euthyroid patients were significantly correlated with the risk of thyroid malignancy. In addition, as Bethesda category proceeded toward malignancy, TSH levels increased. High TSH levels and small nodule diameters can be used as additional parameters in predicting thyroid cancer in euthyroid patients.

PMID:37204842 | DOI:10.14639/0392-100X-N2288

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Understanding the Uptake and Outcomes of Non-occupational Postexposure Prophylaxis Use Through an Online Medical Platform in China: Web-Based Cross-sectional Study

J Med Internet Res. 2023 May 19;25:e42729. doi: 10.2196/42729.

ABSTRACT

BACKGROUND: To date, non-occupational postexposure prophylaxis (PEP) has been widely accepted as a safe and effective intervention for HIV in many countries, yet it remains an underutilized prevention strategy in China. Evidence indicated a high demand for PEP among Chinese men who have sex with men, but the uptake and access to PEP service remain limited. In an era of rapid development of web-based technology, online medical platforms in China hold great promise in facilitating PEP provision and delivery by addressing problems such as accessibility, convenience, privacy protection, and antidiscrimination by integrating online and offline resources. However, there is a paucity of data concerning the uptake and outcomes of online PEP in China.

OBJECTIVE: The aim of this study is to explore online PEP service provision and understand PEP uptake and outcome through a web-based cross-sectional study.

METHODS: From January 2020 to June 2021, we conducted a retrospective web-based survey among those seeking online PEP services via the internet medical platform “HeHealth” using a structured questionnaire. Participants were surveyed on sociodemographic characteristics, sexual and drug-related behaviors, history of preexposure prophylaxis (PrEP) usage, and PEP uptake. Statistical analysis included descriptive analysis, chi-square test, and multivariable logistic regression. P values <.05 were deemed statistically significant.

RESULTS: No HIV seroconversions were observed among 539 PEP users. Our sample demonstrated that most participants seeking online PEP services were gay (397/539, 73.7%), single (470/539, 87.2%), having an education of more than 12 years (493/539, 91.5%), and with an average monthly income of 7000 RMB (1 RMB=US $0.14) or more (274/539, 50.8%). Sexual exposures accounted for 86.8% (468/539) of the cases, with anal sex being the most common indication (389/539, 72.2%) for seeking PEP use. Among 539 participants, 60.7% (327/539) sought online PEP for relatively low-risk exposures, whereas 39.3% (212/539) were considered high-risk exposures. Nearly all (537/539, 99.6%) initiated PEP within 72 hours and 68.6% (370/539) within 24 hours of exposure. All users (539/539) were prescribed a 3-drug regimen, with most comprising 3TC/TDF+DTG (lamivudine, tenofovir disoproxil fumarate, and dolutegravir; 293/539, 54.4%), followed by FTC/TDF+DTG (emtricitabine, tenofovir disoproxil fumarate, and dolutegravir; 158/539, 29.3%). The adjusted model showed that greater odds of PrEP usage were associated with an age of 35 years or older versus the age group of 25-34 years (adjusted odds ratio [AOR] 2.04, 95% CI 1.24-3.37), having an education of 17 years or more versus an education of 12 years or less (AOR 3.14, 95% CI 1.29-7.62), average monthly income of 20,000 RMB or more versus less than 3000 RMB (AOR 2.60, 95% CI 1.09-6.23), and having high-risk sexual behavior during PEP treatment (AOR 2.20, 95% CI 1.05, 3.69).

CONCLUSIONS: The 0% infection rate in this study demonstrated that online PEP could be a valuable risk-reduction option to improve HIV prevention service within China. However, further research is needed to better facilitate PrEP transition among online PEP users.

PMID:37204828 | DOI:10.2196/42729

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Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non-Muscle-Invasive Bladder Cancer

JAMA Netw Open. 2023 May 1;6(5):e2314336. doi: 10.1001/jamanetworkopen.2023.14336.

