Pancreatic ductal adenocarcinoma (PDAC) is a high fatality cancer with one of the worst prognoses in solid tumors. Most patients present with late stage, metastatic disease and are not eligible for ...potentially curative surgery. Despite complete resection, the majority of surgical patients will recur within the first two years following surgery. Postoperative immunosuppression has been described in different digestive cancers. While the underlying mechanism is not fully understood, there is compelling evidence to link surgery with disease progression and cancer metastasis in the postoperative period. However, the idea of surgery-induced immunosuppression as a facilitator of recurrence and metastatic spread has not been explored in the context of pancreatic cancer. By surveying the existing literature on surgical stress in mostly digestive cancers, we propose a novel practice-changing paradigm: alleviate surgery-induced immunosuppression and improve oncological outcome in PDAC surgical patients by administering oncolytic virotherapy in the perioperative period.
Background: Fecal incontinence (FI) is a frequent medical condition, although mostly underreported. It impedes on the quality of life of the patients suffering from this debilitating condition. This ...patient population represents a heterogeneous group, and their medical journey and long-term outcomes are not well described in the Canadian context. The purpose of our study was to describe the characteristics of patients with FI referred at our institution and to report their medical evolution over a long follow-up period of 17 years. Methods: Two Canadian university-affiliated centres were included. This study included all adult patients referred to our institutions with a diagnosis of FI between 2002 and 2019. Patient demographic characteristics, treatment modalities and serial Wexner incontinence scores and quality-of-life measurements were recorded prospectively. Favourable outcome was defined as an improvement in the Wexner score in time. Results: A total of 226 patients were included in this study. Mean follow-up was 41.68 ± 42.00 months. Mean Wexner score on initial evaluation was 14.24 ± 4.42. On initial evaluation, 94.7% of patients chose to have a treatment. The most common first-line treatment was nonsurgical, noninvasive treatments (58.6%), including modification of dietary habits, antidiarrheic agents, bulking agents, biofeedback, and physical therapy. More invasive strategies, like surgery and sacral nerve modulation, as first line therapy were used in 21% and 14.5% of patients, respectively. Following first treatment, mean Wexner score was 6.39. A second treatment was required in 64% of patients. The most common second-line modality was sacral nerve modulation (27.3%). Mean Wexner score following second treatment was 7.24. A third treatment was required in 45% of patients. The most used third therapeutic modality was sacral nerve modulation. Mean Wexner score following third treatment was 6.62. At the end of the study, mean Wexner score at last follow-up was 5.40, which was both clinically and statistically significant. Conclusion: These findings suggest that patients with FI can be managed effectively with nonsurgical, noninvasive treatments and/or sacral nerve modulation but necessitate a multimodal approach. These modalities do improve symptoms significantly. More importantly, this favourable evolution seems to be sustained over the long follow-up period of 17 years in this study.
Background: The aim of this study was to quantify trainees' operative volume and assess the effect of the first wave of COVID-19 on general surgery residents' training at a Canadian academic centre. ...An observational study was performed, focusing on objective operative volumes, hands-on experience, and subjective perceived impact of the pandemic by trainees. Methods: All residents enrolled in our program were included. Quantitative data were collected from anonymized residents' case logs and annual departmental statistics. Qualitative data on residents' perception of the impact of the pandemic was provided by a resident-led focus group. The period of interest, the first wave of the COVID-19 pandemic (January-June 2020), was compared with a reference period (January-June 2019). Case logs of all 21 residents were reviewed. Results: During the first wave of the COVID-19 pandemic, residents logged a total of 475 cases, compared with 914 cases before the pandemic. This represents a decrease of 48% in operative volume; junior residents saw a decrease of 50% and senior residents saw a decrease of 46%. Postgraduate year (PGY)-1 residents were most affected, with a reduction of 58% in operative volume. PGY-4 was the group least affected with a reduction of 37%. When looking at key procedures, junior residents performed 71% fewer laparoscopic appendectomies and 49% fewer laparoscopic cholecystectomies during the pandemic. Senior residents saw a reduction of 55% in lower anterior resections and a reduction of 58% in right hemicolectomies compared with reference period. The resident focus group discussion revealed that 92% of residents think the pandemic had significant drawbacks on their surgical skills and they unanimously reported an overall negative perceived effect on their training. Conclusion: The data provided by this study demonstrate how much the pandemic compromised hands-on exposure of all residents. The reduction in operative volume affected all years of training, especially junior years. This raises concern about the short- and long-term effects on trainees' technical skills. The insights brought by this study will help create personalized mitigating measures and guide future curricula to be more resilient in the face of a next sanitary crisis.
Objective
To examine the growth and evolution of the home health agency (HHA) market and to compare quality performance across HHA ownership categories.
Data Source
Agency characteristics were ...extracted from Medicare cost reports and Provider of Services file. Quality of care and patient characteristics were extracted from Quality of Patient Care Star Ratings and HHA Public Use File.
