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Modern series report a prevalence of pancreatic cysts in the general population of up to 50% in prospective studies. Of these, about half will be pancreatic cystic neoplasms (PCNs) that have varying degrees of malignant potential. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are the most common PCNs and are known predecessors of pancreatic adenocarcinoma. Critically, they are one of the only radiographically identifiable precursors of pancreatic cancer and thus provide an opportunity for early cancer detection and surgical resection with curative intent. The combination of high prevalence and potential for malignant degeneration underscore the relevance of discussing the best management of IPMNs and improving the existing standard of care. Landmark data on IPMN prevalence, guidelines, surveillance, biomarkers, and immune landscape are highlighted.

The need for gender parity within academic surgery has resulted in an analysis of the trends in female authorship in the American general surgery literature.Original articles from five American surgical journals from 1997, 2007, and 2017 were reviewed. Trends in the proportion of female authors were evaluated.There was an incremental increase in female first authors over the three time periods (15% in 1997, 32.2% in 2007, and 52.7% in 2017; P 0.001). The proportion of articles by female senior authors also increased over the study periods (18.7% in 1997, 28.8% in 2007, and 52.6% in 2017; P 0.001). However, there were fewer female authors with basic science research publications than males (17.4% vs. 82.6%, P 0.001).The academic productivity of female surgeons have increased over time likely due to an increase in the number of female academic surgeons in recent years. These findings are encouraging and demonstrate progress in female representation in surgery.

Soper’s pain-brain theory, based on evolutionary biology, represents a provocative breakthrough for both suicidology and positive psychology. The main thesis of the book is that the evolved way of choosing to live rather than to die in the face of unbearable suffering is to develop a zest for happiness and meaning. His new theory can be summed up by a two-by-two matrix of “pain-type” versus “brain-type” of reducing pain, and the “keeper” versus “fender” levels of protecting us from suicide. My main critique is that the brain versus pain distinction is confusing because the brain is the center for all the functions needed for to reduce pain and keep us alive. Similarly, his football metaphor of two levels of defense(“keeper” and “fender”) is incomplete because the best defense is offence, when a good last line of defense can be quickly turned into offence. Therefore, a more fluid way of conceptualizing this distinction may be the dialectically interactive dual systems of life protection (Yin) and life expansion strategies (Yang) (Wong, 2012). Soper’s pain-brain theory is similar to Wong’s general existential positive psychology theory of flourishing through suffering (Wong, 2020a, 2021a). Both approaches emphasize the centrality of suffering and posit that whether suffering results in mental illness and suicide or mental health and flourishing depends on whether we have the wisdom of the soul and the necessary social support.

Regional anesthesia is increasingly used in total joint arthroplasty (TJA). It has shown efficiency benefits as it allows parallel processing of patients in a dedicated block room (BR). However, granular quantification of these benefits to hospital operations is lacking. The goal of this study was to determine the financial effect of establishing a BR using comprehensive operational modeling.A discrete-event simulation model of daily operating room (OR) patient flow for TJA procedures at a mid-sized hospital was developed. Two scenarios were tested: (1) without and (2) with a BR. Scenarios were compared according to staffing requirements, hours/day, and labor costs. The number of ORs and cases varied from 2 to 6 ORs performing 3 to 5 cases. These results were used as the inputs of a discounted cash flow (CF) model. Discounted CF model outputs were CF, net present value, internal rate of return, and return on investment.Mean time savings of incorporating a BR were 68 min/d (range: 30 to 80 min/d), reducing the OR closing time by 1 hour. Incremental labor costs/day from nurse overtime pay ranged from $2,025 to $10,125 with no BR and $1,595 to $9,045 with a BR, which resulted in an increase in profit/day from $360 to $1,605. The CF/annum was $54,363, the net present value was $213,082, the internal rate of return was 12%, and the return on investment was 43.61%.This study demonstrates that under all scenarios, a BR is more profitable than no BR to a hospital performing TJA via a bundled care or private payer remuneration model. A BR was shown to be financially net positive even when considering the necessary financial investment to establish it. In addition, this study demonstrates the potential of combining discrete-event simulation with financial analyses to assess various operational models of care to improve hospital efficiency, such as dedicated trauma rooms and swing rooms.Level III.

