Physical activity and cancer risk: a dose-response analysis for the Global Burden of Disease Study 2019.

OBJECTIVE: Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the dose-response relationships between total physical activity and the risk of breast, colon, lung, gastric, and liver cancers. METHODS: A systematic review and dose-response analysis were conducted using PubMed and Embase from January 1, 1980 to March 20, 2023. Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included. The search was confined to publications in the English language with a specific focus on human studies. Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys (NHANES) and the Global Burden of Disease 2019 database. RESULTS: A total of 98 studies, involving a combined population of 16,418,361 individuals, were included in the analysis. Among the included studies, 57 focused on breast cancer, 17 on lung cancer, 23 on colon cancer, 5 on gastric cancer, and 7 on liver cancer. Overall, elevated levels of physical activity exhibited an inverse correlation with the risk of cancer. The dose-response curve for lung cancer exhibited a non-linear pattern, with the greatest benefit risk reduction observed at 13,200 MET-minutes/week of physical activity, resulting in a 14.7% reduction in risk (relative risk 0.853, uncertainty interval 0.798 to 0.912) compared to the inactive population. In contrast, the dose-response curves for colon, gastric, breast, and liver cancers showed linear associations, indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks. However, the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers. Compared to individuals with insufficient activity (total activity level < 600 MET-minutes/week), individuals with high levels of activity (≥ 8,000 MET-minutes/week) experienced a 10.3% (0.897, 0.860 to 0.934) risk reduction for breast cancer; 5.9% (0.941, 0.884 to 1.001) for lung cancer; 7.1% (0.929, 0.909 to 0.949) for colon cancer; 5.1% (0.949, 0.908 to 0.992) for gastric cancer; 17.1% (0.829, 0.760 to 0.903) for liver cancer. CONCLUSIONS: This study demonstrated a significant inverse relationship between total physical activity and the risk of breast, gastric, liver, colon, and lung cancers.

Development and validation of a clinical score combining the sequential organ failure assessment score with inflammation-based markers to predict outcome of patients with sepsis.

BACKGROUND: Whether combining the Sequential Organ Failure Assessment (SOFA) score at admission with inflammation-based markers can improve performance of prediction and risk stratification of patients with sepsis, compared to use of the SOFA score alone, remains unknown. METHODS: Data from septic patients included in the Medical Information Mart for Intensive Care database (MIMIC-IV) database were used for model development and internal validation. We developed a predictive nomogram model that included SOFA score, Charlson Comorbidity Index (CCI), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and mean corpuscular volume (MCV) values. The primary outcome was the performance of the risk score. RESULTS: Data from 4704 septic patients included in the database were used for the primary cohort and to build the model. The multivariate analyses included SOFA score, CCI, RDW, NLR, LMR, and MCV values. These values were used for nomogram model construction. The nomogram model showed good calibration, and had better discrimination in terms of area under the receiver operating characteristic (AUROC) curve results than use of the SOFA score alone (0.724 (95% CI: 0.705-0.743) vs. 0.585 (95% CI: 0.562-0.609), respectively; P<0.001). It also had better classification in terms of net reclassification improvement (20.5% (95% CI: 16.2%-24.7%; P<0.001)) and integrated discrimination improvement (6.0% (95% CI: 5.1%-6.8%; P<0.001)). The validation cohort results supported these findings. CONCLUSION: The results suggested that this simple-to-use nomogram model provided a relatively accurate risk of death prediction in patients with sepsis.

An optimized method for the induction and purification of mouse bone marrow dendritic cells.

Dendritic cells (DCs) play an essential role in the initiation of adaptive immune responses, but they are rare in all organs. The traditional methods used to increase the yield and purity of DCs are the early removal of granulocyte culture medium and the isolation of high-purity DCs by magnetic-activated cell sorting (MACS). This study provides a more rapid and economical optimization method to obtain more high-purity DCs. (i) We harvested 18% more bone marrow (BM) cells by using forceps to crack the epiphysis instead of cutting it with scissors during BM cell extraction. (ii) When the cells in the culture medium that is discarded on day 3 in the traditional method were centrifuged and then added back to the petri dish, the DC yield on day 5 increased by 61%. (iii) On the third day, the addition of fresh medium and the retention of the original medium rather than discarding it increased the number of DCs harvested on the fifth day by 137%. (i-iii) The improved method cost an average of 74% less than the conventional method and yielded the same number and function of cells. (iv) The initial number of BM cells was increased by 15% in 4-week-old mice compared with 8-week-old mice. (v) The Percoll density centrifugation (PDS) method was used to purify DCs on day 6 after induction, and the purity of the DCs was greater than 90%, which showed no significant difference from the MACS method. However, the yield of the PDS method increased by 21%. In addition, the PDS method has a lower cost, with an average purification cost of 4 CNY ($0.58) compared with 648 CNY ($93.25) for MACS, reducing the cost by 99%. Therefore, high-purity and high-yield DCs can be rapidly obtained through a five-step improvement in the process of BM cell extraction, induction and purification.

