Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Long-term prognostic value of thyroid hormones in left ventricular noncompaction.

PURPOSE: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC). METHODS: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated. RESULTS: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance. CONCLUSION: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.

Prediction of likelihood of conception in dairy cows using milk mid-infrared spectra collected before the first insemination and machine learning algorithms.

Accurate and ex-ante prediction of cows' likelihood of conception (LC) based on milk composition information could improve reproduction management on dairy farms. Milk composition is already routinely measured by mid-infrared (MIR) spectra, which are known to change with advancing stages of pregnancy. For lactating cows, MIR spectra may also be used for predicting the LC. Our objectives were to classify the LC at first insemination using milk MIR spectra data collected from calving to first insemination and to identify the spectral regions that contribute the most to the prediction of LC at first insemination. After quality control, 4,866 MIR spectra, milk production, and reproduction records from 3,451 Holstein cows were used. The classification accuracy and area under the curve (AUC) of 6 models comprising different predictors and 3 machine learning methods were estimated and compared. The results showed that partial least square discriminant analysis (PLS-DA) and random forest had higher prediction accuracies than logistic regression. The classification accuracy of good and poor LC cows and AUC in herd-by-herd validation of the best model were 76.35 ± 10.60% and 0.77 ± 0.11, respectively. All wavenumbers with values of variable importance in the projection higher than 1.00 in PLS-DA belonged to 3 spectral regions, namely from 1,003 to 1,189, 1,794 to 2,260, and 2,300 to 2,660 cm-1. In conclusion, the model can predict LC in dairy cows from a high productive TMR system before insemination with a relatively good accuracy, allowing farmers to intervene in advance or adjust the insemination schedule for cows with a poor predicted LC.

The impact of air pollutants on spontaneous abortion: a case-control study in Tongchuan City.

OBJECTIVES: Studies related to air pollutants and spontaneous abortion in urban northwestern China are scarce, and the main exposure windows of pollutants acting on pregnant women are unclear. STUDY DESIGN: Case-control study. METHODS: Data were collected from pregnant women in Tongchuan City from 2018 to 2019. A total of 289 cases of spontaneous abortion and 1156 cases of full-term labor were included and analyzed using a case-control study. Logistic regression models were developed to explore the relationship between air pollutants and spontaneous abortion after Chi square analysis and Air pollutant description. RESULTS: O3 (odds ratio [OR] = 1.028) is a risk factor for spontaneous abortion throughout pregnancy. PM2.5 (OR = 1.015), PM10 (OR = 1.010), SO2 (OR = 1.026), and NO2 (OR = 1.028) are risk factors for spontaneous abortion in the 30 days before the last menstrual period. PM2.5 (OR = 1.015), PM10 (OR = 1.013), SO2 (OR = 1.036), and NO2 (OR = 1.033) are risk factors for spontaneous abortion in the 30-60 days before the last menstrual period. PM2.5 (OR = 1.028), PM10 (OR = 1.013), SO2 (OR = 1.035), and NO2 (OR = 1.059) are risk factors for spontaneous abortion in the 60-90 days before the last menstrual period. CONCLUSION: Exposure to high levels of air pollutants may be a cause of increased risk of spontaneous abortion, especially in the first trimester of the last menstrual period.

Short-term effects of air pollutants and meteorological factors on outpatients with allergic airway disease in Ningbo, China, 2015-2021.

OBJECTIVES: The allergic airway disease, such as allergic rhinitis, chronic rhinosinusitis, asthma, is a general term of a range of inflammatory disorders affecting the upper and lower airways and lung parenchyma. This study aimed to investigate the short-term effects of air pollutants and meteorological factors on AAD-related daily outpatient visits. STUDY DESIGN: An ecological study. METHODS: Data on outpatient visits due to AAD (n = 4,554,404) were collected from the platform of the Ningbo Health Information from January 1, 2015 to December 31, 2021. A Quasi-Poisson generalized additive regression model was established to analyze the lag effects of air pollution on daily outpatient visits for AAD. Restricted cubic spline functions were used to explore the potential non-linear relationships between air pollutants and meteorological and daily outpatient visits for AAD. RESULTS: PM2.5, PM10, SO2, NO2, or CO were associated with daily outpatient visits for AAD, and there was a significant increasing trend in the cumulative lag effects. SO2 had the largest effect at Lag07, with a 25.3% (95% CI: 21.6%-29.0%) increase in AAD for every 10 µg/m3 increase in exposure concentration. Subgroup analysis showed that the 0-18 years old age group had the strongest effects, especially for AR, and all effects were stronger in the cold season. CONCLUSIONS: Given that patients aged 0-18 are more susceptible to environmental changes, protective measures specifically for children should be taken during dry and cold weather conditions with poor air quality.

Asthma and clinical outcomes of COVID-19 in a community setting.