Leflunomide (Lef) is an agent used in autoimmune disorders that interferes with DNA synthesis. De Novo pyrimidine synthesis is a mechanism of Gemcitabine (Gem) resistance in pancreatic cancer. This study aims to assess the efficacy and changes in the tumor microenvironment of Lef monotherapy and in combination with Gem, in a syngeneic mouse model of pancreatic cancer. Methods: MTS proliferation assays were conducted to assess growth inhibition by Gem (0-20 nM), Lef (0-40 uM) and Gem+Lef in KPC (KrasLSL.G12D/+;p53R172H/+; PdxCretg/+) cells in vitro. An in vivo heterotopic KPC model was used and cohorts were treated with: PBS (control), Gem (75 mg/kg/q3d), Lef (40 mg/kg/d), or Gem+Lef. At d28 post-treatment, tumor burden, proliferation index (Ki67), and vascularity (CD31) were measured. Changes in the frequency of peripheral and intratumoral immune cell subsets were evaluated via FACS. Liquid chromatography-mass spectrometry was used for metabolomics profiling. Results: Lef inhibits KPC cell growth and synergizes with Gem in vitro (P

To determine the impact of dedicated orthopaedic trauma room (DOTR) implementation on operating room efficiency and finances.Retrospective cost-analysis.Single midsized academic-affiliated community hospital in Toronto, Canada.All patients that underwent the most frequently performed orthopaedic trauma procedures (hip hemiarthroplasty, open reduction internal fixation of the ankle, femur, elbow and distal radius), over a 4-year period from 2016 to 2019 were included.Patient data acquired for 2 years before the implementation of a DOTR was compared with data acquired for a 2-year period after its implementation, adjusting for the number of cases performed.The primary outcome was surgical duration. The secondary outcome was financial impact, including after-hours costs incurred and opportunity cost of displaced elective surgeries.One thousand nine hundred sixty orthopaedic cases were examined pre- and post-DOTR. All procedures had reduced total operative time post-DOTR (mean improvement of 33.4%). The number of daytime operating hours increased 21%, whereas after-hours decreased by 37.8%. Overtime staffing costs were reduced by $24,976 alongside increase in opportunity costs of $22,500. This resulted in a net profit of $2476.Our results support the premise that DOTRs improve operating room efficiency and can be cost efficient. Our study also specifically addresses the hesitation regarding potential loss of profit from elective surgeries. Widespread implementation can improve patient care while still remaining financially favorable.Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

IntroductionThis protocol delineates the research design and analytical framework used to evaluate the effectiveness of the WHO-CST (CST, caregiver skills training) in Hong Kong. The WHO-CST aims to enhance the caregiver skills of parents of children with potential autism spectrum disorders (ASD) and/or developmental delays.Methods and analysisIn this study, 130 eligible caregiver–child dyads were recruited and randomly assigned to the experimental and wait-list-control groups. A randomised controlled trial design was adopted to compare the changes between the two groups regarding caregivers’ skills, knowledge and practices when interacting with their children with impairments due to ASD. Assessments were conducted before, immediately after and 1 month after the completion of the WHO-CST programme. The primary measurement tool was the joint engagement rating inventory developed by WHO experts to gauge how parents engage their children. A 10-min video recording of their dyadic interaction and behaviours in a defined play setting was used for the measurement. A set of other measurements of caregivers’ knowledge, confidence and experience of using the caregiving skills were also measured.Ethics and disseminationEthics approval was received from the Human Research Ethics Committee (EA1901033), The University of Hong Kong. The final findings of this study will be disseminated through public reports, peer-reviewed publication or at a conference launched for the WHO-CST programme.Trial registration numberChiCTR2000034585.

Background The advantages of robotic liver surgery are strongest for minor resections, where incision size drives recovery time, but cost remains a concern. We hypothesized that patients who underwent robotic minor liver resections would have superior peri-operative outcomes resulting in decreased cost. Methods We queried the medical record and cost data for patients who underwent open or robotic minor (1–2 segment) liver resection from 1/2016–8/2019. Financial data were normalized to Medicare reimbursements. Results There were 87 patients who underwent minor liver resections (robotic n = 46, open n = 41). Specimen size (173 ± 203 vs 257 ± 481 cm3), surgical duration (233 ± 87 vs 227 ± 83 min), estimated blood loss (187 ± 236 vs 194 ± 165 mL), and margin status (89% vs 93% R0) were similar for robotic and open resections respectively, yet complications (3/46, 7% vs 10/41, 24%, p = 0.02) and length of stay (2.2 ± 2.2 vs 6.2 ± 2.9, p Conclusion Patients undergoing robotic minor hepatectomy had superior peri-operative outcomes resulting in lower total cost of care when compared to open minor hepatectomy. Financial considerations should not adversely influence selection of a robotic approach for minor hepatectomy.

