Nebojša Prijović - Academia.edu (original) (raw)
Papers by Nebojša Prijović
Vaccines, Apr 28, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
BMC Women's Health, Nov 18, 2022
Background: Cervical cancer is often associated with malignant ureteral obstruction and consequen... more Background: Cervical cancer is often associated with malignant ureteral obstruction and consequent hydronephrosis. Hydronephrosis caused in this way can be resolved by placing ureteral stents or performing a percutaneous nephrostomy. Complications that may occur during the retrograde ureteral stent placement are usually mild, but serious complications such as stent migration into the cardiovascular system are also possible. Here we present an unusual case where a ureteral stent entered the abdominal aorta during the cystoscopic ureteral stenting, which was resolved by a cystoscopic stent removal kept in check by endovascular catheters. Case presentations: The 48-year-old female patient was treated in the regional secondary healthcare facility due to bilateral hydronephrosis caused by cervical cancer. The patient had bilateral percutaneous nephrostomies and ureteral stents. Due to the calcification of the left ureteral stent, an urethrorenoscopy with lithotripsy of the calculus in the left ureter was performed in the regional secondary healthcare facility, and the ureteral stent was cystoscopically replaced. The control radiography of the urinary tract showed a misplacement of the left ureteral stent, and a computed tomography showed that the stent was located in the abdominal aorta. The patient was referred to the University Clinical Center of Serbia, where a ureteral stent was cystoscopically removed from the abdominal aorta under the control of endovascular catheters. The patient was in good general condition at all times, with no signs of bleeding, and she was discharged from the hospital on the fourth postoperative day. Conclusions: The migration of a ureteral stent into the abdominal aorta and the cardiovascular system in general is a rare type of ureteral stenting complication whose treatment requires a multidisciplinary approach. In order to prevent such complications, it is necessary to strictly adhere to the indications for the ureteral stent placement in the case of malignant ureteral obstruction. Also, this procedure should be performed according to the current guidelines and controlled by an X-ray or ultrasound.
Current Oncology
Considering the divergent biological behaviors of certain histological subtypes of urothelial car... more Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The numb...
British Journal of Surgery
Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The a... more Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains...
Vaccines
At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro... more At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients’ attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients’ sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. ...
Current Oncology
In recent years, the focus of numerous studies has been the predictive value of inflammatory and ... more In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed stati...
American Journal of Obstetrics and Gynecology
Anaesthesia, 2021
SummaryPeri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this stu... more SummaryPeri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS‐CoV‐2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre‐operative SARS‐CoV‐2 infection were compared with those without previous SARS‐CoV‐2 infection. The primary outcome measure was 30‐day postoperative mortality. Logistic regression models were used to calculate adjusted 30‐day mortality rates stratified by time from diagnosis of SARS‐CoV‐2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre‐operative SARS‐CoV‐2 diagnosis. Adjusted 30‐day mortality in patients without SARS‐CoV‐2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre‐operative SARS‐CoV‐2 diagnosis, mortality was increased in patients having surgery wi...
British Journal of Surgery, 2021
Background This study aimed to determine the impact of pulmonary complications on death after sur... more Background This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. Results This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery be...
Anaesthesia, 2021
SummarySARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critica... more SummarySARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri‐operative or prior SARS‐CoV‐2 were at further increased risk of venous thromboembolism. We conducted a planned sub‐study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS‐CoV‐2 diagnosis was defined as peri‐operative (7 days before to 30 days after surgery); recent (1–6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre‐operative anti‐coagulation for baseline comorbidities was no...
British Journal of Surgery, 2020
BMC Women's Health
Background Cervical cancer is often associated with malignant ureteral obstruction and consequent... more Background Cervical cancer is often associated with malignant ureteral obstruction and consequent hydronephrosis. Hydronephrosis caused in this way can be resolved by placing ureteral stents or performing a percutaneous nephrostomy. Complications that may occur during the retrograde ureteral stent placement are usually mild, but serious complications such as stent migration into the cardiovascular system are also possible. Here we present an unusual case where a ureteral stent entered the abdominal aorta during the cystoscopic ureteral stenting, which was resolved by a cystoscopic stent removal kept in check by endovascular catheters. Case presentations The 48-year-old female patient was treated in the regional secondary healthcare facility due to bilateral hydronephrosis caused by cervical cancer. The patient had bilateral percutaneous nephrostomies and ureteral stents. Due to the calcification of the left ureteral stent, an urethrorenoscopy with lithotripsy of the calculus in the ...