Prospective Study on Energy Expenditure in Patients With Severe Burns.

BACKGROUND: Nutrition therapy is recognized as one of the most significant treatment aspects for burn patients. However, data were limited regarding the actual nutrition practices in patients with severe burn injury. This study aims to explore the measured energy expenditure (MEE) changes in severe burn patients and to evaluate the precision of commonly used predictive formulas for estimating predictive energy expenditure (PEE) in burn patients. METHODS: A prospective multicenter trial was conducted in the intensive care units in the hospitals enrolling the severely burned patients. Data on MEE and PEE were collected and analyzed. RESULTS: Forty-three patients were enrolled from 3 hospitals. All the patients had severe burns. MEE was measured by metabolic cart, and the MEE on the seventh day after severe burns was as high as 65 kcal/kg, which was 267% of the basal metabolic rate. The presence of hypermetabolism was sustained throughout the 21-day afterburn and decreased gradually to 34 kcal/kg thereafter until 4 weeks after injury. Wound percentage after skin-grafting therapy, time course of burn injury, the existence of severe sepsis, and blood infection were significantly associated with higher MEE. Compared with PEE and MEE, Toronto formula could estimate patients' energy requirements with more accuracy; Curreri and Pennisi formula both significantly overestimated the patient's energy expenditure, whereas underestimation occurred with the Harris-Benedict formula. CONCLUSIONS: Severe burn patients were hypermetabolic at the early stage and sustained this status over a long time. The Toronto formula was the unbiased method to predict energy expenditure.

Machine Learning for Precision Health Economics and Outcomes Research (P-HEOR): Conceptual Review of Applications and Next Steps.

Precision health economics and outcomes research (P-HEOR) integrates economic and clinical value assessment by explicitly discovering distinct clinical and health care utilization phenotypes among patients. Through a conceptualized example, the objective of this review is to highlight the capabilities and limitations of machine learning (ML) applications to P-HEOR and to contextualize the potential opportunities and challenges for the wide adoption of ML for health economics. We outline a P-HEOR conceptual framework extending the ML methodology to comparatively assess the economic value of treatment regimens. Latest methodology developments on bias and confounding control in ML applications to precision medicine are also summarized.

Economic variations in patterns of care and outcomes of patients receiving invasive mechanical ventilation in China: a national cross-sectional survey.

BACKGROUND: Ventilation practice may be affected by economic variations, which might result in different outcomes to mechanically ventilated patients. We aimed to investigate the important effect of economic variations in patients with mechanical ventilation (MV) in China. METHODS: We carried out a national prospective multicentre cross-sectional observational study over 1 month of all patients receiving invasive MV for more than 24 hours in 20 intensive care units (ICUs), including patient characteristics, practice of MV, weaning modalities and outcomes, including probability of weaning and survival. Based on the 2012 World Bank classification of counties, patients were divided into high-income and middle-income groups according to gross domestic product per capita in their province of origin. RESULTS: Of the 483 patients enrolled, 291 (60.2%) were from high-income provinces and 192 (39.8%) were from middle-income provinces. Tidal volume, peak pressure, plateau and driving pressure were significantly lower, and the proportion of patients receiving protective ventilation (71.1% vs. 59.9%, P=0.014) was significantly higher in the high-income group than in the middle-income group. The probability of weaning within 28 days was significantly greater in the high-income group than in the middle-income group (P=0.046). Patients in the high-income group had significantly higher median numbers of ventilator-free days within 14 and 28 days than those in the middle-income group (P<0.05). Although the patients did not differ in terms of their demographics, survival within 28 days was significantly higher in the high-income group than in the middle-income group (P=0.025). Driving pressure, positive end-expiratory pressure and spontaneous breathing trial were independently associated with hospital mortality. CONCLUSIONS: Important economic differences exist in the management of MV and patient outcomes. Higher income is associated with a higher proportion of protective ventilation, lower driving pressure, shorter weaning and better survival in mechanically ventilated patients in China.