Improved chemotherapy response rates have lead to "disappearing" colorectal liver metastases (dCRLM). We aim to assess management patterns of dCRLM from an international body of hepatobiliary surgeons.A survey was designed, tested for item relevance, readability and content validity, and distributed to the AHPBA, IHPBA and ANZHPBA.The majority of 226 respondents were15 years from training (69%), practiced in academia (82%) and devoted50% of their practice to hepatobiliary (75%). Surgeons utilize CT(45%) or MRI(47%) for preoperative planning with a preferred imaging interval of6 weeks. Nearly all have experienced dCRLM (99%) and 63% of surgeons have waited a few months to assess for durability of response prior to definitive surgical/ablative therapy. Only 24% place fiducial markers for lesions1-cm prior to neoadjuvant chemotherapy. Intra-operatively, 97% of surgeons perform ultrasound, and 71% ablation. When a tumor has "disappeared," 49% elect for observation and 31% resect if the dCRLM is superficial. Of those electing observation, 87% believe there is effective treatment with progression on surveillance imaging.Nearly all surgeons have experienced dCRLM with half choosing observation over intervention due to the belief that these lesions may be re-addressed in the future.

Elucidating the role of probiotic bacteria in health and disease perhaps constitutes one of the most exciting and fastest growing fields in medicine as we uncover the beneficial roles of these bacteria in many disease processes including cancer. We and others have reported previously that probiotic bacteria play a significant role in the activation of many cells including the cancer fighting natural killer (NK) cells. NK cells are the key immune effectors which control tumor growth and metastasis due to their ability to mediate direct cytotoxicity and/or differentiation of cancer stem cells/undifferentiated tumors through secreted and membrane bound interferon-gamma and tumor necrosis factor-alpha. In this review, we present an overview of recent studies from our laboratory and those of the others on their beneficial effects on immune cell function in particular on NK cells. In addition, we also highlight the current understanding of the role of probiotics in enhancement of the effectiveness of cancer therapeutics. Moreover, we discuss the functional impairment of cancer patients' NK cells and the role of probiotics in reversal of such functional impairment. NK cell-based immuno-therapies in combination with well-selected strains of probiotic bacteria may probably represent one of the best adjunct therapeutic approaches to prevent and treat cancer in the future.

This study investigates how research data contributes to non-academic impacts using a secondary analysis of high-scoring impact case studies from the UK’s Research Excellence Framework (REF). A content analysis was conducted to identify patterns, linking research data and impact. The most prevalent type of research data-driven impact related to “practice” (45%), which included changing how professionals operate, changing organizational culture and improving workplace productivity or outcomes. The second most common category was “government impacts”, including reducing government service costs and enhancing government effectiveness or efficiency. Impacts from research data were developed most frequently through “improved institutional processes or methods” (40%) and developing impact via pre-analyzed or curated information in reports (32%), followed by “analytic software or methods” (26%). The analysis found that research data on their own rarely generate impacts. Instead they require analysis, curation, product development or other forms of significant intervention to leverage broader non-academic impacts.

Background Electrolyte abnormalities are commonly found after major abdominal surgery for malignancy. We hypothesized that the severity of hypophosphatemia developed in pancreatectomy patients would be associated with the incidence of complications postoperatively. Methods A retrospective analysis of an institutional database was conducted for all pancreatic resections (2009-2017). Patient charts were reviewed for demographics, clinicopathologic factors, and perioperative outcomes. Results In a cohort of 283 pancreatectomy patients, 107 (37.8%) and 134 (47.3%) developed mild (2.0-2.5 mg/dL) and moderate/severe hypophosphatemia (Conclusions Assessing the severity and timing of postpancreatectomy hypophosphatemia presents an opportunity for early detection of impending fistula-related complications.