The Lancet
Background The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as ind... more Background The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. Methods First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. Findings In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45•6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84•5 (95% CI 84•1-84•9), which varied between HIC (88•5 [89•0-88•0]), MIC (81•8 [82•5-81•1]), and LIC (66•8 [64•9-68•7]) settings. In the third phase, 1217 (74•6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51•4%) were from HIC, 538 (44•2%) from MIC, and 54 (4•4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3•6% (95% CI 3•0-4•1; p<0•0001) increase in SVR. This was consistent in HIC (4•8% [4•1-5•5]; p<0•0001), MIC (2•8 [2•0-3•7]; p<0•0001), and LIC (3•8 [1•3-6•7%]; p<0•0001) settings. Interpretation The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs.
Pancreatology, 2016
Introduction: HGF/c-MET pathway is an hypoxia-inducible pathway involved in tumor-stroma interact... more Introduction: HGF/c-MET pathway is an hypoxia-inducible pathway involved in tumor-stroma interactions and invasion in pancreatic ductal adenocarcinoma (PDAC). c-MET inhibitors are under clinical development. Aims: We aimed to (i) assess the prognostic value of c-MET overexpression in PDAC and its underlying mechanisms, (ii) characterize the transcriptomic profile of c-MET-high tumors, (iii) study the effects of c-MET inhibitors in 4 characterized PDAC cell lines. Patients & methods: 131 consecutive patients with resected PDAC were retrospectively selected. c-MET expression, hypoxia (CAIX/HIF-1a), and microvascular density were assessed by immunochemistry. MET gene copy number was assessed by FISH and copy number variation assay. c-MET signaling pathway activation was assessed by Western blot (pMET/pAKT/pERK1-2/pSTAT3). Transcriptomic profiles of c-MET-high/ low tumors were obtained and confirmed in 2 independent published datasets. Four c-MET inhibitors (tepotinib/cabozantinib/foretinib/crizotinib) were tested in 6 PDAC cell lines that were characterized for c-MET expression and signaling (HGF dependence and downstream pathway activation). Results: High c-MET expression was independently associated with shorter DFS and OS. There was no correlation between hypoxia-related markers and c-MET expression. No MET amplification was detected. c-MET-high tumors displayed higher levels of p-MET and p-ERK1/2. Transcriptome analyses revealed that c-MET-high tumors were enriched for the poor prognosis "basal-like" and "activated stroma" signatures defined by Moffit et al. High c-MET expression was also associated with signatures related to matrix remodeling (TGFb signaling/axonal guidance), epithelial-to-mesenchymal transition (Wnt/SHH/Notch/migration), and increased proliferation (KRAS addiction/PI3K pathway activation). Crizotinib displayed the highest antiproliferative effects on cell lines. Conclusion: c-MET defines a poor prognosis subgroup of PDAC and may represent a new treatment target.
Vaccines, Apr 28, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
BMC Women's Health, Nov 18, 2022
Background: Cervical cancer is often associated with malignant ureteral obstruction and consequen... more Background: Cervical cancer is often associated with malignant ureteral obstruction and consequent hydronephrosis. Hydronephrosis caused in this way can be resolved by placing ureteral stents or performing a percutaneous nephrostomy. Complications that may occur during the retrograde ureteral stent placement are usually mild, but serious complications such as stent migration into the cardiovascular system are also possible. Here we present an unusual case where a ureteral stent entered the abdominal aorta during the cystoscopic ureteral stenting, which was resolved by a cystoscopic stent removal kept in check by endovascular catheters. Case presentations: The 48-year-old female patient was treated in the regional secondary healthcare facility due to bilateral hydronephrosis caused by cervical cancer. The patient had bilateral percutaneous nephrostomies and ureteral stents. Due to the calcification of the left ureteral stent, an urethrorenoscopy with lithotripsy of the calculus in the left ureter was performed in the regional secondary healthcare facility, and the ureteral stent was cystoscopically replaced. The control radiography of the urinary tract showed a misplacement of the left ureteral stent, and a computed tomography showed that the stent was located in the abdominal aorta. The patient was referred to the University Clinical Center of Serbia, where a ureteral stent was cystoscopically removed from the abdominal aorta under the control of endovascular catheters. The patient was in good general condition at all times, with no signs of bleeding, and she was discharged from the hospital on the fourth postoperative day. Conclusions: The migration of a ureteral stent into the abdominal aorta and the cardiovascular system in general is a rare type of ureteral stenting complication whose treatment requires a multidisciplinary approach. In order to prevent such complications, it is necessary to strictly adhere to the indications for the ureteral stent placement in the case of malignant ureteral obstruction. Also, this procedure should be performed according to the current guidelines and controlled by an X-ray or ultrasound.
Current Oncology
Considering the divergent biological behaviors of certain histological subtypes of urothelial car... more Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The numb...
British Journal of Surgery
Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The a... more Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains...
Vaccines
At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro... more At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients’ attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients’ sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. ...
Current Oncology
In recent years, the focus of numerous studies has been the predictive value of inflammatory and ... more In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed stati...