ABSTRACT

IMPORTANCE: The BCG vaccine-used worldwide to prevent tuberculosis-confers multiple nonspecific beneficial effects, and intravesical BCG vaccine is currently the recommended treatment for non-muscle-invasive bladder cancer (NMIBC). Moreover, BCG vaccine has been hypothesized to reduce the risk of Alzheimer disease and related dementias (ADRD), but previous studies have been limited by sample size, study design, or analyses.

OBJECTIVE: To evaluate whether intravesical BCG vaccine exposure is associated with a decreased incidence of ADRD in a cohort of patients with NMIBC while accounting for death as a competing event.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was performed in patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, treated within the Mass General Brigham health care system. The study included a 15-year follow-up of individuals (BCG vaccine treated or controls) whose condition did not clinically progress to muscle-invasive cancer within 8 weeks and did not have an ADRD diagnosis within the first year after the NMIBC diagnosis. Data analysis was conducted from April 18, 2021, to March 28, 2023.

MAIN OUTCOMES AND MEASURES: The main outcome was time to ADRD onset identified using diagnosis codes and medications. Cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards regression after adjusting for confounders (age, sex, and Charlson Comorbidity Index) using inverse probability scores weighting.

RESULTS: In this cohort study including 6467 individuals initially diagnosed with NMIBC between 1987 and 2021, 3388 patients underwent BCG vaccine treatment (mean [SD] age, 69.89 [9.28] years; 2605 [76.9%] men) and 3079 served as controls (mean [SD] age, 70.73 [10.00] years; 2176 [70.7%] men). Treatment with BCG vaccine was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69-0.99), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74; 95% CI, 0.60-0.91). In competing risks analysis, BCG vaccine was associated with a lower risk of ADRD (5-year risk difference, -0.011; 95% CI, -0.019 to -0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, -0.056; 95% CI, -0.075 to -0.037).

CONCLUSIONS AND RELEVANCE: In this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time.

PMID:37204792 | DOI:10.1001/jamanetworkopen.2023.14336

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Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit: A Secondary Analysis of the SPRINT Randomized Clinical Trial

JAMA Netw Open. 2023 May 1;6(5):e2314443. doi: 10.1001/jamanetworkopen.2023.14443.

ABSTRACT

IMPORTANCE: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients.

OBJECTIVE: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment.

DESIGN, SETTING, AND PARTICIPANTS: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022.

INTERVENTION: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI.

RESULTS: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.

PMID:37204788 | DOI:10.1001/jamanetworkopen.2023.14443

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Prevalence of Giardia duodenalis among Asian children: a systematic review and meta-analysis

Int Health. 2023 May 19:ihad037. doi: 10.1093/inthealth/ihad037. Online ahead of print.

ABSTRACT

Giardia duodenalis is one of the major causes of diarrhea among children. We performed a systematic review and meta-analysis to assess the prevalence of G. duodenalis and associated risk factors among Asian children. We searched online databases (PubMed, Scopus and Web of Science) and Google Scholar search engine for studies published from 1 January 2000 to 15 March 2022 that measured the prevalence of G. duodenalis among Asian children. Accordingly, the pooled prevalence and 95% CIs were estimated using a random-effects meta-analysis model for the included studies. A total of 182 articles from 22 Asian countries met the inclusion criteria. The pooled prevalence of G. duodenalis infection among Asian children was estimated as 15.1% (95% CI 14.1 to 16%). The highest and lowest pooled prevalence values of G. duodenalis infection were estimated for Tajikistan and China as 26.4% (95% CI 22.9 to 30%) and 0.6% (95% CI 0.001 to 1.02%), respectively. The infection had a higher prevalence in males than in females (OR=1.24; 95% CI 1.16 to 1.31; p<0.001), which was statistically significant. Giardiasis is common among Asian children, hence, a prevention and control scheme of this protozoan in children should be considered by health officials and health policymakers, especially in Asian countries where the prevalence is highest.

PMID:37204774 | DOI:10.1093/inthealth/ihad037