Melanoma of unknown primary (MUP) accounts for approximately 3% of melanoma diagnoses. This study sought to evaluate treatment and outcomes for a modern MUP cohort. A retrospective review of MUP was performed at a tertiary referral cancer center. Of 815 melanoma patients, 67 (8.2%) had MUP. Men were more likely to have MUP than women (67% vs. 55%; p = 0.04). The most common sites of MUP were lymph nodes (28%), visceral solid organs (25%), brain (16%), and skin/subcutaneous tissues (10%). Of the patients who underwent tumor genomic profiling, 52% harbored pathogenic BRAF mutations. Of the 24 patients who underwent multi-gene panel testing, all had pathogenic mutations and 21 (88%) had mutations in addition to or exclusive of BRAF, including 11 patients (46%) with telomerase reverse transcriptase promoter mutations. Checkpoint inhibitors (39%) and BRAF-MEK inhibitors (7%) were the most common first-line treatments. Upfront surgical resection was used for 25% of the MUP patients, and 12 of these resections were for curative intent. During a median follow-up period of 22.1 months, the median overall survival (OS) was not met for the patients with MUP isolated to lymph nodes. At 56.8 months, 75% of these patients were alive. The median OS was 37.4 months for skin/soft tissue MUP, 33.3 months for single solid organ viscera MUP, and 29.8 months for metastatic brain MUP. Multigene panel testing identified pathogenic mutations in all tested MUP patients and frequently identified targets outside BRAF. Despite advanced stage, aggressive multimodal therapy for MUP can be associated with 5-year OS and should be pursued for appropriate candidates.

Natural killer (NK) cells are the key immune effectors with the ability to mediate selection and differentiation of a number of different cancer stem cells/undifferentiated tumors via lysis, and secreted or membrane-bound interferon (IFN)-γ and tumor necrosis factor (TNF)-α, respectively, leading to curtailment of tumor growth and metastasis. In this review, we present an overview of our recent findings on the biology and significance of NK cells in selection and differentiation of stem-like tumors using in vitro and in vivo studies conducted in humanized-BLT mice and in cancer patients. In addition, we present current advances in NK cell expansion and therapeutic delivery, and discuss the utility of allogeneic supercharged NK cells in the treatment of cancer patients. Moreover, we discuss the potential loss of NK cell numbers and function at the neoplastic and pre-neoplastic stages of tumorigenesis in induction and progression of pancreatic cancer. Therefore, because of their indispensable role in targeting cancer stem-like/undifferentiated tumors, NK cells should be placed high in the armamentarium of tumor immunotherapy. A combination of allogeneic supercharged NK cells with other immunotherapeutic strategies such as oncolytic viruses, antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies, checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, CAR NK cells, and chemotherapeutic and radiotherapeutic strategies can be used for the ultimate goal of tumor eradication. Keywords: NK cells, cancer stem cells, CSCs, differentiation, cancer immunotherapy, osteoclasts, supercharged NK cells, humanized-BLT mice, pre-neoplastic, KRAS

Background Minimally invasive surgery (MIS) is preferred for distal pancreatectomy but is not always attempted due to the risk of conversion to open. We hypothesized that the total cost for MIS converted to open procedures would be comparable to those that started open. Methods A prospectively collected institutional registry (2011-2017) was reviewed for demographic, clinical, and perioperative cost data for patients undergoing distal pancreatectomy. Results There were 80 patients who underwent distal pancreatectomy: 41 open, 39 MIS (11 laparoscopic and 28 robotic). Conversion to open occurred in 14 of 39 (36%, 3 laparoscopic and 11 robotic). Length of stay was shorter for the MIS completed (6 days; range, 3-8), and MIS converted to open (7 days; range, 4-10) groups, compared with open (10 days; range, 5-36; P = .003). Laparoscopic cases were the least expensive (P = .02). Robotic converted to open procedures had the highest operating room cost. However, the total cost for robotic converted to open cohort was similar to the open cohort due to cost savings associated with a shorter length of stay. Conclusions Despite the higher intraoperative costs of robotic surgery, there is no significant overall financial penalty for conversion to open. Financial considerations should not play a role in selecting a robotic or open approach.