A Novel Pathological Prognostic Score (PPS) to Identify "Very High-Risk" Patients: a Multicenter Retrospective Analysis of 506 Patients with High Risk Gastrointestinal Stromal Tumor (GIST).

BACKGROUND: To determine the better risk stratification based on surgical pathology and to assess the clinical outcomes after curative resection with a new scoring system in high risk gastrointestinal stromal tumor (GIST) patients. METHODS: We retrospectively evaluated 506 high-risk GIST patients who underwent curative resection as initial treatment at four centers from 2001 to 2015. RESULTS: Multivariate analysis revealed that only Ki-67 labeling index (LI) and mitotic index were independent prognostic factors of overall survival (OS). For the two tumor-related pathological factors, Ki-67 LI > 7% and mitotic index ≥ 7/50 high power fields were allocated 1 point each. The total score was defined as the Pathological Prognostic Score (PPS). When Ki-67 LI and mitotic index were replaced by PPS, a multivariate analysis still identified PPS as an independent predictor of OS (HR 2.719; 95% CI 1.309-5.650; P = 0.007). Patients with a PPS of 0, 1, or 2 had a 5-year survival of 91.8, 79.8, and 51.0%, respectively (P = 0.001). Furthermore, an elevated PPS (PPS = 2) was associated with larger tumor size, non-stomach tumor, and open resection (all P < 0.05). CONCLUSION: The PPS independently predicted postoperative survival in high-risk GIST, and it might facilitate the selection of appropriate treatment strategy for these patients.

Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study.

BACKGROUND: Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). METHODS: LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensive-care units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. FINDINGS: Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO2) to the fractional concentration of oxygen in inspired air (FiO2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. INTERPRETATION: Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated. FUNDING: European Society of Intensive Care Medicine, St Michael's Hospital, University of Milan-Bicocca.

Assessment of patient-ventilator breath contribution during neurally adjusted ventilatory assist in patients with acute respiratory failure.

INTRODUCTION: We previously showed in animals that the ratio of inspired tidal volume (Vtinsp) to inspiratory peak electrical activity of the diaphragm (EAdipk) can be used to quantify the respective patient and ventilator breath contributions (PVBCs) during neurally adjusted ventilatory assist (NAVA). The PVBC index has not been tested clinically. METHODS: We studied 12 intubated and mechanically ventilated patients with acute respiratory failure and measured EAdipk, airway (Paw) and inspiratory esophageal pressure (Pes) and Vtinsp. We applied 11 different NAVA levels, increasing them every 3 minutes in steps of 0.3 cm H2O/µV from 0 to 3.0 cmH2O/µV. At each NAVA level, one breath was non-assisted (NAVA level 0). PVBC indices were calculated by relating Vtinsp/EAdipk of the non-assisted breath to Vtinsp/EAdipk of the assisted breath(s) using one ((N1)PVBC) or the mean value of five preceding assisted breaths ((X5)PVBC). During assisted breaths, inspiratory changes in Pes (∆Pes) and transpulmonary (ΔPtp) pressures were used to calculate the relative contribution of patient to total inspiratory lung-distending pressures (ΔPes/ΔPtp). Matching of respiratory drive indices and squaring of the PVBC was evaluated for their effect on the correlation between PVBC and ΔPes/ΔPtp. Linear regression analysis and Bland-Altman analysis were applied to compare indices. RESULTS: Using an average of five assisted breaths prior to the non-assisted breath and squaring the PVBC ((X5)PVBC(2)) improved determination coefficients (P <0.05), adjusted the regression slope and intercept between PVBC and ΔPes/ΔPtp toward identity (P <0.05) and reduced bias (P <0.05). Matching EAdipk between non-assisted and assisted breaths within the range of 0.77 to 1.30 improved the relationship between (X5)PVBC(2) and ΔPes/ΔPtp (P <0.05) and abolished the need for EAdi normalization in the PVBC calculation (R(2) = 0.96; bias = 0.16 ± 0.06; precision = 0.33 ± 0.08 (mean and 95% confidence interval)). CONCLUSIONS: This clinical study confirms previous experimental results showing that the PVBC(2) predicts the contribution of the inspiratory muscles versus that of the ventilator during NAVA, when differences in effort (EAdi) between non-assisted and assisted breaths are limited. PVBC could help to quantify and standardize the adjustment of the level of assist, and hence reduce the risks of excessive ventilatory assist in patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01663480. Registered 9 August 2012.