OBJECTIVES: The association between asthma and COVID-19 mortality remains inconclusive. We examined the association between asthma and clinical outcomes of patients with COVID-19. STUDY DESIGN: A case-control study based on a surveillance cohort in Harris County, Texas. METHODS: Using the data of 21,765 patients who reported having at least one chronic health condition, we investigated the association between asthma and COVID-19 severity, characterized primarily by hospitalization and death. Unconditional logistic regression models were used to estimate the multivariable odds ratio (mOR) and its 95 % confidence interval (CI) of COVID-19 severity associated with asthma and other chronic lung diseases, adjusting for demographic and other comorbidities. A P-value < 0.005 was considered statistically significant after correcting multiple testing. RESULTS: In total, 3034 patients (13.9 %) had asthma, and 774 (3.56 %) had other chronic lung diseases. The case death rate among patients with asthma and other chronic lung diseases was 0.75 % and 19.0 %, respectively. Compared to patients without the respective conditions, patients with asthma had lower odds of death (mOR = 0.44, 95 % CI: 0.27-0.69), while patients with other chronic lung diseases had higher odds of hospitalization (mOR = 2.02, 95 % CI: 1.68-2.42) and death (mOR = 1.95, 95 % CI: 1.52-2.49) (P-values < 0.005). Risk factors for COVID-19 mortality included older age, male gender, diabetes, obesity, hypertension, cardiovascular disease, active cancer, and chronic kidney disease. CONCLUSIONS: The public health surveillance data suggested that preexisting asthma was inversely associated with COVID-19 mortality.

[Applications of artificial intelligence for imaging-driven diagnosis and treatment of bone and soft tissue tumors].

Bone and soft tissue tumors occur in the musculoskeletal system, and malignant bone tumors of bone and soft tissue account for 0.2% of all human malignant tumors, and if not diagnosed and treated in a timely manner, patients may be at risk of a poor prognosis. Image interpretation plays an increasingly important role in the diagnosis of bone and soft tissue tumors. Artificial intelligence (AI) can be applied in clinical treatment to integrate large amounts of multidimensional data, derive models, predict outcomes, and improve treatment decisions. Among these methods, deep learning is a widely employed technique in AI that predominantly utilizes convolutional neural networks (CNN). The network is implemented through repeated training of datasets and iterative parameter adjustments. Deep learning-based AI models have successfully been applied to various aspects of bone and soft tissue tumors, encompassing but not limiting in image segmentation, tumor detection, classification, grading and staging, chemotherapy effect evaluation, recurrence and prognosis prediction. This paper provides a comprehensive review of the principles and current state of AI in the medical image diagnosis and treatment of bone and soft tissue tumors. Additionally, it explores the present challenges and future prospects in this field.

[Expert consensus on the application of critical care ultrasonography in invasive procedures].

The evolution of critical care medicine is inextricably linked to the development of critical care procedures. These procedures not only facilitate diagnosis and treatment of critically ill patients, but also provide valuable insights into disease pathophysiology. While critical care interventions offer undeniable benefits, the potential for iatrogenic complications necessitates careful consideration. The recent surge in critical care ultrasound (US) utilization is a testament to its unique advantages: non-invasiveness, real-time bedside availability, direct visualization of internal structures, elimination of ionizing radiation exposure, repeatability, and relative ease of learning. Recognizing the need to optimize procedures and minimize complications, critical care utrasound study group of Beijing critical care ultrasound research assocition convened a panel of critical care experts to generate this consensus statement. This document serves as a guide for healthcare providers, aiming to ensure patient safety and best practices in critical care.

Effects of cassava root meal on the growth performance, apparent nutrient digestibility, organ and intestinal indices, and slaughter performance of yellow-feathered broiler chickens.

With the global population growth and shortage of food, the competition between humans and animal for food will become increasingly fierce. Therefore, the development of unconventional energy feed cassava feed is of great significance. The objective of this study was to investigate the effects of cassava root meal (CRM) on the growth performance, apparent digestibility, and organ and intestinal indices of broiler chickens. A total of 140 one-day-old chicks were randomly assigned to four dietary treatment groups [control diet (CT), 15% CRM (CRM15), 30% CRM (CRM30), and 45% CRM (CRM45)] with five replicates of seven birds per replicate. The results showed that the body weight of broiler chickens fed diets containing CRM were significantly lower than that in the CT group at 21 and 42 days of age, the average daily gain and average daily feed intake in the CRM group were significantly lower than those in the CT group from 1 to 21 days of age. However, from days 22 to 42, there were no significant differences between CRM15 and CT birds regarding average daily gain and average daily feed intake. but there was no difference in feed conversion rate between the CRM15 and CT groups. At 42 days of age, there were no significant differences between CRM15 and CT birds in in body measurements, the slaughter performance and the percentage of semi-eviscerated yield. The addition of CRM reduced the proportion of breast and thigh muscles during the feeding period, although we detected no significant difference between CRM15 and CT regarding the apparent digestibility of nutrients. Collectively, our findings indicate that 15% cassava was the optimal proportion for supplementing diets for broiler chicken production.

[The mechanical ventilation guided by electrical impedance tomography in acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is a common and critical clinical condition characterized by diffuse damage to the lung interstitium, alveoli, and increased permeability of pulmonary blood vessels. CT can be used to assess the imaging features, severity, and prediction of ARDS, but it requires patient transportation to the CT room and is only a static examination. Electrical impedance tomography (EIT) is an increasingly widely used monitoring tool in clinical applications in recent years. It enables continuous real-time assessment of lung ventilation distribution at the bedside and has high clinical value in optimizing mechanical ventilation parameters for critically ill patients. This article introduces the basic principles of EIT and how to better utilize EIT technology to guide mechanical ventilation treatment for ARDS patients.