Study Design
Agency‐ and state‐level analyses were conducted to describe HHA market trends. Patient characteristics and quality measures were compared across ownership categories of interest.
Data Collection/Extraction Methods
All Medicare‐certified HHAs in operation, 2005‐2018.
Principal Findings
Over the study period, the HHA sector grew substantially, increasing from 7899 to 10 818 agencies, and chain‐owned HHAs doubled in number from 903 (11.4% of all agencies) to 1841 (17.0%). In 2018, across agency types, for‐profit nonchain agencies were the largest category both in the number of agencies (67.8%) and the number of Medicare enrollees served (40.7%). Additionally, for‐profit nonchain agencies grew most in total number, from 4293 (54.3%) to 7337 (67.8%), while for‐profit chain agencies grew most in the number of Medicare enrollees served, from 439 998 (12.9%) to 1 082 385 (28.3%). Regarding patient composition, for‐profit nonchain agencies served the highest proportion of dual eligible beneficiaries (42.2%) and African‐Americans (27.9%) among all agency types. Regarding quality performance, a higher star rating is significantly (P < .01) associated with chain agency status. Moreover, chain HHAs performed better on self‐reported process measures, and risk‐adjusted self‐reported outcome measures; however, they performed worse on risk‐adjusted claims‐based outcome measures. These results were similar across for‐profit and nonprofit chain agencies.
Conclusion
Chains play a growing role in the home health sector. Substantial differences in geographic distribution, patient composition, and quality performance were observed between chain‐ and nonchain HHAs. Examining the growth and performance of multi‐agency chains can help inform quality reporting and monitoring, assess payment adequacy, and facilitate greater transparency and accountability within the HHA marketplace.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Oncolytic virotherapy is a promising treatment option for immunologically cold tumours, such as pancreatic ductal adenocarcinoma (PDAC). Immunologically cold tumours are tumours with low ...rates of tumour infiltrating lymphocytes, allowing them to evade the immune system. Immune checkpoint inhibitors have failed to show clinical efficacy in this disease owing to the relative absence of immune cells in the PDAC tumour microenvironment. Vesicular stomatitis virus (VSV), an oncolytic virus with a long-established safety profile, specifically infects, replicates and lyses cancer cells, without harming healthy cells. Furthermore, infection with VSV stimulates the innate and adaptive immune system to mount a strong anti-tumour immune response toward cancer cells. This host anti-tumour immunity is aimed at both local and distant disease and is mediated by immune-activating proteins released upon immunogenic cell death (ICD) of the cancer cells induced by viral infection. We hypothesized that arming oncolytic VSV with an immune-stimulating transgene (TNFSF14, otherwise known as LIGHT) will generate a significant antitumour immune response in PDAC, leading to durable tumour regression. The first objective of this study was to characterize the fitness of the newly engineered VSV-LIGHT, including its capacity to infect, replicate, induce cell death and produce bioactive LIGHT in PDAC cell lines. The second objective was to assess the ability of VSV-LIGHT to induce immunogenic cell death following lysis of pancreatic cancer cell lines. The third objective will be to test the tumour targeting ability of VSV-LIGHT in vivo. Methods: The oncolytic virus VSV-LIGHT, engineered in our laboratory, was used in this study, and compared with its parental VSV strain. The murine PDAC cell lines Panc02 and MiaPaca1 were used for in vitro experiments. Multiple assays were performed to investigate the research hypothesis, including cytotoxicity, viral replication, and protein production (Western blot, flow cytometry). Results: Our results demonstrated that VSV-LIGHT retains its abilities to infect, replicate and lyse PDAC cell lines despite the insertion of the LIGHT transgene. In addition, we measured bioactive LIGHT following infection. Furthermore, we detected biomarkers of ICD including ATP and HMGB1 following infection with VSV-LIGHT. Conclusion: These results suggest that VSV-LIGHT is a functional virotherapeutic and possesses an immune activating capacity. Taken together, our findings suggest that VSV-LIGHT has translational potential as a viroimmunotherapy for PDAC. The next step is to test our oncolytic virus in the immune competent C57Bl/6-Panc02 mouse model already established in our laboratory.
Gastrosplenic fistula is a rare and potentially fatal clinical entity unknown to most healthcare providers. Its diagnosis and management are challenging; and addressing it too late can have ...devastating consequences for patients. To increase awareness about this pathology, we hereby present a case of asymptomatic gastrosplenic fistula arising from a diffuse large B cell lymphoma in a 60-year-old Caucasian man with no significant medical history. The patient was successfully treated with open
splenectomy and partial gastrectomy. The patient was discharged from the hospital 3 days after the surgery. At 1-month postoperatively, the patient was asymptomatic and presented no complication of the surgery. He went on to finish six cycles of chemotherapy (R-EPOCH, rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) and achieved complete metabolic response. At 2 years after the surgery, the patient remains asymptomatic and presents no sign of disease recurrence.