We have previously demonstrated that natural killer (NK) cells are the main immune effectors that can mediate selection and differentiation of different cancer stem cells and undifferentiated tumors via lysis and secreted or membrane-bound interferon-γ and tumor necrosis factor-α, respectively. This leads to growth inhibition and tumor metastasis curtailment. In this review, we present an overview of our findings on NK cell biology and its significance in selection and differentiation of stem-like tumors using in vitro and in vivo studies conducted in nonobese diabetic/severe combined immunodeficiency (scid)/interleukin-Rγ--, humanized-bone-marrow/liver/thymus (hu-BLT) mice, and those of human cancer patients. Moreover, we present recent advances in NK cell expansion and therapeutic delivery and discuss the superiority of allogeneic supercharged NK cells over their autologous counterparts for cancer treatment. We review potential loss of NK cell numbers and function at neoplastic and preneoplastic stages of tumorigenesis as a potential mechanism for pancreatic cancer induction and progression. We believe that NK cells should be placed highly in the armamentarium of tumor immunotherapy due to their indispensable role in targeting cancer stem-like/poorly differentiated tumors and a variety of other key NK cell functions that are discussed in this report, including their role in CD8+ T-cell expansion and targeting gene knockout or dedifferentiated tumors. The combination of allogeneic supercharged NK cells and other immunotherapeutic strategies such as oncolytic viruses, antibody-dependent cellular cytotoxicity-inducing antibodies, checkpoint inhibitors, chimeric antigen receptor (CAR)-T cells and CAR-NK cells, chemotherapeutics, and radiotherapeutic strategies can be used for optimal eradication of tumors.

Although distributed ledgers frequently are viewed as a revolutionary technology that could transform many markets, the technology has not yet received wide-scale business adoption. This may be due in part to a lack of use cases for which the decentralized and distributed features of distributed ledger technology (DLT) are optimal. But payment directories (known in certain markets as registries), which facilitate the lookup of payments-related information, may be a use case that has specific challenges that take better advantage of these features than other use cases explored by businesses to date. Directories that support routing of information to support payments like aliases for peer-to-peer payments and business-to-business e-invoices may benefit from the use of DLT. DLT allows market participants to maintain and to protect localized information without the competitive, operational, and technical challenges of a centralized database.

This brief article presents a spiritually-oriented model of wellbeing: CasMac

Over the past decade, commercially available inflow tracers have been increasingly used to permanently monitor lower completions without the need for intervention. They have been designed to release selectively to oil or water, typically for clean-up verification, inflow quantification and identifying the location of water breakthrough in oil reservoirs. Naturally, there has been an industry demand and requirement to develop inflow gas tracers to monitor gas reservoirs and identifying the location of gas breakthrough in oil reservoirs. In a green field development, it is important to obtain as much measurements as possible to understand completion efficiency and guide reservoir management decisions. This paper presents the first commercial installation of inflow gas tracer technology that has been deployed in a dry gas field by HESS Malaysia in open hole stand-alone screen completions. It discusses the original monitoring objectives of this application in a full field development and how they evolved due to the gas tracer capabilities and the need for early well and field information. This paper will also discuss the retrofit screen design that allowed the gas tracers embedded in a polymer matrix called gas systems (GS) to be installed inside premium mesh screens. At the wellsite, sampling campaign adjustments were executed depending on the flowing conditions during the clean-up, restarts to obtain relative flow contribution and inflow performance under multi-rate testing conditions. Using a structured approach, the inflow gas monitoring project included feasibility studies, well candidate selection, lessons learnt and developed best practices based on installations in six producing wells in the North Malay Basin (NMB).

From the 1930s to the early 1960s, the dominant paradigm in the field of race relations in the United States was assimilation. One of the most influential theories in the assimilation paradigm was Park’s theory of race relations cycle. However, assimilation theories and the assimilation paradigm for explaining and predicting the development of race relations continue to hold perhaps the middle ground, between chauvinistic nativism and affirmative multiculturalism. Gordon’s theory may be regarded, in some respects, as the last major work on assimilation in the 1960s, before the reemergence of Marxist and neo-Marxist paradigms on race relations that paralleled the shift in the civil rights movement from an emphasis on desegregation to one on black power. In other words, assimilation and the American myth of opportunity and socioeconomic mobility are inseparable in the mindset of Americans, including most scholars who study race relations.