American Journal of Obstetrics and Gynecology
Anaesthesia, 2021
SummaryPeri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this stu... more SummaryPeri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS‐CoV‐2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre‐operative SARS‐CoV‐2 infection were compared with those without previous SARS‐CoV‐2 infection. The primary outcome measure was 30‐day postoperative mortality. Logistic regression models were used to calculate adjusted 30‐day mortality rates stratified by time from diagnosis of SARS‐CoV‐2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre‐operative SARS‐CoV‐2 diagnosis. Adjusted 30‐day mortality in patients without SARS‐CoV‐2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre‐operative SARS‐CoV‐2 diagnosis, mortality was increased in patients having surgery wi...
British Journal of Surgery, 2021
Background This study aimed to determine the impact of pulmonary complications on death after sur... more Background This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. Results This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery be...
Anaesthesia, 2021
SummarySARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critica... more SummarySARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri‐operative or prior SARS‐CoV‐2 were at further increased risk of venous thromboembolism. We conducted a planned sub‐study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS‐CoV‐2 diagnosis was defined as peri‐operative (7 days before to 30 days after surgery); recent (1–6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre‐operative anti‐coagulation for baseline comorbidities was no...
British Journal of Surgery, 2020
BMC Women's Health
Background Cervical cancer is often associated with malignant ureteral obstruction and consequent... more Background Cervical cancer is often associated with malignant ureteral obstruction and consequent hydronephrosis. Hydronephrosis caused in this way can be resolved by placing ureteral stents or performing a percutaneous nephrostomy. Complications that may occur during the retrograde ureteral stent placement are usually mild, but serious complications such as stent migration into the cardiovascular system are also possible. Here we present an unusual case where a ureteral stent entered the abdominal aorta during the cystoscopic ureteral stenting, which was resolved by a cystoscopic stent removal kept in check by endovascular catheters. Case presentations The 48-year-old female patient was treated in the regional secondary healthcare facility due to bilateral hydronephrosis caused by cervical cancer. The patient had bilateral percutaneous nephrostomies and ureteral stents. Due to the calcification of the left ureteral stent, an urethrorenoscopy with lithotripsy of the calculus in the ...
The Lancet
Background The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as ind... more Background The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. Methods First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. Findings In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45•6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84•5 (95% CI 84•1-84•9), which varied between HIC (88•5 [89•0-88•0]), MIC (81•8 [82•5-81•1]), and LIC (66•8 [64•9-68•7]) settings. In the third phase, 1217 (74•6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51•4%) were from HIC, 538 (44•2%) from MIC, and 54 (4•4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3•6% (95% CI 3•0-4•1; p<0•0001) increase in SVR. This was consistent in HIC (4•8% [4•1-5•5]; p<0•0001), MIC (2•8 [2•0-3•7]; p<0•0001), and LIC (3•8 [1•3-6•7%]; p<0•0001) settings. Interpretation The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs.
Pancreatology, 2016
Introduction: HGF/c-MET pathway is an hypoxia-inducible pathway involved in tumor-stroma interact... more Introduction: HGF/c-MET pathway is an hypoxia-inducible pathway involved in tumor-stroma interactions and invasion in pancreatic ductal adenocarcinoma (PDAC). c-MET inhibitors are under clinical development. Aims: We aimed to (i) assess the prognostic value of c-MET overexpression in PDAC and its underlying mechanisms, (ii) characterize the transcriptomic profile of c-MET-high tumors, (iii) study the effects of c-MET inhibitors in 4 characterized PDAC cell lines. Patients & methods: 131 consecutive patients with resected PDAC were retrospectively selected. c-MET expression, hypoxia (CAIX/HIF-1a), and microvascular density were assessed by immunochemistry. MET gene copy number was assessed by FISH and copy number variation assay. c-MET signaling pathway activation was assessed by Western blot (pMET/pAKT/pERK1-2/pSTAT3). Transcriptomic profiles of c-MET-high/ low tumors were obtained and confirmed in 2 independent published datasets. Four c-MET inhibitors (tepotinib/cabozantinib/foretinib/crizotinib) were tested in 6 PDAC cell lines that were characterized for c-MET expression and signaling (HGF dependence and downstream pathway activation). Results: High c-MET expression was independently associated with shorter DFS and OS. There was no correlation between hypoxia-related markers and c-MET expression. No MET amplification was detected. c-MET-high tumors displayed higher levels of p-MET and p-ERK1/2. Transcriptome analyses revealed that c-MET-high tumors were enriched for the poor prognosis "basal-like" and "activated stroma" signatures defined by Moffit et al. High c-MET expression was also associated with signatures related to matrix remodeling (TGFb signaling/axonal guidance), epithelial-to-mesenchymal transition (Wnt/SHH/Notch/migration), and increased proliferation (KRAS addiction/PI3K pathway activation). Crizotinib displayed the highest antiproliferative effects on cell lines. Conclusion: c-MET defines a poor prognosis subgroup of PDAC and may represent a new treatment target.