[Assessment of central venous-to-arterial CO(2) difference during early goal-directed therapy in patients with septic shock].

OBJECTIVE: To detect the changes of central venous-to-arterial carbon dioxide difference (P(cv-a)CO(2)) during early goal-directed therapy (EGDT) in patients with septic shock and evaluate its' value in predicting adequate resuscitation and prognosis. METHODS: From April 2009 to October 2010, 26 septic shock patients were enrolled in the study. EGDT was performed in all the patients immediately after enrollment. According to the whether they achieved early goal with in the 6 hour or not, patients were separated to EGDT achievement and un-achievement groups. At the onset and after the 6 hours EGDT, mean arterial pressure (MAP), cardiac index (CI), central venous oxygen saturation (ScvO(2)), oxygen delivery (DO(2)), oxygen consumption (VO(2)), oxygen extraction ratio (O(2) ext), lactate, P(cv-a)CO(2) were recorded. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and 28 day mortality were compared between 2 groups. RESULTS: There were no significant difference of age and sex between the 15 patients who achieved early goals and 11 patients who did not. EGDT un-achievement patients had higher APACHE II score (21 ± 5) and 28 day mortality (9/11) when compared with EGDT achievement patients (t = 2.985, χ(2) = 4.547, P < 0.05). In EGDT un-achievement group, MAP, CI, DO(2), VO(2), O(2)ext, ScvO(2), Lac, P(cv-a)CO(2) were comparable between the onset and 6 hours after EGDT. However, in EGDT achievement group, MAP ((90 ± 9) mmHg (1 mmHg = 0.133 kPa)), CI ((4.0 ± 1.8) L×min(-1)×m(-2)), DO(2) ((596 ± 274) ml×min(-1)×m(-2)), ScvO(2) (76.9% ± 4.1%) increased, and P(cv-a)CO(2) ((4.2 ± 2.7) mmHg) decreased significantly after 6 hours of EGDT (t values were -3.393, -2.985, -2.103 and -3.195 respectively, all P < 0.05). The changes of P(cv-a)CO(2) between the onset and 6 hours after EGDT, demonstrated high value for predictability of outcome, according to the area under the ROC curve (AUC) was 0.839 (P = 0.004). As a predictor for death, increasing of P(cv-a)CO(2) after 6 hours of EGDT has a sensibility of 100% and specificity of 60%. CONCLUSIONS: Increasing of P(cv-a)CO(2) after EGDT purports inadequate tissue perfusion in patients with septic shock. Changes of P(cv-a)CO(2) during EGDT demonstrated a useful tool to evaluate adequate resuscitation and prognosis.

[Assessment of stroke volume variation and intrathoracic blood volume index on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock].

OBJECTIVE: To assess the significance of stroke volume variation (SVV) and intrathoracic blood volume index (ITBI) on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock. METHODS: Hemorrhagic shock canine model was established with the modified Wiggers' method. The heart rate (HR), mean artery pressure (MAP), central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), intrathoracic blood volume index (ITBI) and stroke volume variation (SVV) were investigated by Swan-Ganz catheter or PiCCO monitor. Graded volume loading (VL) was performed. Successive responsive VLs were performed (increase in SV > 5% after VL) until continuous change in SV < 5% (unresponsive) was reached. RESULTS: Fourteen canines were studied and a total of 134 VLs were performed. In 94 VLs, an increase in SV of more than 5% was reached. In the other 40 VLs, increase in SV was less than 5%. The change of HR, MAP, ITBI, SVV in responsive were more than those of unresponsive after VL. The change of CVP, PAWP in responsive were less than those of unresponsive. Significant correlation was found between DeltaSV after VL and the baseline values of ITBI, SVV. No correlation was found between DeltaSV and HR, MAP, CVP, PAWP. Significant correlations were also found between DeltaSV and DeltaCVP, DeltaPAWP, DeltaITBI, DeltaSVV after fluid loading. No correlation was found between DeltaSV and DeltaHR, DeltaMAP. By using receiver operating characteristic analysis, the area under the curve were 0.872 for SVV and 0.689 for ITBI, more than those of HR, MAP, CVP, PAWP statistically. As SVV value of 9.5% or more will predict an increase in the SV of at least 5% in response to a VL with a sensitivity of 92.6% and a specificity of 82.5%. CONCLUSIONS: SVV and ITBI were more useful indicators than CVP and PAWP on the assessment of responsiveness to volume loading. SVV as a functional preload parameter and for on-line monitoring may help to improve the hemodynamic management.