Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Fluctuation in the Levels of Immunoglobulin M and Immunoglobulin G Antibodies for Cardiolipin and β2-Glycoprotein among Healthy Pregnant Women

Objectives: Antiphospholipid antibodies fluctuate during a healthy normal pregnancy. This study aimed to investigate the levels of both immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies for cardiolipin and β2-glycoprotein (β2GP) among healthy pregnant women. Methods:This study was conducted between May 2010 and December 2012. A total of 75 healthy Omani pregnant women with no history of autoimmune disease were investigated during their pregnancy and 90 days after delivery at the Armed Forces Hospital in Muscat, Oman. A control group of 75 healthy Omani non-pregnant women were also investigated as a comparison. Levels of IgM and IgG antibodies for both anti-cardiolipin antibodies (ACAs) and β2GP were measured using a standard enzymelinked immunosorbent assay. Results: The ACA IgM levels were significantly higher in the control group compared to the pregnant women (P <0.001). No significant differences were observed in the ACA IgM levels between the control group and the pregnant women after delivery. In contrast, ACA IgG levels were significantly higher during pregnancy and after delivery compared with those of the healthy control group (P = 0.007 and 0.002, respectively). The levels of β2GP IgG were significantly higher during pregnancy than after delivery and in the control group (P = 0.001 and <0.001, respectively). Conclusion: In this study, ACA IgG levels increased during healthy pregnancies and after normal deliveries whereas β2GP IgG levels increased transiently during the pregnancies. Both phenomena were found to be significantly associated with a transient decline in the levels of IgM specific for these antigens. Therefore, the levels of these antibodies may be regulated during a healthy pregnancy

A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression.

AIM:The lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68+ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68+ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression. METHODS:CD80, CD86 and PD-L1 expression by CD68+ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry. RESULTS:The count of CD68+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68+CD80+ cells and CD68+PD-L1+ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68+CD80+ cells was higher than that of CD68+CD86+ and CD68+PD-L1+ cells. In addition, the frequencies of CD68+CD80+ and CD68+CD86+ cells were higher in the lobular areas than the portal areas. CONCLUSIONS:Our results show that CD68+ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection

Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection.

The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers.Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas.Chronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade.The upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis

HBV infection is associated with elevated CD68⁺CD86⁺ cell count and percentage in the lobular areas of the liver.

<p>Biopsies from control and HBV-infected individuals were stained with mouse anti-human CD68 and rabbit anti-human CD86 Abs. CD68⁺CD86⁺ cell count in (<b>A</b>) the lobular area and (<b>B</b>) the total (lobular and portal) areas of the liver of control and HBV-infected individuals. CD68⁺CD86⁺ cell percentage in (<b>C</b>) the lobular areas and (<b>D</b>) the total (lobular and portal) areas of the liver of control and HBV-infected individuals. * <i>P</i> value<0.05. ** <i>P</i> value<0.01.</p

CD80 expression correlation with the fibrosis score and inflammation grade in HBV-infected liver.

<p>Biopsies from HBV-infected individuals were stained with mouse anti-human CD68 and rabbit anti-human CD80 Abs. Masson Trichrome stained slides were used to assess the fibrosis score and inflammation grade by Metavir scoring system. <b>A.</b> CD68⁺CD80⁺ cell count in the portal and the fibrosis score. <b>B.</b> The percentage of CD68⁺CD80⁺ cells in lobular areas and the lobular inflammation. * <i>P</i> value<0.05. ** <i>P</i> value<0.01.</p

Counts of CD68⁺ cells, CD68⁺CD80⁺ cells, CD68⁺CD86⁺ cells and CD68⁺PD-L1⁺ cells.

<p>The average count ± S.D. for each areas of the liver is represented as indicated. The <i>p</i> value indicates the significance of differences between HBV-infected and control groups.</p

HCV infection is associated with elevated CD68⁺PD-L1⁺ cell frequency in the liver.

<p>Biopsies from HCV-infected and control individuals were stained with mouse anti-human CD68 and rabbit anti-human PD-L1 Abs. <b>A.</b> CD68⁺PD-L1⁺ cell count in the total (lobular and portal) areas of the liver of HCV-infected and control individuals. CD68⁺PD-L1⁺ cell percentage in (<b>B</b>) the lobular areas and (<b>C</b>) the total (lobular and portal) areas of the liver of control and HCV-infected individuals. * <i>P</i> value<0.05. ** <i>P</i> value<0.01.</p

HCV infection is associated with higher CD68⁺CD80⁺ cell frequency than that of CD68⁺CD86⁺ and CD68⁺PD-L1⁺ cells in the lobular areas of the liver.

<p>Biopsies from HCV-infected individuals were stained with mouse anti-human CD68 and rabbit anti-human CD80, CD86 or PD-L1 Abs. The count of CD68⁺CD80⁺, CD68⁺CD86⁺ and CD68⁺PD-L1⁺ cells in the lobular (<b>A</b>) and the total (lobular and portal; <b>B</b>) areas are shown. The percentage of CD68⁺CD80⁺, CD68⁺CD86⁺ and CD68⁺PD-L1⁺ cell percentage in (<b>C</b>) the lobular and (<b>D</b>) the total (lobular and portal) areas are shown.</p

HCV infection is associated with higher CD68⁺CD80⁺ and CD68⁺CD86⁺ cell frequency in the lobular areas when compared to the portal areas of the liver.

<p>Biopsies from HCV-infected and control individuals were stained as described in the methods. (<b>A</b>) CD68⁺CD80⁺, (<b>B</b>) CD68⁺CD86⁺ and (<b>C</b>) CD68⁺PD-L1⁺ cell count in the lobular and portal areas of the liver of control individuals. (<b>D</b>) CD68⁺CD80⁺, (<b>E</b>) CD68⁺CD86⁺ and (<b>F</b>) CD68⁺PD-L1⁺ cell count and (<b>G</b>) CD68⁺CD80⁺ and (<b>H</b>) CD68⁺CD86⁺ cell percentage in the lobular and portal areas of the liver of HCV-infected patients.</p