Owing to improvements in image recognition via deep learning, machine-learning algorithms could eventually be applied to automated medical diagnoses that can guide clinical decision-making. However, ...these algorithms remain a 'black box' in terms of how they generate the predictions from the input data. Also, high-performance deep learning requires large, high-quality training datasets. Here, we report the development of an understandable deep-learning system that detects acute intracranial haemorrhage (ICH) and classifies five ICH subtypes from unenhanced head computed-tomography scans. By using a dataset of only 904 cases for algorithm training, the system achieved a performance similar to that of expert radiologists in two independent test datasets containing 200 cases (sensitivity of 98% and specificity of 95%) and 196 cases (sensitivity of 92% and specificity of 95%). The system includes an attention map and a prediction basis retrieved from training data to enhance explainability, and an iterative process that mimics the workflow of radiologists. Our approach to algorithm development can facilitate the development of deep-learning systems for a variety of clinical applications and accelerate their adoption into clinical practice.
In the context of scarce primary resources and rising energy prices, the scientific community is becoming all the more engrossed in finding innovative solutions liable to increase energy efficiency. ...The industrial sector, and in particular the manufacturing industry, have a significant share of global energy consumption and greenhouse gas emissions. Therefore, energy efficiency has come to acquire a prominent position in the research literature related to managerial decision making in the manufacturer sector. This is evident in the constant progress in lines of research of primary (original articles) and secondary (review articles) grade on the topic. Taking into consideration this rich body of literature, the objective of this study consists in surveying the recent systematic literature reviews published on energy efficiency in the manufacturing industry between 2016 and 2022. Following descriptive and content analysis, the present study generates and schematizes six categories that represent the current status of research in the area: Energy Diagnostic, Energy Metering, Energy Optimization, Energy and Technology, Energy Efficiency Strategic paradigms, and Energy Efficiency Drivers and barriers. Subsequently, we elaborate an integrative conceptual framework of energy efficiency that illustrates the classification of the six identified categories in terms of three overarching forms of knowledge (Process, Technical, and Leadership Knowledge). This tertiary review offers, thus, a comprehensive overview of the studied field for academia, industry, and policymakers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autophagy is a catabolic process for degradation of intracellular components. Damaged proteins and organelles are engulfed in double-membrane vesicles ultimately fused with lysosomes. These vesicles, ...known as phagophores, develop to form autophagosomes. Encapsulated components are degraded after autophagosomes and lysosomes are fused. Autophagy clears denatured proteins and damaged organelles to produce macromolecules further reused by cells. This process is vital to cell homeostasis under both physiologic and pathologic conditions.
While the role of autophagy in cancer is quite controversial, the majority of studies introduce it as an anti-tumorigenesis mechanism. There are evidences confirming this role of autophagy in cancer. Mutations and monoallelic deletions have been demonstrated in autophagy-related genes correlating with cancer promotion. Another pathway through which autophagy suppresses tumorigenesis is cell cycle. On the other hand, under hypoxia and starvation condition, tumors use angiogenesis to provide nutrients. Also, autophagy flux is highlighted in vessel cell biology and vasoactive substances secretion from endothelial cells. The matrix proteoglycans such as Decorin and Perlecan could also interfere with angiogenesis and autophagy signaling pathway in endothelial cells (ECs). It seems that the connection between autophagy and angiogenesis in the tumor microenvironment is very important in determining the fate of cancer cells.
Matrix glycoproteins can regulate autophagy and angiogenesis linkage in tumor microenvironment. Also, finding details of how autophagy and angiogenesis correlate in cancer will help adopt more effective therapeutic approaches.
Metabolic reprogramming is a potential hallmark of tumor cells to support continuous proliferation. Metabolic heterogeneity in breast cancer patients has been highlighted as the driving cause of ...tumor progression and resistance to anticancer drugs. Studying and identifying distinct metabolic alterations in breast cancer subtypes could offer new perspectives for faster diagnosis and treatment. Given cancer cell dependency on glycolysis, the primary energy source, this enzymatic pathway will play a critical role in targeting therapies. Knowledge about the specific metabolic dependencies of tumors for growth and proliferation can be promising for novel targeted and cell-based therapies. Here, the metabolic status with emphasis on glycolysis of breast cancer cell lines according to their classification was reviewed.
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•Metabolic reprogramming is a potential hallmark of cancer cells to guarantees proliferation.•Metabolic heterogeneity in breast cancer is involved in tumor progression and drug resistance.•Breast cancer cell lines can reflect metabolic heterogeneity.•Cancer cell dependency on glycolysis play a critical role in targeting therapies.•Given to metabolic flexibility, “free size” viewpoint in therapeutic approach is not efficient.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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